NCT02987543 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2023-10-06

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Confirmed Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) - Cohort A Only

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outcome · POSTED

Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A+B

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outcome · POSTED

Time to Pain Progression - Cohort A Only

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outcome · POSTED

Overall Survival (OS) - Cohort A Only

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outcome · POSTED

Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A Only

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility 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. 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.
healthy Volunteers: false
maximum Age: 130 Years
minimum Age: 18 Years
sex: MALE
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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
intervention Names
Drug: olaparib
label
Olaparib
type
EXPERIMENTAL
description
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.
intervention Names
Drug: enzalutamide
Drug: abiraterone acetate
label
Enzalutamide OR abiraterone acetate
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Olaparib
description
300 mg (2x 150 mg tablets) twice daily
name
olaparib
other Names
Lynparza
type
DRUG
arm Group Labels
Enzalutamide OR abiraterone acetate
description
160 mg (4 x 40 mg capsules) once daily
name
enzalutamide
other Names
XTANDI
type
DRUG
arm Group Labels
Enzalutamide OR abiraterone acetate
description
1,000 mg (4 x 250 mg tablets) once daily
name
abiraterone acetate
other Names
ZYTIGA
type
DRUG
arm Group Labels
Enzalutamide OR abiraterone acetate
description
1,000 mg (2 x 500 mg tablets) once daily
name
abiraterone acetate
other Names
ZYTIGA
type
DRUG
arm Group Labels
Enzalutamide OR abiraterone acetate
description
160 mg (4 x 40 mg tablets) once daily
name
enzalutamide
other Names
XTANDI
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 387
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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).
measure
Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A Only
time Frame
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 Outcomes

description
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.
measure
Confirmed Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) - Cohort A Only
time Frame
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).
description
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.
measure
Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A+B
time Frame
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).
description
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.
measure
Time to Pain Progression - Cohort A Only
time Frame
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).
description
Number of Participants with Overall Survival (OS) - Cohort A only.
measure
Overall Survival (OS) - Cohort A Only
time Frame
Approximately 35 months after the first patient was randomised.

Full study description

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.
detailed Description: This is a prospective, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of olaparib versus enzalutamide or abiraterone in subjects with metastatic castration-resistant prostate cancer (mCRPC) who have failed prior treatment with a new hormonal agent (NHA) and have a qualifying tumor mutation in one of 15 genes involved in the homologous recombination repair (HRR) pathway. Subjects will be divided into two cohorts based on HRR gene mutation status. Approximately 340 subjects will be randomized 2:1 (olaparib : investigator choice of enzalutamide or abiraterone acetate) into the trial.

Source references

references

citation
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