Overview

This trial is active, not recruiting.

Conditions newly diagnosed, advanced ovarian cancer, figo stage iii-iv, brca mutation, complete response, partial response, first line platinum chemotherapy
Treatment olaparib 300mg tablets
Phase phase 3
Targets BRCA, PARP
Sponsor AstraZeneca
Collaborator Gynecologic Oncology Group (GOG)
Start date August 2013
End date September 2017
Trial size 397 participants
Trial identifier NCT01844986, D0818C00001

Summary

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

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)
Olaparib/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
Olaparib/placebo tablets p.o 300mg twice daily for up to 2 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.
(Placebo Comparator)
Olaparib/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
Olaparib/placebo tablets p.o 300mg twice daily for up to 2 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.

Primary Outcomes

Measure
Progression Free Survival (PFS) by review of investigator-reported RECIST data
time frame: Radiologic scans performed at baseline then every ~12 weeks up to 3 years (156 weeks) and every ~24 weeks thereafter until objective radiological disease progression. Study data collection expected to last for ~10 years.

Secondary Outcomes

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 or up to 3 years (whichever is earlier), then assessed every 12 weeks. Study data collection expected to last for ~10 years.
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, every 12 weeks until week 156 and then 24 weeks or until the data cut off for the primary analysis, whichever comes first. Study data collection expected to last for ~10 years.
Efficacy in patients with a deleterious or suspected deleterious variant in either of the BRCA genes by assessment of progression free survival.
time frame: Radiologic scans performed at baseline every ~12 weeks for up to 3 years and every ~24 weeks thereafter, until disease progression. Study data collection expected to last for ~10 years.
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 ~10 years.
Efficacy in patients following First Line Platinum Based Chemotherapy by assessment of time to earliest progression by RECIST or Cancer Antigen-125 (CA-125).
time frame: CA125 assessed every 4 weeks for up to 3 years, then every 12 weeks. Radiologic scans performed every ~12 weeks for up to 3 years, then every ~24 weeks until disease progression. Study data collection expected to last for ~10 years.
Efficacy in patients following First Line Platinum Based Chemotherapy by assessment of time from randomisation to second progression.
time frame: Radiologic scans performed at baseline then every~12 weeks for up to 3 years, then every~24 weeks until first progression. Then disease is assessed as per local clinical practice until 2nd progression. Study data collection expected to last for~10 years.
Safety and tolerability of olaparib by assessment and review of laboratory parameters.
time frame: Laboratory parameter assessments collected until study treatment discontinued. Study data collection expected to last ~10 years.
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 ~10 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 ~10 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 ~10 years.

Eligibility Criteria

Female participants from 18 years up to 130 years old.

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.

Additional Information

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.
Principal investigator Prof Paul DiSilvestro, MD
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 information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by AstraZeneca.