A Study to Evaluate Rucaparib in Combination With Nivolumab in Patients With Selected Solid Tumors (ARIES)

Phase 2

Terminated

• Conditions: Epithelial Ovarian Cancer; Primary Peritoneal Carcinoma; High Grade Serous Carcinoma; Endometrioid Adenocarcinoma; Fallopian Tube Cancer
• Interventions: Drug: Rucaparib; Drug: Nivolumab

• Registration Number: NCT03824704
• Lead Sponsor: pharmaand GmbH

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-01-21
• Study First Submitted QC: 2019-01-30
• Study First Posted: 2019-01-31
• Study Start: 2019-08-23
• Primary Completion: 2020-08-24
• Study Completion: 2020-08-24
• Results First Submitted: 2021-05-19
• Results First Submitted QC: 2021-05-19
• Results First Posted: 2021-06-15
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-07
• Last Update Posted: 2023-06-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 1

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort A: Ovarian Cancer Cohort	Rucaparib	Oral rucaparib and Intravenous (IV) nivolumab (combination therapy) * Cohort A1 * Cohort A2
Cohort A: Ovarian Cancer Cohort	Nivolumab	Oral rucaparib and Intravenous (IV) nivolumab (combination therapy) * Cohort A1 * Cohort A2

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.

Trial Locations

Locations (5)

Stephenson Cancer Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Community Cancer Institute; 🇺🇸 Clovis, California, United States

Memorial Health University Medical Center; 🇺🇸 Savannah, Georgia, United States

University of Vermont Medical Center; 🇺🇸 Burlington, Vermont, United States

Women's Cancer Care; 🇺🇸 Covington, Louisiana, United States