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

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ClinicalTrials.gov Identifier: NCT01874353
Recruitment Status : Active, not recruiting
First Posted : June 11, 2013
Results First Posted : February 7, 2018
Last Update Posted : February 7, 2018
Sponsor:
Collaborators:
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Myriad Genetic Laboratories, Inc.
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
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.

Condition or disease Intervention/treatment 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

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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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 295 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Actual Study Start Date : September 3, 2013
Actual Primary Completion Date : September 19, 2016
Estimated Study Completion Date : May 7, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ovarian Cancer
Drug Information available for: Olaparib
U.S. FDA Resources

Arm Intervention/treatment
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.



Primary Outcome Measures :
  1. 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 up to a maximum of 36 months. ]
    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 :
  1. 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 up to a maximum of 36 months). Analyzed at the time of the primary analysis of PFS and a further analysis of OS will be performed at approximately 60% maturity. ]
    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).

  2. 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. Assessed up to a maximum of 36 months. ]
    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.

  3. Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Time From Randomization 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 every 12 weeks until second progression. Assessed up to a maximum of 36 months. ]
    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

  4. 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. ]
    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.

  5. 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 up to a maximum of 36 months. A further analysis of TFST will be performed at approximately 60% OS maturity. ]
    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).

  6. 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 up to a maximum of 36 months. A further analysis of TSST will be performed at approximately 60% OS maturity. ]
    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).

  7. 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 up to a maximum of 36 months. A further analysis of TDT will be performed at approximately 60% OS maturity. ]
    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).

  8. 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. ]
    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).

  9. 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 ]
    To determine the exposure to olaparib in patients receiving olaparib maintenance monotherapy



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Senior)
Sexes 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
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01874353


  Show 123 Study Locations
Sponsors and Collaborators
AstraZeneca
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Myriad Genetic Laboratories, Inc.
Investigators
Principal Investigator: Professor E Pujade-Lauraine, MD, PhD Universite de Paris Descartes, France

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01874353     History of Changes
Other Study ID Numbers: D0816C00002
First Posted: June 11, 2013    Key Record Dates
Results First Posted: February 7, 2018
Last Update Posted: February 7, 2018
Last Verified: January 2018

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

Additional relevant MeSH terms:
Ovarian Neoplasms
Hypersensitivity
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Immune System Diseases
Olaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents