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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2016 by Clovis Oncology, Inc.
Sponsor:
Information provided by (Responsible Party):
Clovis Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT01482715
First received: November 22, 2011
Last updated: January 14, 2016
Last verified: January 2016

November 22, 2011
January 14, 2016
November 2011
April 2017   (final data collection date for primary outcome measure)
  • 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 ] [ Designated as safety issue: Yes ]
  • PK Profile for Single Dose and at Steady State (Part 1 and Part 3 only) [ Time Frame: Days 1 and 15 of Cycle 1 ] [ Designated as safety issue: No ]
    AUC - area under curve from time zero to time t or infinity; Cmax - max concentration; Tmax - time to max concentration; t1/2 - elimination half-life; kel - elimination rate constant; Vss/F - volume of distribution at steady state after nonintravenous administration; Cl/F - total plasma clearance
  • Overall Response Rate per RECIST version 1.1 (Part 2) [ Time Frame: Every 2 - 3 cycles of treatment ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • PK Profile for Single Dose and at Steady State [ Time Frame: Days 1 and 15 of Cycle 1 ] [ Designated as safety issue: No ]
    AUC - area under curve from time zero to time t or infinity; Cmax - max concentration; Tmax - time to max concentration; t1/2 - elimination half-life; kel - elimination rate constant; Vss/F - volume of distribution at steady state after nonintravenous administration; Cl/F - total plasma clearance
  • Overall Response Rate per RECIST version 1.1 (Part 2) [ Time Frame: Every 2 - 3 cycles of treatment ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01482715 on ClinicalTrials.gov Archive Site
  • PK profile (fasted and fed) (Part 1 and PART 3 only) [ Time Frame: Day -7 and Day 1 of Cycle 1 ] [ Designated as safety issue: No ]
    AUC and Cmax
  • Change from baseline in QT/QTc interval (ECG) (Part 1 only) [ Time Frame: Every week (Cycle 1); q3wks (Cycles 2+) ] [ Designated as safety issue: Yes ]
  • 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+) ] [ Designated as safety issue: Yes ]
  • Duration of response per RECIST version 1.1 (Part 2 only) [ Time Frame: Every 2-3 cycles of treatment ] [ Designated as safety issue: No ]
  • Response per RECIST version 1.1 (Part 1 only) [ Time Frame: Every 2-3 cycles of treatment ] [ Designated as safety issue: No ]
  • Overall Survival (Part 2B) [ Time Frame: study data collection expected to last for ~ 2 years ] [ Designated as safety issue: No ]
  • PK profile (fasted and fed) (Part 1 only) [ Time Frame: Day -7 and Day 1 of Cycle 1 ] [ Designated as safety issue: No ]
    AUC and Cmax
  • Change from baseline in QT/QTc interval (ECG) (Part 1 only) [ Time Frame: Every week (Cycle 1); q3wks (Cycles 2+) ] [ Designated as safety issue: Yes ]
  • Incidence of AEs, clinical laboratory abnormalities, and ECG abnormalities [ Time Frame: Every 1-2 weeks (Cycle 1); q3wks (Cycles 2+) ] [ Designated as safety issue: Yes ]
  • Duration of response per RECIST version 1.1 (Part 2 only) [ Time Frame: Every 2-3 cycles of treatment ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study of Oral Rucaparib in Patients With a Solid Tumor (Phase I) or With gBRCA Mutation Ovarian Cancer (Phase II)
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

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 (Currently Enrolling) - 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).

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Ovarian Cancer
  • Fallopian Tube Cancer
  • Peritoneal Cancer
  • Advanced Solid Tumor With Evidence of Germline or Somatic BRCA
Drug: Rucaparib
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.
Other Name: CO-338; PF 01367338, AG 14699
Experimental: Oral Rucaparib monotherapy
Intervention: Drug: Rucaparib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
160
Not Provided
April 2017   (final data collection date for primary outcome measure)

The following eligibility criteria below pertain to patients enrolling into Part 2B or Part 3 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 (Part 2B only).
  • Have received at least three prior chemotherapy regimens and have relapsed disease confirmed by radiologic assessment (Part 2B only).
  • Have an advanced solid tumor, inclusive of lymphoma (Part 3 only).
  • Be willing and able to fast, and to eat a high-fat breakfast on Day -7 or Day 1 of the study (Part 3 only).

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 (Part 1, Part 2). Part 3 patients are permitted to have had previous PARPi, if the following conditions are met:
  • PARPi was not the most recent treatment, and
  • PARPi was discontinued >6 months before first planned dose of rucaparib In all study parts, patients who previously received iniparib are eligible
  • 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 (Part 2B only).
Both
18 Years and older
No
Contact: Clovis Oncology Clinical Trial Information 1-855-262-3040 (USA) clovistrials@emergingmed.com
Contact: Clovis Oncology Clinical Trial Information +1-303-625-5160 (ex-USA) clovistrials@emergingmed.com
United States,   Canada,   Israel,   Spain,   United Kingdom
 
NCT01482715
CO-338-010
No
Not Provided
Not Provided
Clovis Oncology, Inc.
Clovis Oncology, Inc.
Not Provided
Not Provided
Clovis Oncology, Inc.
January 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP