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Title:
A Phase 1b Study of Cobimetinib Administered in Combination with Niraparib, with or without Atezolizumab, to Patients with Advanced Platinum-Sensitive Ovarian Cancer (YO40482)
Protocol Number:
J18174
Phase:
Phase I
Physician:
Stephanie Gaillard
Sites:
Johns Hopkins Kimmel Cancer Center in Baltimore
Purpose:
The purpose of Stage 1 is to evaluate the safety of cobimetinib when administered in combination with niraparib (Cohort 1) and cobimetinib with niraparib plus atezolizumab (Cohort 2).
Eligibility:
Inclusion Criteria-Diagnosis of high-grade serous or Grade 2-3 endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer-Previous treatment with 1-2 prior platinum based treatment regimens-Platinum-sensitive disease-Availability of tumor biopsy tissue prior to first dose of study treatment to determine BRCA and LOH status-Measurable disease-Good blood counts and organ function-Resolved or stabilized toxicities resulting from previous therapy to Grade 1-Negative HIV, Hepatitis B and Hepatitis C test at screening-For women of childbearing potential: Women must remain abstinent or use two contraceptive methods. Women must refrain from donating eggs during this same periodExclusion Criteria-Prior treatment with mitogen-activated protein kinase inhibitor, polyadenosine diphosphate-ribose polymerase inhibitor, or immune checkpoint inhibitor therapies-Prior treatment within 14 days prior to first dose of study treatment-Symptomatic and/or untreated brain metastases-History of significant cardiovascular disease -History of certain lung diseases-History of bleeding disorders-History of severe allergic reactions to the study drugs-Uncontrolled serious medical or psychiatric illness-History of malabsorption or other condition that would interfere with absorption of oral study drugs, including preexisting duodenal stent or ongoing intestinal obstruction-Active tuberculosis
Treatment:
The study will include a safety run-in phase (Stage 1) and a randomization phase (Stage 2). Stage 1 will enable patient enrollment in the randomized phase of the study (Stage 2) with both regimens at the recommended dose levels from Stage 1. Stage 2 is a randomized, dose-expansion phase, evaluating clinical outcomes in patients with advanced platinum-sensitive ovarian cancer.In stage 2, patients are randomized to cohort A or B based on the results from their BRCA and LOH statuses. Patients randomized to cohort A will receive cobimetinib daily by mouth on Days 1-21 in combination with niraparib daily by mouth on Days 1-28 of each 28-day cycle. Patients randomized to cohort B will receive cobimetinib daily by mouth on Days 1-21 in combination with niraparib daily by mouth on Days 1-28 plus atezolizumab by IV infusion at the fixed dose of 840 mg on Days 1 and 15 (+/-3 days) of each 28-day cycle.All patients will continue to receive study treatment until disease progression, unacceptable toxicity, death, or patient or investigator decision to withdraw, whichever occurs first.
Population:
Adult
Last Update
08/08/2020 05:02 AM