This trial is active, not recruiting.

Conditions ovarian cancer, fallopian tube cancer, peritoneal cancer, advanced solid tumor with evidence of germline or somatic brca
Treatment rucaparib
Phase phase 1/phase 2
Targets BRCA, PARP
Sponsor Clovis Oncology, Inc.
Start date November 2011
End date December 2016
Trial size 160 participants
Trial identifier NCT01482715, CO-338-010


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 (Currently Enrolling) - 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).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
rucaparib CO-338; PF 01367338, AG 14699
Oral tablets administered daily with 8 oz (240 mL) of water on an empty stomach or with food; 21-day cycles of treatment. In Part 1, the initial dose level is 40 mg/day (once a day); doses and dosing frequency(e.g. twice a day or three times a day) will be adjusted until Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) are established. Patients enrolled in Part 2 and Part 3 will receive the RP2D for continuous 21-day treatment cycles until disease progression.

Primary Outcomes

Incidence of Grade 3 or 4 adverse events and clinical lab abnormalities defined as DLTs (Part 1)
time frame: Cycle 1 Days 1, 8, 15 and 22
PK Profile for Single Dose and at Steady State (Part 1 and Part 3 only)
time frame: Days 1 and 15 of Cycle 1
Overall Response Rate per RECIST version 1.1 (Part 2)
time frame: Every 2 - 3 cycles of treatment

Secondary Outcomes

PK profile (fasted and fed) (Part 1 and PART 3 only)
time frame: Day -7 and Day 1 of Cycle 1
Change from baseline in QT/QTc interval (ECG) (Part 1 only)
time frame: Every week (Cycle 1); q3wks (Cycles 2+)
Incidence of AEs, clinical laboratory abnormalities, and ECG abnormalities (Part 1, 2, and 3)
time frame: Every 1-2 weeks (Cycle 1); q3wks (Cycles 2+)
Duration of response per RECIST version 1.1 (Part 2 only)
time frame: Every 2-3 cycles of treatment
Response per RECIST version 1.1 (Part 1 only)
time frame: Every 2-3 cycles of treatment
Overall Survival (Part 2B)
time frame: study data collection expected to last for ~ 2 years

Eligibility Criteria

Female participants at least 18 years old.

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.

Additional Information

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
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.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Clovis Oncology, Inc..
Location data was received from the National Cancer Institute and was last updated in July 2016.