A Clinical Study of Cobimetinib Administered in Combination With Niraparib, With or Without Atezolizumab to Patients With Advanced Platinum-sensitive Ovarian Cancer
Sponsor:
Hoffmann-La Roche
Collaborators:
Information provided by (Responsible Party):
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| Tracking Information | |||
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| First Submitted Date ICMJE | September 30, 2018 | ||
| First Posted Date ICMJE | October 4, 2018 | ||
| Last Update Posted Date | October 4, 2018 | ||
| Actual Study Start Date ICMJE | December 31, 2018 | ||
| Estimated Primary Completion Date | November 24, 2022 (Final data collection date for primary outcome measure) | ||
| Current Primary Outcome Measures ICMJE |
Number of patients reporting Adverse Events (AEs)[ Time Frame: From baseline up to 48 months ] The safety profile of Cobimetinib plus Niraparib compared to 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[ Time Frame: From baseline up to 48 months ] The safety profile of Cobimetinib plus Niraparib compared to Cobimetinib plus Niraparib plus Atezolizumabwill be evaluated in terms of number of patients reporting change from baseline in targeted clinical laboratory test results. Investigator-assessed confirmed objective response rate (ORR)[ Time Frame: From baseline up to 48 months ] The efficacy profile of Cobimetinib plus Niraparib compared to 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 the two molecularly defined subgroups: breast cancer susceptibility gene wild type (BRCAwt) /LOHhigh and BRCAwt/LOHlow in each study arm. |
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| Original Primary Outcome Measures ICMJE | Same as current | ||
| Current Secondary Outcome Measures ICMJE |
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| Descriptive Information | |||
| Brief Title ICMJE | A Clinical Study of Cobimetinib Administered in Combination With Niraparib, With or Without Atezolizumab to Patients With Advanced Platinum-sensitive Ovarian Cancer |
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| Official Title ICMJE | A Phase Ib Study of Cobimetinib Administered in Combination With Niraparib, With or Without Atezolizumab, To Patients With Advanced Platinum-sensitive Ovarian Cancer |
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| 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. |
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| Detailed Description | |||
| Study Type ICMJE | Interventional | ||
| Study Phase | Phase 1 | ||
| Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: Masking: Interventional Masking Description: Primary Purpose: Treatment |
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| Intervention ICMJE |
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| Study Arms |
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| Recruitment Information | |||
| Recruitment Status ICMJE | Not yet recruiting | ||
| Estimated Enrollment ICMJE |
70 | ||
| Original Estimated Enrollment ICMJE | Same as current | ||
| Estimated Study Completion Date | November 24, 2022 | ||
| Estimated Primary Completion Date | November 24, 2022 (Final data collection date for primary outcome measure) | ||
| Eligibility Criteria ICMJE | Inclusion Criteria - Ability to comply with the study protocol, in the investigator's judgment - Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the completion of patient-reported outcome questionnaires - Histological diagnosis of high-grade serous or Grade 2 or Grade 3 endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer - Previous treatment with a minimum of one and a maximum of two prior platinum based treatment regimens - Platinum-sensitive disease - Availability of tumor biopsy tissue prior to first dose of study treatment with confirmation by the central laboratory that the sample is not only of adequate quality but also assignable to a molecularly defined subgroup based on breast cancer susceptibility gene (BRCA) and loss of heterozygosity (LOH) status - Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) - Adequate hematologic and organ function - Eastern Cooperative Oncology Group Performance Status of 0 or 1 - Life expectancy of at least 12 weeks - Resolved or stabilized toxicities resulting from previous therapy to Grade 1 - Negative HIV test at screening - Negative hepatitis B surface antigen and total hepatitis B core antibody (HBcAb) test, or positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA < 500 IU/mL test at screening - Negative hepatitis C virus (HCV) antibody test, or positive HCV antibody test followed by a negative HCV RNA test at screening - For women of childbearing potential: Women must remain abstinent or use two contraceptive methods with a failure rate of <1% per year during the treatment period and for at least 3 months after the last dose of cobimetinib, 6 months after the last dose of niraparib, and 5 months after the last dose of atezolizumab. Women must refrain from donating eggs during this same period Exclusion Criteria - Prior treatment with mitogen-activated protein kinase inhibitor, polyadenosine diphosphate-ribose polymerase inhibitor, or immune checkpoint inhibitor therapies - Prior chemotherapy, hormonal therapy, radiotherapy, antibody therapy, or other immunotherapy, gene therapy, vaccine therapy, or treatment with experimental drugs within 14 days prior to first dose of study treatment - Treatment with systemic immunostimulatory agents within 28 days or 5 half-lives of the drug prior to initiation of study treatment - Treatment with systemic immunosuppressive medication 14 days prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the study - History of other malignancy that could affect compliance with the protocol or interpretation of results, or known to have potentially fatal outcome - Symptomatic and/or untreated central nervous system metastases - Surgical procedure, significant traumatic injury within 14 days prior to enrollment, or anticipation of need for major surgical procedure during the study - Minor surgical procedure within 3 days - History or evidence of retinal pathology on ophthalmic examination - Left ventricular ejection fraction below institutional lower limit of normal - History of clinically significant cardiovascular dysfunction - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on the screening chest computed tomography scan - History or evidence of inherited bleeding diathesis or significant coagulopathy at risk for bleeding - History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins, or to any component of the atezolizumab formulation - Known allergy or hypersensitivity to any component of the cobimetinib or niraparib formulation - Active or history of autoimmune disease or immune deficiency including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, anti-phospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barre syndrome, or multiple sclerosis - 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 - Severe infection within 14 days prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia - Treatment with therapeutic oral or IV antibiotics within 7 days prior to initiation of study treatment - Treatment with a live, attenuated influenza vaccine within 28 days prior to study treatment initiation, at any time during the study, and for at least 5 months after the last dose of study drug - Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications - Previous treatment with strong CYP3A inhibitors (such as ketoconazole and clarithromycin), strong CYP3A inducers (such as carbamazepine and phenytoin), and moderate CYP3A inducers (such as efavirenz, modafinil) within 7 days prior to the initiation of study treatment or with ongoing requirements for these medications - Pregnancy or breastfeeding, or intention to become pregnant during the study | ||
| Sex/Gender |
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| Ages | 18 Years and older (Adult, Older Adult) | ||
| Accepts Healthy Volunteers | No | ||
| Listed Location Countries ICMJE | France|Italy|Spain|United States | ||
| Removed Location Countries | |||
| Administrative Information | Has Data Monitoring Committee | ||
| U.S. FDA-regulated Product |
Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No |
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| IPD Sharing Statement |
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| Responsible Party | ， | ||
| Study Sponsor ICMJE | Hoffmann-La Roche | ||
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| Investigators ICMJE |
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| PRS Account | |||
| Verification Date | October 2018 | ||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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