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

Metastatic Castration-resistant Prostate Cancer Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05457257
• Other study ID #: D081LC00002
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: July 29, 2022
• Est. completion date: September 30, 2025

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 43
• Est. completion date: September 30, 2025
• Est. primary completion date: June 28, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Castration-resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• olaparib
300 mg (2x 150 mg tablets) twice daily
• enzalutamide
160 mg (4 x 40 mg capsules) once daily
• abiraterone acetate
1,000 mg (4 x 250 mg tablets) once daily
• Prednisone
5mg(5mg x 1 tablet) twice daily

Locations

Country	Name	City	State
China	Research Site	Beijing
China	Research Site	Bengbu
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chongqing
China	Research Site	Fuzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Hankou,Wuhan
China	Research Site	Hefei
China	Research Site	Jiaxing
China	Research Site	Jinan
China	Research Site	Jinan
China	Research Site	Jining
China	Research Site	Kunming
China	Research Site	Lanzhou
China	Research Site	Linyi
China	Research Site	Nanchang
China	Research Site	Nantong
China	Research Site	Ningbo
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Suzhou
China	Research Site	Taiyuan
China	Research Site	Tianjin
China	Research Site	Wanzhou
China	Research Site	Wuxi
China	Research Site	Wuxi
China	Research Site	XI 'an
China	Research Site	Zhengzhou

Sponsors (4)

Lead Sponsor	Collaborator
AstraZeneca	Foundation Medicine, Inc., Merck Sharp & Dohme LLC, Myriad Genetics, Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Radiological progression free survival (rPFS)	Radiological progression-free survival (rPFS) is defined by radiological progression, as assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) version 1.1 (soft tissue) and Prostate Cancer Working Group-3 (PCWG3) criteria (bone), or death from any cause, whichever occurs first.	From date of randomization to study completion (up to 3 years)
Secondary	Confirmed Objective Response Rate (ORR)	Confirmed ORR is defined as a response of PR or CR in the soft tissue disease according to RECIST 1.1 in the absence of progression on bone scan and confirmed not less than 4 weeks after the initial response was observed, as assessed by BICR in patients with measurable disease using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria.	From date of radomization to study completion(up to 3 years)
Secondary	Overall Survival (OS)	OS defined as time from randomization to death due to any cause.	From date of randomization to study completion (up to 4 years)
Secondary	Time to First Symptomatic Skeletal -Related Event (SSRE)	Time from randomization to first SSRE as defined by any of the following or a combination: Use of radiation therapy to prevent or relieve skeletal symptoms.; Occurrence of new symptomatic pathological bone fractures (vertebral or non-vertebral, resulting from minimal or no trauma).; Occurrence of spinal cord compression.; Orthopedic surgical intervention for bone metastasis.	From date of randomization to study completion (up to 3years)
Secondary	Duration of Response (DoR)	Duration of response (DoR) will be defined as the time from the date of first documented confirmed response (by BICR using RECIST 1.1 and PCWG3) until date of documented progression (by BICR) or death in the absence of disease progression.	From date of radomization to study completion (up to 3 years)
Secondary	Time to Opiate Use for Cancer Pain	Time to opiate use is defined as the time from randomization to the date of opiate use for cancer-related pain in participants who have not received any opiates at baseline.	From date of radomization to study completion (up to 3 years)
Secondary	Prostate Specific Antigen 50 Response (PSA50 response)	Prostate Specific Antigen (PSA) response is defined as the proportion of participants achieving a =50% decrease in PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later.	From date of baseline confirmed to study completion (up to 3 years)
Secondary	Second Progression or Death (PFS2)	Defined as the time from randomization to second progression by investigator assessment of radiological or clinical progression or death from any cause, whichever occurs first.	From date of randomization to study completion (up to 3 years)
Secondary	Number of adverse events	Percentage of patients with any adverse event (AE), adverse event (AE) leading to study drug discontinuation, adverse event (AE) leading to death, serious adverse event (SAE), adverse event (AE) related to study drug, serious adverse event (SAE) related to study drug	From the time of signature of informed consent throughout the treatment period (up to 4 years plus 30 days)