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Summary

for females ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started

Description

Summary

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.

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)

Details

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 (currently enrolling): Evaluation of HRD status and rucaparib efficacy in patients who received at least 3 prior chemotherapy regimens

Keywords

Ovarian Cancer Epithelial Ovarian Cancer Fallopian Tube Cancer Peritoneal Cancer primary peritoneal cancer platinum sensitive relapsed disease PARP Inhibitor rucaparib homologous recombination homologous recombination deficiency genomic scarring loss of heterozygosity CO-338 PF 01367338 AG 14699 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 ARIEL3 ARIEL 3

Eligibility

For females ages 18 years and up

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

Locations

  • California Pacific Medical Center
    San Francisco, California, 94115, United States
  • Palo Alto Medical Foundation Group
    Palo Alto, California, 94304, United States
  • Stanford University
    Stanford, California, 94305, United States
  • Coastal Integrative Cancer Care
    San Luis Obispo, California, 93401, United States
  • Central Coast Medical Oncology
    Santa Maria, California, 93454, United States
  • University of California Los Angeles
    Los Angeles, California, 90404, United States
  • Saint Jude Heritage Medical Center
    Fullerton, California, 92835, United States
  • Comprehensive Cancer Centers of Nevada
    Henderson, Nevada, 89014, United States

Details

Status
in progress, not accepting new patients
Start Date
Sponsor
Clovis Oncology, Inc.
Links
ARIEL trials website
ID
NCT01891344
Phase
Phase 2
Study Type
Interventional
Last Updated
June 1, 2017