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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03732820




Registration number
NCT03732820
Ethics application status
Date submitted
28/09/2018
Date registered
7/11/2018
Date last updated
28/02/2024

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
Number of Participants With Radiological Progression Free Survival (rPFS) Event by Investigator Assessment
Timepoint [1] 0 0
Assessed from date of randomisation to data cut off (DCO1): 30Jul2021 (Approx. 2 years 9 months)
Secondary outcome [1] 0 0
Number of Participants With Overall Survival (OS) Event
Timepoint [1] 0 0
Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months). DCO3 is the final data cut-off for the OS analysis and therefore no further updates will be made.
Secondary outcome [2] 0 0
Number of Participants With Time to First Subsequent Anticancer Therapy or Death (TFST) Event
Timepoint [2] 0 0
Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)
Secondary outcome [3] 0 0
Number of Participants With Time to Pain Progression (TTPP) Event
Timepoint [3] 0 0
Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)
Secondary outcome [4] 0 0
Number of Participants With Opiate Use
Timepoint [4] 0 0
Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)
Secondary outcome [5] 0 0
Number of Participants With First Symptomatic Skeletal Related Event (SSRE)
Timepoint [5] 0 0
Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)
Secondary outcome [6] 0 0
Number of Participants With Second Progression or Death (PFS2) Event
Timepoint [6] 0 0
Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)
Secondary outcome [7] 0 0
Brief Pain Inventory-Short Form (BPI-SF)
Timepoint [7] 0 0
Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)
Secondary outcome [8] 0 0
Functional Assessment of Cancer Therapy- Prostate Cancer (FACT-P)
Timepoint [8] 0 0
Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)

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
Sex
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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/10/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
28/04/2026
Actual
Sample size
Target
Accrual to date
Final
895
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
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United States of America
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Alabama
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Alaska
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Caen Cedex 05
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Pierre Benite
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Quimper Cedex
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France
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Vandoeuvre les Nancy
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Germany
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Bergisch Gladbach
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Bremen
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Duisburg
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Freiburg im Breisgau
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Heinsberg
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Mettmann
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Nürtingen
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Ulm
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Milano
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Napoli
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Pavia
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Maebashi-shi
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Miyazaki-city
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Nagoya-shi
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Osaka-shi
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Osakasayama-shi
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Sagamihara-shi
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Sakura-shi
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Shinjuku-ku
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Japan
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Toon-shi
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Japan
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Korea, Republic of
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Daegu
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Korea, Republic of
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Goyang-si
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Korea, Republic of
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Seoul
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Netherlands
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Hilversum
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Netherlands
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Nijmegen
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Netherlands
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Tilburg
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Slovakia
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Bratislava
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Presov
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Sala
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Slovakia
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Trencín
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Spain
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Barcelona
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Gerona
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Madrid
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Spain
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Malaga
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Spain
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Sevilla
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Turkey
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Adana
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Turkey
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Ankara
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Turkey
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Istanbul
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Izmir
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Turkey
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Karsiyaka
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United Kingdom
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Guildford
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Manchester
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Sheffield
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United Kingdom
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Southampton
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United Kingdom
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Swansea

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 LLC
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/ct2/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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03732820