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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 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: August 8, 2014
Last verified: August 2014

June 7, 2013
August 8, 2014
September 2013
July 2015   (final data collection date for primary outcome 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. ] [ 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.
Same as current
Complete list of historical versions of study NCT01874353 on ClinicalTrials.gov Archive Site
  • 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).
  • 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 relapsed 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: Assessments 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.
Not Provided
Not Provided
 
Olaparib Treatment in BRCA Mutated Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy
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

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Platinum Sensitive
  • BRCA Mutated
  • Relapsed Ovarian Cancer
  • Following Complete or Partial Response to Platinum Based Chemotherapy
  • 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.
  • 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.
  • Experimental: Olaparib 300mg tablets
    Taken orally twice daily
    Intervention: Drug: Olaparib 300mg tablets
  • Placebo Comparator: Placebo tablets
    Taken orally twice daily
    Intervention: Drug: Placebo to match olaparib 300mg
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
440
June 2020
July 2015   (final data collection date for primary outcome measure)

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

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.
Female
18 Years and older
No
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
United States,   Australia,   Belgium,   Brazil,   Canada,   France,   Germany,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Poland,   Russian Federation,   Spain,   United Kingdom
 
NCT01874353
D0816C00002
Yes
AstraZeneca
AstraZeneca
  • European Network of Gynecological Oncology Trial Groups (ENGOT)
  • Myriad Genetics - BRAC Analysis test for FDA Premarket Approval (PMA)
Principal Investigator: Professor E Pujade-Lauraine, MD, PhD Universite de Paris Descartes, France
AstraZeneca
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP