Clinical trial NCT03824704: A Study to Evaluate Rucaparib in Combination With Nivolumab in Patients With Selected Solid Tumors (ARIES)
Official title: A Phase 2, Open-label Study to Evaluate Rucaparib in Combination With Nivolumab in Patients With Selected Solid Tumors (ARIES)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Epithelial Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Carcinoma
High Grade Serous Carcinoma
Endometrioid Adenocarcinoma
Keywords: PARP
PARPi
PARP inhibitor
ARIES
Opdivo
Rucaparib
Nivolumab
PD-1
BRCA
LOH
CO-338
Immunotherapy
BMS-936558
Clovis
Clovis Oncology
Rubraca
Lead sponsor: pharmaand GmbH
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
name: Foundation Medicine
First posted: 2019-01-31
Enrollment: 1
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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.

Primary outcomes:
measure: Objective Response Rate (ORR) by RECIST v1.1 as Assessed by the Investigator
timeFrame: From enrollment until disease progression (up to approximately 2 years)
measure: The Effect of Rucaparib on the Immune Microenvironment
timeFrame: From enrollment to primary completion of study (up to approximately 2 years)
Secondary outcomes:
measure: ORR by RECIST v1.1 and Gynecological Cancer InterGroup (GCIG) Cancer Antigen 125 (CA-125 Criteria)
timeFrame: 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.
measure: Progression-free Survival (PFS)
timeFrame: From randomization until disease progression (up to approximately 2 years)
measure: Duration of Response (DOR)
timeFrame: 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
Other outcomes:
Locations:
city: Clovis
country: United States
facility: Community Cancer Institute
state: California
city: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Covington
country: United States
facility: Women's Cancer Care
state: Louisiana
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
Study officials:
affiliation: Lead Investigator for Ovarian Cohort A
name: Kathleen N Moore, MD
role: PRINCIPAL_INVESTIGATOR
References: