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

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ClinicalTrials.gov Identifier: NCT02983799
Recruitment Status : Active, not recruiting
First Posted : December 6, 2016
Last Update Posted : March 13, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE November 4, 2016
First Posted Date  ICMJE December 6, 2016
Last Update Posted Date March 13, 2019
Actual Study Start Date  ICMJE December 22, 2016
Estimated Primary Completion Date May 21, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 2, 2016)
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)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02983799 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 2, 2016)
  • 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
  • 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
  • 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 treatment to greater than or equal to 8 weeks ]
    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.
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Olaparib Tablets as a Treatment for Ovarian Cancer Subjects With Different HRD Tumor Status
Official Title  ICMJE 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
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Relapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity
Intervention  ICMJE Drug: OLAPARIB
300 mg olaparib tablets taken orally twice daily
Study Arms  ICMJE
  • Experimental: gBRCAm;
    germline BRCA mutant
    Intervention: Drug: OLAPARIB
  • Experimental: sBRCAm and germline BRCA wild type;
    somatic BRCA mutant, germline BRCA wild type
    Intervention: Drug: OLAPARIB
  • Experimental: myChoice® HRD positive and BRCAwt;
    genomic instability positive and no BRCA mutation
    Intervention: Drug: OLAPARIB
  • Experimental: myChoice® HRD negative and BRCAwt
    genomic instability negative and no BRCA mutation
    Intervention: Drug: OLAPARIB
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 12, 2019)
271
Original Estimated Enrollment  ICMJE
 (submitted: December 2, 2016)
120
Estimated Study Completion Date  ICMJE May 21, 2020
Estimated Primary Completion Date May 21, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02983799
Other Study ID Numbers  ICMJE D0816L00003
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date March 2019

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