A Study in Ovarian Cancer Patients Evaluating Rucaparib and Nivolumab as Maintenance Treatment Following Response to Front-Line Platinum-Based Chemotherapy
- Conditions
- Partial ResponseNewly DiagnosedComplete ResponsePrimary PeritonealEpithelial Ovarian CancerFallopian Tube CancerFIGO Stage III-IV
- Interventions
- Registration Number
- NCT03522246
- Lead Sponsor
- pharmaand GmbH
- Brief Summary
This is a Phase 3, randomized, multinational, double-blind, dual placebo-controlled, 4-arm study evaluating rucaparib and nivolumab as maintenance treatment following response to front-line treatment in newly diagnosed ovarian cancer patients. Response to treatment will be analyzed based on homologous recombination (HR) status of tumor samples.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 1097
- Newly diagnosed advanced (FIGO stage III-IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer.
- Completed cytoreductive surgery, including at least a bilateral salpingo-oophorectomy and partial omentectomy, either prior to chemotherapy (primary surgery) or following neoadjuvant chemotherapy (interval debulking)
- Completed first-line platinum-based chemotherapy and surgery with a response, in the opinion of the Investigator
- Sufficient tumor tissue for planned analysis
- ECOG performance status of 0 or 1
- Patients must be 20 years of age to consent in Japan, Taiwan and South Korea; in all other participating countries patients must be 18 years of age to consent
- Pure sarcomas or borderline tumors or mucinous tumors
- Active second malignancy
- Known central nervous system brain metastases
- Any prior treatment for ovarian cancer, other than the first-line platinum regimen
- Evidence of interstitial lung disease or active pneumonitis
- Active, known or suspected autoimmune disease
- Condition requiring active systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A Rucaparib Oral rucaparib + intravenous (IV) nivolumab Arm A Nivolumab Oral rucaparib + intravenous (IV) nivolumab Arm B Rucaparib Oral rucaparib + IV placebo Arm B Placebo IV Infusion Oral rucaparib + IV placebo Arm C Nivolumab Oral placebo + IV nivolumab Arm C Placebo Oral Tablet Oral placebo + IV nivolumab Arm D Placebo Oral Tablet Oral placebo + IV placebo Arm D Placebo IV Infusion Oral placebo + IV placebo Japanese Open-label Safety Cohort Rucaparib Oral rucaparib + IV nivolumab Japanese Open-label Safety Cohort Nivolumab Oral rucaparib + IV nivolumab
- Primary Outcome Measures
Name Time Method Monotherapy Arm B and Arm D: Investigator Assessed Progression-free Survival (PFS) From randomization until disease progression (up to the primary data analysis at approximately 39 months) PFS by investigator was defined as the time from randomization to disease progression, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the investigator, or death due to any cause, whichever occurred first.
Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).Monotherapy Arm B and Arm D: Investigator Assessed PFS From randomization until disease progression (up to the primary data analysis at approximately 39 months) PFS by investigator was defined as the time from randomization to disease progression, according to RECIST v1.1 as assessed by the investigator, or death due to any cause, whichever occurred first.
Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).Combination Therapy Arm A and Arm B: Investigator Assessed PFS From randomization until disease progression (up to the combination therapy interim analysis at approximately 66 months) PFS by investigator was defined as the time from randomization to disease progression, according to RECIST v1.1 as assessed by the investigator, or death due to any cause, whichever occurred first.
Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
- Secondary Outcome Measures
Name Time Method Monotherapy Arm B and Arm D: BICR PFS From randomization until disease progression (up to the primary data analysis at approximately 39 months) PFS was assessed by BICR per RECIST v1.1 as the time from randomization to disease progression, or death due to any cause, whichever occurred first.
Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).Combination Therapy Arm A and Arm B: BICR PFS From randomization until disease progression (up to the combination therapy interim analysis at approximately 66 months) PFS was assessed by BICR per RECIST v1.1 as the time from randomization to disease progression, or death due to any cause, whichever occurred first.
Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).Monotherapy Arm B and Arm D: Overall Survival (OS) From randomization until death due to any cause (up to the primary data analysis at approximately 36 months) OS was defined as the number of days (measured in months) from the date of randomization to the date of death due to any cause.
Monotherapy Arm B and Arm D: OS From randomization until death due to any cause (up to the primary data analysis at approximately 40 months) OS was defined as the number of days (measured in months) from the date of randomization to the date of death due to any cause.
Combination Therapy Arm A and Arm B: OS From randomization until death due to any cause (up to the combination therapy interim analysis at approximately 72 months) OS was defined as the number of days (measured in months) from the date of randomization to the date of death due to any cause.
Monotherapy Arm B and Arm D: Objective Response Rate (ORR) From randomization until disease progression (up to the primary data analysis at approximately 39 months) ORR was defined as the percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR) as assessed by the Investigator per RECIST 1.1.
CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm.
PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.Monotherapy Arm B and Arm D: ORR From randomization until disease progression (up to the primary data analysis at approximately 39 months) ORR was defined as the percentage of participants with CR or PR as assessed by the Investigator per RECIST 1.1.
CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm.
PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.Combination Therapy Arm A and Arm B: ORR From randomization until disease progression (up to the combination therapy interim analysis at approximately 66 months) ORR was defined as the percentage of participants with CR or PR as assessed by the Investigator per RECIST 1.1.
CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm.
PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.Monotherapy Arm B and Arm D: Blinded Independent Central Review (BICR) PFS From randomization until disease progression (up to the primary data analysis at approximately 39 months) PFS was assessed by BICR per RECIST v1.1 as the time from randomization to disease progression, or death due to any cause, whichever occurred first.
Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).Monotherapy Arm B and Arm D: Duration of Response (DOR) From first confirmed response until disease progression (up to the primary data analysis at approximately 30 months) DOR was assessed by the investigator and defined as the interval from the first documentation of objective response (CR or PR per RECIST v1.1) to the earlier of the first documentation of progressive disease (PD) or death from any cause.
CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm.
PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
PD: 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).Monotherapy Arm B and Arm D: DOR From first confirmed response until disease progression (up to the primary data analysis at approximately 33 months) DOR was assessed by the investigator and defined as the interval from the first documentation of objective response (CR or PR per RECIST v1.1) to the earlier of the first documentation of PD or death from any cause.
CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm.
PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
PD: 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).Combination Therapy Arm A and Arm B: DOR From first confirmed response until disease progression (up to the combination therapy interim analysis at approximately 60 months) DOR was assessed by the investigator and defined as the interval from the first documentation of objective response (CR or PR per RECIST v1.1) to the earlier of the first documentation of PD or death from any cause.
CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm.
PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
PD: 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
Trial Locations
- Locations (237)
Arizona Oncology Associates, PC - HAL
🇺🇸Phoenix, Arizona, United States
Arizona Oncology Associates, PC - HOPE
🇺🇸Tucson, Arizona, United States
The University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
John Muir Clinical Research Center
🇺🇸Concord, California, United States
UCLA Women's Health Clinical Research Unit
🇺🇸Los Angeles, California, United States
Kaiser Permanente Northern California
🇺🇸San Francisco, California, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
Rocky Mountain Cancer Centers
🇺🇸Lakewood, Colorado, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Florida Gynecologic Oncology
🇺🇸Fort Myers, Florida, United States
Scroll for more (227 remaining)Arizona Oncology Associates, PC - HAL🇺🇸Phoenix, Arizona, United States