Olaparib Tablets as a Treatment for Ovarian Cancer Subjects With Different HRD Tumor Status

March 22, 2022 updated by: AstraZeneca

Non-Randomized, Open-Label Phase II Study to Assess Olaparib Tablets as a Treatment for Subjects With Different HRD Tumor Status and With Platinum-Sensitive, Relapsed, High-Grade Serous or High-Grade Endometrioid Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That Have Received at Least 1 Prior Line of Chemotherapy

This is a non-randomized, open-label study to assess olaparib tablets as a treatment for subjects with different homologous recombination deficiency (HRD) tumor status and with platinum-sensitive, relapsed, high-grade serous or high-grade endometrioid ovarian cancer. Subjects should have received at least 1 prior line of platinum-based chemotherapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a Phase II, open-label, non-randomized, multi-center study assessing the efficacy and safety of olaparib tablets 300 mg (two 150 mg tablets) given orally twice daily (bid) in subjects with platinum-sensitive or partially platinum-sensitive, relapsed, high-grade serous or high-grade endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received at least 1 prior line of platinum-based chemotherapy.

The study will assess the effectiveness of olaparib tablets as measured by the objective response rate (ORR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, in subjects with germline BRCA mutations (gBRCAm), somatic BRCA mutations (sBRCAm), or potential aberrations in homologous recombination deficiency (HRD) as determined by myChoice® HRD, as well as in subjects without identifiable HRD. This study will utilize Myriad BRACAnalysis CDx® for germline BRCA analysis and a tumor test (myChoice® HRD) for tumor BRCA analysis and HRD status. Four cohorts will be identified based upon the genetic testing described above:

  • Cohort 1: gBRCAm,
  • Cohort 2: sBRCAm and germline BRCA wild type,
  • Cohort 3: myChoice® HRD positive (genomic instability positive) and BRCA wild type (BRCAwt) (no BRCA mutation),
  • Cohort 4: myChoice® HRD negative (genomic instability negative) and BRCAwt (no BRCA mutation).

Study Type

Interventional

Enrollment (Actual)

272

Phase

  • Phase 2

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Research Site
    • British Columbia
      • Vancouver, British Columbia, Canada, VSZ 4E6
        • Research Site
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0V9
        • Research Site
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 1V7
        • Research Site
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Research Site
      • Kingston, Ontario, Canada, K7L 2V7
        • Research Site
      • Mississauga, Ontario, Canada, L5M 2N1
        • Research Site
      • Toronto, Ontario, Canada, M4N 3M5
        • Research Site
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • Research Site
      • Montreal, Quebec, Canada, H1T 2M4
        • Research Site
      • Montreal, Quebec, Canada, H2X 0A9
        • Research Site
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Research Site
  • United States
    • Alaska
      • Anchorage, Alaska, United States, 99508
        • Research Site
    • California
      • La Jolla, California, United States, 92093
        • Research Site
      • Los Angeles, California, United States, 90017
        • Research Site
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Research Site
    • Connecticut
      • Hartford, Connecticut, United States, 06102
        • Research Site
      • New Haven, Connecticut, United States, 06519
        • Research Site
    • Delaware
      • Newark, Delaware, United States, 19718
        • Research Site
    • Florida
      • South Miami, Florida, United States, 33143
        • Research Site
    • Illinois
      • Skokie, Illinois, United States, 60077
        • Research Site
    • Louisiana
      • Shreveport, Louisiana, United States, 71103
        • Research Site
    • Maryland
      • Silver Spring, Maryland, United States, 20910
        • Research Site
    • Massachusetts
      • Springfield, Massachusetts, United States, 01199
        • Research Site
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Research Site
      • Detroit, Michigan, United States, 48201
        • Research Site
    • Minnesota
      • Minneapolis, Minnesota, United States, 55407
        • Research Site
      • Saint Paul, Minnesota, United States, 55125
        • Research Site
    • New Jersey
      • Berkeley Heights, New Jersey, United States, 07922
        • Research Site
      • Hackensack, New Jersey, United States, 07601
        • Research Site
      • Newark, New Jersey, United States, 07103
        • Research Site
      • Teaneck, New Jersey, United States, 07666
        • Research Site
    • New York
      • Bronx, New York, United States, 10461
        • Research Site
      • New York, New York, United States, 10021
        • Research Site
      • New York, New York, United States, 10032
        • Research Site
      • New York, New York, United States, 10065
        • Research Site
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27103
        • Research Site
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Research Site
    • Oregon
      • Portland, Oregon, United States, 97227
        • Research Site
    • Pennsylvania
      • Abington, Pennsylvania, United States, 19001
        • Research Site
      • Philadelphia, Pennsylvania, United States, 19104
        • Research Site
      • Pittsburgh, Pennsylvania, United States, 15224
        • Research Site
    • Rhode Island
      • Providence, Rhode Island, United States, 02905
        • Research Site
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • Research Site
    • Texas
      • Houston, Texas, United States, 77030
        • Research Site
    • Virginia
      • Annandale, Virginia, United States, 22003
        • Research Site
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 126 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Provision of written signed informed consent prior to any study specific procedures;
  • Female subjects with histologically diagnosed relapsed high-grade serous or high-grade endometrioid ovarian cancer;
  • At least 1 lesion (measurable by RECIST v1.1) that can be accurately assessed at baseline by computed tomography (CT)/magnetic resonance imaging (MRI) and is suitable for repeated assessment;
  • Subjects must have received at least 1 prior platinum-based line of chemotherapy for ovarian cancer. Note: There is no limit on the number of lines of chemotherapy;
  • Subjects must be partially-platinum-sensitive (defined as progression 6 to 12 months after the end of the last platinum-based chemotherapy) or platinum sensitive (defined as progression > 12 months after the end of the last platinum-based chemotherapy);
  • Subjects must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment;
  • ECOG performance status 0 to 1;
  • Subjects must have a life expectancy greater than or equal to 16 weeks;
  • Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on Day 1;
  • Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations; and
  • Formalin fixed, paraffin embedded tumor sample (either archival or fresh sample) from the primary or recurrent cancer must be available for central testing. If there is not written confirmation of the availability of an archived or fresh tumor sample prior to enrollment, the subject is not eligible for the study.

Exclusion Criteria:

  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca Representative staff and/or staff at the study site);
  • Previous enrollment in the present study;
  • Exposure to any investigational product (IP) within 30 days or 5 half-lives (whichever is longer) prior to start of study treatment;
  • Any previous treatment with a PARP inhibitor, including olaparib;
  • Subjects who have platinum-resistant or refractory disease defined as progression during or within 6 months of the last platinum-based chemotherapy;
  • Other malignancy within the last 5 years (few exceptions apply);
  • Resting ECG with clinically significant abnormal findings;
  • Subjects receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment;
  • Concomitant use of known strong CYP3A inhibitors or moderate CYP3A inhibitors;
  • Concomitant use of known strong or moderate CYP3A inducers;
  • Persistent toxicities (> Common Terminology Criteria for Adverse Event [CTCAE] grade 2) caused by previous cancer therapy, excluding alopecia;
  • Subjects with MDS/AML or with features suggestive of MDS/AML;
  • Subjects with pneumonitis or at risk of pneumonitis;
  • Subjects with symptomatic uncontrolled brain metastases;
  • Major surgery within 2 weeks of starting study treatment, and subjects must have recovered from any effects of any major surgery;
  • Subjects considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, or active, uncontrolled infection;
  • Breast feeding women;
  • Immunocompromised subjects, e.g., subjects who are known to be serologically positive for human immunodeficiency virus;
  • Subjects with known active hepatitis (i.e., Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: gBRCAm;
germline BRCA mutant
Drug: OLAPARIB
300 mg olaparib tablets taken orally twice daily
Experimental: sBRCAm and germline BRCA wild type;
somatic BRCA mutant, germline BRCA wild type
Drug: OLAPARIB
300 mg olaparib tablets taken orally twice daily
Experimental: myChoice® HRD positive and BRCAwt;
genomic instability positive and no BRCA mutation
Drug: OLAPARIB
300 mg olaparib tablets taken orally twice daily
Experimental: myChoice® HRD negative and BRCAwt
genomic instability negative and no BRCA mutation
Drug: OLAPARIB
300 mg olaparib tablets taken orally twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate, Defined as the Percentage of Subjects With a Best Overall Response of Confirmed Complete Response (CR) or Partial Response (PR)
Time Frame: From first dose up until progression, or last evaluable assessment in the absence of progression (up to 36 months)
To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using ORR according to RECIST v1.1 criteria (Investigator determined)
From first dose up until progression, or last evaluable assessment in the absence of progression (up to 36 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response, for Those Subjects With a Confirmed Response of CR or PR
Time Frame: From the date of the measurement criteria for CR or PR are first met until the date of documented progression or death in the absence of disease progression (up to 36 months)
To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using duration of response
From the date of the measurement criteria for CR or PR are first met until the date of documented progression or death in the absence of disease progression (up to 36 months)
CA-125 Response Rate, Defined as the Percentage of Subjects With a CA-125 Response According to GCIG Criteria Divided by the Number of Subjects Evaluable for CA-125 Response
Time Frame: From baseline to Day 1 of each cycle and end of study treatment visit (up to 36 months)
To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using CA-125 response rate
From baseline to Day 1 of each cycle and end of study treatment visit (up to 36 months)
Disease Control Rate Defined as the Percentage of Subjects Who Have a Best Overall Response of CR or PR or SD at Greater Than or Equal to 8 Weeks Divided by the Number of Subjects in the Efficacy Analysis Set, Prior to Any PD Event
Time Frame: From first dose up until progression, or last evaluable assessment in the absence of progression
To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using disease control rate (DCR). DCR is defined as the percentage of subjects with a best overall response of CR or PR (at any time up to and including the defined analysis cut-off point) or who have demonstrated stable disease (SD) for at least 8 weeks from first dose, divided by the number of subjects in the efficacy analysis set.
From first dose up until progression, or last evaluable assessment in the absence of progression
Progression Free Survival
Time Frame: From first dose to earlier date of assessment of objective progression or death by any cause in the absence of progression (up to 36 months)
To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using progression free survival
From first dose to earlier date of assessment of objective progression or death by any cause in the absence of progression (up to 36 months)
Time to Any Progression
Time Frame: From first dose to earlier date of CA-125 progression or RECIST v1.1 progression, or death by any cause in absence of progression (up to 36 months)
To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using time to any progression
From first dose to earlier date of CA-125 progression or RECIST v1.1 progression, or death by any cause in absence of progression (up to 36 months)
Overall Survival
Time Frame: From date of first dose to date of death from any cause (up to 48 months)
To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using overall survival
From date of first dose to date of death from any cause (up to 48 months)
HRD Status as Per HRRm Gene Panel Assessment Will be Correlated With Clinical Outcome (ORR) for Subjects Enrolled in the 2 Cohorts With BRCAwt (Cohorts 3 and 4)
Time Frame: At baseline
To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using HRRm gene panel status related to clinical outcome
At baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 22, 2016

Primary Completion (Actual)

December 3, 2020

Study Completion (Actual)

December 3, 2020

Study Registration Dates

First Submitted

November 4, 2016

First Submitted That Met QC Criteria

December 2, 2016

First Posted (Estimate)

December 6, 2016

Study Record Updates

Last Update Posted (Actual)

April 13, 2022

Last Update Submitted That Met QC Criteria

March 22, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D0816L00003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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