Clinical Trials /

Olaparib Tablets as a Treatment for Ovarian Cancer Subjects With Different HRD Tumor Status

NCT02983799

Description:

This is a non-randomized, open-label study to assess olaparib tablets as a treatment for subjects with different homologous recombination deficiency (HRD) tumor status and with platinum-sensitive, relapsed, high-grade serous or high-grade endometrioid ovarian cancer. Subjects should have received at least 1 prior line of platinum-based chemotherapy.

Related Conditions:
  • Fallopian Tube Carcinoma
  • High Grade Ovarian Serous Adenocarcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Olaparib Tablets as a Treatment for Ovarian Cancer Subjects With Different HRD Tumor Status
  • Official Title: Non-Randomized, Open-Label Phase II Study to Assess Olaparib Tablets as a Treatment for Subjects With Different HRD Tumor Status and With Platinum-Sensitive, Relapsed, High-Grade Serous or High-Grade Endometrioid Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That Have Received at Least 1 Prior Line of Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: D0816L00003
  • NCT ID: NCT02983799

Conditions

  • Relapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity

Interventions

DrugSynonymsArms
OLAPARIBgBRCAm;

Purpose

This is a non-randomized, open-label study to assess olaparib tablets as a treatment for subjects with different homologous recombination deficiency (HRD) tumor status and with platinum-sensitive, relapsed, high-grade serous or high-grade endometrioid ovarian cancer. Subjects should have received at least 1 prior line of platinum-based chemotherapy.

Detailed Description

      This is a Phase II, open-label, non-randomized, multi-center study assessing the efficacy and
      safety of olaparib tablets 300 mg (two 150 mg tablets) given orally twice daily (bid) in
      subjects with platinum-sensitive or partially platinum-sensitive, relapsed, high-grade serous
      or high-grade endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer,
      who have received at least 1 prior line of platinum-based chemotherapy.

      The study will assess the effectiveness of olaparib tablets as measured by the objective
      response rate (ORR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST)
      v1.1, in subjects with germline BRCA mutations (gBRCAm), somatic BRCA mutations (sBRCAm), or
      potential aberrations in homologous recombination deficiency (HRD) as determined by myChoice®
      HRD, as well as in subjects without identifiable HRD. This study will utilize Myriad
      BRACAnalysis CDx® for germline BRCA analysis and a tumor test (myChoice® HRD) for tumor BRCA
      analysis and HRD status. Four cohorts will be identified based upon the genetic testing
      described above:

        -  Cohort 1: gBRCAm,

        -  Cohort 2: sBRCAm and germline BRCA wild type,

        -  Cohort 3: myChoice® HRD positive (genomic instability positive) and BRCA wild type
           (BRCAwt) (no BRCA mutation),

        -  Cohort 4: myChoice® HRD negative (genomic instability negative) and BRCAwt (no BRCA
           mutation).
    

Trial Arms

NameTypeDescriptionInterventions
gBRCAm;Experimentalgermline BRCA mutant
  • OLAPARIB
sBRCAm and germline BRCA wild type;Experimentalsomatic BRCA mutant, germline BRCA wild type
  • OLAPARIB
myChoice® HRD positive and BRCAwt;Experimentalgenomic instability positive and no BRCA mutation
  • OLAPARIB
myChoice® HRD negative and BRCAwtExperimentalgenomic instability negative and no BRCA mutation
  • OLAPARIB

Eligibility Criteria

        Inclusion Criteria:

          -  Provision of written signed informed consent prior to any study specific procedures;

          -  Female subjects with histologically diagnosed relapsed high-grade serous or high-grade
             endometrioid ovarian cancer;

          -  At least 1 lesion (measurable by RECIST v1.1) that can be accurately assessed at
             baseline by computed tomography (CT)/magnetic resonance imaging (MRI) and is suitable
             for repeated assessment;

          -  Subjects must have received at least 1 prior platinum-based line of chemotherapy for
             ovarian cancer. Note: There is no limit on the number of lines of chemotherapy;

          -  Subjects must be partially-platinum-sensitive (defined as progression 6 to 12 months
             after the end of the last platinum-based chemotherapy) or platinum sensitive (defined
             as progression > 12 months after the end of the last platinum-based chemotherapy);

          -  Subjects must have normal organ and bone marrow function measured within 28 days prior
             to administration of study treatment;

          -  ECOG performance status 0 to 1;

          -  Subjects must have a life expectancy greater than or equal to 16 weeks;

          -  Postmenopausal or evidence of non-childbearing status for women of childbearing
             potential: negative urine or serum pregnancy test within 28 days of study treatment
             and confirmed prior to treatment on Day 1;

          -  Subject is willing and able to comply with the protocol for the duration of the study
             including undergoing treatment and scheduled visits and examinations; and

          -  Formalin fixed, paraffin embedded tumor sample (either archival or fresh sample) from
             the primary or recurrent cancer must be available for central testing. If there is not
             written confirmation of the availability of an archived or fresh tumor sample prior to
             enrollment, the subject is not eligible for the study.

        Exclusion Criteria:

          -  Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
             Representative staff and/or staff at the study site);

          -  Previous enrollment in the present study;

          -  Exposure to any investigational product (IP) within 30 days or 5 half-lives (whichever
             is longer) prior to start of study treatment;

          -  Any previous treatment with a PARP inhibitor, including olaparib;

          -  Subjects who have platinum-resistant or refractory disease defined as progression
             during or within 6 months of the last platinum-based chemotherapy;

          -  Other malignancy within the last 5 years (few exceptions apply);

          -  Resting ECG with clinically significant abnormal findings;

          -  Subjects receiving any systemic chemotherapy or radiotherapy (except for palliative
             reasons) within 3 weeks prior to study treatment;

          -  Concomitant use of known strong CYP3A inhibitors or moderate CYP3A inhibitors;

          -  Concomitant use of known strong or moderate CYP3A inducers;

          -  Persistent toxicities (> Common Terminology Criteria for Adverse Event [CTCAE] grade
             2) caused by previous cancer therapy, excluding alopecia;

          -  Subjects with MDS/AML or with features suggestive of MDS/AML;

          -  Subjects with pneumonitis or at risk of pneumonitis;

          -  Subjects with symptomatic uncontrolled brain metastases;

          -  Major surgery within 2 weeks of starting study treatment, and subjects must have
             recovered from any effects of any major surgery;

          -  Subjects considered a poor medical risk due to a serious, uncontrolled medical
             disorder, non-malignant systemic disease, or active, uncontrolled infection;

          -  Breast feeding women;

          -  Immunocompromised subjects, e.g., subjects who are known to be serologically positive
             for human immunodeficiency virus;

          -  Subjects with known active hepatitis (i.e., Hepatitis B or C) due to risk of
             transmitting the infection through blood or other body fluids
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate, defined as the percentage of subjects with a best overall response of confirmed complete response (CR) or partial response (PR)
Time Frame:From first dose up until progression, or last evaluable assessment in the absence of progression (up to 36 months)
Safety Issue:
Description:To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using ORR according to RECIST v1.1 criteria (Investigator determined)

Secondary Outcome Measures

Measure:Duration of response, for those subjects with a confirmed response of CR or PR
Time Frame:From the date of the measurement criteria for CR or PR are first met until the date of documented progression or death in the absence of disease progression (up to 36 months)
Safety Issue:
Description:To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using duration of response
Measure:CA-125 response rate, defined as the percentage of subjects with a CA-125 response according to GCIG criteria divided by the number of subjects evaluable for CA-125 response
Time Frame:From baseline to Day 1 of each cycle and end of study treatment visit (up to 36 months)
Safety Issue:
Description:To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using CA-125 response rate
Measure:Disease control rate defined as the percentage of subjects who have a best overall response of CR or PR or SD at greater than or equal to 8 weeks divided by the number of subjects in the efficacy analysis set, prior to any PD event
Time Frame:From first treatment to greater than or equal to 8 weeks
Safety Issue:
Description:To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using disease control rate (DCR). DCR is defined as the percentage of subjects with a best overall response of CR or PR (at any time up to and including the defined analysis cut-off point) or who have demonstrated stable disease (SD) for at least 8 weeks from first dose, divided by the number of subjects in the efficacy analysis set.
Measure:Progression free survival
Time Frame:From first dose to earlier date of assessment of objective progression or death by any cause in the absence of progression (up to 36 months)
Safety Issue:
Description:To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using progression free survival
Measure:Time to any progression
Time Frame:From first dose to earlier date of CA-125 progression or RECIST v1.1 progression, or death by any cause in absence of progression (up to 36 months)
Safety Issue:
Description:To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using time to any progression
Measure:Overall survival
Time Frame:From date of first dose to date of death from any cause (up to 48 months)
Safety Issue:
Description:To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using overall survival
Measure:HRD status as per HRRm gene panel assessment will be correlated with clinical outcome (ORR) for subjects enrolled in the 2 cohorts with BRCAwt (cohorts 3 and 4)
Time Frame:At baseline
Safety Issue:
Description:To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using HRRm gene panel status related to clinical outcome

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • BRCA, ovarian, platinum, chemotherapy

Last Updated

January 4, 2018