Overview

This trial is active, not recruiting.

Conditions ovarian cancer, fallopian tube cancer, peritoneal cancer
Treatments rucaparib, placebo
Phase phase 3
Target PARP
Sponsor Clovis Oncology, Inc.
Start date January 2014
End date March 2017
Trial size 540 participants
Trial identifier NCT01968213, CO-338-014

Summary

Patients enrolled into this study will be stratified into 3 groups based on gene mutations identified in their tumor tissue. The purpose of this study is to evaluate patient response to maintenance treatment with rucaparib versus placebo. Response to treatment will be analyzed based on homologous recombination (HR) status of tumor samples.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
Oral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole.
rucaparib CO-338; PF 01367338, AG 14699
Oral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole.
(Placebo Comparator)
Oral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole.
placebo
Oral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole.

Primary Outcomes

Measure
Disease progression according to RECIST Version 1.1, as assessed by the investigator, or death from any cause (investigator Progression Free Survival or invPFS), in molecularly defined subgroups
time frame: Every 12 calendar weeks (within 7 days prior is permitted) after start of treatment until treatment discontinuation due to disease progression. Study data collection expected to last for ~3 years.

Secondary Outcomes

Measure
Disease progression according to RECIST v1.1, as assessed by Independent Radiology Review (IRR), or death from any cause (irrPFS), in molecularly defined subgroups
time frame: Every 12 calendar weeks (within 7 days prior is permitted) after start of treatment until treatment discontinuation due to disease progression. Study data collection expected to last for ~3 years.
Time to a specified decrease in the DSR P subscale of the FOSI-18 patient reported outcome questionnaire
time frame: Screening, Day 1 of each treatment cycle, Treatment Discontinuation visit, and 28-day Follow-up visit. Study data collection expected to last for ~3 years.
Time to a specified decrease in the total score of the FOSI-18 patient reported outcome questionnaire
time frame: Screening, Day 1 of each treatment cycle, Treatment Discontinuation visit, and 28-day Follow-up visit. Study data collection expected to last for ~3 years.
Overall Survival (OS)
time frame: Continuously for ~5 years after patient enrolls into study.
Incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications
time frame: Continuously for ~3 years after patient enrolls into study.
Individual model parameter estimates of rucaparib and covariates identification (PK)
time frame: Cycle 1 Day 15, and Cycle 2 Day 1, Cycle 2 Day 15, Cycle 4 Day 1, and Cycle 7 Day 1. Study data collection expected to last for ~7 months.

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria: - Confirmed diagnosis of high-grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer. - Received ≥2 prior platinum-based treatment regimens including platinum based regimen that must have been administered immediately prior to maintenance therapy in this trial. - Received no more than 1 non-platinum chemotherapy regimen. Prior hormonal therapy will not be counted as a non-platinum regimen. - Must have had at least a 6-month disease-free period following prior treatment with the penultimate platinum-based chemotherapy and achieved a response. - For the last chemotherapy course prior to study entry, patients must have received a platinum-based doublet chemotherapy regimen and have achieved a CR or PR (as defined by RECIST) and/or a GCIG CA-125 response. - Have sufficient archival tumor tissue for analysis. Exclusion Criteria: - History of prior cancer except for non-melanoma skin cancer, breast cancer curatively > 3 years ago, curatively treated solid tumor (>5 years ago without evidence of recurrence), and synchronous endometrial cancer (Stage 1A) with ovarian cancer. - Prior treatment with any PARP inhibitor, including rucaparib. Patients who received prior iniparib are eligible. - Untreated or symptomatic central nervous system metastases. - Pre-existing duodental stent and/or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of study drug. - Required drainage of ascites during the final 2 cycles of their last platinum-based regimen and/or during the period between the last dose of chemotherapy of that regimen and randomization to maintenance treatment in this study.

Additional Information

Official title Phase 3 Study of Rucaparib as Switch Maintenance After Platinum in Relapsed High Grade Serous and Endometrioid Ovarian Cancer (ARIEL3)
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). Clinical data have shown that ovarian cancer patients with and without evidence of a gBRCA mutation benefit from treatment with a PARP and that maintenance treatment with a PARP inhibitor following a response to platinum-based treatment increases PFS in patients with ovarian cancer. While patients with a BRCA mutation derived the most benefit, patients without evidence of a BRCA mutation also derived significant benefit. Patients enrolled into this study will be stratified into 3 groups based on tumor HRD status. The purpose of this study is to identify which of these groups of patients will most likely benefit from treatment with rucaparib. It is anticipated that rucaparib will provide therapeutic benefit and increase PFS in patients with HRD associated with a BRCA gene mutation or other HR gene alteration.
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.