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

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ClinicalTrials.gov Identifier: NCT03824704
Recruitment Status : Not yet recruiting
First Posted : January 31, 2019
Last Update Posted : February 11, 2019
Sponsor:
Collaborators:
Bristol-Myers Squibb
Foundation Medicine
Information provided by (Responsible Party):
Clovis Oncology, Inc.

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, or locally advanced unresectable/metastatic transitional cell urothelial carcinoma.

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

Patients entering the following cohort must have a sample of tumor tissue available for mutational analysis:

  • Cohort B: Urothelial Cancer

Condition or disease Intervention/treatment Phase
Epithelial Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Carcinoma Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter Urothelial Carcinoma High Grade Serous Carcinoma Endometrioid Adenocarcinoma Urothelial Carcinoma Bladder Urothelial Carcinoma Ureter Regional Urothelial Carcinoma Ureter Metastatic Urothelial Carcinoma Ureter Local Urothelial Carcinoma Bladder Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter Urothelial Carcinoma Ureter Drug: Rucaparib Drug: Nivolumab Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 139 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-label Study to Evaluate Rucaparib in Combination With Nivolumab in Patients With Selected Solid Tumors (ARIES)
Estimated Study Start Date : February 2019
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2022


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:
  • Rubraca
  • CO-338

Drug: Nivolumab
IV nivolumab will be administered once every 4 weeks
Other Names:
  • Opdivo
  • BMS-936558

Experimental: Cohort B: Urothelial Cancer Cohort
Oral rucaparib and Intravenous (IV) nivolumab (combination therapy)
Drug: Rucaparib
Oral rucaparib will be administered twice daily
Other Names:
  • Rubraca
  • CO-338

Drug: Nivolumab
IV nivolumab will be administered once every 4 weeks
Other Names:
  • Opdivo
  • BMS-936558




Primary Outcome Measures :
  1. Objective response rate (ORR) 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) ]
    Cohort A1 and B only

  2. To study the effect of rucaparib on the immune microenvironment [ Time Frame: From enrollment to primary study 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 :
  1. ORR by RECIST v1.1 and 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 ]
    Cohort A1 only

  2. Progression-free survival (PFS) [ Time Frame: From randomization until disease progression (up to approximately 2 years) ]
    Cohorts A1 and B only

  3. Duration of response (DOR) [ 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 ]
    Cohorts A1 and B only

  4. Overall survival (OS) [ 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 ]
    Cohort B only

  5. Safety and tolerability of rucaparib in combination with nivolumab: incidence of adverse events, clinical laboratory abnormalities and clinical dose modifications [ Time Frame: From randomization until disease progression (up to approximately 2 years) ]
    The evaluation of the incidence of adverse events, clinical laboratory abnormalities and clinical dose modifications; All Cohorts



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Cohort A1 and A2 Ovarian Cancer-Only Inclusion Criteria

  • 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

Cohort B Urothelial Cancer-Only Inclusion Criteria

  • Locally advanced unresectable or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureter, urinary bladder, or urethra). Mixed transitional/non-transitional cell histologies are allowed.
  • Not eligible to receive cisplatin chemotherapy and have declined carboplatin chemotherapy OR had disease progression during or after platinum-containing chemotherapy.
  • Measurable disease (RECIST v1.1)
  • Have a sample of tumor tissue available for analysis.
  • ECOG performance status ≤ 2 (cisplatin ineligible patients) or ECOG performance status ≤ 1 (prior platinum patients)

General Exclusion Criteria (All patients)

  • 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.

Cohort A1 and A2 Ovarian Cancer-Only Exclusion Criteria

  • Non-epithelial tumors (pure sarcomas) or ovarian tumors with low malignant potential (ie, borderline tumors) or mucinous tumors. Mixed Mullerian tumors/carcinosarcomas are allowed.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03824704


Contacts
Contact: Clovis Oncology Clinical Trial infomration 1-855-262-3040 (USA) clovistrials@emergingmed.com
Contact: Clovis Oncology Clinical Trial infomration +1-303-625-5160 (ex-US) clovistrials@emergingmed.com

Sponsors and Collaborators
Clovis Oncology, Inc.
Bristol-Myers Squibb
Foundation Medicine
Investigators
Principal Investigator: Kathleen N Moore, MD Lead Investigator for Ovarian Cohort A
Principal Investigator: Abhishek Tripathi, MD Lead Investigator for Urothelial Cohort B

Responsible Party: Clovis Oncology, Inc.
ClinicalTrials.gov Identifier: NCT03824704     History of Changes
Other Study ID Numbers: CO-338-097
First Posted: January 31, 2019    Key Record Dates
Last Update Posted: February 11, 2019
Last Verified: February 2019

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Clovis Oncology, Inc.:
PARP
PARPi
PARP inhibitor
ARIES
Opdivo
Rucaparib
Nivolumab
PD-1
BRCA
LOH
CO-338
Immunotherapy
BMS-936558
Clovis
Clovis Oncology
Rubraca

Additional relevant MeSH terms:
Carcinoma
Adenocarcinoma
Fallopian Tube Neoplasms
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Kidney Neoplasms
Ureteral Neoplasms
Carcinoma, Endometrioid
Cystadenocarcinoma, Serous
Urinary Bladder Neoplasms
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Fallopian Tube Diseases
Adnexal Diseases
Genital Diseases, Female
Endocrine Gland Neoplasms
Ovarian Diseases
Endocrine System Diseases
Gonadal Disorders
Urologic Neoplasms
Kidney Diseases
Urologic Diseases
Ureteral Diseases
Endometrial Neoplasms
Uterine Neoplasms
Cystadenocarcinoma