Overview

This trial is active, not recruiting.

Conditions ovarian cancer, epithelial ovarian cancer, fallopian tube cancer, peritoneal cancer
Treatment oral rucaparib
Phase phase 2
Target PARP
Sponsor Clovis Oncology, Inc.
Collaborator Foundation Medicine
Start date September 2013
End date March 2017
Trial size 480 participants
Trial identifier NCT01891344, CO-338-017

Summary

The purpose of this study is to determine which patients with ovarian, fallopian tube, and primary peritoneal cancer will best respond to treatment with rucaparib.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
rucaparib
oral rucaparib CO-338
600 mg BID

Primary Outcomes

Measure
Disease Progression (RECIST v1.1) as assessed by investigator, or death from any cause, in molecularly-defined subgroups identified by a prospectively defined HRD signature (PART 1)
time frame: Screening; at the end of every 8 weeks (±4 days) of treatment; at disease progression; study data collection expected to last for ~2 years
ORR by RECIST v1.1 (PART 2)
time frame: Screening; at the end of every 8 weeks (±4 days) of treatment; at disease progression; study data collection expected to last for ~2 years

Secondary Outcomes

Measure
ORR by RECIST v1.1 (PART 1)
time frame: Screening; at the end of every 8 weeks (±4 days) of treatment; at disease progression; study data collection expected to last for ~2 years (RECIST v1.1).
Disease Progression (RECIST v1.1) as assessed by investigator, or death from any cause, in molecularly-defined subgroups identified by a prospectively defined HRD signature (PART 2)
time frame: Screening; at the end of every 8 weeks (±4 days) of treatment; at disease progression; study data collection expected to last for ~2 years
ORR by RECIST v1.1 and GCIG CA-125 criteria
time frame: Screening; at the end of every 8 weeks (±4 days) of treatment; at disease progression; study data collection expected to last for ~2 years
Duration of response per RECIST v1.1
time frame: Screening; at the end of every 8 weeks (±4 days) of treatment; at disease progression; study data collection expected to last for ~2 years
Incidence of adverse events, clinical laboratory abnormalities, and dose modifications
time frame: Every day starting with signing of consent until 28 days after discontinuation of treatment; study data collection expected to last for ~2 years
Trough (Cmin) level rucaparib concentrations
time frame: 2 weeks, 1 month, 2 months and 3 months after 1st dose
Overall Survival (PART 2)
time frame: study data collection expected to last for ~2 years

Eligibility Criteria

Female participants at least 18 years old.

The following eligibility criteria pertain to patients enrolling into PART 2 of the study: Inclusion: - Have a histologically confirmed diagnosis of high grade serous or Grade 2 or Grade 3 endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer - Received at least 3 prior chemotherapy regimens. Non-chemotherapy regimens and maintenance therapies administered as single agent treatment will not count as a chemotherapy regimen - Relapsed/progressive disease as confirmed by CT scan - Have biopsiable and measurable disease. Note: biopsy is optional for patients known to harbor a deleterious gBRCA mutation - Have sufficient archival formalin-fixed paraffin-embedded (FFPE) tumor tissue available for planned analyses Exclusion: - History of prior cancers except for those that have been curatively treated, with no evidence of cancer currently (provided all chemotherapy was completed >6 months prior and/or bone marrow transplant >2 years prior to first dose of rucaparib). - Prior treatment with any PARP inhibitor - Symptomatic and/or untreated central nervous system metastases - Pre-existing duodenal stent and/or any other gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of rucaparib - Hospitalization for bowel obstruction within 3 months prior to enrollment

Additional Information

Official title A Phase 2, Open-Label Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2)
Description Rucaparib is an orally available, small molecule inhibitor of poly-adenosine diphosphate [ADP] ribose polymerase (PARP) being developed for treatment of ovarian cancer associated with homologous recombination (HR) DNA repair deficiency (HRD). The safety and efficacy of rucaparib has been evaluated in several Phase 1 and Phase 2 studies. An oral formulation is the focus of current development efforts. Rucaparib is currently being investigated as monotherapy in patients with cancer associated with breast cancer susceptibility gene 1 (BRCA1) or BRCA2 mutations. Clinical data with PARP inhibitors indicate there is an ovarian cancer patient population beyond just those with germline BRCA (gBRCA) mutations that may benefit from treatment with a PARP inhibitor. This study will define a molecular signature of HRD in ovarian cancer that correlates with response to rucaparib and enables selection of appropriate ovarian cancer patients for treatment with rucaparib. The HRD signature will be based on an association between the extent of genomic scarring (a downstream consequence of HRD) in a patient's tumor and observed clinical benefit from rucaparib treatment. Genomic scarring can be assessed by quantifying the extent of loss of heterozygosity across the tumor genome (tumor genomic LOH). One of the main advantages of detecting tumor genomic LOH is that it can identify HRD tumors regardless of the underlying mechanisms, which include both known (i.e., BRCA mutations) and unknown genetic and other mechanisms. Once determined, this signature will be prospectively applied to ARIEL2 PART 2 and ARIEL3. This Phase 2 study (ARIEL2) will also compare archival versus recently collected tumor tissue in order to validate the use of archival tumor tissue for assessment of HRD status in ARIEL3. This study will include 2 parts: PART 1 (completed enrollment): Evaluation of HRD status and rucaparib efficacy in patients who received ≥1 prior platinum-based regimen and had platinum-sensitive disease PART 2 (currently enrolling): Evaluation of HRD status and rucaparib efficacy in patients who received at least 3 prior chemotherapy regimens
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Clovis Oncology, Inc..
Location data was received from the National Cancer Institute and was last updated in July 2016.