Metastatic castration-resistant prostate cancer MedDRA version: 21.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
Male
Inclusion 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 fulfil 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 =65 years) yes F.1.3.1 Number of subjects for this age range 396
Exclusion criteria
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 MDS/AML or with features suggestive of MDS/AML. 3. Clinically significant cardiovascular disease Association Class II-IV heart failure or cardiac ejection fraction measurement of 10 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 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 CYP17 (17a-hydroxylase/C17,20-lyase) inhibitor (eg, abiraterone, orteronel). 21. Concomitant use of known strong CYP3A 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 CYP3A inducers (eg, phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine or St John’s wort) or moderate CYP3A 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 hypers
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of the combination of olaparib and abiraterone vs placebo and abiraterone by investigator assessment of rPFS in patients with mCRPC who have received no prior cytotoxic chemotherapy or NHA at mCRPC stage.;Secondary Objective: To determine the efficacy of the combination of olaparib and abiraterone vs placebo and abiraterone by assessment of OS, TFST, and TTPP. To further evaluate the efficacy of the combination of olaparib and abiraterone vs placebo and abiraterone by assessment of time to opiate use, time to an SSRE, and PFS2. To assess the effect of the combination of olaparib and abiraterone vs placebo and abiraterone on disease related symptoms and HRQoL using BPI-SF and FACT - Prostate Cancer (FACT-P). To evaluate tumour and blood samples for mutations in BRCA1, BRCA2, ATM and 11 other HRR genes. To determine steady-state exposure to abiraterone and its active metabolite ?4-abiraterone in the presence and absence of olaparib. To evaluate the safety and tolerability of the combination of olaparib and abiraterone vs placebo and abiraterone. To determine steady-state exposure to olaparib when co-administered with abiraterone.;Primary end point(s): Radiological progression free survival (rPFS) - defined as the time from randomisation to 1) radiological progression, assessed by investigator per RECIST 1.1 (soft tissue) and PCWG-3 criteria (bone), or 2) death from any cause, whichever occurs first;Timepoint(s) of evaluation of this end point: At baseline and every 8 weeks (± 7 days) until week 24 and every 12 weeks (± 7 days) thereafter, relative to the date of randomisation, until objective radiological disease progression is confirmed by the investigator. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall survival (OS) 2. Time to first subsequent anticancer therapy or death (TFST) 3. Time to pain progression (TTPP) 4. Time to first opiate use for cancer-related pain 5. Time to first symptomatic skeletal-related event (SSRE) 6. Time to second progression or death (PFS2) 7. BPI-SF: progression in pain severity domain, change in pain interference domain 8. FACT-P total score, FACT-G total score, trial outcome index, functional well-being, physical well being, prostate cancer subscale, and FACT Advanced Prostate Symptom Index 6 (FAPSI 6) 9. HRR gene status 10. Plasma concentration data at steady state for olaparib, abiraterone, and ?4-abiraterone in the subset of patients evaluable for PK;Timepoint(s) of evaluation of this end point: 1. Time from randomisation to the earlier of the first subsequent anticancer therapy start date following study treatment discontinuation or death from any cause. 2. Time from randomisation to pain progression 3. Time from randomisation to death from any cause. 4. Time from randomisation to the first opiate use for cancer-related pain. 5. Time from randomisation to the first SSRE. 6. Time from randomisation to second progression or clinical progression or death 7. Subjects will complete the BPI-SF daily on the ePRO device for 7 days just prior to day 1 baseline visit and every 4 weeks 8. Every 4 weeks (starting on Day 1) in the first year and every 8 weeks thereafter 9. At baseline 10. Visit 4 | — |
Countries
Australia, Belgium, Brazil, Canada, Chile, China, Czechia, France, Germany, Italy, Japan, Korea, Republic of, Netherlands, Slovakia, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca AB
Outcome results
None listed