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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 : September 24, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment Phase
Relapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity Drug: OLAPARIB Phase 2

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

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 272 participants
Allocation: Non-Randomized
Intervention Model: Parallel 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 Serous or High-Grade Endometrioid Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That Have Received at Least 1 Prior Line of Chemotherapy
Actual Study Start Date : December 22, 2016
Estimated Primary Completion Date : August 27, 2020
Estimated Study Completion Date : August 27, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ovarian Cancer
Drug Information available for: Olaparib

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




Primary Outcome Measures :
  1. 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 :
  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
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 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

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


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Locations
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United States, Alaska
Research Site
Anchorage, Alaska, United States, 99508
United States, California
Research Site
La Jolla, California, United States, 92093
Research Site
Los Angeles, California, United States, 90017
United States, Colorado
Research Site
Aurora, Colorado, United States, 80045
United States, Connecticut
Research Site
Hartford, Connecticut, United States, 06102
Research Site
New Haven, Connecticut, United States, 06520
United States, Delaware
Research Site
Newark, Delaware, United States, 19718
United States, Florida
Research Site
Miami, Florida, United States, 33143
United States, Illinois
Research Site
Skokie, Illinois, United States, 60046
United States, Maryland
Research Site
Silver Spring, Maryland, United States, 20910
United States, Massachusetts
Research Site
Springfield, Massachusetts, United States, 01199
United States, Michigan
Research Site
Detroit, Michigan, United States, 48201
Research Site
Detroit, Michigan, United States, 48202
United States, Minnesota
Research Site
Minneapolis, Minnesota, United States, 55407
Research Site
Woodbury, Minnesota, United States, 55125
United States, New Jersey
Research Site
Berkely 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
United States, New York
Research Site
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
United States, North Carolina
Research Site
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
Research Site
Cincinnati, Ohio, United States, 45219
United States, Oregon
Research Site
Portland, Oregon, United States, 97227
United States, Pennsylvania
Research Site
Abington, Pennsylvania, United States, 19001
Research Site
Philadelphia, Pennsylvania, United States, 19104
Research Site
Pittsburgh, Pennsylvania, United States, 15224
United States, Rhode Island
Research Site
Providence, Rhode Island, United States, 02905
United States, Tennessee
Research Site
Germantown, Tennessee, United States, 38138
United States, Texas
Research Site
Houston, Texas, United States, 77030
United States, Virginia
Research Site
Annandale, Virginia, United States, 22003
United States, Wisconsin
Research Site
Milwaukee, Wisconsin, United States, 53226
Canada, Alberta
Research Site
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
Research Site
Vancouver, British Columbia, Canada, VSZ 4E6
Canada, Manitoba
Research Site
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Nova Scotia
Research Site
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
Research Site
Hamilton, Ontario, Canada, L8V 5C2
Research Site
Kingston, Ontario, Canada, K7L 2V7
Research Site
Mississauga, Ontario, Canada, L5M 2N1
Research Site
Toronto, Ontario, Canada, M4N3M5
Canada, Quebec
Research Site
Montreal, Quebec, Canada, H1T 2M4
Research Site
Montreal, Quebec, Canada, H2X 0A9
Research Site
Montreal, Quebec, Canada, H4A 3J1
Research Site
Sherbrooke, Quebec, Canada, J1H 5N4
Sponsors and Collaborators
AstraZeneca

Additional Information:
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02983799     History of Changes
Other Study ID Numbers: D0816L00003
First Posted: December 6, 2016    Key Record Dates
Last Update Posted: September 24, 2019
Last Verified: September 2019

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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:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Olaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents