A Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by Clovis Oncology, Inc.
Sponsor:
Collaborator:
Foundation Medicine
Information provided by (Responsible Party):
Clovis Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT01891344
First received: June 20, 2013
Last updated: May 7, 2015
Last verified: May 2015

June 20, 2013
May 7, 2015
September 2013
March 2017   (final data collection date for primary outcome measure)
  • Disease Progression (RECIST v1.1) as assessed by investigator, or death from any cause, in molecularly-defined subgroups identified by a prospectively defined HRD signature (PART 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 ]
  • ORR by RECIST v1.1 (PART 2) [ 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; within 7 days of every odd numbered cycle, i.e. prior to the start of Cycle 3, 5, 7, etc; at disease progression; study data collection expected to last for ~2 years ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01891344 on ClinicalTrials.gov Archive Site
  • ORR by RECIST v1.1 (PART 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 (RECIST v1.1). ] [ Designated as safety issue: No ]
  • Disease Progression (RECIST v1.1) as assessed by investigator, or death from any cause, in molecularly-defined subgroups identified by a prospectively defined HRD signature (PART 2) [ 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 ]
  • ORR by RECIST v1.1 and GCIG CA-125 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 ] [ Designated as safety issue: No ]
  • Duration of response per RECIST v1.1 [ 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 rucaparib concentrations [ Time Frame: 2 weeks, 1 month, 2 months and 3 months after 1st dose ] [ Designated as safety issue: No ]
  • Overall Survival (PART 2) [ Time Frame: study data collection expected to last for ~2 years ] [ Designated as safety issue: No ]
  • Duration of response per RECIST version 1.1 [ Time Frame: Screening; within 7 days of every odd numbered cycle, i.e. prior to the start of Cycle 3, 5, 7, etc; at disease progression; study data collection expected to last for ~2 years ] [ Designated as safety issue: No ]
  • Progression-free survival per RECIST version 1.1 [ Time Frame: Screening; within 7 days of every odd numbered cycle, i.e. prior to the start of Cycle 3, 5, 7, etc; 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 ]
Not Provided
Not Provided
 
A Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2)
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)

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.

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

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Ovarian Cancer
  • Epithelial Ovarian Cancer
  • Fallopian Tube Cancer
  • Peritoneal Cancer
Drug: Oral rucaparib
600 mg BID
Other Names:
  • CO-338
  • PF 01367338
  • AG 14699
Experimental: Ovarian cancer
rucaparib
Intervention: Drug: Oral rucaparib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
480
Not Provided
March 2017   (final data collection date for primary outcome measure)

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
Female
18 Years and older
No
Contact: Clovis Oncology Clinical Trial Information 1-855-262-3040 (USA) clovistrials@emergingmed.com
Contact: Clovis Oncology Clinical Trial Information +1-303-625-5160 (ex-USA) clovistrials@emergingmed.com
United States,   Australia,   Canada,   France,   Spain,   United Kingdom
 
NCT01891344
CO-338-017
No
Clovis Oncology, Inc.
Clovis Oncology, Inc.
Foundation Medicine
Not Provided
Clovis Oncology, Inc.
May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP