Clinical trial NCT05457257: Clinical Study to Assess the Efficacy and Safety of Olaparib in Chinese Patients With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Prior Treatment With a New Hormonal Agent and Have BRCA1/2 Mutations
Official title: A Randomized, Open-label Study to Assess the Efficacy and Safety of Olaparib Versus Enzalutamide or Abiraterone Acetate in Chinese Men With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Prior Treatment With a New Hormonal Agent and Have BRCA1/2 Mutations (PROfound-CN)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Metastatic Castration-resistant Prostate Cancer
Keywords: metastatic castration-resistant prostate cancer (mCRPC)
BRCA1/2 mutations
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
name: Foundation Medicine
name: Myriad Genetics, Inc.
First posted: 2022-07-13
Enrollment: 43
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of Olaparib compared with standard of care (Enzalutamide or Abiraterone Acetate) in Chinese men with metastatic castration-resistant prostate cancer who have failed prior treatment with a new hormonal agent and have BRCA1/2 mutations.

Detailed description: This is a Phase IV, randomized, open-label, 2-arm, multicenter study evaluating the efficacy and safety of olaparib in Chinese men with metastatic castration-resistant prostate cancer (mCRPC) who have failed prior treatment with a new hormonal agent (NHA) and have BRCA1/2 mutations. Approximately 42 subjects will be randomized in a 2:1 ratio to olaparib or to investigator's choice of NHA (enzalutamide or abiraterone acetate).

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. Radiological progression at study entry while on androgen deprivation therapy (or after bilateral orchiectomy).
6. Deleterious or suspected deleterious BRCA1/2 mutation in tumor tissue.
7. Normal organ and bone marrow function measured within 28 days prior to administration of study treatment.
8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.

Exclusion criteria：

1. Any previous treatment with a poly (adenosine diphosphate \[ADP\] ribose) polymerase (PARP) inhibitor, including olaparib.
2. Subjects who had any previous treatment with DNA-damaging cytotoxic chemotherapy, except if for non-prostate cancer indication and last dose \> 5 years prior to randomization.
3. History of another primary malignancy except for malignancy treated with curative intent with no known active disease for ≥5 years before the first dose of study intervention and of low potential risk for recurrence.
4. Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention.

Primary outcomes:
measure: Radiological progression free survival (rPFS)
timeFrame: From date of randomization to study completion (up to 3 years)
Secondary outcomes:
measure: Confirmed Objective Response Rate (ORR)
timeFrame: From date of radomization to study completion(up to 3 years)
measure: Overall Survival (OS)
timeFrame: From date of randomization to study completion (up to 4 years)
measure: Time to First Symptomatic Skeletal -Related Event (SSRE)
timeFrame: From date of randomization to study completion (up to 3years)
measure: Duration of Response (DoR)
timeFrame: From date of radomization to study completion (up to 3 years)
measure: Time to Opiate Use for Cancer Pain
timeFrame: From date of radomization to study completion (up to 3 years)
measure: Prostate Specific Antigen 50 Response (PSA50 response)
timeFrame: From date of baseline confirmed to study completion (up to 3 years)
measure: Second Progression or Death (PFS2)
timeFrame: From date of randomization to study completion (up to 3 years)
measure: Number of adverse events
timeFrame: From the time of signature of informed consent throughout the treatment period (up to 4 years plus 30 days)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Research Site
city: Bengbu
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Fuzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Jiaxing
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Jining
country: China
facility: Research Site
city: Kunming
country: China
facility: Research Site
city: Lanzhou
country: China
facility: Research Site
city: Linyi
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nantong
country: China
facility: Research Site
city: Ningbo
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Suzhou
country: China
facility: Research Site
city: Taiyuan
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Wanzhou
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuxi
country: China
facility: Research Site
city: Wuxi
country: China
facility: Research Site
city: XI 'an
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
Study officials:
affiliation: Sun Yat-sen University
name: Fangjian Zhou, M.D.
role: PRINCIPAL_INVESTIGATOR
References: