Back to resultsOlaparib 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
Primary Purpose
Platinum Sensitive Relapsed Ovarian Cancer
Status
Withdrawn
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
OLAPARIB
PLACEBO
Sponsored by
About this trial
This is an interventional treatment trial for Platinum Sensitive Relapsed Ovarian Cancer focused on measuring Ovarian cancer, Platinum, Somatic BRCA mutation, Homologous recombination repair
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
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
1/OLAPARIB
2/PLACEBO
Arm Description
olaparib 300 mg oral tablets; twice daily
placebo matching olaparib 300 mg oral tablets; twice daily
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
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)
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 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
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)
Plasma mutation status
To determine if p53, somatic BRCA and other HRR mutations are present in plasma prior to chemotherapy
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 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 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 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
Full Information
NCT ID
NCT02392676
First Posted
February 23, 2015
Last Updated
April 29, 2016
Sponsor
AstraZeneca
Collaborators
Myriad Genetic Laboratories, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02392676
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Withdrawn
Why Stopped
Study is unlikely to be feasible given the evolving ovarian cancer landscape and alternative studies have the potential to meet future clinical demand.
Study Start Date
July 2016 (undefined)
Primary Completion Date
June 2019 (Anticipated)
Study Completion Date
June 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
Collaborators
Myriad Genetic Laboratories, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Platinum Sensitive Relapsed Ovarian Cancer
Keywords
Ovarian cancer, Platinum, Somatic BRCA mutation, Homologous recombination repair
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1/OLAPARIB
Arm Type
Experimental
Arm Description
olaparib 300 mg oral tablets; twice daily
Arm Title
2/PLACEBO
Arm Type
Placebo Comparator
Arm Description
placebo matching olaparib 300 mg oral tablets; twice daily
Intervention Type
Drug
Intervention Name(s)
OLAPARIB
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
PLACEBO
Intervention Description
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
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS) using modified RECIST 1.1 in the cohort of patients with sBRCA ovarian cancer
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)
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
Secondary Outcome Measure Information:
Title
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
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)
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
Title
Overall Survival (OS) in patients with sBRCAm ovarian cancer and in the ITT population consisting of all randomised patients
Description
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
Title
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
Description
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
Title
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
Description
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
Title
Plasma mutation status
Description
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
Title
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
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
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
Title
Time from randomisation to second progression (PFS2) in patients with sBRCAm ovarian cancer and in the ITT population consisting of all randomised patients
Description
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
Title
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
Description
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
Title
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
Description
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
Other Pre-specified Outcome Measures:
Title
Number of AEs in all patients who received at least one dose of randomised investigational product, olaparib or placebo
Description
To assess the safety and tolerability of olaparib maintenance monotherapy by assessment of AEs
Time Frame
assessed up to 60 months
Title
Changes in Vital signs in all patients who received at least one dose of randomised investigational product, olaparib or placebo
Description
To assess the safety and tolerability of olaparib maintenance monotherapy by assessment of vital signs
Time Frame
assessed up to 60 months
Title
Changes in Physical examination results in all patients who received at least one dose of randomised investigational product, olaparib or placebo
Description
To assess the safety and tolerability of olaparib maintenance monotherapy by assessment of physical examination parameters
Time Frame
assessed up to 60 months
Title
Changes in safety laboratory parameters in all patients who received at least one dose of randomised investigational product, olaparib or placebo
Description
To assess the safety and tolerability of olaparib maintenance monotherapy by safety laboratory (consisting of clinical chemistry and haematology)parameters assessment
Time Frame
assessed up to 60 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
96 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charlie Gourley, Prof.
Organizational Affiliation
University of Edinburgh
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Carol Aghajanian, MD
Organizational Affiliation
MSKCC
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Mobile
State/Province
Alabama
Country
United States
Facility Name
Research Site
City
Phoenix
State/Province
Arizona
Country
United States
Facility Name
Research Site
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Research Site
City
Stanford
State/Province
California
Country
United States
Facility Name
Research Site
City
Augusta
State/Province
Georgia
Country
United States
Facility Name
Research Site
City
Park Ridge
State/Province
Illinois
Country
United States
Facility Name
Research Site
City
Iowa City
State/Province
Iowa
Country
United States
Facility Name
Research Site
City
Louisville
State/Province
Kentucky
Country
United States
Facility Name
Research Site
City
Covington
State/Province
Louisiana
Country
United States
Facility Name
Research Site
City
Scarborough
State/Province
Maine
Country
United States
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
Country
United States
Facility Name
Research Site
City
Albany
State/Province
New York
Country
United States
Facility Name
Research Site
City
Oklahoma City
State/Province
Oklahoma
Country
United States
Facility Name
Research Site
City
Philadelphia
State/Province
Pennsylvania
Country
United States
Facility Name
Research Site
City
Milwaukee
State/Province
Wisconsin
Country
United States
Facility Name
Research Site
City
Goyang-si
Country
Korea, Republic of
Facility Name
Research Site
City
Seongnam-si
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
Country
Korea, Republic of
Facility Name
Research Site
City
Chiclayo
Country
Peru
Facility Name
Research Site
City
Lima
Country
Peru
Facility Name
Research Site
City
Quezon City
Country
Philippines
Facility Name
Research Site
City
Birmingham
Country
United Kingdom
Facility Name
Research Site
City
Cambridge
Country
United Kingdom
Facility Name
Research Site
City
Coventry
Country
United Kingdom
Facility Name
Research Site
City
Edinburgh
Country
United Kingdom
Facility Name
Research Site
City
London
Country
United Kingdom
Facility Name
Research Site
City
Manchester
Country
United Kingdom
Facility Name
Research Site
City
Oxford
Country
United Kingdom
Facility Name
Research Site
City
Sutton
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
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
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