Clinical Trials

Title Protocol No. & Open Date Open Date Cancer Site Principal Investigator/ Physician Summary
Abbvie M16-298 (MERU) M16-298  03/14/2017  Lung  Moh’d Khushman, MD 

Protocol: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Rovalpituzumab Tesirine as Maintenance Therapy Following First-Line Platinum-Based Chemotherapy in Subjects with Extensive Stage Small Cell Lung Cancer (MERU)

Inclusion Criteria:  Histologically or cytologically confirmed advanced or metastatic Small Cell Lung Cancer (SCLC) with documented first disease progression during or following front-line platinum-based systemic regimen;  High Delta-like protein 3 (DLL3) expression defined as having ≥ 75% tumor cells staining positive; Must have measurable disease; must have measurable disease; Recovery to Grade 0 or 1 of any clinically significant toxicity (excluding alopecia) prior to initiation of study drug administration.

Exclusion Criteria:  Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms;  known leptomeningeal metastases; Received more than one prior systemic therapy regimen for SCLC; Serious infection within 2 weeks prior to randomization, including any Grade 3 or higher viral, bacterial, or fungal infection; History of active malignancies other than SCLC within the past 2 years prior to study entry, with the exception of in situ cancer which was curatively treated; Prior exposure to topotecan, irinotecan or any other topoisomerase I inhibitors.

 

Clinical Trials.Gov Link:  https://clinicaltrials.gov/ct2/show/NCT03033511?term=M16-298&recrs=a&rank=1

 
Abbvie M16-289 (Tahoe) M16-289  03/14/2017  Lung  Moh’d Khushman, MD 

Protocol: A Randomized, Open-Label, Multicenter, Phase 3 Study of Rovalpituzumab Tesirine Compared with Topotecan for Subjects with Advanced or Metastatic DLL3high Small Cell Lung Cancer (SCLC) who have First Disease Progression During or Following Front-Line Platinum-Based Chemotherapy (TAHOE)

Inclusion Criteria:  Histologically or cytologically confirmed advanced or metastatic Small Cell Lung Cancer (SCLC) with documented first disease progression during or following front-line platinum-based systemic regimen;  High Delta-like protein 3 (DLL3) expression defined as having ≥ 75% tumor cells staining positive; Must have measurable disease; must have measurable disease; Recovery to Grade 0 or 1 of any clinically significant toxicity (excluding alopecia) prior to initiation of study drug administration.

Exclusion Criteria:  Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms;  known leptomeningeal metastases; Received more than one prior systemic therapy regimen for SCLC; Serious infection within 2 weeks prior to randomization, including any Grade 3 or higher viral, bacterial, or fungal infection; History of active malignancies other than SCLC within the past 2 years prior to study entry, with the exception of in situ cancer which was curatively treated; Prior exposure to topotecan, irinotecan or any other topoisomerase I inhibitors.

 

Clinical Trials.Gov Link: https://clinicaltrials.gov/ct2/show/NCT03061812?term=M16-289&recrs=a&rank=1

 
ADXS001-02 AIM2CERV ADXS11-001  01/10/2017  Cervical  Jennifer Scalici, MD 

Protocol Tiltle: A phase 3 trial of ADXS11-001 administered following chemo-radiation as adjuvant treatment for high risk locally advanced cervical cancer

Inclusion Criteria: Patient must have biopsy confirmed diagnosis of squamous cell, adenocarcinoma, or adenosquamous carcinoma of the cervix; FIGO stage IB2, IIB with biopsy proven pelvic node metastases, 2 or more pelvic nodes by CT or MRI measuring ≥ 1.5 cm in shortest dimension, 2 or more pelvic nodes by PET with SUV ≥ 2.5 cm or all FIGO stage IIIA, IIIB, IVA or any FIGO stage with para-aortic lymph node metastases criteria; must have received CCRT with curative intent according to either institutional or national guidelines with a minimum of at least 4 weeks exposure with cisplatin and a minimum of 40 Gy external beam radiation therapy (EBRT); completion of CCRT, including brachytherapy, defined as the last dose of radionat or chemotherapy, must be completed by no more than 10 weeks prior to the initiation of the screening period; GOG performance scale of 0 or 1

Exclusion Criteria: patient has not achieved disease-free status after completion of CCRT administered with curative intent; has FIGO stage IVB; has histologies other than squamous cell, adenocarcinoma or adenosquamous carcinoma of the cervix; had any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for other invasive malignancies within 2 years (concurrent use of hormones for non-cancer-related conditions is acceptable); has implanted medical device(s) that pose a high risk for colonization and/or cannot be easily removed; currently receiving or have a known plan to receive in the future a PI3K or TNF inhibitors; has received a live vaccine within 30 days prior to the first dose of study treatment; history of other invasive malignancies within 3 years of randomization; has bilateral hyronephrosis unless at least one side has been stented and renal function fulfills the required inclusion criteria; has known active CNS metastases and/or carcinomatous meningitis; has liver cirrhosis or any other impaired hepatic function as dtermined by serum enzymes; has undergone a previous hysterectomy.

Clinical Trials.Gov Link:  https://www.clinicaltrials.gov/ct2/show/NCT02853604?term=ADXS001-02&rank=1

 
Alliance A011106 (ALTERNATE) A011106  03/10/2014  Breast  Lynn Dyess, MD 

Protocol Title:  "ALTernate approaches for clinical stage II or III Estrogen Receptor positive breast cancer NeoAdjuvant Treatment (ALTERNATE) in postmenopausal women: A Phase III Study (Alliance A011106)."

Inclusion criteria: ECOG performance status 0-2; Postmenopausal; Pathologic confirmation of invasive breast cancer diagnosed by core needle biopsy; Clinical T2-T4c, any N, M0 invasive breast cancer; estrogen receptor positive with an Allred score of 6, 7 or 8;  Invasive breast cancer is HER2 negative defined as 0 or 1+ by IHC

Exclusion criteria: Inflammatory breast cancer; Surgical axillary staging procedure prior to study entry; Clinical or radiographic evidence of metastatic disease; Hormone replacement therapy of any type, megestrol acetate, or raloxifene within one week prior to registration; Tumor ER Allred score between 0-5 or HER2 positive by IHC (3+)

Clinical Trails.Gov Link:  http://clinicaltrials.gov/ct2/show/NCT01953588?term=Alliance+A011106&rank=1

 

 
Alliance A011202 A011202  09/08/2015  Breast  Lynn Dyess, MD 

Protocol Tiltle:  "A randomized phase III trial comparing axillary lymph node dissection to axillary radiation in breast cancer patients (cT1-3N1) who have positive sentinel lymph node disease after neoadjuvant chemotherapy."

Inclusion Criteria:  ECOG status 0-1. Clinical stage T1-3 N1 M0 breast cancer at diagnosis (prior to the start of neoadjuvant chemotherapy) by American Joint Committee on Cancer (AJCC) staging 7th edition. No inflammatory breast cancer. No other malignancy within 5 years of registration with the exception of basal cell or squamous cell carcinoma of the skin treated with local resection only or carcinoma in situ of the cervix. All patients must have had an axillary ultrasound with fine needle aspiration (FNA) or core needle biopsy of axillary lymph nodes documenting axillary metastasis at the time of diagnosis, prior to or at most 14 days after starting neoadjuvant chemotherapy. Patients must have had estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2) status by immunohistochemistry [IHC] and/or fluorescence in situ hybridization [FISH] evaluated on diagnostic core biopsy. Patients with HER-2 positive tumors must have received neoadjuvant trastuzumab, trastuzumab + pertuzumab, or other approved anti-HER-2 therapy (either with all or with a portion of the neoadjuvant chemotherapy regimen). Patients must have completed at least 6 cycles of neoadjuvant chemotherapy consisting of an anthracycline and/or taxane-based regimen without evidence of disease progression in the breast or the lymph nodes.

Exclusion Criteria: Neoadjuvant endocrine or radiation therapy. Sentinel lymph node (SLN) surgery/excisional biopsy for pathological confirmation of axillary status prior to or during neoadjuvant chemotherapy. Prior ipsilateral axillary surgery, such as excisional biopsy of lymph node(s) or treatment of hidradenitis.

Clinical Trails.Gov Link:  https://clinicaltrials.gov/ct2/show/NCT01901094?term=A011202&rank=1

 
Alliance A021501 A021501  05/09/2017  Pancreatic  William Taylor, MD 

Protocol:  Preoperative Extended Chemotherapy vs. Chemotherapy Plus Hypofractionated Radiation Therapy For Borderline Resectable Adenocarcinoma Of The Head Of The Pancreas

Inclusion Criteria: Cytologic or histologic proof of adenocarcinoma of the pancreatic head or uncinate process; TNM Stage: TX, T1-4N0-1orNxM0;  Must meet any one or more of the following on CT/MRI: 1) An interface is present between the primary tumor and the superior mesenteric vein or portal vein and measures ≥ 180° of the circumference of the vessel wall, 2) Short-segment occlusion of the SMV-PV is present with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction, 3) Short segment interface (of any degree) is present between tumor and hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and reconstruction, 4) An interface is present between the tumor and superior mesenteric artery or celiac axis measuring < 180° of the circumference of the vessel wall.

 Exclusion Criteria:  Patients with less extensive disease than the above four (4) criteria; Patients with more extensive disease than the above 4 criteria; Any interface between the tumor and the aorta.

 

Clinical Trials.Gov Link:https://clinicaltrials.gov/ct2/show/NCT02839343?term=A021501&recrs=a&rank=1

 
Alliance Prospect N1048  12/03/2015  Rectal  Moh’d Khushman, MD 

Protocol Title:  "A Phase II/III Trial of Neoadjuvant FOLFOX with Selective Use of Combined Modality Chemoradiationversus Preoperative Combined Modality Chemoradiation for Locally Advanced Rectal Cancer Patients Undergoing Low Anterior Resection with Total Mesorectal Excision (PROSPECT)."

Inclusion Criteria: Diagnosis of rectal adenocarcinoma, the standard treatment recommendation in the absence of a clinical trial would be combined modality neoadjuvant chemoradiation followed by curative intent surgical resection.

Exclusion Criteria: Clinical T4 tumors, Evidence that the tumor is adherent to or invading the mesorectal fascia on imaging studies such that the surgeon would not be able to perform an RO resection (one with negative margins). Chemotherapy within 5 years prior to registration, Exceptions are colonic polyps, non-melanoma skin cancer or carcinoma-in-situ of the cervix

Clinical Trails.Gov Link:    https://clinicaltrials.gov/ct2/show/NCT01515787?term=n1048&rank=1

 
AstrZeneca D8488C00001 D8488C00001  02/22/2018  Ovarian  Rodney Rocconi, MD 

Protocol Title: A single arm, open-label, Phase IIb study to assess the efficacy and safety of the combination of cediranib and olaparib tablets in women with recurrent
platinum resistant epithelial ovarian cancer, including fallopian tube and/or primary peritoneal cancer who do not carry a deleterious or suspected deleterious germline BRCA mutation

Inclusion Criteria:  Ability and willingness to provide written informed consent, and to comply with the requirements of the protocol; Females aged ≥18 years with previous histologically proven diagnosis of high grade serous, high grade endometroid or clear cell ovarian cancer, fallopian tube or primary peritoneal carcinoma; No evidence of deleterious or suspected deleterious germline mutation in BRCA1 or BRCA2 genes; Recurrent platinum-resistant disease, defined as disease progression within 6 months (182 days) of the last receipt of platinum-based chemotherapy; CT/MRI evidence of measurable disease as per RECIST 1.1 defined as at least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) and which is suitable for accurate repeated measurements; Eastern Cooperative Oncology Group (ECOG) performance status 0-2; Life expectancy ≥12 weeks; Prior receipt of antiangiogenic treatment, including but not limited to bevacizumab, is optional. If used, it can be used in the first line or recurrent setting; At least three prior lines of therapy for advanced ovarian cancer as defined in the protocol; Confirmation of the availability of a tumor sample from the primary or recurrent cancer must be provided; Patients must have adequate organ and bone marrow function; Adequately controlled blood pressure; Adequately controlled thyroid function, with no symptoms of thyroid dysfunction; Able to swallow and retain oral medications and without gastrointestinal illnesses that would preclude absorption of cediranib or olaparib; Postmenopausal or evidence of non-childbearing status for women of childbearing potential as confirmed by a negative urine or serum pregnancy test within 7 days prior to start of IPs

 

Exclusion Criteria: Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site); Previous enrollment in the present study; Exposure to any IP during the last 4 weeks prior to enrollment; Previous treatment with PARP inhibitor. For this study, BSI-201 (iniparib) is not considered as PARPi; Recent cancer-directed therapies: Radiotherapy (RT) within 4 weeks, chemotherapy or other systemic anti-cancer therapy within 4 weeks, or prior anti-angiogenic treatment (e.g., bevacizumab) within 6 weeks prior to starting treatment; Cancer antigen-125 (CA-125) only disease without RECIST 1.1 measurable disease; Major surgical procedure within 2 weeks prior to starting treatment; patients must have recovered from any effects of any major surgery and surgical wound should have healed prior to starting treatment; Clinically significant signs and/or symptoms of bowel obstruction within 3 months prior to starting treatment; History of intra-abdominal abscess within 3 months prior to starting treatment ;History of GI perforation. Patients with a history of abdominal fistula will be considered eligible if the fistula was surgically repaired, there has been no evidence of fistula for at least 6 months prior to starting treatment, and patient is deemed to be at low risk of recurrent fistula ;Other malignancy within the last 5 years;Persisting ≥Grade 2 CTCAE toxicity (except alopecia and Grade 2 peripheral neuropathy) from previous anti-cancer treatment(s); Central nervous system metastases; Patients with any of the following: History of myocardial infarction within 6 months prior to starting treatment; Unstable angina; Resting electrocardiogram (ECG) with clinically significant abnormal findings; New York Heart Association functional classification of III or IV; Left ventricular ejection fraction (LVEF) < lower limit of normal (LLN) per institutional guidelines, or <55%, if threshold for normal not otherwise specified by institutional guidelines, for patients with the following risk factors: Prior treatment with anthracyclines; Prior treatment with trastuzumab; Prior central thoracic RT, including exposure of heart to therapeutic doses of ionizing RT; History of myocardial infarction within 6-12 months prior to start of IPs; Prior history of other significant impaired cardiac function; History of stroke or transient ischemic attack within 6 months; Uncontrolled intercurrent illness; Patients with myelodysplastic syndrome (MDS)/ treatment-related acute myeloid leukemia (t-AML) or with features suggestive of MDS/AML; No prior allogenic bone marrow transplant or double umbilical cord blood transplantation; Known active human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection on antiviral treatment; Concomitant use of known strong or moderate CYP3A inhibitors; Concomitant use of known strong or moderate CYP3A inducers

Clinical Trials.Gov Link: https://clinicaltrials.gov/ct2/show/NCT02889900?term=D8488C00001&rank=1

 
BMS 209-812 BMS 209-812  10/12/2017  Hodgkin Lymphoma  Sachin Pai, MD 

Protocol Title:  A Study of Nivolumab Plus Brentuximab Vedotin Versus Brentuximab Vedotin Alone in Patients With Advanced Stage Classical Hodgkin Lymphoma, Who Are Relapsed/ Refractory or Who Are Not Eligible for Autologous Stem Cell Transplant, (CheckMate 812)

 

Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1; Participants must have a pathologic diagnosis of classical Hodgkin lymphoma (cHL) who are relapsed or refractory with one of the following: 1) Autologous stem cell transplant (ASCT) ineligible patients; 2) Patients after failure of ASCT; Must have at least one lesion that is > 15 mm (1.5 cm) in the longest diameter and avid by Fluoro Deoxy Glucose (FDG) Positron Emission Tomography (PET) scan.

 

Exclusion Criteria: Known central nervous system lymphoma; Participants with nodular lymphocyte-predominant Hodgkin lymphoma (HL); Participants with known history of pancreatitis or progressive multifocal leukoencephalopathy (PML)

 

Clinical Trials. Gov Link: https:https://clinicaltrials.gov/ct2/show/NCT03138499?term=209-812&rank=1//clinicaltrials.gov/ct2/show/NCT03138499?term=209-812&rank=1

 
Calithera CX-839-007 CX-839-007  07/14/2017  Breast  Carole Norden, MD 

Protocol: A Multicenter Phase 2 Study of the Glutaminase Inhibitor CB-839 in Comination with Paclitaxel in Patients with Advanced Triple Negative Breast Cancer (TNBC) Including Patients of African Ancestry and Non-African Ancestry

 Inclusion Criteria: Meets criteria for 1 of the 4 defined study cohorts; TNBC defined as ER and PR negative (<1%) and HER-2 negative (FISH negative or IHC 0-1+);  Metastatic disease or locally-advanced disease not amenable to curative intent treatment; Adequate hepatic, renal, cardiac, and hematologic function; ECOG performance status 0-1; Recovery to baseline or ≤ Grade 1 CTCAE.

 Exclusion Criteria: Known brain metastases or CNS cancer unless adequately treated with radiotherapy and/or surgery and stable for ≥ 2 mo; Unable to receive oral medications; Known hypersensitivity to Cremophor®-based agents; Major surgery within 28 days of C1D1.

 

Clinical Trials.Gov Link: https://clinicaltrials.gov/ct2/show/NCT03057600?term=CX-839-007&recrs=a&rank=1

 
Caris Registry TCREG-001-00-V2-1209  09/16/2013  Solid Tumor  Michael Finan, MD 

Protocol Title: "A Registry of Caris Life Sciences Molecular Intelligence™ Service (Biomarker Assessment Results) Intended for Correlation with Cancer Clinical Outcomes."

Inclusion Criteria: Age greater than or equal to 19 years; Solid Tumor analyzed by Caris Molecular Intelligence™ Service Profile(s) and/or Next-Generation Sequencing

Exclusion Criteria: Individual test orders, defined as single biomarker assessment; prisoners-patients

Clinical Trials.Gov Link: https://clinicaltrials.gov/ct2/show/NCT02678754?term=Caris+Registry&rank=1

 
Celgene HEOR-PANC-ABX-USA-0804161 0804161  11/30/2017  Pancreatic  Thomas W. Butler, MD 

Protocol Title:  "A Prospective Quality of Life Study in Metastatic Pancreatic Cancer"

 

Inclusion Criteria:  Aged ≥ 18 years; Able to read, comprehend, and complete questionnaires and interview in English; Has access to an internet-connected computer/ tablet/ smart-phone; Has clinician-confirmed diagnosis of metastatic (not locally advanced) adenocarcinoma of the pancreas; Treatment: Patient is receiving either Abraxane plus gemcitabine (A/G) or FOLFIRINOX (FFX) as a first line therapy for metastatic pancreatic cancer (may include modified FFX or A/G); Stage of treatment: Patient has not been on therapy for more than one month (i.e, 3 doses of Abraxane; or 2 doses of fluorouracil [5 FU]) (you may include patients who are due to start therapy within the next 6 weeks); Written informed consent given prior to any study-related procedures

 

Exclusion Criteria:  Has a mental or physical condition that would prevent completion of questionnaires or participation in interviews; Pancreatic cancer has metastasized to the brain; Has another primary malignancy with the exception of: squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, uteri, nonmelanomatous skin cancer, carcinoma in-situ of the breast, or incidental histological finding of prostate cancer (TNM stage of T1a or T1b); Currently enrolled in any other cancer-related interventional study or quality of life (QOL) study (registry studies and post-marketing safety studies are permitted);  Documented history in the past 12 months of alcohol or other substance abuse

 
Celsion 201-17-201 201-17-201  07/31/2018  Ovary, Peritoneum, Fallopian Tube  Rodney Rocconi, MD 

Protocol: A Phase I/II Study Evaluating the Dosing, Safety, Efficacy, and Biological Activity of Intraperitoneal GEN-1 (IL-12 Plasmid Formulated With PEG-PEI-Cholesterol Lipopolymer) Administered in Combination With Neoadjuvant Chemotherapy (NACT) in Patients Newly Diagnosed With Advanced Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Inclusion Criteria:  Patients must have histologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma per pre-treatment biopsies by laparoscopy, or interventional radiology or CT guided core biopsy. Histologic documentation of the original primary tumor is required via the pathology report. Patients must have an International Federation of Gynecology and Obstetrics (FIGO) of III or IV. Patients with the following histologic epithelial cell types are eligible: High grade serous adenocarcinoma, endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, or adenocarcinoma not otherwise specified (N.O.S.). Patients must have adequate: Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl. This ANC cannot have been induced or supported by granulocyte colony stimulating factors. Platelets greater than or equal to 100,000/mcl. Renal function: Creatinine ≤1.5 x institutional upper limit normal (ULN). Hepatic function: Bilirubin ≤ 1.5 x ULN. SGOT (AST) and SGPT (ALT) ≤ 3.0 x ULN and alkaline phosphatase ≤ 2.5 x ULN. Neurologic function: Neuropathy (sensory and motor) less than or equal to Grade 1. Patients should be free of active infection requiring parenteral antibiotics or a serious uncontrolled medical illness or disorder within four weeks of study entry. Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to the first treatment. Continuation of hormone replacement therapy is permitted. Patients must have a performance status score of 0, 1 or 2 by Eastern Cooperative Group (ECOG) criteria. Patients of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of protocol therapy and be practicing an effective form of contraception. If applicable, patients must discontinue breastfeeding prior to study entry. Patients must have satisfactory results for the baseline laboratory analyses and diagnostic procedures as specified in the protocol. Patients must have signed an IRB-approved informed consent and authorization permitting release of personal health information. Patients must be at least 18 years old.

Exclusion Criteria:  Patients who have received prior treatment with GEN-1. History of allergic reactions attributed to compounds of similar chemical or biologic composition to GEN-1 or other agents used in this study. Patients who have received oral or parenteral corticosteroids within 2 weeks of study entry or who have a clinical requirement for ongoing systemic immunosuppressive therapy such as chronic steroid use not related to chemotherapy administration. Patients receiving treatment for active autoimmune disease. "Active" refers to any condition currently requiring therapy. Examples of autoimmune disease include systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease and rheumatoid arthritis. Patients with other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies as noted in the protocol are excluded if there is any evidence of other malignancy being present within the last three years. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy. Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded. Prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease. Patients who have received prior chemotherapy for any abdominal or pelvic tumor are excluded. Patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease. Patients with known active hepatitis. Patients with concurrent severe medical problems unrelated to the malignancy that would significantly limit full compliance with the study or expose the patient to extreme risk or decreased life expectancy. Patients of childbearing potential, not practicing adequate contraception, patients who are pregnant, or patients who are breastfeeding are not eligible for this trial. Patients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study. Patients with any condition/anomaly that would interfere with the appropriate placement of the IP catheter for study drug administration including: abdominal surgery within 4 weeks of study entry (for reasons other than IP port placement), intestinal dysfunction, or suspected extensive adhesions from prior history or finding at laparoscopy.

 

Clinical Trials.Gov Link:  https://clinicaltrials.gov/ct2/show/NCT03393884?term=201-17-201&rank=1

 
Chiltern Sotio SP005 SP005  11/01/2014  Prostate  David Clarkson, MD 

Prostate Title:  "A Randomized, Double Blind, Multicenter, Parallel-Group, Phase III Study to Evaluate Efficacy and Safety of DCVAC/PCa Versus Placebo in Men with Metastatic Castration Resistant Prostate Cancer Eligible for 1st Line Chemotherapy."

Inclusion Criteria: Histologically or cytologically confirmed prostate adenocarcinoma; Presence of skeletal or soft-tissue/visceral/nodal metastasis; ECOG Performance status 0-2. Disease progression despite ADT as indicated by:  PSA increase that is ≥ 2 mg/mL and ≥ 25% above the minimum PSA as reached during ADT or above the pre-treatment level OR Progression of measurable lymph nodes (≥ 15mm) or visceral lesion measurable

Exclusion Criteria:  Confirmed brain and/or leptomeningeal metastases; Current symptomatic cord compression; Prior chemotherapy for prostate cancer; Treatment with anti-androgens, inhibitors of adrenal-produced androgens or other hormonal tumor-focused treatment performed on the day of screening or within previous four weeks

Clinical Trails.Gov Link: https://clinicaltrials.gov/ct2/show/NCT02111577?term=SP005&rank=1

 
ECOG-ACRIN EA1131 EA1131  09/21/2015  Breast  Carole Norden, MD 

Protocol Tiltle:  "A Randomized Phase III Post-Operative Trial of Platinum Based Chemotherapy Vs. Capecitabine in Patients with Residual Triple-Negative Basal-Like Breast Cancer following Neoadjuvant Chemotherapy."

Inclusion Criteria: ECOG performance status 0 or 1 within 2 weeks prior to screening, Female and male patients must have histologically confirmed triple negative (estrogen receptor negative [ER-]/progesterone receptor negative [PR-]/human epidermal growth factor receptor-2 negative [HER2-]) invasive breast cancer, clinical stage II-III at diagnosis (American Joint Committee on Cancer [AJCC] 7th edition) based on initial evaluation by clinical examination and/or breast imaging, Patients must have completed neoadjuvant taxane +/- anthracycline; patients must NOT have received cisplatin or carboplatin or capecitabine as part of their neoadjuvant therapy regimen, Must have completed definitive resection of primary tumor, Post neoadjuvant chemotherapy, patients must be found to have residual invasive cancer in the breast at the time of definitive surgery; residual cancer is defined as a contiguous focus of residual invasive cancer, in the breast, measuring >= 1 cm in diameter, and with more than minimal cellularity, as per local pathologist determination, Post-mastectomy radiotherapy is required for all patients with: Primary tumor >= 5 cm (prior to neoadjuvant chemotherapy [clinically] or at the time of definitive surgery) or involvement of 4 or more lymph nodes at the time of definitive surgery & or patients with primary tumors < 5 cm or with < 4 involved lymph nodes prior to neoadjuvant chemotherapy and at the time of definitive surgery, provision of post-mastectomy radiotherapy is at the discretion of the treating physician, Breast radiotherapy (whole breast or partial) is required for patients who underwent breast-conserving therapy, including lumpectomy or partial mastectomy, Laboratory values must be obtained within 8 weeks prior to screening for protocol therapy, Hemoglobin (Hgb) > 9.0 g/dL, Platelets > 100 mm^3, Absolute neutrophil count (ANC) > 1500 mm^3, Calculated creatinine clearance of > 50 mL/min using the Cockcroft-Gault formula, Bilirubin =< 1.5 x ULN upper limit of normal (except in patients with documented Gilbert's disease, who must have a total bilirubin =< 3.0 mg/dL), Aspartate aminotransferase (AST, serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 x upper limit of normal (ULN), Alanine aminotransferase (ALT, serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN, No stage IV (metastatic) disease, however no specific staging studies are required in the absence of symptoms or physical exam findings that would suggest distant disease, No clinically significant infections as judged by the treating investigator, Patients with active >= Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4 grade 2 neuropathy are ineligible, Adjuvant chemotherapy after surgery other than that specified in this protocol is not allowed; luteinizing hormone-releasing hormone (LHRH) agonists and adjuvant bisphosphonate or denosumab use is allowed, Patients must have archived formalin-fixed paraffin-embedded (FFPE) tumor tissue specimen from the residual disease on the definitive surgical specimen available for PAM50 analysis for stratification.

Clinical Trails.Gov Link:  https://clinicaltrials.gov/ct2/show/NCT02445391?term=EA1131&rank=1

 
Eli Lilly I4T-MC-JVDD I4T-MC-JVDD  03/25/2016  Gastric (Stomach)  Moh’d Khushman, MD 

Protocol Title:  "Safety and Effectiveness of Ramucirumab in Patients with Advanced Gastric Cancer in European Union and North America:  A prospective Observational Registry."

Inclusion Criteria:  Advanced gastric cancer or GEJ adenocarcinoma that has progressed after prior chemotherapy and have initiated Ramucirumab treatment.

Exclusion Criteria:  Received more than 1 line of chemotherapy for advanced gastric or GEJ, or currently participating in any other study.

 

 
Gradalis CL-PTL-126 CL-PTL-126  03/17/2017  Ovarian  Rodney Rocconi, MD 

Protocol: A Randomized, Intra-patient Crossover, Safety,Biomarker and Anti-Tumor Activity Assessment of the Combination of Atezolizumab and Vigil in Patients with Advanced Gynecological Cancers

Inclusion Criteria: Successful manufacturing of at least 4 vials of Vigil; Failure to meet the eligibililty criteria for Protocol CL-PTL-119 due to i) histology of ovarian cancer and failure to achieve a complete clinical response following primary debulking surgery and standard paclitaxel/carboplatin therapy OR, ii) a histologic diagnosis of another gynecologic malignancy which is not ovarian cancer; ECOG performance status (PS) ≤ 1; Estimated survival ≥ 6 months; Measureable or evaluable disease; Adequate organ and bone marrow function.

Exclusion Criteria: Rceived more than two additional chemotherapy regimens for platinum resistant/refractory ovarian cancer, after their initial treatment with paclitaxel/carboplatin, OR have received more than two additional chemotherapy regimens for the treatment of another gynecologic malignancy; Participation in another clinical study with an investigational product within the last 3 weeks prior to study start; Patients with autoimmune diseases are excluded from enrollment with the exception of patients with hypothyroidism on stable thyroxine replacement, and patients with T1DM on stable insulin replacement; Receipt of steroid therapy within the 2 weeks of the first dose of study therapy; Post-surgery complication; Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.

 

Clinical Trials.Gov Link: https://clinicaltrials.gov/ct2/show/NCT03073525?term=CL-PTL-126&recrs=a&rank=1

 
Halozyme HALO 109-301 HALO 109-301  05/25/2016  Pancreatic  William Taylor, MD 

Protocol Title:  "Phase 3, Randomized, double-blind, placebo-controlled, Multicenter Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) in Combination with Nab-Paclitaxel plus Gemcitabine Compared with Placebo Plus nab-paclitaxel and Gemcitabine in subjects with Hyaluronan-high Stage IV previously Untreated Pancreatic Ductal Adenocarcinoma."

Inclusion Criteria:  Stage 4 pancreatic ductal adenocarcinoma with histological confirmation via archived or fresh core biopsy/ HA-high based ; 1 measurable lesion, If adjuvant treatment received recurrence must be >6 months after last dose; ECOG 0-1; life expectance > 3 months; adequate lab values

Exclusion Criteria:  Evidence of DVT/ PE or other known TE event, no previous treatment for metastatic disease, known CNS mets, NYHA class III or IV cardiac disease, no MI, CVA or TIA in last 12 months, known HIV, Hepatitis B or C; current use of megestrol acetate (10 day wash out) no immunization with live vaccine up to 2 wks prior to day 1.  Hypersensitivity to PEGPH20, gemcitabine and nab-paclitaxel.

Clinical Trials.Gov Link:  https://clinicaltrials.gov/ct2/show/NCT02715804?term=109-301&rank=1

 
INCB INCB 01158-101  12/04/2017  Solid Tumor  Sachin Pai, MD 

Protocol Title: Safety, Pharmacokinetics, and Pharmacodynamics of Escalating Oral Doses of the Arginase Inhibitor INCB001158 (formerly known as CB-1158) as a Single Agent and in Combination with Immune Checkpoint Therapy in Patients with Advanced/Metastatic Solid Tumors.

  

Inclusion Criteria: Must be age 18 or older; Ability to provide written informed consent in accordance with federal, local, and institutional guidelines; Histological or cytological diagnosis of metastatic cancer or locally advanced cancer that is not amenable to local therapy; Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1; Life Expectancy of at least 3 months; Adequate hepatic, renal, cardiac, and hematologic function; Measurable disease by RECISTv1.1 criteria; Resolution of treatment-related toxicities; Willingness to avoid pregnancy or fathering children; Prior anti-PD-1 treatment for combination dose expansion cohorts 3a - 3d.

  

Exclusion Criteria: Currently pregnant or lactating; Unable to receive oral medications; Unable to receive oral or IV hydration; Intolerance to prior anti-PD-1/PD-L1 therapy; Prior anti-PD-1 treatment for combination dose expansion cohorts 3e - 3h; Prior severe hypersensitivity reaction to another monoclonal antibody (mAb); Any other current or previous malignancy within 3 years except protocol allowed malignancies; Chemotherapy, Tyrosine Kinase Inhibitor therapy, radiation therapy or hormonal therapy within 2 weeks; Immunotherapy or biological therapy, or investigational agent within 3 weeks (Note: some cohort exceptions allow anti-PD-1 therapy); Active known or suspected exclusionary autoimmune disease; Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other systemic immunosuppressive medications within 2 weeks; Concomitant therapy with valproic acid/valproate-containing therapies; Concomitant therapy with allopurinol and other xanthine oxidase inhibitors; History of known risks factors for bowel perforation; Symptomatic ascites or pleural effusion; Major surgery within 28 days before Cycle 1 Day 1; Active infection requiring within 2 weeks prior to first dose of study drug; Patients who have HIV, Hepatitis B or C; Conditions that could interfere with treatment or protocol-related procedures; Active, non-stable brain metastases or CNS disease; Known deficiencies or suspected defect in the urea cycle; Received live-virus vaccination within 30 days (seasonal flu vaccine allowed if non-live virus); NSCLC with EGFR or ALK mutation.

  

Clinical Trials.Gov Link: https://clinicaltrials.gov/ct2/show/NCT02903914?term=INCB+01158-101&rank=1

 
Ipsen MM-398-07-02-03 MM-398-07-02-03  07/31/2018  Pancreatic  Moh’d Khushman, MD 

Protocol: A Randomized, Open-label Phase 2 Study of Nanoliposomal Irinotecan (Nal-IRI)-Containing Regimens Versus Nab-Paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma

Inclusion Criteria:  Histologically or cytologically confirmed adenocarcinoma of the pancreas that has not been previously treated in the metastatic setting, Unresectable, locally advanced or metastatic disease; diagnosed within 6 weeks prior to screening, At least one tumor lesion measurable by CT or MRI scan (according to RECIST v1.1), ECOG performance status of 0 or 1 at screening and within 72 hours prior to first dose if first dose occurs more than 72 hours post-screening, Adequate hematological, hepatic, renal and cardiac function, Recovered from the effects of any prior surgery or radiotherapy, Patient has a Karnofsky performance status (KPS) ≥ 70 at Screening, and within 72 hours prior to date of first dose if first dose occurs more than 72 hours after screening (Part 1B only)

Exclusion Criteria:  Prior treatment of pancreatic cancer in the metastatic setting (or locally advanced setting) with surgery (placement of stent is allowed), radiotherapy, chemotherapy or investigational therapy ,Prior treatment of pancreatic cancer with chemotherapy in adjuvant setting, except those where at least 12 months have elapsed since completion of the last dose and no persistent treatment-related toxicities present, Uncontrolled Central Nervous System (CNS) metastases, Clinically significant gastrointestinal disorder, History of any second malignancy in the last 3 years. Patients with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible, Presence of any contraindications for nal-IRI, irinotecan, 5-FU, leucovorin, oxaliplatin, Use of strong CYP3A4 or CYP2C8 inhibitors or inducers or presence of any other contra indications for irinotecan, Pregnant or breast feeding, Neuroendocrine or acinar pancreatic carcinoma, Serum albumin < 3 g/dL at screening visit and within 72 hours prior to first dose if first dose occurs more than 72 hours post screening, Patients with symptoms and signs of clinically unacceptable deterioration of primary disease at time of screening, Previous treatment with irinotecan-based, nab-paclitaxel-based or gemcitabine-based resulting in disease progression

 

Clinical Trials.Gov Link:  https://clinicaltrials.gov/ct2/show/NCT02551991?term=MM-398-07-02-03&rank=1

 
Lumicell CL0006 CL0006  07/31/2018  Breast  Lynn Dyess, MD 

Protocol: Feasibility Study Phase C: Expansion Into Multiple Institutions for Training in the Use of the LUM Imaging System for Intraoperative Detection of Residual Cancer in the Tumor Bed of Female Subjects With Breast Cancer

Inclusion Criteria:  Histologically or cytologically confirmed primary invasive breast cancer, ductal carcinoma in situ (DCIS) or a combination of invasive breast cancer and DCIS. Subjects who had diagnostic surgical biopsies are excluded from participation. Female, age of 18 years or older. Scheduled for a lumpectomy for a breast malignancy. Able and willing to follow study procedures and instructions. Received and signed an informed consent form. No uncontrolled serious medical problems except for the diagnosis of cancer. Normal organ and marrow function within limits as defined below: Leukocytes > 3,000/mcL, Platelets > 75,000/mcL, total bilirubin within normal institutional limits, AST (SGOT)/ALT (SGPT) < 2.5 X institutional upper limit of normal, Creatinine ≤ 1.5 mg/dL or creatinine clearance > 60 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal. ECOG performance status of 0 or 1.

Exclusion Criteria:  pregnant at the time of diagnosis of their breast cancer. Sexually active and not willing/able to use medically acceptable forms of contraception (hormonal or barrier method of birth control, abstinence) upon entering the study and for 60 days after injection of LUM015. Have taken an investigational drug within 30 days of enrollment. Prolonged QTc interval defined as greater than 480 ms. Will have administration of methylene blue or any blue dye for sentinel lymph node mapping on the day of the surgery prior to imaging the lumpectomy cavity with the LUM Imaging Device. Have not recovered from adverse events due to other pharmaceutical or diagnostic agents. Uncontrolled hypertension defined as persistent systolic blood pressure > 180 mm Hg, or diastolic blood pressure > 110 mm Hg; subjects with known HTN should be stable within these ranges while under pharmaceutical therapy. History of anaphylactic reaction attributed to any contrast agent or drugs containing polyethylene glycol (PEG). Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, COPD or asthma requiring hospitalization within the past 12 months, or psychiatric illness/social situations that would limit compliance with study requirements. HIV-positive individuals on combination antiretroviral therapy. Investigator feels participation is not in the best interest of the subject. Undergoing a second lumpectomy procedure because of positive margins in a previous surgery prior to entering this study. Prior ipsilateral breast cancer surgeries, mastectomies, breast reconstructions or implants. Prior ipsilateral reduction mammoplasties (breast reductions) performed less than 2 years prior to enrollment to this study. Previously treated with systemic therapies to treat the cancer to be removed during this clinical investigation, such as neo-adjuvant chemotherapy or hormonal therapy

 

Clinical Trials.Gov Link: https://clinicaltrials.gov/ct2/show/NCT03321929?term=CL0006&rank=1

 
MATCH (EAY131) EAY131  05/19/2016  Solid Tumor  Rodney Rocconi, MD 

Protocol Title:  "Targeted therapy directed by genetic testing in treating patients with advanced refractory solid tumors or lymphomas."

Inclusion Criteria: Patients must have histologically documented solid tumors or histologically confirmed diagnosis of lymphoma that has progressed following at least one line of standard systemic therapy. Patients must have tumor amenable to image guided or direct vision biopsy and be willing and able to undergo a tumor biopsy for molecular profiling; biopsy must not be considered to be more than minimal risk to the patient. Presence of one or more of the specific “actionable” mutations/amplifications of interest (see protocol).

Exclusion Criteria:  Patients who require coumadin derivative anticoagulants, except low weight heparin for prophylactic use; uncontrolled illnesses including CHF, unstable angina, arrhythmia, cardiac metastases. Any prior radiotherapy or major surgery unless > 4 weeks prior to study treatment. Palliative radiation must be completed at least 2 weeks prior to study enrollment.

Clinical Trails.Gov Link:  https://clinicaltrials.gov/ct2/show/NCT02465060?term=EAY131&rank=1

 
NRG BR005 BR005  05/09/2017  Breast  Lynn Dyess, MD 

Protocol: A Phase II Trial Assessing the Accuracy of Tumor Bed Biopsies in Predicting Pathologic Response in Patients with Clinical/Radiologic Complete Response after Neoadjuvant Chemotherapy in Order to Explore the Feasibility of Breast Conserving Treatment without Surgery

Inclusion Criteria: (ECOG) performance status of 0 or 1; must have had ER analysis performed on the primary breast tumor collected prior to neoadjuvant therapy; must have had HER2 testing performed on the primary breast tumor collected prior to neoadjuvant chemotherapy; must have a biopsy marker placed within the tumor bed with imaging confirmation; Patients with operable focal or multifocal and who have completed neoadjuvant chemotherapy with a clinical complete response; achieved a complete or near complete radiologic tumor response on breast imaging with mammogram, ultrasound, and MRI; must be undergoing breast conserving therapy.

Exclusion Criteria:T4 tumors including inflammatory breast cancer;  metastatic disease; Lumpectomy performed prior to study entry;  history of prior radiation therapy in the affected breast;  synchronous ipsilateral invasive breast cancer or any prior history of ipsilateral invasive breast cancer; invasive lobular carcinoma; have multicentric disease; treated with neoadjuvant hormonal therapy only; atients without breast biopsy marker documented by imaging at tumor bed site prior to initiation of neoadjuvant therapy.

 

Clinical Trials.Gov Link: https://clinicaltrials.gov/ct2/show/NCT03188393?term=NRG+BR005&recrs=a&rank=1

 
NRG GI002 GI002  04/11/2017  Rectal  Clayton Smith, MD 

Protocol: A Phase II Clinical Trial Platform of Sensitization Utilizing Total Neoadjuvant Therapy (TNT) in Rectal Cancer

Inclusion Criteria:Diagnosis of adenocarcinoma of the rectum with the major portion of the tumor intact; The tumor must be clinically determined to be locally advanced stage II or stage III rectal cancer; At least two (2) untreated core biopsy specimens from the untreated tumor (formalin-fixed, paraffin-embedded [FFPE]) must have been collected previously and be available for submission per protocol requirements.

Exclusion Criteria: Rectal cancer histology other than adenocarcinoma; Definitive clinical or radiologic evidence of metastatic disease; History of prior invasive rectal malignancy, regardless of disease-free interval; Cardiac disease that would preclude the use of any of the drugs included in the GI002 treatment regimen; Sensory or motor neuropathy >= grade 2; Active inflammatory bowel disease; Active seizure disorder uncontrolled by medication; Any antineoplastic therapy for this cancer before randomization; Synchronous colon cancer; Other invasive malignancy within 5 years before randomization; exceptions are colonic polyps, non-melanoma skin cancer or carcinoma-in-situ of the cervix; Chemotherapy within 5 years before randomization.

 

Clinical Trials.Gov Link: https://clinicaltrials.gov/ct2/show/NCT02921256?term=NRG+GI002&recrs=a&rank=1

 
NRG-GU003 GU003  12/08/2017  Prostate  Clayton Smith, MD 

Protocol Title: A RANDOMIZED PHASE III TRIAL OF HYPOFRACTIONATED POST-PROSTATECTOMY RADIATION THERAPY (HYPORT) VERSUS CONVENTIONAL POST-PROSTATECTOMY RADIATION THERAPY (COPORT).

  

Inclusion Criteria: PRIOR TO STEP 1 REGISTRATION- Adenocarcinoma of the prostate treated primarily with radical prostatectomy; Any type of radical prostatectomy will be permitted, including retropubic, perineal, laparoscopic, or robotically assisted;  no time limit for the date of radical prostatectomy;One of the following pathologic T-classifications: pT2 or pT3; Patients with positive surgical margins are eligible; One of the following pathologic N-classifications: pN0, pNX; If a lymph node dissection is performed, the number of lymph nodes removed per side of the pelvis and the extent of the pelvic lymph node dissection (obturator versus (vs.) extended lymph node dissection) should be noted whenever possible; No clinical evidence of regional lymph node metastasis; Computed tomography (CT) (with contrast if renal function is acceptable; a noncontrast CT is permitted if the patient is not a candidate for contrast), magnetic resonance imaging (MRI), nodal sampling, or dissection of the pelvis within 120 days prior to step 1 registration; Patients with pelvic lymph nodes equivocal or questionable by imaging are eligible if the nodes are =< 1 cm in the short axis; A post-radical prostatectomy study entry PSA >= 45 days after prostatectomy and within 30 days prior to step 1, < 2.0 ng/mL; No evidence of a local recurrence in the prostate fossa  within 60 days prior to step 1 registration; Patients with equivocal or questionable DRE findings should have an MRI of the pelvis to exclude the presence of a prostate fossa mass; Patients with equivocal or questionable exam findings by DRE or MRI are eligible if a biopsy of the lesion is negative for tumor; No evidence of bone metastases (M0) on bone scan (Na F positron emission tomography (PET)/CT is an acceptable substitute) within 120 days prior to step 1 registration; Equivocal bone scan findings are allowed if plain films and/or MRI are negative for metastasis; Zubrod performance status 0-1 within 60 days prior to step 1 registration; The patient or a legally authorized representative must provide study-specific informed consent prior to step 1 registration; Willingness and ability to complete the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire; Only English and French-speaking patients are eligible to participate; PRIOR TO STEP 2 REGISTRATION- The EPIC-26 must be completed in full and entered within 10 business days after step 1 registration; NRG Oncology Statistical and Data Management Center has 3 business days to score the results and send a notification to the site to proceed to step 2 randomization.

  

Exclusion Criteria: A post-prostatectomy PSA nadir >= 0.2 ng/mL AND Gleason >= 7; pT2 with a negative surgical margin and PSA < 0.1 ng/mL;androgen deprivation therapy started prior to prostatectomy for > 6 months (180 days) duration; Androgen deprivation therapy started after prostatectomy and prior to step 1 registration for > 6 weeks (42 days); Neoadjuvant chemotherapy before or after prostatectomy; Prior invasive (except non-melanoma skin cancer) malignancy unless disease-free for a minimum of 3 years and not in the pelvis; (for example, carcinoma in situ of the oral cavity is permissible if disease free for a minimum of 3 years; however, patients with prior history of bladder cancer are not allowed no matter the disease free duration); prior hematological (e.g., leukemia, lymphoma, myeloma) malignancy is not allowed; Previous chemotherapy for any other disease site if given within 3 years prior to step 1; Prior radiotherapy, including brachytherapy, to the region of the study cancer that would result in overlap of radiation therapy treatment volumes; Severe, active co-morbidity, defined as follows: Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months, Transmural myocardial infarction within the last 6 months, Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 1 registration, Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 1 registration, Severe hepatic disease, defined as a diagnosis of Child-Pugh class B or C hepatic disease, Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4 count < 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol, End-stage renal disease (ie, on dialysis or dialysis has been recommended), Prior allergic reaction to the study drugs involved in this protocol, History of inflammatory bowel disease, prior bowel surgeries (or colostomy) for any reason, or prior partial/radical cystectomy for any reason

 

Clinical Trials.Gov Link:https://clinicaltrials.gov/ct2/show/NCT03274687?term=NRG+GU003&rank=1

 
NRG-HN004 NRG-HN004  05/03/2018  Head and Neck  Sachin Pai, MD 

Protocol: Randomized Phase II/III Trial of Radiotherapy With Concurrent MEDI4736 (Durvalumab) vs. Radiotherapy With Concurrent Cetuximab in Patients With Stage III-IVB Head and Neck Cancer With a Contraindication to Cisplatin

Inclusion Criteria:  Pathologically confirmed, previously untrested, unresected squamous cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, or carcinoma of unknown head/neck primary within 60 days prior to step 1 registration, stage III-IVB head and neck squamous cell carcinoma (HNSCC), Patients must have a contraindication to cisplatin as defined in the following bullet points; sites must complete the online tool at comogram.org prior to step 1 registration to determine if the patient is eligible; the scores must be recorded on a case report form (CRF), Age < 70 with severe comorbidity or vulnerability to cisplatin, For patients with oropharyngeal or unknown primaries: p16 determination by immunohistochemistry (defined as greater than 70% strong nuclear or nuclear and cytoplasmic staining of tumor cells), confirmed by central pathology review, Note: for patients with oral cavity, laryngeal, and hypopharyngeal primaries, analysis of p16 status prior to step 2 registration/randomization is not required (p16 status will be analyzed centrally post-hoc); step 2 registration for these patients can be completed after step 1 registration

Exclusion Criteria:  prior invasive malignancy withint the past 3 years, prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields, prior immunotherapy, prior systemic therapy including cytoxic chemotherapy, biologic/targeted therapy or immune therapy for the study cancer, distant metastases, Zubrod performance status >= 3, Patients with oral cavity cancer are excluded from participation if the patient is medically operable and resection of the primary tumor is considered technically feasible by an oral or head and neck cancers surgical subspecialist;(please consult the surgical oncology co-principal investigator [PI], Steven Chang, Doctor of Medicine [MD], if clarification is needed on an individual case), Unstable angina and/or congestive heart failure requiring hospitalization within 3 months prior to step 1 registration, Transmural myocardial infarction within 3 months prior to step 1 registration, Respiratory illness requiring hospitalization at the time of step 1 registration, Note: if the respiratory illness is resolved and the patient meets the eligibility status above, then the patient can be considered for the trial, Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to require oxygen therapy within 1 year prior to step 1 registration, Clinically apparent jaundice and/or known coagulation defects, Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]), History of active primary immunodeficiency including, but not limited to acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; Note: human immunodeficiency virus (HIV) testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatment involved in this protocol may be immunosuppressive; patients with known HIV, CD4 counts >= 200/uL, and undetectable viral loads who are stable on an antiretroviral regimen may be included, Current or prior use of immunosuppressive medication within 14 days before step 1 registration, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid, Receipt of live attenuated vaccination within 30 days prior to step 1 registration, Medical or psychiatric illness which would compromise the patient's ability to tolerate treatment or limit compliance with study requirements, Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception during treatment and for 6 months after the last dose of cetuximab or MEDI14736 (durvalumab); this exclusion is necessary because the treatment involved in this study may be significantly teratogenic; women who are breastfeeding are also excluded, Prior allergic reaction or hypersensitivity to cetuximab or MEDI4736 (durvalumab) or any of study drug excipients, History of (non-infectious) pneumonitis that required steroids or current pneumonitis, History of allogenic organ transplantation, Uncontrolled hypertension, Uncontrolled cardiac arrhythmia, Uncontrolled serious chronic gastrointestinal condition associated with diarrhea, Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), hepatitis B (known positive hepatitis B virus [HBV] surface antigen [HBsAg] result), hepatitis C; patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible; patients positive for hepatitis C (hepatitis C virus [HCV]) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)

Clinical Trials.Gov Link: https://clinicaltrials.gov/ct2/show/NCT03258554?term=NRG-HN004&rank=1

 
NSABP Foundation B-59 B-59  05/05/2018  Breast  Lynn Dyess, MD 

Protocol: A Randomized, Double-Blind, Phase III Clinical Trial of Neoadjuvant Chemotherapy With Atezolizumab or Placebo in Patients With Triple-Negative Breast Cancer Followed by Adjuvant Continuation of Atezolizumab

Inclusion Criteria: The patient must have consented to participate and, prior to beginning specific study procedures, must have signed and dated an appropriate IRB-approved consent form that conforms to federal and institutional guidelines for study treatment and for submission of tumor samples as required by NSABP B-59/GBG 96-GeparDouze for baseline correlative science studies. The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy.  A pretreatment research core biopsy of the primary tumor must be performed with submission of 2 cores for required correlative studies. These specimens will NOT be returned to the site.  Local testing on the diagnostic core must have determined the tumor to be ER-negative, PgR-negative, and HER2-negative by current ASCO/CAP guidelines. (If local testing has determined a tumor to be HER2 equivocal or to have a borderline ER/PgR status (% IHC staining < 10% for both) and other eligibility criteria are met, material may be submitted for central testing to determine eligibility.)  Central testing for ER, PgR, and HER2 will be performed, and the tumor must be determined to be ER-negative, PgR-negative, and HER2-negative by current ASCO/CAP Guidelines Recommendations. Material from either the diagnostic core biopsy or the research biopsy can be used for central testing depending on local preferences and standards.  The ECOG performance status must be 0-1.  The primary tumor can be clinical stage T2 or T3, if clinically node negative according to AJCC 7th Edition. If the regional lymph nodes are cN1 and cytologically or histologically positive or cN2-N3 with or without a biopsy, the primary breast tumor can be clinically T1c, T2, or T3.  Ipsilateral axillary lymph nodes must be evaluated by imaging (mammogram, ultrasound, and/or MRI) within 84 days prior to study entry. If suspicious or abnormal, FNA or core biopsy is recommended. Findings of these evaluations will be used to define the nodal status prior to study entry according to the following criteria:  Nodal status - negative (Imaging of the axilla is negative; Imaging is suspicious or abnormal but the FNA or core biopsy of the questionable node[s] on imaging is negative) Nodal status - positive (FNA or core biopsy of the node[s] is cytologically or histologically suspicious or positive; Imaging is suspicious or abnormal but FNA or core biopsy was not performed.) Patients with synchronous bilateral or multicentric HER2-negative breast cancer are eligible as long as the highest risk tumor is ER-negative and PgR-negative and meets stage eligibility criteria. All of the other invasive tumors must also be HER2-negative by ASCO/CAP Guidelines based on local testing. Central testing to confirm TNBC status is only required for the highest risk tumor.  Blood counts performed within 28 days prior to randomization must meet the following criteria: ANC must be ≥ 1500/mm3; platelet count must be ≥ 100,000/mm3; and hemoglobin must be ≥10 g/dL.  The following criteria for evidence of adequate hepatic function performed within 28 days prior to randomization must be met: total bilirubin must be ≤ ULN for the lab unless the patient has a bilirubin elevation > ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin; and alkaline phosphatase must be ≤ 2.5 x ULN for the lab; and AST and ALT must be ≤ 1.5 x ULN for the lab.  Patients with AST or ALT or alkaline phosphatase > ULN are eligible for inclusion in the study if liver imaging (CT, MRI, PET-CT, or PET scan) performed within 28 days prior to randomization does not demonstrate metastatic disease and the requirements in criterion (just above) are met.  Patients with alkaline phosphatase that is > ULN but less than or equal to 2.5 x ULN or with unexplained bone pain are eligible for inclusion in the study if bone imaging (bone scan, PET-CT scan, or PET scan) performed within 28 days prior to randomization does not demonstrate metastatic disease.  Patients with N2 or N3 nodal disease or T3 primary disease must undergo liver and bone imaging (as described in 4.1.13 and 4.1.14) within 28 days prior to randomization, irrespective of baseline lab results, and studies must not demonstrate metastatic disease. Chest imaging with chest x-ray PA and Lateral, CT of the chest, or PET-CT must also be performed.  Creatinine clearance ≥ 40 mL/min (see Section 7.2.1 for instructions regarding calculation of creatinine clearance) performed within 28 days prior to randomization.  PT/INR ≤ ULN within 28 days of randomization. Patients receiving therapeutic anti-coagulants are not eligible.  A serum TSH and AM cortisol must be obtained within 28 days prior to randomization to obtain a baseline value.  LVEF assessment must be performed within 42 days prior to randomization. (LVEF assessment performed by echocardiogram is preferred; however, MUGA scan may be substituted based on institutional preferences.) The LVEF must be ≥ 55% regardless of the cardiac imaging facility's lower limit of normal.  For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab/placebo or 12 months after the last dose of chemotherapy.  A woman is considered to be of childbearing potential if she is not postmenopausal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).  Examples of contraceptive methods with a failure rate of < 1% per year include: bilateral tubal ligation; male partner sterilization; hormonal contraceptives that inhibit ovulation; hormone-releasing intrauterine devices; copper intrauterine devices.  The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.  Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria: Excisional biopsy or lumpectomy performed prior to study entry.  FNA alone to diagnose the breast cancer.  Surgical axillary staging procedure prior to randomization. Exception: FNA or core biopsy of an axillary node is permitted for any patient. A pre-neoadjuvant therapy sentinel lymph node biopsy for patients with clinically negative axillary nodes is prohibited.  Definitive clinical or radiologic evidence of metastatic disease.  Previous history of contralateral invasive breast cancer. (Patients with synchronous and/or previous contralateral DCIS or LCIS are eligible.)  Previous history of ipsilateral invasive breast cancer or ipsilateral DCIS. (Patients with synchronous or previous ipsilateral LCIS are eligible.)  History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to study entry.  Treatment including radiation therapy, chemotherapy, or targeted therapy, for the currently diagnosed breast cancer prior to randomization.  Previous therapy with anthracyclines or taxanes for any malignancy.  Cardiac disease (history of and/or active disease) that would preclude the use of the drugs included in the treatment regimens. This includes but is not confined to: Active cardiac disease: angina pectoris that requires the use of anti-anginal medication; ventricular arrhythmias except for benign premature ventricular contractions; supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; conduction abnormality requiring a pacemaker; valvular disease with documented compromise in cardiac function; or symptomatic pericarditis.  History of cardiac disease: myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular function within 6 months prior to randomization; history of documented CHF; or documented cardiomyopathy.  Uncontrolled hypertension defined as sustained systolic BP > 150 mmHg or diastolic BP > 90 mmHg. (Patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria.) Patients requiring greater than or equal to 3 BP medications are not eligible.  History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.  Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells.  Known allergy or hypersensitivity to the components of the atezolizumab formulation.  Known allergy or hypersensitivity to the components of the doxorubicin, cyclophosphamide, carboplatin, or paclitaxel formulations.  Known allergy or hypersensitivity to liposomal or pegylated G-CSF formulations.  Active or history of autoimmune disease or immune deficiency, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis for a more comprehensive list of autoimmune diseases and immune deficiencies) with the following exceptions: Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.  Patients with controlled Type 1 diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.  Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are permitted provided all of following conditions are met: Rash must cover < 10% of body surface area; Disease is well controlled at baseline and requires only low-potency topical corticosteroids; No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.  History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.  Patients known to be HIV positive.  Active hepatitis B virus (HBV) infection, defined as having a positive hepatitis B surface antigen (HBsAg) test at screening. Patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test at screening, are eligible for the study if active HBV infection is ruled out on the basis of HBV DNA viral load per local guidelines.  Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test at screening confirmed by a polymerase chain reaction (PCR) positive for HCV RNA.  Patients with clinically active tuberculosis.  Severe infection within 28 days prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.  Prior allogeneic stem cell or solid organ transplantation.  Administration of a live, attenuated vaccine within 28 days prior to randomization or anticipation that such vaccine will be required during the study. Patients must agree not to receive live, attenuated influenza vaccine (e.g., FluMist) within 28 days prior to randomization, during treatment or within 5 months following the last dose of atezolizumab/placebo.  Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications.  Prior treatment with CD137 agonists or immune checkpoint-blockade therapies, including anti-CD40, anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies.  Treatment with systemic immunosuppressive medications (including but not limited to interferons, IL-2) within 28 days or 5 half-lives of the drug, whichever is longer, prior to randomization.  Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti−tumor necrosis [anti-TNF] factor agents) within 14 days prior to randomization or anticipation of need for systemic immunosuppressive medications during the study.  Nervous system disorder (paresthesias, peripheral motor neuropathy, or peripheral sensory neuropathy) ≥ Grade 2, per the CTCAE v4.0.  Symptomatic peripheral ischemia.  Pregnancy or lactation at the time of randomization or intention to become pregnant during the study. (Note: Negative serum pregnancy test must be obtained within 14 days prior to randomization).  Use of any investigational agent within 28 days prior to randomization.

 

Clinical Trials.Gov Link: https://clinicaltrials.gov/ct2/show/NCT03281954?term=b-59&rank=1 

 
ONT-380-206 ONT-380-206  10/31/2016  Breast  Carole Norden, MD 

Protocol Title:  Phase 2 Randomized, Double-Blinded, Controlled Study of ONT-380 vs Placebo in Combination With Capecitabine and Trastuzumab in Patients With Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Carcinoma (HER2CLIMB).

Inclusion Criteria:  Patient must have histologically confirmed HER2+ breast carcinoma; have received previous treatment with taxane, trastuzumab, pertuzumab, and T-DM1; have progression of unresectable locally advanced or metastatic breast cancer after last systemic therapy; have measure or non-measurable disease assessable by RECIST 1.1; ECOG status of 0 or 1; life expectancy of at least 6 months; have adequate hepatic function; have creatinine clearance ≥ 50 mL/min; INR and aPTT ≤ 1.5 x ULN unless on medication know to alter INR and aPTT (note: Warfarin is a prohibited con med); LVEF ≥ 50% as assessed by ECHO or MUGA documented within 4 weeks prior to first dose of study medication; no evidence of brain metastases; untreated CNS brain metastases not needing immediate local therapy; previous treated brain metastases.

Exclusion Criteria:  Patient has been treated with lapatinib within 12 hours of starting study treatment or neratinib, afatinib, or other investigational HER2/EGFR or HER2 TKI at any time previously; previously been treated with capecitabine for metastatic disease; history of exposure to Doxorubicin or liposomal doxorubicin > 360 mg/m2, Epirubicin > 720 mg/m2, Mitoxantrone > 120 mg/m2, Idarubicin > 90 mg/m2, Other anthracyclines (e.g., liposomal doxorubicin) > the equivalent of 360 mg/m2 of doxorubicin; history of allergic reactions to trastuzumab, capecitabine or ONT-380; has received treatment with any systemic anti-cancer thereapy, non-CNS radiation, or experimental agent ≤ 3 weeks of first dose of study treatment; have any toxicity related to prior cancer therapies that has not resolved to ≤ grade 1; clinically significant cardiac disease; have known myocardial infarction or unstable angina within 6 months prior to study treatment; known carrier of Hepatitis B or C; HIV positive; require therapy with warfarin or other coumarin derivatives; have known dihydropyrimidine dehydrogenase deficiency; have used a strong CYP3A4 inducer or inhibitor within 3 elimination half-lives of the inhibitor or inducer prior to first dose of study treatment; and untreated lesions > 2.0 cm in size; ongoing use of systemic corticosteroids for control of symptoms of SNC metastases <28 days prior to first dose; any lesion thought to require immediate local therapy; known leptomeningeal disease; poorly controlled seizures

 

Clinical Trails.Gov Link:  https://clinicaltrials.gov/ct2/show/NCT02614794?term=ONT-380-206&rank=1

 

 
PALLAS PALLAS AFT-05  09/01/2016  Breast  Carole Norden, MD 

Protocol Title:  "A randomized phase III trial of Palbociclib with standard adjuvant endocrine therapy versus standard adjuvant endocrine therapy alone for hormone receptor positive (HR+) / human epidermal growth factor receptor 2 (HER2)-negative early breast cancer."

Inclusion Criteria: ECOG performance status 0-1; pre and postmenapausal women or men with stage II (Stage IIA limited to a max of 100 patients) or stage III early invasive breast cancer; patients with multicentric and/or multifocal and/or bilateral early invasive breast cancer whose histopathologically examined tumors all meet pathologic criteria for ER+ and/or PR+ and HER2-; patients must have undergone breast surgery for current malignancy; patients must be after last dose of chemotherapy and/or biologic therapy; patients must be after last dose of radiotherapy; patients must have sufficient resolution of any surgical side effects; patients must either be initiating or already started adjuvant hormonal treatment; patients who received neoadjuvant endocrine therapy are eligible as long as they are enrolled within 12 months of initial histological diagnosis and after completing no more than 6 months of adjuvant endocrine therapy

Exclusion Criteria: Prior therapy with any CDK inhibitor; patients with stage I or IV breast cancer; history of allergic reaction attributed to compounds of chemical or biologic composition similar to palbociclib

 

Clinical Trails.Gov Link:  https://clinicaltrials.gov/ct2/show/NCT02513394?term=AFT-05&rank=1

 

 
RTOG 0924 RTOG 0924  02/11/2014  Prostate  Weisi Yan, MD 

Protocol Title:  "Androgen Deprivation Therapy and High Dose Radiotherapy With or Without Whole-Pelvic Radiotherapy in Unfavorable Intermediate or Favorable High Risk Prostate Cancer: A Phase III Randomized Trial."

Inclusion Criteria: Pathologically proven diagnosis of prostatic adenocarcinoma within 180 days of registration; clinically negative lymph nodes as established by imaging within 90 days prior to registration; no evidence of bone metastases; Zubrod performance status 0-1

Exclusion Criteria: Prior invasive (except non-melanoma skin cancer) malignancy unless disease-free for 3 years; previous radical surgery (prostatectomy) or cryosurgery for prostate cancer

Clinical Trails.Gov Link:  https://clinicaltrials.gov/ct2/show/NCT01368588?term=RTOG+0924&rank=1

 
RTOG 1304/NSABP B-51 RTOG 1304  03/01/2014  Breast  Weisi Yan, MD 

Protocol Title:  "A Randomized Phase III Clinical Trial Evaluating Post-Mastectomy Chestwall and Regional Nodal XRT and Post-Lumpectomy Regional Nodal XRT in Patients with Positive Axillary Nodes Before Neoadjuvant ChemotherapyWho Convert to Pathologically Negative Axillary Nodes After Neoadjuvant Chemotherapy."

Inclusion Criteria: ECOG performance status of 0 or 1; patient must have clinically T1-3, N1 breast cancer at the time of diagnosis; must have pathologic onfirmation of axillary nodal involvement at presentation; ER analysis performed on the primary breast tumor before neoadjuvant therapy; HER2 testing performed on the primary breast tumor before neoadjuvant chemotherapy; completed a minimum of 12 weeks of standard neoadjuvant chemotherapy consisting of anthracycline and/or taxane-based regimen; for patients who receive adjuvant chemotherapy after surgery, a maximum of 12 weeks of intended chemotherapy may be administered but must be completed before randomization; patients with HER+ tumors must have received neoadjuvant trastuzumab or other anti-HER2 therapy; at the time of surgery, all removed axillary nodes must be histologically free from cancer; for patients who undergo mastectomy, that margins must be histologically free of residual tumor

Exclusion Criteria: definitive clinical or radiologic evidence of metastatic disease; T4 tumors including inflammatory breast cancer; documentation of axillary nodal positivity before neoadjuvant therapy by sentinel node biopsy alone; N2 or N3 disease detected clinically or by imaging; patients with microscopic positive margins after definitive surgery; any prior history of ipsilateral invasive breast cancer or ipsilateral DCIS treated with radiation therapy; history of non-malignancies; any radiation therapy for currently diagnosed breast cancer prior to randomization; prior breast or thoracic radiation therapy for any condition; active collagen vascular disease

 

Clinical Trails.GovLink: https://clinicaltrials.gov/ct2/show/NCT01872975?term=nsabp+b-51&rank=1

 
SWOG 1418 SWOG 1418  02/16/2018  Breast  Carole Norden, MD 

Protocol: A Randomized, Phase III Trial to Evaluate the Efficacy and Safety of MK-3475 as Adjuvant Therapy for Triple Receptor-Negative Breast Cancer with > 1 cm Residual Invasive Cancer or Positive Lymph Nodes (ypN+) After Neoadjuvant Chemotherapy

Inclusion Criteria: Patients must have histologically confirmed estrogen receptor (ER)-, progesterone receptor (PR)- and HER2-negative (triple-negative, TNBC) or ER, PR, and HER2 equivocal status and must not have received and not be planning to receive adjuvant anti-HER2 or endocrine therapies after completion of neoadjuvant chemotherapy;Patients must not have metastatic disease; Patients must not have locally recurrent disease; It is preferred that axillary lymph node sampling is performed after completion of neoadjuvant chemotherapy to allow more accurate assessment of pathologic response; patients must have a complete axillary lymph node dissection after neoadjuvant chemotherapy in the following situations; Patients must have a minimum of five, available unstained slides from the residual (post-neoadjuvant) invasive tumor in primary site or lymph node; the tumor tissue must be adequate for PD-L1 testing, which typically requires a minimum of 100 cancer cells per slide; Patients must be offered the opportunity to participate in specimen banking; Patients must have had neoadjuvant chemotherapy followed by surgery; the recommended neoadjuvant treatment should include 16-24 weeks of a third generation chemotherapy regimen as recommended by National Comprehensive Cancer Network (NCCN) guidelines for triple negative breast cancer; patients who cannot complete all planned treatment cycles for any reason are considered high risk and therefore are eligible for the study if they have residual disease; patients must have resolution of adverse event(s) of the most recent prior chemotherapy to grade 1 or less, except alopecia and =< grade 2 neuropathy which are allowed; Patients must have completed their final breast surgery (rendering them free from disease) with clear resection margins for invasive cancer and DCIS; Patients for whom radiation therapy (RT) to the affected breast or chest wall and regional nodal areas is clinically indicated as per NCCN treatment guidelines, should receive RT after randomization when possible, and receive MK-3475 (pembrolizumab) concurrent with RT, if randomized to the experimental arm; however, RT administered, or initiated, prior to registration is also allowed; pembrolizumab may be added to ongoing radiation, or started after its completion, if randomized to the experimental arm, provided there are no > grade 2 radiation-related skin toxicities; patients who have not yet started radiation must specify at the time of screening registration whether or not they will receive RT and the extent of intended RT; Patients must not have had prior immunotherapy with anti-PD-L1, anti-PD-1, anti-CTLA4 or similar drugs; patients must not be planning to receive any of the prohibited therapies during the screening or treatment phases of the study; Patients must not be planning to receive concomitantly other biologic therapy, hormonal therapy, other chemotherapy, surgery or other anti-cancer therapy except radiation therapy while receiving treatment on this protocol; however, patients receiving extended adjuvant endocrine therapy for an earlier ER positive breast cancer treated with curative intent and without recurrence for at least 5 years may continue with their endocrine therapy; Patients must have Zubrod performance status =< 2; Patients must not have a history of (non-infectious) pneumonitis that required steroids or evidence of active pneumonitis; Patients must not have an active infection requiring systemic therapy; Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment; Patients must not have received live vaccines within 30 days prior to registration; examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine; seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed; Patients must not have known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection prior to registration; Patients must not have known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection prior to registration; Patients must not be registered to step 2 until receiving confirmation from the Southwest Oncology Group (SWOG) Statistical Center that the patient's tissue specimen was adequate for PD-L1 testing; patients must be registered within 7 days of receiving the e-mail notification confirming submission was evaluable for PD-L1 status; Absolute neutrophil count (ANC) >= 1,500 microliter (mcL), obtained within 28 days prior to step 2 registration; Platelets >= 100,000/mcL, obtained within 28 days prior to step 2 registration; Hemoglobin >= 9 g/dL, obtained within 28 days prior to step 2 registration; A serum thyroid-stimulating hormone (TSH) must be obtained within 28 days prior to step 2 registration to obtain a baseline value; Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (except Gilbert's syndrome, who must have a total bilirubin < 3.0 mg/dL), obtained within 28 days prior to step 2 registration; Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x IULN, obtained within 28 days prior to step 2 registration; Alkaline phosphatase =< 2.5 x IULN, obtained within 28 days prior to step 2 registration; Serum creatinine =< IULN OR measured or calculated creatinine clearance >= 60 mL/min, obtained within 28 days prior to step 2 registration; Women of childbearing potential must have a negative urine or serum pregnancy test within 28 day prior to registration; women/men of reproductive potential must have agreed to use an effective contraceptive method for the course of the study through 120 days after the last dose of study medication; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or vasectomy; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures; patients must not be pregnant or nursing; Site must verify that there is no known change in the step 1 eligibility since initial registration

Clinical Trials.Gov Link:  https://clinicaltrials.gov/ct2/show/NCT02954874?term=S1418&rank=1

 
SWOG 1513 S1513  05/09/2017  Pancreatic  Moh’d Khushman, MD 

Protocol: “Randomized Phase II Study of 2nd Line FOLFIRI versus Modified FOLFIRI with PARP Inhibitor ABT-888 (Veliparib) (NSC-737664) in Metastatic Pancreatic Cancer.”

Inclusion Criteria: Patients must have histologically or cytologically documented pancreatic adenocarcinoma; patients with pancreatic neuroendocrine tumors, lymphoma of the pancreas, or ampullary cancer are not eligible; Patients must have metastatic disease that is measurable; Patients must have had one and only one prior regimen of systemic therapy for metastatic disease unless the patient meets the criteria below; Prior systemic therapy and chemoradiotherapy for treatment of resectable, borderline resectable or locally advanced unresectable disease is allowed and does not count toward prior therapy for metastatic disease; Patients who received systemic therapy with gemcitabine/nab-paclitaxel for resectable or borderline/locally advanced unresectable disease and progressed with metastatic disease within 3 months of the past dose of systemic therapy are eligible; Patients must have a Zubrod performance status of 0-1

Exclusion Criteria: History of brain metastases; received prior irinotecan-based chemotherapy; received prior PARP inhibitor therapy including, but not limited to ABT-888, olaparib, rucaparib, and talazoparib (BMN637); any clinically significant and uncontrolled major medical condition(s) including, but not limited to uncontrolled nausea/vomiting/diarrhea; active uncontrolled infection; symptomatic congestive heart failure (New York Heart Association [NYHA] class >= II); unstable angina pectoris or cardiac arrhythmia; psychiatric illness/social situation that would limit compliance with study requirements; active seizure or history of seizure; known Gilbert's syndrome; known hypersensitivity to irinotecan, fluorouracil, or leucovorin.

 

Clinical Trials.Gov Link: https://clinicaltrials.gov/ct2/show/NCT02890355?term=S1513&recrs=a&rank=1 

 
SWOG 1609 (DART) SWOG 1609  05/01/2017  Solid Tumor  Sachin Pai, MD 

Protocol: "DART: DUAL ANTI-CTLA-4 AND ANTI-PD-1 BLOCKADE IN RARE TUMORS”

Inclusion Criteria: Patients must have histologically confirmed rare cancer and/or cancer of unknown primary, that did not have a match to a molecularly-guided therapy on EAY131 "National Cancer Institute (NCI)-Molecular Analysis for Therapy Choice (MATCH)" protocol or who progressed on molecularly-matched therapy and have no further molecularly-matched treatment recommendations per EAY131, "NCI-MATCH", Patients that are determined to have a rare cancer with unknown primary site are eligible provided that there is histologic documentation of metastatic malignancy with no discernible primary site identified from histopathologic review, physical exam and associated cross-sectional imaging of the chest, abdomen, and pelvis, No other prior malignancy is allowed except for the following: Adequately managed stage I or II cancer from which the patient is currently in complete remission, any other cancer from which the patient has been disease free for five years, adequately managed stage I or II follicular thyroid or prostate cancer is also eligible, wherein patient is not required to be in complete remission, Patients with clinically controlled thyroiditis or pituitary disorders on stable replacement therapy are eligible.

Exclusion Criteria: Patients are not eligible if they have had or are planned for solid organ transplant; patients who have received allogeneic hematopoietic stem cell transplant are eligible if the transplant occurred at least 90 days prior to registration, patient has no prior acute graft versus host disease (GVHD), and within 48 hours of registration, patient demonstrates at least 90% engraftment, defined as: absolute neutrophil count (ANC) >= 500 mcl, measured over 3 consecutive days or 1 day with an ANC >= 1,000 mcl, or platelets >= 50,000 mcl measured, wherein the patient did not receive any platelet transfusions within 7 days prior to laboratory assessment, patients with autoimmune disease who are otherwise eligible under criterion 5.3 k must not have received steroid and immunosuppressive therapy within 28 days prior to registration; Patients must not have active autoimmune disease that has required systemic treatment in past 2 years; Patients must not have any uncontrolled intercurrent illness including (not limited to): symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 24 weeks prior to registration, unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4 grade >= 2), known psychiatric illness that would limit study compliance, intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (>= grade 3)

 

Clinical Trial.Gov Link: https://clinicaltrials.gov/ct2/show/NCT02834013?term=SWOG+1609&rank=1

 
Tesaro 3000-02-004 3000-02-004  05/29/2018  Ovarian  Rodney Rocconi, MD 

Protocol: Phase 2, Single-arm, Open-label Study to Evaluate the Safety and Efficacy of Niraparib Combined With Bevacizumab as Maintenance Treatment in Patients With Advanced Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer Following Front-line Platinum-based Chemotherapy With Bevacizumab

 Inclusion Criteria: Patients must be female, be ≥ 18 years of age, be able to understand the study procedures, and agree to participate in the study by providing written informed consent. Patients must have newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) Stage IIIB to IV epithelial ovarian, fallopian tube, or peritoneal cancer and have recovered from debulking surgery. Patients must have high-grade serous or endometrioid or high-grade predominantly serous or endometrioid histology, regardless of HRD or germline breast cancer susceptibility gene (gBRCA) mutation status. Patients with non mucinous epithelial ovarian cancer and gBRCA mutation are eligible. Patients must have completed front-line, platinum-based chemotherapy with CR, PR, or NED and have first study treatment dose within 12 weeks of the first day of the last cycle of chemotherapy: A platinum-based regimen must have consisted of a minimum of 6 and a maximum of 9 treatment cycles. Patients who discontinued platinum-based therapy early as a result of non hematologic toxicity specifically related to the platinum regimen (ie, neurotoxicity or hypersensitivity) are eligible if they have received a minimum of 4 cycles of the platinum regimen. IV, intraperitoneal, or neoadjuvant platinum-based chemotherapy is allowed; for weekly therapy, 3 weeks is considered 1 cycle. Interval debulking is allowed. Patients must have received, prior to enrollment, a minimum of 3 cycles of bevacizumab in combination with the last 3 cycles of platinum-based chemotherapy. Patients who undergo interval debulking surgery are eligible if they have received only 2 cycles of bevacizumab in combination with the last 3 cycles of platinum-based chemotherapy. Patients must have had 1 attempt at optimal debulking surgery. Patients must have either CA-125 in the normal range or CA-125 decrease by more than 90% during front-line therapy that is stable for at least 7 days (ie, no increase > 15% from nadir). Patients must have adequate organ function, defined as (Note: Complete Blood Count (CBC) test should be obtained without transfusion or receipt of stimulating factors within 2 weeks before obtaining screening blood sample): Absolute neutrophil count (ANC) ≥ 1,500/µL Platelet count ≥ 100,000/µL Hemoglobin ≥ 9 g/dL Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min using Cockcroft-Gault equation Total bilirubin ≤ 1.5 × ULN OR direct bilirubin ≤ 1 × ULN Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN unless liver metastases are present, in which case they must be ≤ 5 × ULN Patients must have an Eastern Cooperative Oncology Group (ECOG) score of 0 or 1. Patients must have normal blood pressure or well-controlled hypertension. Patient must agree to complete PROs (quality of life [QoL] questionnaire) throughout the study, including after study treatment discontinuation. Patients must be able to take oral medication. Patient must agree to undergo tumor HRD testing at screening. The tumor sample must be submitted for HRD testing during the Screening Period. Patients do not have to wait for the HRD test result to be enrolled. If archival tumor tissue is not available for testing, the patient must agree to undergo a fresh biopsy. Patients of childbearing potential must have a negative serum or urine pregnancy test (beta human chorionic gonadotropin) within 72 hours prior to receiving the first dose of study treatment. Patients must be postmenopausal, free from menses for > 1 year, surgically sterilized, or willing to use adequate contraception to prevent pregnancy or must agree to abstain from activities that could result in pregnancy throughout the study, starting with enrollment through180 days after the last dose of study treatment. 

Exclusion Criteria: Patients with ovarian tumors of non-epithelial origin (eg, germ cell tumor) or any low grade tumors. Patients with clinically significant cardiovascular disease (eg, significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina < 6 months to enrollment, New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade II or greater peripheral vascular disease, and history of cerebrovascular accident (CVA) within 6 months). Patients with gastrointestinal disorders or abnormalities that would interfere with absorption of study treatment. History of bowel obstruction, including sub-occlusive disease, related to the underlying disease or history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscesses. Evidence of rectosigmoid involvement by pelvic examination or bowel involvement on computed tomography (CT) scan or clinical symptoms of bowel obstruction. Patient has proteinuria as demonstrated by urine protein:creatinine ratio ≥ 1.0 at screening or urine dipstick for proteinuria ≥ 2 (patients discovered to have ≥ 2 proteinuria on dipstick at baseline should undergo a 24-hour urine collection and must demonstrate < 2 g of protein in 24 hours to be eligible). Patient has any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). Patient has received treatment previously with a PARP inhibitor. Other than ovarian cancer, the patient has been diagnosed or treated for invasive cancer less than 5 years prior to study enrollment. Patients with cervical carcinoma in situ, non melanomatous skin cancer, and ductal carcinoma in situ definitively treated are allowed. Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, non malignant systemic disease, or active, uncontrolled infection. Patient has known contraindication to PARP inhibitors or vascular endothelial growth factor (VEGF) inhibitors. Patient is at increased bleeding risk due to concurrent conditions (eg, major injuries or surgery within the past 28 days prior to start of study treatment, history of CVA, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months). Patient is immunocompromised (patients with splenectomy are allowed). Patient has known, active hepatic disease (ie, hepatitis B or C). Patient has a QT interval prolongation > 480 ms at screening. If a patient has a prolonged QT interval and the prolongation is deemed to be due to a pacemaker upon Investigator evaluation (ie, the patient otherwise has no cardiac abnormalities), then the patient may be eligible to participate in the study following discussion with the Medical Monitor. Patient is pregnant, breastfeeding, or expecting to conceive children while receiving study drug or for 180 days after the last dose of study drug.

 

Clinical Trials.Gov Link: https://clinicaltrials.gov/ct2/show/NCT03326193?term=3000-02-004&rank=1 

 
Tesaro 3000-02-004 Tesaro 3000-02-004  12/04/2017  Ovary, Peritoneum, Fallopian Tube  Rodney Rocconi, MD 

Protocol Title: Phase 2, A Study of Niraparib Combined With Bevacizumab Maintenance Treatment in Patients With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy.

  

Inclusion Criteria: Must be female, be ≥ 18 years of age, be able to understand the study procedures, and agree to participate in the study by providing written informed consent; Newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) Stage IIIB to IV epithelial ovarian, fallopian tube, or peritoneal cancer and have recovered from debulking surgery; high-grade serous or endometrioid or high-grade predominantly serous or endometrioid histology, regardless of HRD or germline breast cancer susceptibility gene (gBRCA) mutation status. Patients with non mucinous epithelial ovarian cancer and gBRCA mutation are eligible; completed front-line, platinum-based chemotherapy with CR, PR, or NED and have first study treatment dose within 12 weeks of the first day of the last cycle of chemotherapy:A platinum-based regimen must have consisted of a minimum of 6 and a maximum of 9 treatment cycles. Patients who discontinued platinum-based therapy early as a result of non hematologic toxicity specifically related to the platinum regimen (ie, neurotoxicity or hypersensitivity) are eligible if they have received a minimum of 4 cycles of the platinum regimen. IV, intraperitoneal, or neoadjuvant platinum-based chemotherapy is allowed; for weekly therapy, 3 weeks is considered 1 cycle. Interval debulking is allowed; Patients must have received, prior to enrollment, a minimum of 3 cycles of bevacizumab in combination with the last 3 cycles of platinum-based chemotherapy. Patients who undergo interval debulking surgery are eligible if they have received only 2 cycles of bevacizumab in combination with the last 3 cycles of platinum-based chemotherapy; Patients must have had 1 attempt at optimal debulking surgery; Patients must have either CA-125 in the normal range or CA-125 decrease by more than 90% during front-line therapy that is stable for at least 7 days (ie, no increase > 15% from nadir); Patients must have adequate organ function; Eastern Cooperative Oncology Group (ECOG) score of 0 or 1; Normal blood pressure or well-controlled hypertension; Agree to complete PROs (quality of life [QoL] questionnaire) throughout the study, including after study treatment discontinuation; Able to take oral medication; Patient must agree to undergo tumor HRD testing at screening; Patients of childbearing potential must have a negative serum or urine pregnancy test (beta human chorionic gonadotropin) within 72 hours prior to receiving the first dose of study treatment; Must be postmenopausal, free from menses for > 1 year, surgically sterilized, or willing to use adequate contraception to prevent pregnancy or must agree to abstain from activities that could result in pregnancy throughout the study, starting with enrollment through180 days after the last dose of study treatment.

  

Exclusion Criteria:  Ovarian tumors of non-epithelial origin (eg, germ cell tumor) or any low grade tumors; Clinically significant cardiovascular disease (eg, significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina < 6 months to enrollment, New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade II or greater peripheral vascular disease, and history of cerebrovascular accident (CVA) within 6 months); Gastrointestinal disorders or abnormalities that would interfere with absorption of study treatment; History of bowel obstruction, including sub-occlusive disease, related to the underlying disease or history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscesses. Evidence of rectosigmoid involvement by pelvic examination or bowel involvement on computed tomography (CT) scan or clinical symptoms of bowel obstruction; Proteinuria as demonstrated by urine protein:creatinine ratio ≥ 1.0 at screening or urine dipstick for proteinuria ≥ 2 (patients discovered to have ≥ 2 proteinuria on dipstick at baseline should undergo a 24-hour urine collection and must demonstrate < 2 g of protein in 24 hours to be eligible); Any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML); Received treatment previously with a PARP inhibitor; Other than ovarian cancer, the patient has been diagnosed or treated for invasive cancer less than 5 years prior to study enrollment. Patients with cervical carcinoma in situ, non melanomatous skin cancer, and ductal carcinoma in situ definitively treated are allowed. Considered a poor medical risk due to a serious, uncontrolled medical disorder, non malignant systemic disease, or active, uncontrolled infection; Known contraindication to PARP inhibitors or vascular endothelial growth factor (VEGF) inhibitors; Increased bleeding risk due to concurrent conditions (eg, major injuries or surgery within the past 28 days prior to start of study treatment, history of CVA, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months); Immunocompromised (patients with splenectomy are allowed); Known, active hepatic disease (ie, hepatitis B or C). A QT interval prolongation > 480 ms at screening. If a patient has a prolonged QT interval and the prolongation is deemed to be due to a pacemaker upon Investigator evaluation (ie, the patient otherwise has no cardiac abnormalities), then the patient may be eligible to participate in the study following discussion with the Medical Monitor;  Pregnant, breastfeeding, or expecting to conceive children while receiving study drug or for 180 days after the last dose of study drug                                                

ClincalTrials.Gov Link: https://clinicaltrials.gov/ct2/show/NCT03326193?term=Tesaro+3000-02-004&rank=1

 
University of Chicago UC IRB 13-1235  10/03/2017  Ovary, Peritoneum, Fallopian Tube  Rodney Rocconi, MD 

Protocol Title: A Randomized Placebo Controlled Phase II Trial of Metformin in Conjunction With Chemotherapy Followed by Metformin Maintenance Therapy in Advanced Stage Ovarian, Fallopian Tube and Primary Peritoneal Cancer

 

Inclusion Criteria:  The subject and her physician must agree to six cycles of one of the standard of care regimens allowed on this protocol; these regimens (starting dosage) include: IV paclitaxel 175 mg/m^2 and carboplatin area under the curve (AUC) 5-6 every 21 days; IV docetaxel 75 mg/m^2 and carboplatin AUC 5-6 every 21 days; IV paclitaxel 80 mg/m^2 day 1, 8, and 15 and carboplatin AUC 5-6 day 1 every 21 days; ECOG performance status =< 2; Leukocytes >= 3,000/mcL; absolute neutrophil count >= 1,500/mcL;  platelets >= 100,000/mcL;  total bilirubin =< upper normal institutional limits (except for patients with Gilbert's disease who are eligible despite elevated serum bilirubin level); AST(SGOT)/ALT(SGPT) =< 2.0 × institutional upper limit of normal; creatinine =< OR institutional ULN OR creatinine clearance >= 60 mL/min/1.73 m^2; blood glucose =< 126 mg/dL fasting or =< 140 mg/dL nonfasting; women of child-bearing potential must agree to use an effective method of birth control on trial, as the safety of metformin in pregnancy has not been established; an effective method of birth control includes surgical sterilization of woman or her partner, abstinence, or two barrier methods (e.g. condom plus diaphragm); hormonal methods of birth control are not permitted on this study; ability to understand and the willingness to sign a written informed consent document

 

Exclusion Criteria: Mucinous adenocarcinoma, borderline tumors; subjects who will undergo intraperitoneal chemotherapy; subjects receiving neoadjuvant chemotherapy for whom interval debulking surgery (assuming adequate response to therapy) is not planned; subjects receiving chemotherapy regimens not specified in the inclusion criteria; subjects should not be participating in other clinical trials of interventions designed to reduce risk of ovarian cancer recurrence or plan to receive off -protocol maintenance therapy (e.g. paclitaxel or bevacizumab); subjects with known diabetes, fasting glucose over 126 mg/dL or random glucose over 140 mg/dL and those taking metformin, sulfonylureas, thiazolidenediones or insulin for any reason; patients who are receiving any other investigational agents; subjects with comorbidities which would lead to a clinical expectation that they will not survive two years for reasons other than ovarian cancer; concurrent active invasive malignancy or one previously diagnosed with a greater than 30% chance of recurrence in the next two years; history of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin; subjects must not have conditions associated with increased risk of metformin-associated lactic acidosis, including New York Heart Association class III or IV congestive heart failure, history of acidosis of any type, alcoholic liver disease, or habitual intake of 3 or more alcoholic beverages per day; uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements;  pregnant or nursing women are excluded from this stud

 

Clinical Trials.Gov Link:  https://clinicaltrials.gov/ct2/show/NCT02122185?term=UC+IRB13-1235&rank=1

 
University of Chicago UC IRB17-0686 UC IRB17-0686  02/19/2018  Melanoma  Arthur Frankel, MD 

Protocol Title: Phase II study of pembrolizumab and ipilimumab following initial anti-PD1/L1 antibody

Inclusion Criteria:  Be willing and able to provide written informed consent for the trial; Be 18 years of age on day of signing informed consent; Have experienced disease progression or stable disease lasting at least 24 weeks during treatment with an anti-PD1/L1 antibody as the treatment regimen immediately prior to accrual to this study. Have measurable disease based on irRECIST 1.1.;Have a performance status of 0 or 1 on the ECOG Performance Scale.;Hematological Absolute neutrophil count (ANC) ≥1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment); Renal Serum creatinine OR Measured or calculateda creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN; Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases Albumin >2.5 mg/dL; Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants; Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants; Creatinine clearance should be calculated per institutional standard; Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required; Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year; Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

 

Exclusion Criteria: Has received study therapy (including investigational device) as part of a clinical trial within 4 weeks of the first dose of treatment, with the exclusion of an anti-PD1/L1 antibody given as either a single agent or non-CTLA-4 antibody containing combination; Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment; Has a known history of active TB (Bacillus Tuberculosis); Hypersensitivity to pembrolizumab or any of its excipients; Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 (excluding commercial or investigational anti-PD1 or anti-PD-L1 antibodies as single agents) or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier; Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent; Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer; Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability; Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment; Has known history of, or any evidence of active, non-infectious pneumonitis; Has an active infection requiring systemic therapy; Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator; Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial; Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment; Has received prior therapy with an anti-CTLA4 agent; Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies); Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected); Has received a live vaccine within 30 days of planned start of study therapy.

 

Clinical Trials.Gov Link: https://clinicaltrials.gov/ct2/show/NCT02743819?term=IRB17-0686&rank=1

 
University of Virginia & Merck (UVA-LACC-PD201) UVA-LACC-PD201  07/12/2016  Cervical  Jennifer Scalici, MD 

Protocol Title:  "A Randomized Phase Ii Study of Chemoradiation and Pembrolizumab for Locally Advanced Cervical Caner."

Inclusion Criteria: Histologically confirmed invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, stages IB2, IIA, IIB, IIIB and IVA, Stage IB1 with + pelvic or para0aortic nodes base on MRI also eligible; no evidence of distant metastases; recurrent cervical cancer is not eligible; ECOG performance status of 0-2.

Exclusion Criteria: Malignancy within the prior 5 years (exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy); diagnosis of immunodeficiency; know history of HIV, Hepatitis B/C, active TB, inflammatory bowel disease; hypersensitivity to pembrolizumab or any of its excipients; active autoimmune disease that has required systemic treatment in the past 2 years; known history or evidence of pneumonitis; known active CNS metastases and/or carcinomatous meningitis.

Clinical Trials.Gov Link:  https://clinicaltrials.gov/ct2/show/NCT02635360?term=UVA-LACC-PD201&rank=1

 

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