Olaparib Tablets as a Treatment for Ovarian Cancer Subjects With Different HRD Tumor Status
Condition: Relapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Intervention: OLAPARIB
Intervention description: 300 mg olaparib tablets taken orally twice daily
Intervention MeSH terms: Olaparib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 272.0
Sex: Female
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: BRCA, ovarian, platinum, chemotherapy

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.
    

Eligibility 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