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Study of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men with Metastatic Castration-Resistant Prostate Cancer (PROfound Study)

Phase 1
Conditions
Metastatic castration-resistant prostate cancer
MedDRA version: 20.0Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: LLTClassification code 10076506Term: Castration-resistant prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2016-000300-28-FR
Lead Sponsor
AstraZeneca
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
Male
Target Recruitment
340
Inclusion Criteria

1. Histologically confirmed diagnosis of prostate cancer.
2. Candidate for treatment with enzalutamide or abiraterone with documented evidence of mCRPC.
3. Subjects must have progressed on prior new hormonal agent (e.g. abiraterone acetate and/or enzalutamide) for the treatment of mCRPC.
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 by the Lynparza HRR Assay

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Any previous treatment with PARP inhibitor, including olaparib
2. Subjects who have any previous treatment with DNA-damaging cytotoxic chemotherapy.
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 myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
5. Subjects with known brain metastases.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To determine the efficacy (as assessed by rPFS) of olaparib versus investigator choice of enzalutamide or abiraterone acetate in men with mCRPC with BRCA1, BRCA2 or ATM qualifying mutations (Cohort A) ;Secondary Objective: To determine the efficacy of olaparib versus investigator choice of enzalutamide or abiraterone acetate in subjects with HRR qualifying gene mutations measured by objective response rate in Cohort A, rPFS in Cohort A+B, time to pain progression in Cohort A and overall survival in Cohort A<br><br>;Primary end point(s): Radiological progression free survival (rPFS) by blinded independent central review (BICR) using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria;Timepoint(s) of evaluation of this end point: At baseline and every 8 weeks (± 7 days), relative to the date of randomization, until objective radiological disease progression by BICR using RECIST 1.1 (soft tissue) and PCWG3 (bone)<br>criteria<br><br>
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): Confirmed ORR by BICR assessment in subjects with measurable disease using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria<br><br>rPFS by BICR using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria<br><br>Pain progression based on BPI-SF item 3 worst pain in 24 hours” and opiate analgesic use (AQA score)<br><br>Overall survival;Timepoint(s) of evaluation of this end point: At baseline and every 8 weeks (± 7 days), relative to the date of randomization, until objective radiological disease progression by BICR<br><br>Subjects will complete the BPI-SF daily on the ePRO device for the 7 days just prior to day 1 baseline visit and every 4 weeks<br><br>The status of ongoing, withdrawn (from the study) and lost to follow-up” subjects at the time of an overall survival analysis should be obtained by the site personnel by checking the subject notes, hospital records, contacting the subject’s general practitioner and checking publicly available death registries.
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