Endometrioid Adenocarcinoma, Epithelial Ovarian Cancer, Fallopian Tube Cancer, High Grade Serous Carcinoma, Primary Peritoneal Carcinoma
Conditions
Keywords
PARP, PARPi, PARP inhibitor, ARIES, Opdivo, Rucaparib, Nivolumab, PD-1, BRCA, LOH, CO-338, Immunotherapy, BMS-936558, Clovis, Clovis Oncology, Rubraca
Brief summary
This is an open label Phase 2, 2-stage, 2-cohort study to evaluate rucaparib in combination with nivolumab in patients with high-grade serous or endometroid ovarian cancer. Patients entering the following cohorts must have BRCA mutational status confirmed by a central lab: * Cohort A1: No BRCA mutation in tumor; high level of LOH (loss of heterozygosity) * Cohort A2: BRCA mutation in tumor
Interventions
DRUGRucaparib
Oral rucaparib will be administered twice daily
DRUGNivolumab
IV nivolumab will be administered once every 4 weeks
Sponsors
Bristol-Myers Squibb
Foundation Medicine
pharmaand GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
General Inclusion Criteria: * ≥ 18 years of age * Adequate organ function * Life expectancy ≥ 16 weeks * Women of childbearing potential must have a negative serum pregnancy test * High-grade serous or endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer * Received 1 or 2 prior regimens, including ≥ 1 prior platinum-based therapy and have platinum-sensitive disease * Relapsed/progressive disease (confirmed by radiologic assessment) * Willing and able to have a biopsy of tumor at screening and after 4 weeks of treatment. * Measurable disease (RECIST v1.1)- Cohort A1 only * ECOG performance status of 0 to 1 General
Exclusion criteria
* Active second malignancy * Central nervous system brain metastases * Evidence of interstitial lung disease, active pneumonitis, myocarditis, or history of myocarditis. * Active, known or suspected autoimmune disease (eg, autoimmune hepatitis). * Condition requiring systemic treatment with either corticosteroids * Prior treatment with a PARP inhibitor or immune checkpoint inhibitor. * Non-epithelial tumors (pure sarcomas) or ovarian tumors with low malignant potential (ie, borderline tumors) or mucinous tumors. Mixed Mullerian tumors/carcinosarcomas are allowed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) by RECIST v1.1 as Assessed by the Investigator | From enrollment until disease progression (up to approximately 2 years) | Objective response rate (ORR) is defined as the percentage of patients with a best confirmed response of complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by the investigator. |
| The Effect of Rucaparib on the Immune Microenvironment | From enrollment to primary completion of study (up to approximately 2 years) | Change in expression of the immune marker PD-L1 pre and post-rucaparib treatment; Cohort A2 only |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR by RECIST v1.1 and Gynecological Cancer InterGroup (GCIG) Cancer Antigen 125 (CA-125 Criteria) | For patients with measurable disease, every 8 weeks after the start of combination treatment for 3 years, then every 24 weeks thereafter until disease progression or up to 25 months. Study data collection expected to last for 2 years. | Objective Response Rate (ORR) is defined as the percentage of patients with a best confirmed response of complete response (CR) or partial response (PR) by RECIST v1.1 as assessed by the investigator or a confirmed response per Gynecological Cancer InterGroup (GCIG) cancer antigen 125 (CA-125 criteria) |
| Progression-free Survival (PFS) | From randomization until disease progression (up to approximately 2 years) | Progression-Free Survival (PFS) is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first. |
| Duration of Response (DOR) | For patients with measurable disease, every 12 weeks after the start of combination treatment for 3 years, then every 24 weeks thereafter until disease progression. Study data collection expected to last for 2 years | Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first response until the first date that progressive disease (PD) is documented. |
Countries
United States
Participant flow
Recruitment details
1 subject was recruited from 1 site in the United States. The Sponsor then discontinued the study due to low accrual.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Ovarian Cancer Cohort Patients received combination therapy, including oral rucaparib 600mg administered twice daily starting on Cycle 1 Day 1 and intravenous (IV) nivolumab 480mg administered on Day 1 of every 4-week cycle, starting on Cycle 2 Day 1. | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study Terminated by Sponsor | 1 |
Baseline characteristics
| Characteristic | Cohort A: Ovarian Cancer Cohort |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
Primary
Objective Response Rate (ORR) by RECIST v1.1 as Assessed by the Investigator
Objective response rate (ORR) is defined as the percentage of patients with a best confirmed response of complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by the investigator.
Time frame: From enrollment until disease progression (up to approximately 2 years)
Population: This study was discontinued by the sponsor so no data is available for this outcome measure.
Primary
The Effect of Rucaparib on the Immune Microenvironment
Change in expression of the immune marker PD-L1 pre and post-rucaparib treatment; Cohort A2 only
Time frame: From enrollment to primary completion of study (up to approximately 2 years)
Population: This study was discontinued by the sponsor so no data is available for this outcome measure.
Secondary
Duration of Response (DOR)
Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first response until the first date that progressive disease (PD) is documented.
Time frame: For patients with measurable disease, every 12 weeks after the start of combination treatment for 3 years, then every 24 weeks thereafter until disease progression. Study data collection expected to last for 2 years
Population: This study was discontinued by the sponsor so no data is available for this outcome measure.
Secondary
ORR by RECIST v1.1 and Gynecological Cancer InterGroup (GCIG) Cancer Antigen 125 (CA-125 Criteria)
Objective Response Rate (ORR) is defined as the percentage of patients with a best confirmed response of complete response (CR) or partial response (PR) by RECIST v1.1 as assessed by the investigator or a confirmed response per Gynecological Cancer InterGroup (GCIG) cancer antigen 125 (CA-125 criteria)
Time frame: For patients with measurable disease, every 8 weeks after the start of combination treatment for 3 years, then every 24 weeks thereafter until disease progression or up to 25 months. Study data collection expected to last for 2 years.
Population: This study was discontinued by the sponsor so no data is available for this outcome measure.
Secondary
Progression-free Survival (PFS)
Progression-Free Survival (PFS) is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first.
Time frame: From randomization until disease progression (up to approximately 2 years)
Population: This study was discontinued by the sponsor so no data is available for this outcome measure.