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)
Rochester, Minn., Jacksonville, Fla.
Trial status: Open for Enrollment
Why is this study being done?
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.
Who is eligible to participate?
- Confirmed diagnosis of high-grade epithelial ovarian (serous or endometrioid histology), fallopian tube, or primary peritoneal cancer
- Relapsed/progressive disease as confirmed by CT scan
- Received ≥1 prior platinum-based treatment regimen
- Received platinum-based regimen as last treatment; continuous or switch maintenance treatment as part of this regimen is permitted
- Sensitive to last platinum regimen (disease progression >6 months after the last dose of platinum)
- If <55 years of age at diagnosis, prior history of breast cancer, or close relative (first or second degree) with ovarian cancer or early onset (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