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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Patients should continue with therapy until objective radiological disease progression as per RECIST 1.1 despite rises in CA-125. All patients should continue to receive study treatment until objective radiological disease progression as per RECIST 1.1 as assessed by the investigator or the patient experiences unacceptable toxicity or they meet any other discontinuation criteria
Patients should continue with therapy until objective radiological disease progression as per RECIST 1.1 despite rises in CA-125. All patients should continue to receive study treatment until objective radiological disease progression as per RECIST 1.1 as assessed by the investigator or the patient experiences unacceptable toxicity or they meet any other discontinuation criteria
Research Site
Mobile, Alabama, United States
Progression Free Survival (PFS) using modified RECIST 1.1 in the cohort of patients with sBRCA ovarian cancer
To determine the efficacy of olaparib maintenance monotherapy compared to placebo by assessment of progression free survival (PFS) using blinded independent central review (BICR)
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
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
To determine the efficacy of olaparib maintenance monotherapy compared to placebo by assessment of progression free survival (PFS)using blinded independent central review (BICR)
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
Overall Survival (OS) in patients with sBRCAm ovarian cancer and in the ITT population consisting of all randomised patients
To determine the efficacy of olaparib maintenance monotherapy compared to placebo by assessment of overall survival (OS)
Time frame: From the date of randomisation until death due to any cause, assessed up to 60 months
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
To determine the efficacy of olaparib maintenance monotherapy compared to placebo by assessment of Time from randomisation to first subsequent therapy or death
Time frame: From the date of randomisation to the earlier of first subsequent therapy start date, assessed up to 60 months
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Research Site
Phoenix, Arizona, United States
Research Site
Los Angeles, California, United States
Research Site
Stanford, California, United States
Research Site
Augusta, Georgia, United States
Research Site
Park Ridge, Illinois, United States
Research Site
Iowa City, Iowa, United States
Research Site
Louisville, Kentucky, United States
Research Site
Covington, Louisiana, United States
Research Site
Scarborough, Maine, United States
...and 19 more locations
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
To compare the effects of olaparib maintenance monotherapy compared to placebo on Health-related Quality of Life (HRQoL)
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
Plasma mutation status
To determine if p53, somatic BRCA and other HRR mutations are present in plasma prior to chemotherapy
Time frame: cfDNA sample collected during pre-screening, assessed up to 40 months
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
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
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
Time from randomisation to second progression (PFS2) in patients with sBRCAm ovarian cancer and in the ITT population consisting of all randomised patients
To determine the efficacy of olaparib maintenance monotherapy compared to placebo by assessment of Time from randomisation to second progression
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
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
To determine the efficacy of olaparib maintenance monotherapy compared to placebo by assessment of Time from randomisation to second subsequent therapy of death
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
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
To determine the efficacy of olaparib maintenance monotherapy compared to placebo by assessment of Time from randomisation to study treatment discontinuation or death
Time frame: From the date of randomisation to the earlier of the date of study treatment discontinuation or death, assessed up to 60 months