A Study of Oral Rucaparib in Patients With a Solid Tumor (Phase I) or With gBRCA Mutation Ovarian Cancer (Phase II)

Brief Title

A Study of Oral Rucaparib in Patients With a Solid Tumor (Phase I) or With gBRCA Mutation Ovarian Cancer (Phase II)

Official Title

A Phase I/II, Open-Label, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Oral Rucaparib in Patients With gBRCA Mutation Ovarian Cancer or Other Solid Tumor

Brief Summary

      Part 1 (Completed Enrollment) - The purpose of the first part of the study was to evaluate
      the safety of different doses and dosing regimens of oral rucaparib administered daily to
      patients with solid tumors.

      Part 2A (Completed Enrollment) and Part 2B (Completed Enrollment) - The purpose of the second
      part of the study is to determine the safety and clinical activity of the RP2D of oral
      rucaparib administered daily to patients with a known deleterious BRCA mutation (germline or
      somatic).

      Part 3 (Completed Enrollment) - The purpose of the third part of the study is to further
      evaluate PK of higher dose strength tablets at the RP2D in patients with any advanced solid
      tumor, inclusive of lymphoma, with evidence of a BRCA mutation (germline or somatic).

Detailed Description

      Rucaparib (CO-338; formerly known as PF 01367338 and AG 14699) 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 BRCA1 or BRCA2 mutations.
      For this study, it is anticipated that rucaparib will promote cell death in the
      BRCA-deficient tumor cells of ovarian cancer patients with evidence of a germline mutation,
      thereby limiting tumor progression and providing therapeutic benefit.

Study Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

Incidence of Grade 3 or 4 adverse events and clinical lab abnormalities defined as DLTs (Part 1)

Secondary Outcome

 PK profile (fasted and fed) (Part 1 and PART 3 only)

Condition

Ovarian Cancer

Intervention

Rucaparib

Study Arms / Comparison Groups

 Oral Rucaparib monotherapy

Description:

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

November 2011

Completion Date

May 2019

Primary Completion Date

March 2019

Eligibility Criteria

        The following eligibility criteria below pertain to patients enrolling into Part 2B of the
        study.

        Inclusion Criteria:

          -  Have a known deleterious BRCA mutation (gBRCA or sBRCA) (as determined by a local
             laboratory that has received an international or country-specific, quality standards
             certification)

          -  Have evidence of measurable disease as defined by RECIST Version 1.1

          -  Have sufficient archival FFPE tumor tissue available for planned analyses. Archival
             tissue from the most recently collected biopsy or debulking surgery should be
             provided, if available.

          -  Have a histologically confirmed diagnosis of high-grade epithelial ovarian, fallopian
             tube, or primary peritoneal cancer

          -  Have received at least three prior chemotherapy regimens and have relapsed disease
             confirmed by radiologic assessment

        Exclusion Criteria:

          -  Active second malignancy, i.e., patient known to have potentially fatal cancer present
             for which she may be (but not necessarily) currently receiving treatment

             a. Patients with a history of malignancy that has been completely treated, with no
             evidence of that cancer currently, are permitted to enroll in the trial provided all
             chemotherapy was completed >6 months prior and/or bone marrow transplant (BMT) >2
             years prior to first dose of rucaparib

          -  Prior treatment with any PARP inhibitor.

          -  Untreated or symptomatic central nervous system (CNS) metastases. Patients with
             asymptomatic CNS metastases are eligible provided they have been clinically stable for
             at least 4 weeks.

          -  Received treatment with chemotherapy, radiation, antibody therapy or other
             immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or experimental
             drugs 14 days prior to first dose of rucaparib and/or ongoing adverse effects from
             such treatment > NCI CTCAE Grade 1 (Grade 2 non-hematologic toxicity to most recent
             treatment may be permitted with prior advanced approval from Sponsor).

          -  Hospitalization for bowel obstruction within 3 months prior to enrollment.

Gender

Female

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, ,

Location Countries

Canada

Location Countries

Canada

Administrative Informations

NCT ID

NCT01482715

Organization ID

CO-338-010

Responsible Party

Sponsor

Study Sponsor

Clovis Oncology, Inc.

Collaborators

 Foundation Medicine

Study Sponsor

, ,

Verification Date

June 2019