Clinical Trials /

ARIEL4: A Study of Rucaparib Versus Chemotherapy BRCA Mutant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients

NCT02855944

Description:

The purpose of this study is to determine how patients with ovarian, fallopian tube, and primary peritoneal cancer will best respond to treatment with rucaparib versus chemotherapy.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: ARIEL4: A Study of Rucaparib Versus Chemotherapy BRCA Mutant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients
  • Official Title: ARIEL4 (Assessment of Rucaparib In Ovarian CancEr TriaL): A Phase 3 Multicenter, Randomized Study of Rucaparib Versus Chemotherapy in Patients With Relapsed, BRCA Mutant, High Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Clinical Trial IDs

  • ORG STUDY ID: CO-338-043
  • NCT ID: NCT02855944

Conditions

  • Ovarian Cancer
  • Epithelial Ovarian Cancer
  • Fallopian Tube Cancer
  • Peritoneal Cancer

Interventions

DrugSynonymsArms
ChemotherapyCisplatin, carboplatin, carboplatin/paclitaxel, carboplatin/gemcitabine, paclitaxelChemotherapy
RucaparibCO-338, AG 14699, PF 01367338, RubracaRucaparib

Purpose

The purpose of this study is to determine how patients with ovarian, fallopian tube, and primary peritoneal cancer will best respond to treatment with rucaparib versus chemotherapy.

Detailed Description

      Rucaparib 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 breast cancer susceptibility gene 1
      (BRCA1) or BRCA2 mutations.

      While PARP inhibitors have demonstrated consistent robust clinical activity in patients with
      relapsed ovarian cancer associated with HRD, prospective studies evaluating efficacy and
      safety of PARPi versus standard of care chemotherapy have been limited. The primary purpose
      of this Phase 3 study is to compare the efficacy and safety of rucaparib versus chemotherapy
      as treatment for relapsed ovarian cancer in patients with a deleterious BRCA1/2 mutation in
      their tumor.
    

Trial Arms

NameTypeDescriptionInterventions
RucaparibExperimentalDrug: Oral rucaparib 600 mg BID Other Names: •CO-338 PF 01367338 AG 14699 Rubraca
  • Rucaparib
ChemotherapyActive ComparatorMonotherapy platinum (cisplatin or carboplatin) or platinum-based doublet chemotherapy (carboplatin/paclitaxel, carboplatin/gemcitabine, or cisplatin/gemcitabine administered per local standard of care and regulations. Specific comparator will depend on platinum status and investigator decision. Single agent paclitaxel will be administered per local standard of care and regulations. Specific comparator will depend on platinum status and investigator decision.
  • Chemotherapy

Eligibility Criteria

        Inclusion Criteria:

          -  Be 18 years of age at the time the informed consent form is signed

          -  Have a histologically confirmed diagnosis of high-grade serous or Grade 2 or Grade 3
             endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer

          -  Received ≥ 2 prior chemotherapy regimens and have relapsed or progressive disease as
             confirmed by radiologic assessment

          -  Have biopsiable and evaluable disease. Note: biopsy is optional for patients known to
             harbor a BRCA1/2 mutation

          -  Have sufficient archival formalin-fixed paraffin-embedded (FFPE) tumor tissue
             available for planned analyses

        Exclusion Criteria:

          -  History of prior cancers except for those that have been curatively treated, with no
             evidence of cancer currently (provided all chemotherapy was completed >6 months prior
             and/or bone marrow transplant >2 years prior to first dose of rucaparib).

          -  Prior treatment with any PARP inhibitor

          -  Symptomatic and/or untreated central nervous system metastases

          -  Pre-existing duodenal stent and/or any other gastrointestinal disorder or defect that
             would, in the opinion of the Investigator, interfere with absorption of rucaparib

          -  Women who are pregnant or breast feeding

          -  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:Investigator assessed progression-free survival (invPFS) by RECIST Version 1.1 for rucaparib versus chemotherapy
Time Frame:Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed for the duration of the study, ~4 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Efficacy of rucaparib versus chemotherapy as measured by overall survival (OS)
Time Frame:study data collection expected to last for ~5 years
Safety Issue:
Description:
Measure:Safety and tolerability of rucaparib versus chemotherapy assessed by AEs reported; clinical laboratory investigations; Vital signs; 12 lead ECGs; Physical examinations; and ECOG performance status
Time Frame:study data collection expected to last for ~4 years
Safety Issue:
Description:This is a composite outcome. It will be assessed by Incidence, type, seriousness, and severity of AEs reported; clinical laboratory investigations (hematology and serum chemistry); Vital signs (blood pressure, heart rate, and body temperature); 12 lead ECGs; Physical examinations; and ECOG performance status

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Clovis Oncology, Inc.

Trial Keywords

  • ovarian cancer
  • fallopian tube cancer
  • primary peritoneal cancer
  • peritoneal cancer
  • platinum sensitive
  • relapsed disease
  • PARP Inhibitor
  • PARP
  • rucaparib
  • ruca
  • homologous recombination
  • homologous recombination deficiency
  • genomic scarring
  • loss of heterozygosity
  • CO-338
  • PF-01367338
  • PF 01367338
  • CO-338-043
  • platinum sensitive ovarian cancer
  • platinum sensitive fallopian tube cancer
  • platinum sensitive primary peritoneal cancer
  • platinum sensitive peritoneal cancer
  • gynecological cancer
  • Clovis
  • Clovis oncology
  • ARIEL2
  • ARIEL 2
  • ARIEL-2
  • ARIEL-3
  • ARIEL 3
  • ARIEL3
  • ARIEL4
  • ARIEL-4
  • ARIEL 4
  • A4
  • advanced OC
  • platinum resistant ovarian cancer
  • platinum resistant primary ovarian cancer
  • Rubraca
  • High grade serous
  • Partially platinum sensitive

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