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

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Status and phase: Completed; Phase 2; Phase 1

Conditions: Advanced Solid Tumor With Evidence of Germline or Somatic BRCA; Peritoneal Cancer; Fallopian Tube Cancer; Ovarian Cancer

Treatments: Drug: Rucaparib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01482715

CO-338-010

2011-004250-26 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 136 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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136 participants in 4 patient groups

Part 1 (Phase 1)

Experimental group

Description:

Rucaparib 40, 80, 160, 300, 500 mg QD and 240, 360, 480, 600, 840 mg BID, for continuous 21-day cycles. Patients in Part 1 were initially treated in a Dose-escalation Evaluation Period (Cycle 1) and could then continue to receive treatment in an optional Treatment-extension Period (Cycle 2 and beyond).

Treatment:

Drug: Rucaparib

Part 2A (Phase 2)

Experimental group

Description:

Rucaparib 600 mg BID for 21-day cycles.

Treatment:

Drug: Rucaparib

Part 2B (Phase 2)

Experimental group

Description:

Rucaparib 600 mg BID for 21-day cycles.

Treatment:

Drug: Rucaparib

Part 3 (Phase 2)

Experimental group

Description:

Rucaparib 600 mg BID for 21-day cycles. Patients also received a single administration of 600 mg rucaparib on both Day -7 and Day 1 for assessing the effect of food on PK.

Treatment:

Drug: Rucaparib