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

Brief Title

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

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)

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.

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

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD (Homologous Recombination Deficiency) Subgroups (Part 1 of Study)

Secondary Outcome

 Objective Response Rate (ORR) by RECIST v1.1 (Part 1 of Study)

Condition

Ovarian Cancer

Intervention

Oral rucaparib

Study Arms / Comparison Groups

 Ovarian cancer

Description:  rucaparib

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

Start Date

October 30, 2013

Completion Date

September 28, 2021

Primary Completion Date

November 5, 2019

Eligibility 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

Gender

Female

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, ,

Location Countries

Australia

Location Countries

Australia

Administrative Informations

NCT ID

NCT01891344

Organization ID

CO-338-017

Responsible Party

Sponsor

Study Sponsor

Clovis Oncology, Inc.

Collaborators

 Foundation Medicine

Study Sponsor

, ,

Verification Date

January 2022