Overview

This trial is active, not recruiting.

Conditions platinum sensitive, brca mutated, relapsed ovarian cancer, following complete or partial response to platinum based chemotherapy
Treatments olaparib 300mg tablets, placebo to match olaparib 300mg
Phase phase 3
Target PARP
Sponsor AstraZeneca
Collaborator European Network of Gynaecological Oncology Trial Groups (ENGOT)
Start date September 2013
End date September 2016
Trial size 729 participants
Trial identifier NCT01874353, D0816C00002

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Taken orally twice daily
olaparib 300mg tablets
300mg Olaparib or placebo tablets taken orally twice daily until objective radiological disease progression as per RECIST as assessed by the investigator (or as long as in the investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria). Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity.
(Placebo Comparator)
Taken orally twice daily
placebo to match olaparib 300mg
300mg Olaparib or placebo tablets taken orally twice daily until objective radiological disease progression as per RECIST as assessed by the investigator (or as long as in the investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria). Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity.

Primary Outcomes

Measure
Progression Free Survival (PFS) by central review of RECIST data.
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. Study data collection expected to last until 2018.

Secondary Outcomes

Measure
Efficacy in patients following platinum based chemotherapy by assessment of overall survival
time frame: Survival assessed every 4 weeks until treatment discontinues, then assessed every 12 weeks. Study data collection expected to last until 2018.
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. Study data collection expected to last until 2018.
Efficacy in patients following platinum based chemotherapy by assessment of time from randomisation 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 until second progression. Study data collection expected to last until 2018
Change from baseline in Health-Related Quality of Life (HRQoL) as assessed by the individual domains of 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 24 months or until the data cut-off for the primary analysis, whichever is first. Study data collection expected to last until 2018
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. Study data collection expected to last until 2018.
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, 0.5-1 hour, 1-3 hours 3-6 hours and 6-12 hours.
Safety and tolerability of olaparib by assessment of the number of AEs.
time frame: AEs collected from informed consent until post treatment 30-day follow-up period. Study data collection expected to last until 2018.
Safety and tolerability of olaparib by review of laboratory parameters, ECG and vital signs
time frame: ssessments until study treatment discontinuation. Study data collection expected to last until 2018.
Efficacy of olaparib by time to first subsequent therapy or death (TFST).
time frame: Time elapsed from randomisation to first subsequent therapy or death. Assessed at time of primary PFS analysis and at final OS analysis. Study data collection expected to last ~7 years.
Efficacy of olaparib by time to second subsequent therapy or death (TSST).
time frame: Time elapsed from randomisation to second subsequent therapy or death. Assessed at time of primary PFS analysis and at final OS analysis. Study data collection expected to last ~7 years.
Efficacy of olaparib by time from randomisation to study treatment discontinuation or death (TDT).
time frame: Time elapsed from randomisation to study treatment discontinuation or death. Assessed at time of primary PFS analysis and at final OS analysis. Study data collection expected to last ~7 years.

Eligibility Criteria

Female participants from 18 years up to 130 years old.

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.

Additional Information

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
Principal investigator Professor E Pujade-Lauraine, MD, PhD
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.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by AstraZeneca.