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Trial record 1 of 1 for:    02983799
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Olaparib Tablets as a Treatment for Ovarian Cancer Subjects With Different HRD Tumor Status

This study is currently recruiting participants.
Verified September 2017 by AstraZeneca
Sponsor:
ClinicalTrials.gov Identifier:
NCT02983799
First Posted: December 6, 2016
Last Update Posted: September 19, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
AstraZeneca
  Purpose
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 ovarian cancer. Subjects should have received at least 2 prior lines of platinum-based chemotherapy.

Condition Intervention Phase
Relapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity Drug: OLAPARIB Phase 2

An investigational treatment associated with this study has been approved for sale to the public.   More info ...

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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 Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That Have Received at Least 2 Prior Lines of Chemotherapy

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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)


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 120
Actual Study Start Date: December 22, 2016
Estimated Study Completion Date: October 23, 2019
Estimated Primary Completion Date: October 23, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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 epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received at least 2 prior lines 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).
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 130 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provision of written signed informed consent prior to any study specific procedures;
  • Female subjects with histologically diagnosed relapsed high-grade serous ovarian cancer (including primary peritoneal and/or fallopian tube 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 2 prior platinum-based lines of chemotherapy for ovarian cancer. Note: There is no limit on the number of non-platinum-based 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;
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (see Appendix F);
  • 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
  Contacts and Locations
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): NCT02983799


Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

  Show 23 Study Locations
Sponsors and Collaborators
AstraZeneca
  More Information

Additional Information:
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02983799     History of Changes
Other Study ID Numbers: D0816L00003
First Submitted: November 4, 2016
First Posted: December 6, 2016
Last Update Posted: September 19, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AstraZeneca:
BRCA, ovarian, platinum, chemotherapy

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
Olaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents