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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Clovis Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT01482715
First received: November 22, 2011
Last updated: July 5, 2016
Last verified: July 2016
  Purpose

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).


Condition Intervention Phase
Ovarian Cancer
Fallopian Tube Cancer
Peritoneal Cancer
Advanced Solid Tumor With Evidence of Germline or Somatic BRCA
Drug: Rucaparib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Clovis Oncology, Inc.:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 160
Study Start Date: November 2011
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oral Rucaparib monotherapy 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01482715

Locations
United States, California
UCSF
San Francisco, California, United States, 94155
United States, Florida
Sarah Cannon Research Institute
Sarasota, Florida, United States, 34232
United States, Massachusetts
Dana-Farber Cancer Institute (Part 3 only)
Boston, Massachusetts, United States, 02215
United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, MSG 2M9
Israel
Sheba Medical Center
Ramat Gan, Israel, 52621
Tel Aviv Sourasky Medical Center
Tel Aviv, Israel, 632394
Spain
Hospital Vall d'Hebron
Barcelona, Spain, 8035
United Kingdom
Guy's and St Thomas NHS Foundation Trust
London, England, United Kingdom, SE1 9RT
Royal Marsden NHS Foundation Trust
London, England, United Kingdom, SW3 6JJ
Imperial College Healthcare
London, England, United Kingdom, W12 0HS
Newcastle University
Newcastle Upon Tyne, England, United Kingdom, UK NE7
Institution of Cancer Science, University of Glasgow Wolfson Wohl Cancer Research
Glasgow, Scotland, United Kingdom, G61 1QH
University College London Cancer Institute
London, United Kingdom, WC1E 6BT
Sponsors and Collaborators
Clovis Oncology, Inc.
  More Information

Responsible Party: Clovis Oncology, Inc.
ClinicalTrials.gov Identifier: NCT01482715     History of Changes
Other Study ID Numbers: CO-338-010 
Study First Received: November 22, 2011
Last Updated: July 5, 2016
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Canada: Health Canada
Israel: Ministry of Health
Spain: Ministry of Health

Keywords provided by Clovis Oncology, Inc.:
gBRCA ovarian cancer
platinum sensitive
PARP Inhibitor
Rucaparib
CO-338
PF 01367338
AG 14699
BRCA1
BRCA2
platinum sensitive ovarian cancer
platinum sensitive gBRCA ovarian cancer
gynecological cancer
relapsed disease
homologous recombination deficiency
HRD

Additional relevant MeSH terms:
Ovarian Neoplasms
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Rucaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on December 02, 2016