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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03732820




Registration number
NCT03732820
Ethics application status
Date submitted
28/09/2018
Date registered
7/11/2018
Date last updated
6/01/2020

Titles & IDs
Public title
Study on Olaparib Plus Abiraterone as First-line Therapy in Men With Metastatic Castration-resistant Prostate Cancer
Scientific title
A Randomised, Double-blind, Placebo-controlled, Multicentre Phase III Study of Olaparib Plus Abiraterone Relative to Placebo Plus Abiraterone as First-line Therapy in Men With Metastatic Castration-resistant Prostate Cancer (PROpel Study)
Secondary ID [1] 0 0
2018-002011-10
Secondary ID [2] 0 0
D081SC00001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Castration-resistant Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - olaparib
Treatment: Drugs - abiraterone acetate

Experimental: olaparib plus abiraterone - Olaparib is available as a film-coated tablet containing 100 milligrams (mg) or 150 milligrams (mg) of olaparib. Subjects will be administered olaparib orally at a dose of 300 milligrams (mg) twice daily (bid). The initial dosage of 300 milligrams (mg) twice daily will be composed of 2 x 150 milligrams (mg) tablets per dose. The 100 milligrams (mg) and 150 milligrams (mg) tablets will be used to manage dose reductions during the study.
Abiraterone acetate with prednisone or prednisolone will be sourced locally as commercially available materials. Subjects will be administered abiraterone orally at a dose of 1000 milligrams (mg) once daily, in combination with prednisone or prednisolone 5 milligrams (mg) administered orally twice daily.

Placebo Comparator: placebo plus abiraterone - Placebo to match olaparib is available as a film-coated tablet in 100 milligrams (mg) or 150 milligrams (mg). Subjects will be administered placebo orally at a dose of 300 milligrams (mg) twice daily (bid). The initial dosage of 300 milligrams (mg) twice daily will be composed of 2 x 150 milligrams (mg) tablets per dose. The 100 milligrams (mg) and 150 milligrams (mg) tablets will be used to manage dose reductions during the study.
Abiraterone acetate with prednisone or prednisolone will be sourced locally as commercially available materials. Subjects will be administered abiraterone orally at a dose of 1000 milligrams (mg) once daily, in combination with prednisone or prednisolone 5 milligrams (mg) administered orally twice daily.


Treatment: Drugs: olaparib
300 mg (2 x 150 milligrams (mg) tablets) twice daily

Treatment: Drugs: abiraterone acetate
1000 milligrams (mg) once daily

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Radiological progression free survival (rPFS) - Radiological progression free survival (rPFS) - defined as the time from randomisation to
radiographic progression, assessed by investigator per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 (soft tissue) and Prostate Cancer Working Group-3 (PCWG-3) criteria (bone), or
death from any cause, whichever occurs first
Timepoint [1] 0 0
From date of randomization to study completion (up to 4 years)
Secondary outcome [1] 0 0
Time to first subsequent anticancer therapy or death (TFST) - Time from randomisation to the earlier of the first subsequent anticancer therapy start date following study treatment discontinuation or death from any cause
Timepoint [1] 0 0
From date of randomization to study completion (up to 4 years)
Secondary outcome [2] 0 0
Time to pain progression (TTPP) - Time to pain progression (TTPP) is defined as the time from randomisation to pain progression based on the Brief Pain Inventory-Short Form (BPI-SF) Item 3 "worst pain in 24 hours" and opiate analgesic use (analgesic quantification algorithm [AQA] score)
Timepoint [2] 0 0
From date of randomization to study completion (up to 4 years)
Secondary outcome [3] 0 0
Overall survival (OS) - Time from randomisation to death from any cause
Timepoint [3] 0 0
From date of randomization to study completion (up to 4 years)
Secondary outcome [4] 0 0
Time to opiate use - Time from randomisation to the first opiate use for cancer-related pain
Timepoint [4] 0 0
From date of randomization to study completion (up to 4 years)
Secondary outcome [5] 0 0
Time to a Symptomatic Skeletal-Related Event (SSRE) - A Symptomatic Skeletal-Related Event (SSRE) is defined as use of radiation therapy to bone in order to prevent or relieve skeletal complications, occurrence of new symptomatic pathological bone fractures (vertebral or non-vertebral, resulting from minimal or no trauma), occurrence of radiologically confirmed spinal cord compression or a tumour-related orthopaedic surgical intervention.
Timepoint [5] 0 0
From date of randomization to study completion (up to 4 years)
Secondary outcome [6] 0 0
Circulating Tumour Cells (CTC) conversion - Proportion of patients who achieve a decline in the number of Circulating Tumour Cells (CTCs) from =5 cells/7.5 mL at baseline to <5 cells/7.5 mL at any time post baseline in whole blood (Circulating Tumour Cells (CTC) conversion rate)
Timepoint [6] 0 0
From date of randomization to study completion (up to 4 years)
Secondary outcome [7] 0 0
Time to second progression or death (PFS2) - Time from randomisation to second progression or clinical progression or death
Timepoint [7] 0 0
From date of randomization to study completion (up to 4 years)
Secondary outcome [8] 0 0
Brief Pain Inventory-Short Form (BPI-SF) - To assess progression in pain severity domain, change in pain interference domain, and pain palliation
Timepoint [8] 0 0
From date of randomization to study completion (up to 4 years)
Secondary outcome [9] 0 0
Functional Assessment of Cancer Therapy- Prostate Cancer (FACT-P) - Functional Assessment of Cancer Therapy- Prostate Cancer (FACT-P) total score, Functional Assessment of Cancer Therapy- General (FACT-G) total score, trial outcome index, functional well-being, physical well-being, prostate cancer subscale, and Functional Assessment of Cancer Therapy (FACT) Advanced Prostate Symptom Index-6 (FAPSI-6)
Timepoint [9] 0 0
From date of randomization to study completion (up to 4 years)
Secondary outcome [10] 0 0
Homologous Recombination Repair (HRR) gene status - Tumour and blood samples for mutations in Breast Cancer 1 gene (BRCA1), or Breast Cancer 2 gene (BRCA2), Ataxia-telangiectasia mutated (ATM) and 12 other Homologous Recombination Repair (HRR) genes will be evaluated.
Timepoint [10] 0 0
At baseline
Secondary outcome [11] 0 0
Maximum plasma concentration at steady state [Cmax,ss] - To characterize the steady state Pharmacokinetics (PK) of olaparib, in the presence of abiraterone.
Timepoint [11] 0 0
Week 5 from 45 min before the first olaparib dose, up to 9 hours post dose
Secondary outcome [12] 0 0
Time to maximum plasma concentration at steady state (Cmax,ss) [tmax,ss] - To characterize the steady state Pharmacokinetics (PK) of olaparib, in the presence of abiraterone.
Timepoint [12] 0 0
Week 5 from 45 min before the first olaparib dose, up to 9 hours post dose
Secondary outcome [13] 0 0
Minimum plasma concentration at steady state [Cmin,ss] - To characterize the steady state Pharmacokinetics (PK) of olaparib, in the presence of abiraterone.
Timepoint [13] 0 0
Week 5 from 45 min before the first olaparib dose, up to 9 hours post dose
Secondary outcome [14] 0 0
Partial area under the concentration-time curve in 0-8 h [AUC0-8]) - To characterize the steady state Pharmacokinetics (PK) of olaparib, in the presence of abiraterone.
Timepoint [14] 0 0
Week 5 from 45 min before the first olaparib dose, up to 9 hours post dose
Secondary outcome [15] 0 0
Maximum plasma concentration at steady state [Cmax,ss] - To characterize the steady state Pharmacokinetics (PK) of abiraterone and its active metabolite ?4-abiraterone, in the presence and absence of olaparib.
Timepoint [15] 0 0
Week 5 from 45 min before the abiraterone dose, up to 9 hours post dose
Secondary outcome [16] 0 0
Time to maximum plasma concentration at steady state (Cmax,ss) [tmax,ss] - To characterize the steady state Pharmacokinetics (PK) of abiraterone and its active metabolite ?4-abiraterone, in the presence and absence of olaparib.
Timepoint [16] 0 0
Week 5 from 45 min before the abiraterone dose, up to 9 hours post dose
Secondary outcome [17] 0 0
Minimum plasma concentration at steady state [Cmin,ss] - To characterize the steady state Pharmacokinetics (PK) of abiraterone and its active metabolite ?4-abiraterone, in the presence and absence of olaparib.
Timepoint [17] 0 0
Week 5 from 45 min before the abiraterone dose, up to 9 hours post dose
Secondary outcome [18] 0 0
Partial area under the concentration-time curve [AUC0-8]) - To characterize the steady state Pharmacokinetics (PK) of abiraterone and its active metabolite ?4-abiraterone, in the presence and absence of olaparib.
Timepoint [18] 0 0
Week 5 from 45 min before the abiraterone dose, up to 9 hours post dose
Secondary outcome [19] 0 0
Number of adverse events - Percentage of patients with any adverse event (AE), adverse event (AE) leading to study drug discontinuation, adverse event (AE) leading to death, serious adverse event (SAE), adverse event (AE) related to study drug, serious adverse event (SAE) related to study drug
Timepoint [19] 0 0
From the time of signature of informed consent throughout the treatment period (up to 4 years plus 30 days)
Secondary outcome [20] 0 0
Vital signs-blood pressure - To assess systolic and diastolic blood pressure as variable of safety and tolerability of the combination of olaparib and arbiraterone vs placebo and arbiraterone
Timepoint [20] 0 0
From the time of signature of informed consent throughout the treatment period (up to 4 years plus 30 days)
Secondary outcome [21] 0 0
Vital signs-pulse rate - To assess pulse rate as variable of safety and tolerability of the combination of olaparib and arbiraterone vs placebo and arbiraterone
Timepoint [21] 0 0
From the time of signature of informed consent throughout the treatment period (up to 4 years)
Secondary outcome [22] 0 0
Vital signs-body temperature - To assess body temperature as variable of safety and tolerability of the combination of olaparib and arbiraterone vs placebo and arbiraterone
Timepoint [22] 0 0
From the time of signature of informed consent throughout the treatment period (up to 4 years)
Secondary outcome [23] 0 0
ECG - To assess 12 lead resting ECG as variable of safety and tolerability of the combination of olaparib and arbiraterone vs placebo and arbiraterone. According to Clinical Study Protocol all ECGs should be assessed by the investigator as to whether they are clinically significantly abnormal / not clinically significantly abnormal.
Timepoint [23] 0 0
From the time of signature of informed consent throughout the treatment period (up to 4 years)
Secondary outcome [24] 0 0
Change in Albumin (g/L) - Data for Albumin recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [24] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [25] 0 0
Change in Alkaline phosphatase (U/L) - Data for Alkaline phosphatase recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [25] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [26] 0 0
Change in Aspartate aminotransferase (U/L) - Data for Aspartate aminotrasnferase recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [26] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [27] 0 0
Change in Amylase (U/L) - Data for Amylase recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [27] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [28] 0 0
Change in Alanine aminotransferase (U/L) - Data for Alanine aminotransferase recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [28] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [29] 0 0
Change in Total bilirubin (µmol/L) - Data for Total bilirubin recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [29] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [30] 0 0
Change in Direct bilirubin - Data for Direct bilirubin recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [30] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [31] 0 0
Change in Calcium (mmol/L) - Data for Calcium recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [31] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [32] 0 0
Change in Chloride (mmol/L) - Data for Chloride recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [32] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [33] 0 0
Change in Creatinine (µmol/L) - Data for Creatinine recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [33] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [34] 0 0
Change in Gamma glutamyltransferase (U/L) - Data for Gamma glutamyltransferase recorded in the eCRF will be listed and summarized by treatment group.
Timepoint [34] 0 0
At screening only
Secondary outcome [35] 0 0
Change in Fasting gucose (mmol/L) - Data for Fasting glucose recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [35] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [36] 0 0
Change in Lactate dehydrogenase (U/L) - Data for Lactate dehydrogenase recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [36] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [37] 0 0
Change in Magnesium (mmol/L) - Data for Magnesium recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [37] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [38] 0 0
Change in Potassium (mmol/L) - Data for Potassium recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [38] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [39] 0 0
Change in Phosphorus ((mmol/L) - Data for Phosphorus will be recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [39] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [40] 0 0
Change in Sodium (mmol/L) - Data for Sodium recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [40] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [41] 0 0
Change in Carbon dioxide (mEq/L ) - Data for Carbon dioxide recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [41] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [42] 0 0
Change in Total protein (g/L) - Data for protein recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [42] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [43] 0 0
Change in Urea or blood urea nitrogen, depending on the local practice (mmol/L) - Data for urea or urea nitrogen recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [43] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [44] 0 0
Change in absolute neutrophil count (/L) - Data for absolute neutrophil recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [44] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [45] 0 0
Change in absolute lymphocyte count (/L) - Data for absolute lymphocyte recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [45] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [46] 0 0
Change in haemoglobin (g/L) - Data for haemoglobin recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [46] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [47] 0 0
Change in platelet count with differential (/L) - Data for platelet count with differential recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [47] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [48] 0 0
Change in total white blood cell count with differential(/L) - Data for WBC count recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [48] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [49] 0 0
Change in red blood cell count (/l) - Data for RBC count recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [49] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [50] 0 0
Change in Haematocrit (%) - Data for Haematocrit recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [50] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [51] 0 0
Change in Mean Cell Volume (fL) - Data for MCV count recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [51] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [52] 0 0
Urinalysis:change in blood - Data for blood testing recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [52] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [53] 0 0
Urinalysis: Change in protein - Data for urine protein recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [53] 0 0
At scheduled visits from screening to 30 days after last dose of study medication
Secondary outcome [54] 0 0
Urinalysis: change in glucose - Data for urine glucose recorded in the eCRF will be listed and summarized by treatment group and visit.
Timepoint [54] 0 0
At scheduled visits from screening to 30 days after last dose of study medication

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
99 Years
Gender
Males
Can healthy volunteers participate?
No
Key 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 (17a-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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Box Hill
Recruitment hospital [2] 0 0
Research Site - Darlinghurst
Recruitment hospital [3] 0 0
Research Site - Greenslopes
Recruitment hospital [4] 0 0
Research Site - Herston
Recruitment hospital [5] 0 0
Research Site - Kingswood
Recruitment hospital [6] 0 0
Research Site - Kurralta Park
Recruitment hospital [7] 0 0
Research Site - St Albans
Recruitment hospital [8] 0 0
Research Site - Waratah
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
4120 - Greenslopes
Recruitment postcode(s) [4] 0 0
4029 - Herston
Recruitment postcode(s) [5] 0 0
2747 - Kingswood
Recruitment postcode(s) [6] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [7] 0 0
3021 - St Albans
Recruitment postcode(s) [8] 0 0
2298 - Waratah
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Alaska
Country [3] 0 0
United States of America
State/province [3] 0 0
Arizona
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
Montana
Country [14] 0 0
United States of America
State/province [14] 0 0
Nebraska
Country [15] 0 0
United States of America
State/province [15] 0 0
New Jersey
Country [16] 0 0
United States of America
State/province [16] 0 0
New York
Country [17] 0 0
United States of America
State/province [17] 0 0
North Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Ohio
Country [19] 0 0
United States of America
State/province [19] 0 0
Oregon
Country [20] 0 0
United States of America
State/province [20] 0 0
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AstraZeneca
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck Sharp & Dohme Corp.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT03732820
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Fred Saad, MD
Address 0 0
University of Montreal Hospital Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
information.center@astrazeneca.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03732820