ariel4: a study of rucaparib versus chemotherapy brca mutant ovarian, fallopian tube, or primary peritoneal cancer patients

Conditions: Ovarian Cancer; Epithelial Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer

Summary: the purpose of this study is to determine how patients with ovarian, fallopian tube, and primary peritoneal cancer will best respond to treatment with rucaparib versus chemotherapy.

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. while parp inhibitors have demonstrated consistent robust clinical activity in patients with relapsed ovarian cancer associated with hrd, prospective studies evaluating efficacy and safety of parpi versus standard of care chemotherapy have been limited. the primary purpose of this phase 3 study is to compare the efficacy and safety of rucaparib versus chemotherapy as treatment for relapsed ovarian cancer in patients with a deleterious brca1/2 mutation in their tumor.

Eligibility criteria:
inclusion criteria: * be 18 years of age at the time the informed consent form is signed * 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 ≥ 2 prior chemotherapy regimens and have relapsed or progressive disease as confirmed by radiologic assessment * have biopsiable and evaluable disease. note: biopsy is optional for patients known to harbor a brca1/2 mutation * have sufficient archival formalin-fixed paraffin-embedded (ffpe) tumor tissue available for planned analyses exclusion criteria: * 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 * women who are pregnant or breast feeding * hospitalization for bowel obstruction within 3 months prior to enrollment

Keywords: ovarian cancer fallopian tube cancer primary peritoneal cancer peritoneal cancer platinum sensitive relapsed disease parp inhibitor parp rucaparib ruca homologous recombination homologous recombination deficiency genomic scarring loss of heterozygosity co-338 pf-01367338 pf 01367338 co-338-043 platinum sensitive ovarian cancer platinum sensitive fallopian tube cancer platinum sensitive primary peritoneal cancer platinum sensitive peritoneal cancer gynecological cancer clovis clovis oncology ariel2 ariel 2 ariel-2 ariel-3 ariel 3 ariel3 ariel4 ariel-4 ariel 4 a4 advanced oc platinum resistant ovarian cancer platinum resistant primary ovarian cancer rubraca high grade serous partially platinum sensitive