|Title||University of Chicago UC IRB17-0686|
|Principal Investigator/ Physician||Arthur Frankel, MD|
|Protocol No.||UC IRB17-0686|
|Sponsor||University of Chicago|
|Contact Email||MCI Clinical Trials|
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
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