Clinical Trials /

Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Ovarian Cancer Following First Line Platinum Based Chemotherapy.

NCT01844986

Description:

Olaparib Monotherapy in Patients with BRCA Mutated Ovarian Cancer following First Line Platinum Based Chemotherapy.

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

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Ovarian Cancer Following First Line Platinum Based Chemotherapy.
  • Official Title: A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Advanced (FIGO Stage III-IV) Ovarian Cancer Following First Line Platinum Based Chemotherapy.

Clinical Trial IDs

  • ORG STUDY ID: D0818C00001
  • NCT ID: NCT01844986

Conditions

  • Newly Diagnosed
  • Advanced Ovarian Cancer
  • FIGO Stage III-IV
  • BRCA Mutation
  • Complete Response
  • Partial Response
  • First Line Platinum Chemotherapy

Interventions

DrugSynonymsArms
Olaparib 300mg tabletsOlaparib tablets p.o. 300mg twice daily

Purpose

Olaparib Monotherapy in Patients with BRCA Mutated Ovarian Cancer following First Line Platinum Based Chemotherapy.

Detailed Description

      A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Olaparib
      Maintenance Monotherapy in Patients with BRCA Mutated Advanced (FIGO Stage III-IV) Ovarian
      Cancer following First Line Platinum Based Chemotherapy
    

Trial Arms

NameTypeDescriptionInterventions
Olaparib tablets p.o. 300mg twice dailyExperimentalOlaparib/placebo tablets p.o 300mg twice daily for up to 3 years or until objective radiological disease progression as per RECIST as assessed by the Investigator. Patients with evidence of stable disease (or those who have progressed), may continue on treatment beyond 2 years, if in the patient's best interest. Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity
  • Olaparib 300mg tablets
Placebo tablets p.o. twice dailyPlacebo ComparatorOlaparib/placebo tablets p.o 300mg twice daily for up to 3 years or until objective radiological disease progression as per RECIST as assessed by the Investigator. Patients with evidence of stable disease (or those who have progressed), may continue on treatment beyond 2 years, if in the patient's best interest. Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity
  • Olaparib 300mg tablets

Eligibility Criteria

        Inclusion Criteria:

          -  Female patients with newly diagnosed, histologically confirmed, high risk advanced
             (FIGO stage III - IV) BRCA mutated high grade serous or high grade endometrioid
             ovarian cancer, primary peritoneal cancer and / or fallopian - tube cancer who have
             completed first line platinum based chemotherapy (intravenous or intraperitoneal).

          -  Stage III patients must have had one attempt at optimal debulking surgery (upfront or
             interval debulking). Stage IV patients must have had either a biopsy and/or upfront or
             interval debulking surgery.

          -  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 completed first line platinum (e.g. carboplatin or cisplatin),
             containing therapy (intravenous or intraperitoneal) prior to randomisation:

          -  Patients must have, in the opinion of the investigator, clinical complete response or
             partial response and have no clinical evidence of disease progression on the post
             treatment scan or rising CA-125 level, following completion of this chemotherapy
             course. Patients with stable disease on the post-treatment scan at completion of first
             line platinum-containing therapy are not eligible for the study.

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

        Exclusion Criteria:

          -  BRCA1 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 with early stage disease (FIGO Stage I, IIA, IIB or IIC)

          -  Stable disease or progressive disease on the post-treatment scan or clinical evidence
             of progression at the end of the patient's first line chemotherapy treatment.

          -  Patients where more than one debulking surgery has been performed before randomisation
             to the study. (Patients who, at the time of diagnosis, are deemed to be unresectable
             and undergo only a biopsy or oophorectomy but then go on to receive chemotherapy and
             interval debulking surgery are eligible).

          -  Patients who have previously been diagnosed and treated for earlier stage ovarian,
             fallopian tube or primary peritoneal cancer.

          -  Patients who have previously received chemotherapy for any abdominal or pelvic tumour,
             including treatment for prior diagnosis at an earlier stage for their ovarian,
             fallopian tube or primary peritoneal cancer. (Patients who have received prior
             adjuvant chemotherapy for localised breast cancer may be eligible, provided that it
             was completed more than three years prior to registration, and that the patient
             remains free of recurrent or metastatic disease).

          -  Patients with synchronous primary endometrial cancer unless both of the following
             criteria are met: 1) stage <2 2) less than 60 years old at the time of diagnosis of
             endometrial cancer with stage IA or IB grade 1 or 2, or stage IA grade 3 endometrioid
             adenocarcinoma OR ≥ 60 years old at the time of diagnosis of endometrial cancer with
             Stage IA grade 1 or 2 endometrioid adenocarcinoma. Patients with serous or clear cell
             adenocarcinoma or carcinosarcoma of the endometrium are not eligible.
      
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 156 weeks, then every 24 weeks thereafter until objective radiological disease progression. Analysis of data assessed up to a maximum of 54 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 high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy.

Secondary Outcome Measures

Measure:Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Overall Survival
Time Frame:Survival assessed every 4 weeks until treatment discontinues, then every 12 weeks (analysis of data assessed up to a maximum of 54 months). Analysed at the PFS analysis 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 high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of overall survival (OS)
Measure:Efficacy in Patients Following First Line 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 156 weeks, then every 24 weeks until objective radiological disease progression. Analysis of data assessed up to a maximum of 54 months.
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 to earliest progression by RECIST or Cancer Antigen-125 (CA-125)
Measure:Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Second Progression
Time Frame:Following first progression disease then assessed per local practice every 12 weeks until second progression. Analysis of data assessed up to a maximum of 54 months.
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 randomisation to second progression (PFS2)
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 will be given to the patient at baseline, at Day 29 and then every 12 weeks for 156 weeks, then every 24 weeks or until the data cut off for the PFS analysis, change in TOI over 24 months reported
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 high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy. The TOI ranges from 0-100 and a higher score indicates a higher HRQoL.
Measure:Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to First Subsequent Therapy or Death (TFST)
Time Frame:Assessed every 12 weeks following treatment discontinuation. Analysis of data assessed up to a maximum of 54 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 randomisation to first subsequent therapy or death (TFST)
Measure:Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Second Subsequent Therapy or Death (TSST)
Time Frame:Assessed every 12 weeks following treatment discontinuation. Analysis of data assessed up to a maximum of 54 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 randomisation to second subsequent therapy or death (TSST)
Measure:Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Study Treatment Discontinuation or Death (TDT)
Time Frame:Time elapsed from randomization to study treatment discontinuation or death. Analysis of data assessed up to a maximum of 54 months. A further analysis of TDT may 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 randomisation 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 156 weeks, then every 24 weeks thereafter, assessed until disease progression. Analysis of data assessed up to a maximum of 54 months.
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 potential future BRCA mutation assays (gene sequencing and large rearrangement analysis)

Details

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

Trial Keywords

  • BRCA
  • Ovarian Cancer
  • Chemotherapy
  • PARP inhibitor
  • First Line
  • FIGO Stage III
  • FIGO Stage IV

Last Updated

May 14, 2021