A Study to Evaluate Rucaparib in Combination With Nivolumab in Patients With Selected Solid Tumors (ARIES)
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort A: Ovarian Cancer Cohort Oral rucaparib and Intravenous (IV) nivolumab (combination therapy) Cohort A1 Cohort A2 |
Drug: Rucaparib
Oral rucaparib will be administered twice daily
Other Names:
Drug: Nivolumab
IV nivolumab will be administered once every 4 weeks
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Community Cancer Institute | Clovis | California | United States | 93611 |
| 2 | Memorial Health University Medical Center | Savannah | Georgia | United States | 31404 |
| 3 | Women's Cancer Care | Covington | Louisiana | United States | 70433 |
| 4 | Stephenson Cancer Center | Oklahoma City | Oklahoma | United States | 73104 |
| 5 | University of Vermont Medical Center | Burlington | Vermont | United States | 05041 |
Sponsors and Collaborators
- Clovis Oncology, Inc.
- Bristol-Myers Squibb
- Foundation Medicine
Investigators
- Principal Investigator: Kathleen N Moore, MD, Lead Investigator for Ovarian Cohort A
Study Documents (Full-Text)
More Information
Publications
None provided.- CO-338-097
Study Results
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. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Cohort A: Ovarian Cancer Cohort |
|---|---|
| Arm/Group Description | 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. |
| Period Title: Overall Study | |
| STARTED | 1 |
| COMPLETED | 0 |
| NOT COMPLETED | 1 |
Baseline Characteristics
| Arm/Group Title | Cohort A: Ovarian Cancer Cohort |
|---|---|
| Arm/Group Description | 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. |
| Overall Participants | 1 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
0
0%
|
| >=65 years |
1
100%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
1
100%
|
| Male |
0
0%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
0
0%
|
| Not Hispanic or Latino |
1
100%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
1
100%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
Outcome Measures
| Title | Objective Response Rate (ORR) by RECIST v1.1 as Assessed by the Investigator |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| This study was discontinued by the sponsor so no data is available for this outcome measure. |
| Arm/Group Title | Cohort A: Ovarian Cancer Cohort |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 0 |
| Title | The Effect of Rucaparib on the Immune Microenvironment |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| This study was discontinued by the sponsor so no data is available for this outcome measure. |
| Arm/Group Title | Cohort A: Ovarian Cancer Cohort |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 0 |
| Title | ORR by RECIST v1.1 and Gynecological Cancer InterGroup (GCIG) Cancer Antigen 125 (CA-125 Criteria) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| This study was discontinued by the sponsor so no data is available for this outcome measure. |
| Arm/Group Title | Cohort A: Ovarian Cancer Cohort |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 0 |
| Title | Progression-free Survival (PFS) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| This study was discontinued by the sponsor so no data is available for this outcome measure. |
| Arm/Group Title | Cohort A: Ovarian Cancer Cohort |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 0 |
| Title | Duration of Response (DOR) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This study was discontinued by the sponsor so no data is available for this outcome measure. |
| Arm/Group Title | Cohort A: Ovarian Cancer Cohort |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 0 |
Adverse Events
| Time Frame | Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug. | |
|---|---|---|
| Adverse Event Reporting Description | If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). | |
| Arm/Group Title | Cohort A: Ovarian Cancer Cohort | |
| Arm/Group Description | 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. | |
All Cause Mortality |
||
| Cohort A: Ovarian Cancer Cohort | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/1 (0%) | |
Serious Adverse Events |
||
| Cohort A: Ovarian Cancer Cohort | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/1 (100%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 1/1 (100%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Cohort A: Ovarian Cancer Cohort | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/1 (100%) | |
| Endocrine disorders | ||
| Adrenal insufficiency | 1/1 (100%) | 1 |
| Gastrointestinal disorders | ||
| Nausea | 1/1 (100%) | 1 |
| Diarrhoea | 1/1 (100%) | 4 |
| Constipation | 1/1 (100%) | 4 |
| Dsypepsia | 1/1 (100%) | 1 |
| General disorders | ||
| Fatigue | 1/1 (100%) | 5 |
| Chest pain | 1/1 (100%) | 1 |
| Investigations | ||
| Blood creatinine increased | 1/1 (100%) | 1 |
| Metabolism and nutrition disorders | ||
| Hyperglycaemia | 1/1 (100%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Back pain | 1/1 (100%) | 1 |
| Nervous system disorders | ||
| Tremor | 1/1 (100%) | 1 |
| Dizziness | 1/1 (100%) | 2 |
| Cognitive disorder | 1/1 (100%) | 1 |
| Headache | 1/1 (100%) | 2 |
| Hypoaesthesia | 1/1 (100%) | 1 |
| Psychiatric disorders | ||
| Insomnia | 1/1 (100%) | 2 |
| Panic attack | 1/1 (100%) | 3 |
| Renal and urinary disorders | ||
| Chronic kidney disease | 1/1 (100%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||
| Dyspnoea | 1/1 (100%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Hair texture abnormal | 1/1 (100%) | 1 |
| Vascular disorders | ||
| Hot flush | 1/1 (100%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Sponsor's agreements with investigators require proposed public disclosures of trial results to be submitted to Sponsor for review prior to publication. Sponsor may request deletion of confidential information or a delay in publication to address intellectual property concerns, but Sponsor may not suppress publication of the trial results indefinitely. Sponsor may request delay of a single-center publication until after the release of a multi-site publication or an agreed upon period of time.
Results Point of Contact
| Name/Title | Medical Information Department |
|---|---|
| Organization | Clovis Oncology, Inc. |
| Phone | +1 415 409 7220 |
| medinfo@clovisoncology.com |
- CO-338-097