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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02987543




Registration number
NCT02987543
Ethics application status
Date submitted
15/11/2016
Date registered
9/12/2016
Date last updated
28/05/2021

Titles & IDs
Public title
Study of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer (PROfound Study)
Scientific title
A Phase III, Open Label, Randomized Study to Assess the Efficacy and Safety of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Prior Treatment With a New Hormonal Agent and Have Homologous Recombination Repair Gene Mutations (PROfound)
Secondary ID [1] 0 0
D081DC00007
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 - enzalutamide
Treatment: Drugs - abiraterone acetate
Treatment: Drugs - abiraterone acetate
Treatment: Drugs - enzalutamide

Experimental: Olaparib - Olaparib is available as a film-coated tablet containing 150 mg or 100 mg of olaparib. Subjects will be administered study treatment orally at a dose of 300 mg twice daily (bid). The planned dose of 300 mg bid will be made up of two x 150 mg tablets twice daily, with 100 mg tablets used to manage dose reductions

Active Comparator: Enzalutamide OR abiraterone acetate - Enzalutamide:
Enzalutamide is available as capsules or tablets containing 40 mg of enzalutamide. Subjects will be administered study treatment orally at a dose of 160 mg once daily.
Abiraterone acetate with prednisone: Abiraterone acetate is available as tablets containing 250 mg or 500 mg of abiraterone acetate. Subjects will be administered study treatment orally at a dose of 1,000 mg once daily in combination with prednisone 5 mg administered twice daily orally. Prednisolone is permitted for use instead of prednisone if necessary.


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

Treatment: Drugs: enzalutamide
160 mg (4 x 40 mg capsules) once daily

Treatment: Drugs: abiraterone acetate
1,000 mg (4 x 250 mg tablets) once daily

Treatment: Drugs: abiraterone acetate
1,000 mg (2 x 500 mg tablets) once daily

Treatment: Drugs: enzalutamide
160 mg (4 x 40 mg tablets) 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) by Blinded Independent Central Review (BICR) - Cohort A Only - The time from randomisation until the date of objective radiological disease progression (determined by RECIST 1.1 (soft tissue) and Prostate Cancer Working Group 3 (PCWG-3) (bone)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression. Progression is defined using (i) Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue, as a >=20% increase in the sum of diameters of target lesions and an absolute increase of >=5mm taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters; (ii) Prostate Cancer Working Group 3 (PGWG-3) for bone as >= 2 new bone lesions on the 1st week 8 scan compared to baseline. The confirmatory scan, >=6 weeks later, must show >=2 more new bone lesions (for a total of >=4 new bone lesions since baseline).
Timepoint [1] 0 0
Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
Secondary outcome [1] 0 0
Confirmed Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) - Cohort A Only - ORR is the percentage of patients with at least one visit response of Complete response (CR) or Partial response (PR), in their soft tissue disease assessed by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), in the absence of progression on bone scan assessed by Prostate Cancer Working Group 3 (PCWG3)). Per RECIST v1.1, CR=Disappearance of all target lesions; PR = >=30% decrease in the sum of diameters of target lesions; For each treatment group, ORR is the number of patients with a CR and PR.
Timepoint [1] 0 0
Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
Secondary outcome [2] 0 0
Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A+B - The time from randomisation until the date of objective radiological disease progression (by RECIST 1.1 and Prostate Cancer Working Group 3 (PGWG-3)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression.
Timepoint [2] 0 0
Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
Secondary outcome [3] 0 0
Time to Pain Progression - Cohort A Only - Time from randomisation to time point at which worsening in pain is observed (ie date of pain progression - date of randomisation + 1). Based on average Brief Pain Inventory - short form (BPI-SF) worst pain [Item 3] and Analgesic Quantification Algorithm [AQA] score.
Timepoint [3] 0 0
Every 4 weeks from randomisation (for 7 consecutive days) throughout the study (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
Secondary outcome [4] 0 0
Overall Survival (OS) - Cohort A Only - Number of Participants with Overall Survival (OS) - Cohort A only.
Timepoint [4] 0 0
Approximately 35 months after the first patient was randomised.

Eligibility
Key inclusion criteria
Inclusion criteria

1. Histologically confirmed diagnosis of prostate cancer.

2. Documented evidence of metastatic castration resistant prostate cancer (mCRPC).

3. Subjects must have progressed on prior new hormonal agent (e.g. abiraterone acetate
and/or enzalutamide) for the treatment of metastatic prostate cancer and/or CRPC .

4. Ongoing therapy with LHRH analog or bilateral orchiectomy.

5. Radiographic progression at study entry while on androgen deprivation therapy (or
after bilateral orchiectomy).

6. Qualifying HRR mutation in tumor tissue.
Minimum age
18 Years
Maximum age
130 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria

1. Any previous treatment with PARP inhibitor, including olaparib.

2. Subjects who have any previous treatment with DNA-damaging cytotoxic chemotherapy,
except if for non-prostate cancer indication and last dose > 5 years prior to
randomization.

3. Other malignancy (including MDS and MGUS) within the last 5 years except: adequately
treated non-melanoma skin cancer or other solid tumors curatively treated with no
evidence of disease for =5 years.

4. Subjects with known brain metastases.

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
Open (masking not used)
Who is / are masked / blinded?



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
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)
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Research Site - Adelaide
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5000 - Adelaide
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3128 - Box Hill
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3168 - Clayton
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4120 - Greenslopes
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4029 - Herston
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2109 - Macquarie University
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3000 - Melbourne
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6009 - Nedlands
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2031 - Randwick
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2298 - Waratah
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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
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Foundation Medicine, Inc.
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/Industry
Name [3] 0 0
Myriad Genetics, Inc.
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the efficacy and safety of olaparib versus
enzalutamide or abiraterone acetate in subjects with metastatic castration-resistant prostate
cancer who have failed prior treatment with a new hormonal agent and have homologous
recombination repair gene mutations.
Trial website
https://clinicaltrials.gov/show/NCT02987543
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Johann de Bono, M.D., Ph.D.
Address 0 0
The Institute of Cancer Research, United Kingdom
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
Other publications