A Clinical Study of Cobimetinib Administered in Combination With Niraparib, With or Without Atezolizumab to Patients With Advanced Platinum-sensitive Ovarian Cancer
- Conditions
- OVARIAN CANCER
- Interventions
- Registration Number
- NCT03695380
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
The study will include a safety run-in phase (Stage 1) and a randomization phase (Stage 2).
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).
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.
All patients will continue to receive study treatment until disease progression (according to "Response Evaluation Criteria in Solid Tumors" (RECIST), Version 1.1, unacceptable toxicity, death, or patient or investigator decision to withdraw, whichever occurs first.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 77
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Cobimetinib - Niraparib Cobimetinib Stage 2 - Patients will receive cobimetinib PO QD on Days 1-21 (21/7 schedule) in combination with niraparib PO QD on Days 1-28 of each 28-day cycle at the established dose for the doublet regimen in Stage 1, Cohort 1. Arm B: Cobimetinib - Niraparib - Atezolizumab Niraparib Stage 2 - Patients will receive cobimetinib PO QD on Days 1-21 (21/7 schedule) in combination with niraparib QD on Days 1-28 at the established doses for the triplet regimen in Stage 1,Cohort 2 plus atezolizumab by IV infusion at the fixed dose of 840 mg on Days 1 and 15 (+/-3 days) of each 28-day cycle. Arm A: Cobimetinib - Niraparib Niraparib Stage 2 - Patients will receive cobimetinib PO QD on Days 1-21 (21/7 schedule) in combination with niraparib PO QD on Days 1-28 of each 28-day cycle at the established dose for the doublet regimen in Stage 1, Cohort 1. Arm B: Cobimetinib - Niraparib - Atezolizumab Cobimetinib Stage 2 - Patients will receive cobimetinib PO QD on Days 1-21 (21/7 schedule) in combination with niraparib QD on Days 1-28 at the established doses for the triplet regimen in Stage 1,Cohort 2 plus atezolizumab by IV infusion at the fixed dose of 840 mg on Days 1 and 15 (+/-3 days) of each 28-day cycle. Cohort 1 - Cobimetinib - Niraparib Cobimetinib Stage 1 - Patients in Cohort 1 will be treated with cobimetinib plus niraparib. Cobimetinib: Patients will receive a starting dose of 60 mg by mouth (PO) daily (QD) on Days 1-21 of each 28-day cycle. Niraparib: Patients will receive a starting dose of 200 mg of niraparib PO QD on Days 1-28 of each 28-day cycle. Arm B: Cobimetinib - Niraparib - Atezolizumab Atezolizumab Stage 2 - Patients will receive cobimetinib PO QD on Days 1-21 (21/7 schedule) in combination with niraparib QD on Days 1-28 at the established doses for the triplet regimen in Stage 1,Cohort 2 plus atezolizumab by IV infusion at the fixed dose of 840 mg on Days 1 and 15 (+/-3 days) of each 28-day cycle. Cohort 2 - Cobimetinib - Niraparib - Atezolizumab Cobimetinib Stage 1 - Patients in Cohort 2 will be treated with cobimetinib plus niraparib and atezolizumab. Cobimetinib: Patients will receive a starting dose of 60 mg by mouth (PO) daily (QD) on Days 1-21 of each 28-day cycle. Niraparib: Patients will receive a starting dose of 200 mg of niraparib PO QD on Days 1-28 of each 28-day cycle. Atezolizumab: Patients will also receive atezolizumab administered as an IV infusion at a fixed dose of 840 mg on Days 1 and 15 (+/-3 days) of each 28-day cycle.
- Primary Outcome Measures
Name Time Method Investigator-assessed confirmed objective response rate (ORR) From baseline up to 48 months The efficacy profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumab will be evaluated in terms of investigator-assessed confirmed ORR, as determined using RECIST v1.1 in the Intention To Treat (ITT) population and in molecularly defined subgroups by loss of heterozygosity (LOH) status.
Number of patients reporting Adverse Events (AEs) From baseline up to 48 months The safety profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumab will be evaluated in terms of number of patients reporting serious and non-serious AEs with severity graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI - CTCAE v5.0)
Change from baseline in targeted clinical laboratory test results From baseline up to 48 months The safety profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumabwill be evaluated in terms of number of patients reporting change from baseline in targeted clinical laboratory test results.
- Secondary Outcome Measures
Name Time Method Serum concentration of atezolizumab Day 1 of Cycle 1, 2 and 3 and at treatment discontinuation visit, up to 48 months The PK profile of cobimetinib plus niraparib plus atezolizumab will be evaluated in terms of Serum concentration of atezolizumab at specified timepoints (Arm B only).
Number of patients with Anti-Drug Antibodies (ADA) Day 1 of Cycle 1, 2 and 3 and at treatment discontinuation visit, up to 48 months The immunogenicity profile of Atezolizumab is evaluated in terms of number of patients with ADA at baseline and during the study.
Progression-free survival (PFS) From Baseline up to 48 months The efficacy profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumab will be evaluated in terms of PFS after randomization, defined as the time from randomization to the first occurrence of disease progression or relapse, as determined by the investigator using RECIST v1.1, or death from any cause during the study, whichever occurs first, in the ITT population and in the molecularly defined subgroups by LOH status.
Duration of response (DOR) From baseline up to 48 months The efficacy profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumab will be evaluated in terms of DOR, defined for patients achieving at least one confirmed Partial Response (PR), which is measured from the first observation of a Complete Response (CR) or a PR to the time of disease progression in the ITT population and in the molecularly defined subgroups by LOH status.
Overall survival (OS) From baseline up to 48 months The efficacy profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumab will be evaluated in terms of OS after randomization, defined as the time from randomization until death from any cause in the ITT population and in the molecularly defined subgroups by LOH status.
Plasma concentration of cobimetinib and niraparib Arm A: Day 15 of Cycle 1 and 2 - Arm B: Day 15 of Cycle 1 The Pharmacokinetic (PK) profile of cobimetinib plus niraparib is evaluated in terms of Plasma concentration at specified timepoints.
Trial Locations
- Locations (20)
Medical College of Georgia; Obstetrics & Gynecolog
🇺🇸Augusta, Georgia, United States
Stephenson Cancer Center Investigational Pharmacy
🇺🇸Oklahoma City, Oklahoma, United States
Florida Hospital Cancer Institute; Clinical Research Department
🇺🇸Orlando, Florida, United States
Istituto Nazionale Tumori Fondazione G. Pascale
🇮🇹Napoli, Campania, Italy
Moores Cancer Center at UC San Diego Health
🇺🇸La Jolla, California, United States
Tennessee Oncology; Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Fondazione Policlinico Universitario "A. Gemelli"; Unità di Fase 1: Unità di Farmacologia Clinica
🇮🇹Rome, Lazio, Italy
Hospital Universitari Vall dHebron; Oncology
🇪🇸Barcelona, Spain
Istituto Europeo di Oncologia; Svil. Nuovi Farmaci per Terapie Innovative
🇮🇹Milano, Lombardia, Italy
Centro Oncologico de Galicia COG; Medical Oncology
🇪🇸A Coruna, LA Coruña, Spain
Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia
🇪🇸Jaen, Spain
Hospital Clinico San Carlos; Servicio de Oncologia
🇪🇸Madrid, Spain
Medical College of Wisconsin; Department of Obstetrics and Gynecology
🇺🇸Milwaukee, Wisconsin, United States
Hospital ClÃnico Universitario de Valencia; Servicio de OncologÃa
🇪🇸Valencia, Spain
Washington University School of Medicine; Dept of Medicine/Div of Medical Oncology
🇺🇸Saint Louis, Missouri, United States
ICO Girona
🇪🇸Girona, Spain
Clinica Universidad de Navarra Madrid; Servicio de OncologÃa
🇪🇸Madrid, Spain
University of Arizona Cancer Center, North
🇺🇸Tucson, Arizona, United States
Mayo Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
Hospital Ramon y Cajal; Servicio de Oncologia
🇪🇸Madrid, Spain