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

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ClinicalTrials.gov Identifier: NCT01891344
Recruitment Status : Active, not recruiting
First Posted : July 3, 2013
Last Update Posted : June 15, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief 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.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Epithelial Ovarian Cancer Fallopian Tube Cancer Peritoneal Cancer Drug: Oral rucaparib Phase 2

Detailed Description:

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


Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 480 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Study Start Date : September 2013
Primary Completion Date : April 2017


Arms and Interventions

Arm Intervention/treatment
Experimental: Ovarian cancer
rucaparib
Drug: Oral rucaparib
600 mg BID
Other Names:
  • CO-338
  • PF 01367338
  • AG 14699


Outcome Measures

Primary Outcome Measures :
  1. 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 ]
  2. 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 ]

Secondary Outcome Measures :
  1. 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). ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. Trough (Cmin) level rucaparib concentrations [ Time Frame: 2 weeks, 1 month, 2 months and 3 months after 1st dose ]
  7. Overall Survival (PART 2) [ Time Frame: study data collection expected to last for ~2 years ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01891344


  Show 75 Study Locations
Sponsors and Collaborators
Clovis Oncology, Inc.
Foundation Medicine
More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Clovis Oncology, Inc.
ClinicalTrials.gov Identifier: NCT01891344     History of Changes
Other Study ID Numbers: CO-338-017
First Posted: July 3, 2013    Key Record Dates
Last Update Posted: June 15, 2017
Last Verified: June 2017

Keywords provided by Clovis Oncology, Inc.:
ovarian cancer
fallopian tube cancer
primary peritoneal cancer
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

Additional relevant MeSH terms:
Ovarian Neoplasms
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Hypersensitivity
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Immune System Diseases
Neoplasms by Histologic Type
Rucaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents