Clinical Trials

Title   Tesaro 3000-02-004
Principal Investigator/ Physician   Rodney Rocconi, MD
Protocol┬áNo.   3000-02-004
Open Date   05/29/2018
Gender   Female
Cancer Site   Ovarian
Status   Closed to Enrollment
Sponsor   Tesaro Inc.
Contact Email   MCI Clinical Trials
Summary  

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 

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