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.
Inclusion Criteria
- 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
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT01891344.
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 (completed enrollment): Evaluation of HRD status and rucaparib efficacy in
patients who received at least 3 prior chemotherapy regimens
Trial PhasePhase II
Trial Typetreatment
Lead Organizationpharmaand GmbH
- Primary IDCO-338-017
- Secondary IDsNCI-2013-01733, 2013-000517-20, S13-00035
- ClinicalTrials.gov IDNCT01891344