A Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2)
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.
Epithelial Ovarian Cancer
Fallopian Tube Cancer
Drug: Oral rucaparib
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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)|
- Progression-free survival per RECIST version 1.1 [ 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 ] [ Designated as safety issue: No ]
- Best overall response rate achieved (from baseline to disease progression) per RECIST version 1.1 and GCIG CA-125 response 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 (RECIST v1.1). ] [ Designated as safety issue: No ]Screening, Day 1 of every cycle, at the end of every 8 weeks (±4 days) of treatment, as clinically indicated, and at disease progression (GCIG CA-125 response criteria).
- Duration of response per RECIST version 1.1 [ 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: Yes ]
- Trough (Cmin) level of rucaparib concentrations [ Time Frame: 2 weeks, 1 month, 2 months and 3 months after 1st dose ] [ Designated as safety issue: No ]
|Study Start Date:||September 2013|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Ovarian cancer
All patients with platinum-sensitive, relapsed, high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer will take oral rucaparib
Drug: Oral rucaparib
All patients will ingest rucaparib twice a day continuously until disease progression. Patients may take rucaparib on an empty stomach or with food. Each dose should be taken with at least 8 oz (240 mL) of room temperature water. Tablets should be swallowed whole. Each patient will take the Recommended Phase 2 Dose established in the CO-338-010 study.
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 in the final analysis of the planned Phase 3 pivotal study (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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01891344
|Contact: Clovis Oncology Clinical Trial Information||1-855-262-3040 (USA)||email@example.com|
|Contact: Clovis Oncology Clinical Trial Information||+1-303-625-5160 (ex-USA)||firstname.lastname@example.org|
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