A Study to Examine Olaparib Maintenance Retreatment in Patients With Epithelial Ovarian Cancer.
Condition: Epithelial Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Intervention: Active Comparator: Olaparib tablets; Placebo
Intervention description: Olaparib
300mg Olaparib tablets taken orally twice daily (except where this dose and formulation was previously not tolerated) until objective radiological disease progression as per RECIST 1.1 or as long as in the Investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria.; Placebo
300mg placebo tablets taken orally twice daily (except where this dose and formulation was previously not tolerated) until objective radiological disease progression as per RECIST 1.1 or as long as in the Investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria.
Intervention MeSH terms: Olaparib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 220.0
Sex: Female
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: polymerisation inhibitor (PARPi); PARPi re-treatment; BRCA1/2 (+ve); BRCA1/2 (-ve); Olaparib; ovarian cancer; progression free survival (PFS)

Summary:

      The OReO study will be a Phase IIIb, randomised, double-blind, placebo-controlled,
      multicentre study to assess the efficacy and tolerability of Olaparib retreatment, versus
      matching placebo, in non-mucinous epithelial ovarian cancer (EOC) patients (including
      patients with primary peritoneal and/or fallopian tube cancer)
    

Eligibility criteria:

        Inclusion criteria

          -  Provision of informed consent prior to any study specific procedures

          -  Female patients ≥18 years of age, with histologically diagnosed relapsed non-mucinous
             epithelial ovarian cancer (EOC) (including primary peritoneal and/or fallopian tube
             cancer) (Non-mucinous EOC includes patients with serous, endometrioid, and
             transitional cell tumours, and those with mixed histology where one of these subtypes
             is predominant (>50%). Inclusion of other subtypes should first be discussed with the
             Medical Monitor).

          -  Documented BRCA1/2 status.

          -  Patients must have received one prior PARPi therapy PARPi therapy includes any agent
             (including Olaparib) used in a maintenance setting For the BRCA1/2 (+ve) cohort, the
             duration of first PARPi exposure must have been ≥18 months following a first line of
             chemotherapy or ≥12 months following a second or subsequent line of chemotherapy For
             the BRCA1/2 (-ve) cohort, the duration of first PARPi exposure must have been ≥12
             months following a first line of chemotherapy or ≥6 months following a second or
             subsequent line of chemotherapy For the last chemotherapy course immediately prior to
             randomisation on the study Patients must have received a platinum-based chemotherapy
             regimen (carboplatin, cisplatin or oxaliplatin) and have received at least 4 cycles of
             treatment Patients must be, in the opinion of the investigator, in response (partial
             or complete radiological response) or may have no evidence of disease (if optimal
             cytoreductive surgery was conducted prior to chemotherapy) and no evidence of a rising
             CA-125, as defined below, following completion of this chemotherapy course
             Pre-treatment CA-125 measurements must meet criterion specified below

          -  If the first value is within upper limit of normal (ULN) the patient is eligible to be
             randomised and a second sample is not required

          -  If the first value is greater than ULN a second assessment must be performed at least
             7 days after the first. If the second assessment is ≥ 15% more than the first the
             patient is not eligible.

        Patients must not have received bevacizumab during this course of treatment. Bevacizumab
        use as part of an earlier line of chemotherapy is permitted Patients must not have received
        any investigational agent during this course of treatment Patients must be randomised
        within 8 weeks of their last dose of chemotherapy (last dose is the day of the last
        infusion)

          -  Patients must have normal organ and bone marrow function measured within 28 days of
             randomization.

          -  Eastern Cooperative Oncology Group performance status 0-1

          -  Patients must have a life expectancy ≥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

          -  At least one lesion (measurable and/or non-measurable) that can be accurately assessed
             at baseline with computed tomography (CT) or magnetic resonance imaging (MRI) and is
             suitable for repeated assessment. or No measurable disease following a complete
             response to most recent chemotherapy (+/- surgery)

          -  A formalin fixed, paraffin embedded (FFPE) tumour sample from the cancer of sufficient
             quantity and quality (as specified in the Covance Central Laboratory Services Manual)
             must be available for future central testing of tumour genetic status.

          -  For inclusion in the optional biomarker research, patients must sign an informed
             consent for biomarker research.

        Exclusion criteria:

          -  Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
             staff and/or staff at the study site).

          -  Participation in another clinical study with an investigational product during the
             chemotherapy course immediately prior to randomisation.

          -  Other malignancy within the last 5 years except the ones detailed in the exclusion
             criteria section of study protocol.

          -  Resting electrocardiogram (ECG) with corrected QT interval (QTc) >470 msec on 2 or
             more time points within a 24 hour period or family history of long QT syndrome6.
             Patients receiving any systemic chemotherapy or radiotherapy (except for palliative
             radiotherapy) within 3 weeks prior to study treatment.

          -  Concomitant use of known strong cytochrome P450 (CYP) subfamily 3A (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
             or higher) caused by previous cancer therapy, excluding alopecia and stable Grade 2
             peripheral neuropathy .

          -  Patients with current or previous myelodysplastic syndrome (MDS)/acute myeloid
             leukaemia (AML) or with features suggestive of MDS/AML.

          -  Patients with symptomatic uncontrolled brain metastases.

          -  Immunocompromised patients, e.g., patients who are known to be serologically positive
             for human immunodeficiency virus (HIV).

          -  Patients with a known hypersensitivity to Olaparib or any of the excipients of the
             product.

          -  Patients with a known active hepatitis (i.e..Hepatitis B or C).

          -  Patient who have received a whole blood transfusion within 30 days prior to screening
             tests (packed red blood cells and platelet transfusions are acceptable).