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.
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
Drug | Synonyms | Arms |
---|
Olaparib 300mg tablets | | Olaparib 300mg tablets |
Placebo to match olaparib 300mg | | Placebo 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
Name | Type | Description | Interventions |
---|
Olaparib 300mg tablets | Experimental | Taken orally twice daily | |
Placebo tablets | Placebo Comparator | Taken 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 until 19 Sep 2016 DCO (16 Jan 2017 DCO for China Cohort); 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 until 03 Feb 2020 DCO; up to a maximum of 75 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 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 at baseline then every 4 wks. Radiologic scans at baseline then every ~12 wks up to 72 wks, then every ~ 24 wks until objective radiological disease progression. Assessed until 19Sep2016 DCO (16Jan2017 DCO for China Cohort); up to a max of 36 mths. |
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: | Scans at baseline then every 12 wks for 72 wks, then every 24 wks until first progression. Assessments then per local practice every 12 wks until second progression. Assessed until 19Sep2016 DCO (16Jan2017 DCO for China Cohort); up to a max of 36 mths |
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. Assessed until 19 Sep 2016 DCO. |
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 until 03 Feb 2020 DCO; up to a maximum of 75 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 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 until 03 Feb 2020 DCO; up to a maximum of 75 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 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 until 03 Feb 2020 DCO; up to a maximum of 75 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 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. Assessed until 19 Sep 2016 DCO. |
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. Assessed until 19 Sep 2016 DCO. |
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
Last Updated
July 14, 2021