Clinical Trials /

Olaparib Treatment in BRCA Mutated Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy

NCT01874353

Description:

A Phase III, randomised, double-blind, placebo-controlled, multi-centre study to assess the efficacy of olaparib maintenance monotherapy in relapsed high grade serous ovarian cancer (HGSOC) patients (including patients with primary peritoneal and / or fallopian tube cancer) or high grade endometrioid cancer with BRCA mutations (documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function)) who have responded following platinum based chemotherapy.

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

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Olaparib Treatment in BRCA Mutated Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy
  • Official Title: Phase III Randomised, Double Blind, Placebo Controlled Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed BRCA Mutated Ovarian Cancer Patients With a Complete or Partial Response Following Platinum Based Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: D0816C00002
  • NCT ID: NCT01874353

Conditions

  • Platinum Sensitive
  • BRCA Mutated
  • Relapsed Ovarian Cancer
  • Following Complete or Partial Response to Platinum Based Chemotherapy

Interventions

DrugSynonymsArms
Olaparib 300mg tabletsOlaparib 300mg tablets
Placebo to match olaparib 300mgPlacebo tablets

Purpose

A Phase III, randomised, double-blind, placebo-controlled, multi-centre study to assess the efficacy of olaparib maintenance monotherapy in relapsed high grade serous ovarian cancer (HGSOC) patients (including patients with primary peritoneal and / or fallopian tube cancer) or high grade endometrioid cancer with BRCA mutations (documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function)) who have responded following platinum based chemotherapy.

Detailed Description

      Comparison of olaparib against a placebo in patients with ovarian cancer whose cancer has
      already improved by taking platinum based chemotherapy. The patients must also have a fault
      in their DNA which codes for the BRCA protein. The BRCA protein helps mend broken DNA in the
      cells of the body; if this protein doesn't work properly it can increase the chance of
      getting cancer. The aim of this study is to see whether patients taking olaparib tablets last
      longer until their cancer gets worse, compared to those taking the placebo tablet. The study
      is also looking to see if there is an overall improvement to how long the patients survive
      whilst taking olaparib tablets compared to the placebo tablets; and the quality of their life
      whilst living with ovarian cancer.
    

Trial Arms

NameTypeDescriptionInterventions
Olaparib 300mg tabletsExperimentalTaken orally twice daily
  • Olaparib 300mg tablets
Placebo tabletsPlacebo ComparatorTaken orally twice daily
  • Placebo to match olaparib 300mg

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must be ≥ 18 years of age.

               -  Female patients with histologically diagnosed relapsed high grade serous ovarian
                  cancer (including primary peritoneal and / or fallopian tube cancer) or high
                  grade endometrioid cancer.

               -  Documented mutation in BRCA1 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 received at least 2 previous lines of platinum containing
                  therapy prior to randomisation

        For the penultimate chemotherapy course prior to enrolment on the study:

        • Patient defined as platinum sensitive after this treatment; defined as disease
        progression greater than 6 months after completion of their last dose of platinum
        chemotherapy

        For the last chemotherapy course immediately prior to randomisation on the study:

          -  Patients must be, in the opinion of the investigator, in response (partial or complete
             radiological response), or may have no evidence of disease (if optimal cytoreductive
             surgery was conducted prior to chemotherapy), and no evidence of a rising CA-125,
             following completion of this chemotherapy course

          -  Patient must have received a platinum based chemotherapy regimen (e.g. carboplatin or
             cisplatin) and have received at least 4 cycles of treatment

          -  Patients must be randomized within 8 weeks of their last dose of chemotherapy

          -  Maintenance treatment is allowed at the end of the penultimate platinum regimen,
             including bevacizumab

        Exclusion Criteria:

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

          -  BRCA 1 and/or BRCA2 mutations that are considered to be non detrimental (e.g.,
             "Variants of uncertain clinical significance" or "Variant of unknown significance" or
             "Variant, favor polymorphism" or "benign polymorphism" etc.)

          -  Patients who have had drainage of their ascites during the final 2 cycles of their
             last chemotherapy regimen prior to enrolment on the study.
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS) Using Investigator Assessment According to Modified Response Evaluation Criteria In Solid Tumours (RECIST 1.1)
Time Frame:Radiologic scans performed at baseline then every ~12 weeks up to 72 weeks, then every ~ 24 weeks thereafter until objective radiological disease progression. Assessed up to a maximum of 36 months.
Safety Issue:
Description:To determine the efficacy by progression free survival (PFS) (using investigator assessment according to modified Response Evaluation Criteria In Solid Tumours (RECIST 1.1)) of olaparib maintenance monotherapy compared to placebo in BRCA mutated relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy.

Secondary Outcome Measures

Measure:Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Overall Survival
Time Frame:Survival assessed every 4 weeks until treatment discontinues, then every 12 weeks (assessed up to a maximum of 36 months). Analyzed at the time of the primary analysis of PFS and a further analysis of OS will be performed at approximately 60% maturity.
Safety Issue:
Description:To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy by assessment of overall survival (OS).
Measure:Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Time to Earliest Progression by RECIST or Cancer Antigen (CA-125) or Death
Time Frame:CA-125 performed at baseline then every 4 weeks. Radiologic scans performed at baseline then every ~12 weeks up to 72 weeks, then every ~ 24 weeks until objective radiological disease progression. Assessed up to a maximum of 36 months.
Safety Issue:
Description:To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy by assessment of time to earliest progression by RECIST or CA-125 or death.
Measure:Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Time From Randomization to Second Progression
Time Frame:Radiologic scans performed at baseline then every 12 weeks for 72 weeks, then every 24 weeks thereafter until first progression. Disease then assessed per local practice every 12 weeks until second progression. Assessed up to a maximum of 36 months.
Safety Issue:
Description:To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated relapsed ovarian cancer patients who are in complete response or partial response following first line platinum based chemotherapy by assessment of time from randomization up to second progression
Measure:Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O)
Time Frame:Questionnaires completed by patient at baseline, Day 29 and then every 12 weeks for 12 months.
Safety Issue:
Description:To compare the effects of olaparib maintenance monotherapy compared to placebo on Health-related Quality of Life (HRQoL) as assessed by the trial outcome index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O) in BRCA mutated relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy. The TOI ranges from 0-100 and a higher score indicates a higher HRQoL.
Measure:Efficacy of Olaparib by Time to First Subsequent Therapy or Death (TFST).
Time Frame:Time elapsed from randomization to first subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation. Assessed up to a maximum of 36 months. A further analysis of TFST will be performed at approximately 60% OS maturity.
Safety Issue:
Description:To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomization to first subsequent therapy or death (TFST).
Measure:Efficacy of Olaparib by Time to Second Subsequent Therapy or Death (TSST).
Time Frame:Time elapsed from randomization to second subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation. Assessed up to a maximum of 36 months. A further analysis of TSST will be performed at approximately 60% OS maturity.
Safety Issue:
Description:To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomization to second subsequent therapy or death (TSST).
Measure:Efficacy of Olaparib by Time From Randomization to Study Treatment Discontinuation or Death (TDT).
Time Frame:Time elapsed from randomization to study treatment discontinuation or death. Assessed up to a maximum of 36 months. A further analysis of TDT will be performed at approximately 60% OS maturity.
Safety Issue:
Description:To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomization to study treatment discontinuation or death (TDT).
Measure:Efficacy in Patients With a Deleterious or Suspected Deleterious Variant in Either of the BRCA Genes by Assessment of PFS.
Time Frame:Radiologic scans performed at baseline then every ~12 weeks for the first 72 weeks, then every ~24 weeks thereafter, assessed until disease progression.
Safety Issue:
Description:To assess efficacy of olaparib in patients identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (gene sequencing and large rearrangement analysis).
Measure:To Determine the Exposure to Olaparib by Pharmacokinetic Analysis
Time Frame:Pharmacokinetics sampling to be performed in a subset of patients. Sampling times: Day 1 pre-dose & 1 hour; Day 15 pre-dose & 1 hour; Day 29 pre-dose
Safety Issue:
Description:To determine the exposure to olaparib in patients receiving olaparib maintenance monotherapy

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • BRCA
  • Ovarian cancer
  • Chemotherapy
  • PARP Inhibitor
  • Platinum sensitive

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