Study on Olaparib Plus Abiraterone as First-line Therapy in Men With Metastatic Castration-resistant Prostate Cancer
Condition: Metastatic Castration-resistant Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: olaparib; abiraterone acetate
Intervention description: 300 mg (2 x 150 milligrams (mg) tablets) twice daily; 1000 milligrams (mg) once daily
Intervention MeSH terms: Olaparib; Abiraterone Acetate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 796.0
Sex: Male
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: metastatic castration-resistant prostate cancer (mCRPC)

Summary:

      The purpose of this study is to evaluate the efficacy and safety (including evaluating side
      effects) of combination of olaparib and abiraterone versus placebo and abiraterone in
      patients with metastatic castration-resistant prostate cancer (mCRPC) who have received no
      prior cytotoxic chemotherapy or new hormonal agents (NHAs) at metastatic castration-resistant
      prostate cancer (mCRPC) stage.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Capable of giving signed informed consent, which includes compliance with the
             requirements and restrictions listed in the informed consent form and in the study
             protocol.

          2. Provision of signed and dated, written informed consent form prior to any mandatory
             study specific procedures, sampling, and analyses.

          3. For inclusion in i) the optional exploratory genetic research and ii) the optional
             biomarker research, patients must fulfill the following criteria:

               -  Provision of informed consent for genetic research prior to collection of sample.

               -  Provision of informed consent for biomarker research prior to collection of
                  sample.

             If a patient declines to participate in the optional exploratory genetic research or
             the optional biomarker research, there will be no penalty or loss of benefit to the
             patient. The patient will not be excluded from other aspects of the study.

          4. Patients must be ≥18 years of age (or ≥19 years of age in South Korea) at the time of
             signing the informed consent form. For patients enrolled in Japan who are <20 years of
             age, written informed consent should be obtained from the patient and from his legally
             acceptable representative.

          5. Histologically or cytologically confirmed prostate adenocarcinoma.

          6. Metastatic status defined as at least 1 documented metastatic lesion on either a bone
             scan or a computed tomography(CT)/ magnetic resonance imaging (MRI) scan.

          7. First-line metastatic castration-resistant prostate cancer (mCRPC).

          8. Ongoing androgen deprivation with gonadotropin-releasing hormone analogue or bilateral
             orchiectomy, with serum testosterone <50 nanograms per decilitre (ng/dL) (<2.0
             nanomoles per litre (nmol/L)) within 28 days before randomisation. Patients receiving
             androgen deprivation therapy (ADT) at study entry should continue to do so throughout
             the study.

          9. Candidate for abiraterone therapy with documented evidence of progressive disease.

         10. Patients must have normal organ and bone marrow function measured within 28 days prior
             to administration of study treatment.

         11. Eastern Cooperative Oncology Group (ECOG) performance status 0-1, with no
             deterioration over the previous 2 weeks.

         12. The participant has, in the opinion of the investigator, a life expectancy of at least
             6 months.

         13. Prior to randomisation, sites must confirm availability of either an archival formalin
             fixed, paraffin embedded (FFPE) tumour tissue sample, or a new biopsy taken during the
             screening window, which meets the minimum pathology and sample requirements in order
             to enable homologous recombination repair (HRR) status subgroup analysis of the
             primary endpoint radiographic progression-free survival (rPFS). If there is not
             written confirmation of the availability of tumour tissue prior to randomisation, the
             patient is not eligible for the study.

         14. Male patients must use a condom during treatment and for 3 months after the last dose
             of olaparib+abiraterone when having sexual intercourse with a pregnant woman or with a
             woman of childbearing potential. Female partners of male patients should also use a
             highly effective form of contraception if they are of childbearing potential.

        Exclusion Criteria:

          1. Has a known additional malignancy that has had progression or has required active
             treatment in the last 5 years.

          2. Patients with myelodysplastic syndrome (MDS)/ acute myeloid leukaemia (AML) or with
             features suggestive of yelodysplastic syndrome (MDS)/ acute myeloid leukaemia (AML).

          3. Clinically significant cardiovascular disease Association Class II-IV heart failure or
             cardiac ejection fraction measurement of <50% during screening as assessed by
             echocardiography or multigated acquisition scan.

          4. Planned or scheduled cardiac surgery or percutaneous coronary intervention procedure.

          5. Prior revascularisation procedure (significant coronary, carotid, or peripheral artery
             stenosis).

          6. Uncontrolled hypertension (systolic blood pressure (BP) ≥160 millimeters of mercury
             (mmHg) or diastolic blood pressure (BP) ≥95 millimeters of mercury (mmHg)).

          7. History of uncontrolled pituitary or adrenal dysfunction.

          8. Active infection or other medical condition that would make prednisone/prednisolone
             use contraindicated.

          9. Any chronic medical condition requiring a systemic dose of corticosteroid >10
             milligrams (mg) prednisone/prednisolone per day.

         10. Patients who are considered a poor medical risk due to a serious, uncontrolled medical
             disorder, non-malignant systemic disease or active, uncontrolled infection.

         11. Persistent toxicities (Common Terminology Criteria for Adverse Events [CTCAEs] grade
             >2) caused by previous cancer therapy, excluding alopecia.

         12. Patients with brain metastases. A scan to confirm the absence of brain metastases is
             not required.

         13. Patients with spinal cord compression are excluded unless they are considered to have
             received definitive treatment for this and have evidence of clinically stable disease
             for 4 weeks.

         14. Patients who are unevaluable for both bone and soft tissue progression

         15. Patients who are unable to swallow orally administered medication and patients with
             gastrointestinal disorders likely to interfere with absorption of the study
             medication.

         16. Immunocompromised patients

         17. Patients with known active hepatitis infection (ie, hepatitis B or C).

         18. Any previous treatment with Polyadenosine 5'diphosphoribose [poly (ADP ribose)]
             polymerase (PARP) inhibitor, including olaparib.

         19. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative
             reasons) within 3 weeks prior to study treatment. Patients who receive palliative
             radiotherapy need to stop radiotherapy 1 week before randomisation.

         20. Any previous exposure to a Cytochrome P450 (CYP) 17 (17α-hydroxylase/C17,20-lyase)
             inhibitor (eg, abiraterone, orteronel).

         21. Concomitant use of known strong Cytochrome P450 (CYP) 3A inhibitors (eg, itraconazole,
             telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or
             cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate
             CYP3A inhibitors (eg, ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil).
             The required washout period prior to starting study treatment is 2 weeks.

         22. Concomitant use of known strong Cytochrome P450 (CYP) 3A inducers (eg, phenobarbital,
             enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine
             or St John's wort) or moderate Cytochrome P450 (CYP) 3A inducers (eg, bosentan,
             efavirenz or modafinil). The required period prior to starting study treatment is 5
             weeks for phenobarbital and enzalutamide and 3 weeks for other agents.

         23. Major surgery within 2 weeks of starting study treatment and patients must have
             recovered from any effects of any major surgery.

         24. Previous allogenic bone marrow transplant or double umbilical cord blood
             transplantation (dUCBT).

         25. Participation in another clinical study with an investigational product or
             investigational medical devices within 1 month of randomisation.

         26. History of hypersensitivity to olaparib or abiraterone, any of the excipients of
             olaparib or abiraterone, or drugs with a similar chemical structure or class to
             olaparib or abiraterone.

         27. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
             and Merck staff and/or staff at the study site).

         28. Judgment by the investigator that the patient should not participate in the study if
             the patient is unlikely to comply with study procedures, restrictions and
             requirements.

         29. Previous randomisation in the present study.