Olaparib Treatment in BRCA Mutated Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy

This study is currently recruiting participants.
Verified April 2014 by AstraZeneca
Sponsor:
Collaborators:
European Network of Gynecological Oncology Trial Groups (ENGOT)
Myriad Genetics - BRAC Analysis test for FDA Premarket Approval (PMA)
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01874353
First received: June 7, 2013
Last updated: April 4, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Platinum Sensitive
BRCA Mutated
Relapsed Ovarian Cancer
Following Complete or Partial Response to Platinum Based Chemotherapy
Drug: Olaparib 300mg tablets
Drug: Placebo to match olaparib 300mg
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    To determine the efficacy by progression free survival (using blinded independent central review) 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:
  • 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. ] [ Designated as safety issue: No ]
    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).

  • 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. ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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 randomisation up to second progression

  • Time to deterioration of Health-Related Quality of Life (HRQoL) as assessed by TOI and FACT-O [ Time Frame: Paper questionnaires completed by patient at baseline, at Day 29 and then in line with RECIST assessments, until disease progression. Study data collection expected to last until 2018. ] [ Designated as safety issue: No ]
    To compare the effects of olaparib maintenance monotherapy compared to placebo on the rate of deterioration of 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.

  • 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. ] [ Designated as safety issue: No ]
    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).

  • 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. ] [ Designated as safety issue: No ]
    To determine the exposure to olaparib in patients receiving olaparib maintenance monotherapy

  • 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. ] [ Designated as safety issue: Yes ]
    To assess the safety and tolerability of olaparib maintenance monotherapy in BRCA mutated relapsed ovarian cancer patients.

  • 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. ] [ Designated as safety issue: Yes ]
    To assess the safety and tolerability of olaparib maintenance monotherapy in BRCA mutated relapsed ovarian cancer patients.

  • 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. ] [ Designated as safety issue: No ]
    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 randomisation to first subsequent therapy or death (TFST).

  • 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. ] [ Designated as safety issue: No ]
    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 randomisation to second subsequent therapy or death (TSST).

  • 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. ] [ Designated as safety issue: No ]
    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 randomisation to study treatment discontinuation or death (TDT).


Estimated Enrollment: 440
Study Start Date: September 2013
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Olaparib 300mg tablets
Taken orally twice daily
Drug: 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: Placebo tablets
Taken orally twice daily
Drug: 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.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01874353

Contacts
Contact: Elizabeth Lowe ClinicalTrialTransparency@astrazeneca.com
Contact: AstraZeneca Cancer Study Locator Service http://www.emergingmed.com/networks/AstraZeneca 001-877-400-4656 astrazeneca@emergingmed.com

  Show 121 Study Locations
Sponsors and Collaborators
AstraZeneca
European Network of Gynecological Oncology Trial Groups (ENGOT)
Myriad Genetics - BRAC Analysis test for FDA Premarket Approval (PMA)
Investigators
Principal Investigator: Professor E Pujade-Lauraine, MD, PhD Universite de Paris Descartes, France
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01874353     History of Changes
Other Study ID Numbers: D0816C00002
Study First Received: June 7, 2013
Last Updated: April 4, 2014
Health Authority: Australia: National Health and Medical Research Council
Brazil: National Health Surveillance Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
China: National Natural Science Foundation
Canada: Canadian Institutes of Health Research
Israel: Israeli Health Ministry Pharmaceutical Administration
Japan: Pharmaceuticals and Medical Devices Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Russia: FSI Scientific Center of Expertise of Medical Application
Spain: Spanish Agency of Medicines

Keywords provided by AstraZeneca:
BRCA
Ovarian cancer
Chemotherapy
PARP Inhibitor
Platinum sensitive

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on April 17, 2014