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
136
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
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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