Phase 2 Multicohort Study to Evaluate the Safety and Efficacy of Novel Treatment Combinations in Patients With Recurrent Ovarian Cancer

Status: Active

Description

This study is a phase 2, multi-cohort study, which will assess the safety and efficacy of new treatment combinations in patients with recurrent ovarian cancer.

Eligibility Criteria

Inclusion Criteria

  • Inclusion Criteria: - Patient has histologically diagnosed high-grade recurrent epithelial (ie, serous, endometrioid, mucinous, clear cell) ovarian, fallopian tube, or primary peritoneal cancer or recurrent carcinosarcoma of the ovary. Patients with high-grade mixed histology are also eligible. - Patient has measurable disease according to RECIST v1.1 - Patient has an ECOG performance status of 0 or 1 - Patient has adequate organ function, defined as follows: 1. Absolute neutrophil count ≥1,500/µL 2. Platelets ≥100,000/µL 3. Hemoglobin ≥9 g/dL 4. Serum creatine ≤1.5x upper limit of normal (ULN) or calculated creatinine clearance ≥50mL/min using Crockcroft-Gault equation. 5. Total bilirubin ≤1.5x ULN, except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome may enroll if direct bilirubin is ≤1.5x ULN for the direct bilirubin. 6. Asparate aminotransferase and alanine aminotransferase ≤2.5x ULN, unless liver metastases are present, in which case they must be ≤5x ULN 7. International normalized ration or prothrombin time (PT) ≤1.5x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants 8. Activated partial thromboplastin time ≤1.5x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants. - Patient of childbearing potential is not breastfeeding, has a negative serum pregnancy test within 72 hours prior to taking study treatment, and agrees to abstain from activities that could result in pregnancy from enrollment through 180 days after the last dose of study treatment; or patient is of non-childbearing potential. - Patient is willing to undergo a pre-treatment tumor biopsy, unless an appropriate archival tumor tissue is available. Additionally, patient must be willing to undergo 1 on-treatment biopsy, provided it is deemed safe and feasible by the Investigator. For Cohort A, in addition to the general inclusion criteria, patients must also meet the following additional criterion to be considered eligible to participate in this study: - Patient must be resistant to the most recent platinum-based therapy. Patients with primary platinum-refractory disease are not eligible. - Patient must not have received any prior therapy for ovarian cancer with a PARP inhibitor. - Patient has had 1 to 2 prior lines of anticancer therapy for ovarian cancer. Exclusion Criteria (Patients will not be eligible for study entry if any of the following criteria are met): - Patient has not recovered (ie, to Grade ≤1 or to baseline) from prior chemotherapy-induced adverse events. - Patient has a known diagnosis of immunodeficiency or is receiving systemic steroid therapy exceeding an equivalent of prednisone 10 mg daily or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment - Patient is currently participating in a treatment study or has participated in a study of an investigational agent within 4 weeks of the first dose of treatment - Patient has received prior systemic anticancer therapy including cytotoxic chemotherapy, PARP inhibitor, immune checkpoint inhibitors, hormonal therapy given with the intention to treat ovarian cancer, or biological therapy within 3 weeks of the first dose of study treatment - Patient has received live vaccine within 30 days of planned start of study therapy - Patient has symptomatic uncontrolled brain or leptomeningeal metastases - Patient had major surgery within 4 weeks of starting the study - Patient has a known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cancer that is considered to be low risk for progression by the investigator - Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection - Patient has a history or current evidence of any condition, therapy or laboratory abnormality that might confound the results of the study, might interfere with the patient's participation for the full duration of the study treatment, or is not in the best interest of the patient to participate - Patient has known active hepatitis B or hepatitis C For Cohort A, patients will not be eligible for study entry if the following additional exclusion criteria are met: - Patient has known hypersensitivity to TSR-042, bevacizumab, niraparib, their components, or their excipients - Patient has a known history of myelodysplastic syndrome or acute myeloid leukemia - Patient has active autoimmune disease that has required systemic treatment in the past 2 years (ie, 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) is not considered a form of systemic treatment - Patient received prior treatment with an anti-PI-1 or anti-PD-L1 agent - Patient has received prior treatment with anti-angiogenic therapy with the exception of bevacizumab. - Patient has bowel obstruction, had bowel obstruction within the past 3 months, or is otherwise judged by the Investigator to be at high risk for bowel obstruction related to the underlaying disease. - Patient has proteinuria as demonstrated by urine protein: creatine ratio ≥1.0 at screening or urine dipstick for proteinuria ≥2 - 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 hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months) - Patient has a history of recent major thromboembolic event defined as follows: 1. Pulmonary embolism diagnosed within 3 months of enrollment 2. Lower extremity deep venous thrombosis diagnosed within 3 months of enrollment

Locations & Contacts

California

Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: In review
Contact: Nabilah Abdehlaal
Phone: 310-794-6918
Email: nabdelaal@mednet.ucla.edu
Palo Alto
Stanford Cancer Institute Palo Alto
Status: Active
Name Not Available

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: Active
Name Not Available

Massachusetts

Boston
Brigham and Women's Hospital
Status: Active
Name Not Available
Dana-Farber Cancer Institute
Status: Active
Name Not Available
Massachusetts General Hospital Cancer Center
Status: Active
Name Not Available

Minnesota

Rochester
Mayo Clinic
Status: Temporarily closed to accrual
Name Not Available

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: Active
Name Not Available

Trial Objectives and Outline

This study is a phase 2, multi-cohort study, which assesses the safety (such as AEs, Lab values, etc.) and efficacy of anti-tumor activity of new treatment combinations (niraparib, TSR-042, and bevacizumab in patients with recurrent ovarian cancer.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Tesaro Inc

Trial IDs

Primary ID 3000-02-005
Secondary IDs NCI-2018-01619
Clinicaltrials.gov ID NCT03574779