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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)

NCT01482715

Description:

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).

Related Conditions:
  • Lymphoma
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: CO-338-010
  • NCT ID: NCT01482715

Conditions

  • Ovarian Cancer
  • Fallopian Tube Cancer
  • Peritoneal Cancer
  • Advanced Solid Tumor With Evidence of Germline or Somatic BRCA

Interventions

DrugSynonymsArms
RucaparibCO-338; PF 01367338, AG 14699Oral Rucaparib monotherapy

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 (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.
    

Trial Arms

NameTypeDescriptionInterventions
Oral Rucaparib monotherapyExperimental
  • Rucaparib

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

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
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:PK profile (fasted and fed) (Part 1 and PART 3 only)
Time Frame:Day -7 and Day 1 of Cycle 1
Safety Issue:
Description:AUC and Cmax
Measure:Change from baseline in QT/QTc interval (ECG) (Part 1 only)
Time Frame:Every week (Cycle 1); q3wks (Cycles 2+)
Safety Issue:
Description:
Measure: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+)
Safety Issue:
Description:
Measure:Duration of response per RECIST version 1.1 (Part 2 only)
Time Frame:Every 2-3 cycles of treatment
Safety Issue:
Description:
Measure:Response per RECIST version 1.1 (Part 1 only)
Time Frame:Every 2-3 cycles of treatment
Safety Issue:
Description:
Measure:Overall Survival (Part 2B)
Time Frame:study data collection expected to last for ~ 2 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Clovis Oncology, Inc.

Trial Keywords

  • 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

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