Clinical Trials /

Olaparib Maintenance Treatment Versus Placebo in Patients With PSR Ovarian Cancer Who Are in CR or PR to Platinum-based Chemotherapy and Whose Tumours Carry sBRCAm or HRR-associated Genes Mutations

NCT02392676

Description:

Olaparib administered as monotherapy in the maintenance setting improves progression free survival compared to placebo in patients whose tumours carry loss of function (deleterious or suspected deleterious) somatic BRCA mutations or loss of function (deleterious or suspected deleterious) mutation in non-BRCA Homologous Recombination Repair (HRR) -associated genes who have a complete or partial response to platinum-based chemotherapy.

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

Withdrawn

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Olaparib Maintenance Treatment Versus Placebo in Patients With PSR Ovarian Cancer Who Are in CR or PR to Platinum-based Chemotherapy and Whose Tumours Carry sBRCAm or HRR-associated Genes Mutations
  • Official Title: A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Olaparib Maintenance Monotherapy in Patients With Platinum Sensitive Relapsed Ovarian Cancer Who Are in Complete or Partial Response Following Platinum Based Chemotherapy and Whose Tumours Carry Loss of Function Somatic BRCA Mutation(s) or Loss of Function Mutation(s) in Tumour Homologous Recombination Repair -Associated Genes

Clinical Trial IDs

  • ORG STUDY ID: D0816C00009
  • NCT ID: NCT02392676

Conditions

  • Platinum Sensitive Relapsed Ovarian Cancer

Interventions

DrugSynonymsArms
OLAPARIB1/OLAPARIB
PLACEBO2/PLACEBO

Purpose

Olaparib administered as monotherapy in the maintenance setting improves progression free survival compared to placebo in patients whose tumours carry loss of function (deleterious or suspected deleterious) somatic BRCA mutations or loss of function (deleterious or suspected deleterious) mutation in non-BRCA Homologous Recombination Repair (HRR) -associated genes who have a complete or partial response to platinum-based chemotherapy.

Detailed Description

      This is a phase III, randomised, double-blind, placebo-controlled, multi-centre study to
      assess the efficacy of olaparib maintenance monotherapy in relapsed high grade epithelial
      ovarian cancer patients (including patients with primary peritoneal and / or fallopian tube
      cancer) who have responded following platinum based chemotherapy. The study population will
      be enrolled as two separate cohorts that will enrol simultaneously. The confirmatory cohort
      will consist of patients who carry a somatic BRCA mutation (documented mutation in BRCA1 or
      BRCA2 that is predicted to be deleterious or suspected deleterious) which are detected in
      tumour material but absent from germline blood testing ; the exploratory cohort will include
      patients with a mutation (documented mutation predicted to be deleterious or suspected
      deleterious) in non BRCA HRR-associated genes which are detected in tumour material
      regardless of their germline status.
    

Trial Arms

NameTypeDescriptionInterventions
1/OLAPARIBExperimentalolaparib 300 mg oral tablets; twice daily
  • OLAPARIB
2/PLACEBOPlacebo Comparatorplacebo matching olaparib 300 mg oral tablets; twice daily
  • PLACEBO

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must be ≥ 18 years of age

          -  Histologically diagnosed relapsed high grade epithelial ovarian cancer (including
             primary peritoneal and/ or fallopian tube cancer)

          -  Documented deleterious or suspected deleterious somatic BRCA 1 and/or BRCA 2 somatic
             mutation or evidence of non- BRCA HRR-associated gene mutation in the tumour.

          -  At least 2 previous lines of platinum containing therapy prior to randomisation.

          -  CA-125 measurements prior to randomised treatment

          -  Patients must have normal organ and bone marrow function measured within 28 days of
             randomisation

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Postmenopausal or evidence of non-childbearing status for women of childbearing
             potential

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

          -  Provision of a blood sample for cfDNA biomarker analysis in Pre-Screening Part 1

          -  Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary or recurrent
             cancer must be available for central testing. If archival tumour sample is not
             available tumour sample from fresh biopsy is acceptable, for all patients eligible to
             participate in Pre-Screening part 2.

        Exclusion Criteria:

          -  Documented germline mutation in BRCA1 and/or BRCA2 that is predicted to be deleterious
             or suspected deleterious (known or predicted to be detrimental/lead to loss of
             function).

          -  Patients who have had drainage of their ascites from the final 2 cycles of their last
             chemotherapy regimen prior to randomisation on the study

          -  Participation in another clinical study with an investigational product during the
             chemotherapy course immediately prior to randomisation

          -  Any previous treatment with a PARP inhibitor, including olaparib

          -  Patients with a known hypersensitivity to olaparib or any of the excipients of the
             product

          -  Prior malignancy in the last 5 years, unless curatively treated and recurrence free
             (few exceptions apply)

          -  Patients receiving any systemic chemotherapy (including chemotherapy received as the
             most recent anticancer therapy) or radiotherapy (except for palliative reasons) within
             3 weeks prior to study randomised treatment

          -  Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) CTCAE
             grade 2) caused by previous cancer therapy, excluding CTCAE grade 2 peripheral
             neuropathy

          -  Patients with myelodysplastic syndrome/acute myeloid leukaemia (t-AML) or with
             features suggestive of MDS/AML

          -  Patients with symptomatic uncontrolled brain metastases

          -  Major surgery within 2 weeks of starting study randomised treatment and patients must
             have recovered from any effects of any major surgery

          -  Patients considered a poor medical risk
      
Maximum Eligible Age:96 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS) using modified RECIST 1.1 in the cohort of patients with sBRCA ovarian cancer
Time Frame:From date of randomization until the date of first documented progression or date of death (by any cause, in the absence of disease progression) whichever came first, assessed up to 40 months
Safety Issue:
Description:To determine the efficacy of olaparib maintenance monotherapy compared to placebo by assessment of progression free survival (PFS) using blinded independent central review (BICR)

Secondary Outcome Measures

Measure:Progression Free Survival (PFS) using modified RECIST 1.1. in the Intent to Treat Population (ITT) consisting of all randomised patients with sBRCAm or HRR-associated gene mutations
Time Frame:From date of randomization until the date of first documented progression or date of death (by any cause, in the absence of disease progression), whichever came first, assessed up to 60 months
Safety Issue:
Description:To determine the efficacy of olaparib maintenance monotherapy compared to placebo by assessment of progression free survival (PFS)using blinded independent central review (BICR)
Measure:Overall Survival (OS) in patients with sBRCAm ovarian cancer and in the ITT population consisting of all randomised patients
Time Frame:From the date of randomisation until death due to any cause, assessed up to 60 months
Safety Issue:
Description:To determine the efficacy of olaparib maintenance monotherapy compared to placebo by assessment of overall survival (OS)
Measure:Time from randomisation to first subsequent therapy or death (TFST) in patients with sBRCAm ovarian cancer and in the ITT population consisting of all randomised patients
Time Frame:From the date of randomisation to the earlier of first subsequent therapy start date, assessed up to 60 months
Safety Issue:
Description:To determine the efficacy of olaparib maintenance monotherapy compared to placebo by assessment of Time from randomisation to first subsequent therapy or death
Measure:Trial outcome index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O) in sBRCA and HRR associated gene mutated relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy
Time Frame:Administered at baseline, at day 29 then every 8 weeks (+/- 1 week) regardless of treatment discontinuation or disease progression, assessed up to 24 months
Safety Issue:
Description:To compare the effects of olaparib maintenance monotherapy compared to placebo on Health-related Quality of Life (HRQoL)
Measure:Plasma mutation status
Time Frame:cfDNA sample collected during pre-screening, assessed up to 40 months
Safety Issue:
Description:To determine if p53, somatic BRCA and other HRR mutations are present in plasma prior to chemotherapy
Measure:Time to earliest progression by RECIST 1.1 or CA-125 or Death in patients with sBRCAm ovarian cancer and in the ITT population consisting of all randomised patients
Time Frame:From randomisation to the earliest date of investigator assesed RECIST or CA-125 progression or death by any cause, assessed up to 60 months
Safety Issue:
Description:To determine the efficacy of olaparib maintenance monotherapy compared to placebo by assessment of Time to earliest progression by RECIST 1.1 or CA-125 or Death. Progression or recurrence based on serum CA-125 levels will be defined on the basis of a progressive serial elevation of serum CA-125
Measure:Time from randomisation to second progression (PFS2) in patients with sBRCAm ovarian cancer and in the ITT population consisting of all randomised patients
Time Frame:From the date of randomisation to the earliest of the progression event subsequent to that used for the primary variable PRS or death, assessed up to 60 months
Safety Issue:
Description:To determine the efficacy of olaparib maintenance monotherapy compared to placebo by assessment of Time from randomisation to second progression
Measure:Time from randomisation to second subsequent therapy or death (TSST) in patients with sBRCAm ovarian cancer and in the ITT population consisting of all randomised patients
Time Frame:From the date of randomisation to the earlier of the date of second subsequent chemotherapy start date or death date, assessed up to 60 months
Safety Issue:
Description:To determine the efficacy of olaparib maintenance monotherapy compared to placebo by assessment of Time from randomisation to second subsequent therapy of death
Measure:Time from randomisation to study treatment discontinuation or death (TDT) in patients with sBRCAm ovarian cancer and in the ITT population consisting of all randomised patients
Time Frame:From the date of randomisation to the earlier of the date of study treatment discontinuation or death, assessed up to 60 months
Safety Issue:
Description:To determine the efficacy of olaparib maintenance monotherapy compared to placebo by assessment of Time from randomisation to study treatment discontinuation or death

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Withdrawn
Lead Sponsor:AstraZeneca

Trial Keywords

  • Ovarian cancer
  • Platinum
  • Somatic BRCA mutation
  • Homologous recombination repair

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