Saruparib (AZD5305) vs Placebo in Men With Metastatic Castration-Sensitive Prostate Cancer Receiving Physician's Choice New Hormonal Agents

Metastatic Castration-Sensitive Prostate Cancer Clinical Trial

— EvoPAR-PR01  

Official title:

A Randomized, 2-cohort, Double-blind, Placebo-controlled, Phase III Study of Saruparib (AZD5305) in Combination With Physician's Choice New Hormonal Agents in Patients With HRRm and Non-HRRm Metastatic Castration-Sensitive Prostate Cancer (EvoPAR-Prostate01)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06120491
• Other study ID #: D9723C00001
• Secondary ID: 2023-504214-30-0
• Status: Recruiting
• Phase: Phase 3
• Start date: November 21, 2023
• Est. completion date: April 30, 2031

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The intention of the study is to demonstrate superiority of Saruparib (AZD5305) + physician's choice NHA relative to placebo + physician's choice NHA by assessment of radiographic progression-free survival (rPFS) in participants with mCSPC.

Description:

Approximately 1800 adult participants with mCSPC will be assigned to one of two cohorts (550 HRRm and 1250 non-HRRm) and randomized in a 1:1 ratio to receive either Saruparib (AZD5305) with NHA or placebo with NHA. They will receive their assigned treatment and regular tumor evaluation scans until disease progression, or until treatment is stopped for another reason. All patients will be followed for survival until the end of the study. Independent data monitoring committee (DMC) composed of independent experts will be convened to confirm the safety and tolerability of Saruparib + physicians choice NHA.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1800
• Est. completion date: April 30, 2031
• Est. primary completion date: January 11, 2028
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

• Male = 18 years of age
• Histologically documented prostate adenocarcinoma which is de novo or recurrent and castration-sensitive. Participants with pathologic features of small cell, neuroendocrine, sarcomatoid, spindle cell, or signet cell histology are not eligible.
• Metastatic disease as documented by the investigator prior to randomisation, with clear evidence of = 1 bone lesion and/or = 1 soft tissue lesion that is suitable for repeated assessment with CT and/or MRI.
• Participant is receiving ADT with a GnRH analogue or has undergone bilateral orchiectomy starting = 14 days and < 4 months prior to randomisation
• ECOG performance status of 0 or 1 with no deterioration over the 2 weeks prior to randomisation.
• Provision of FFPE tumour tissue sample and blood sample (for ctDNA)
• Confirmed HRRm status by central tumour tissue and/or ctDNA test is required to determine cohort eligibility
• Adequate organ and bone marrow function as described in study protocol
• Participants must not father children or donate sperm from signing ICF, during the study intervention and for 6 months after the last dose of study intervention.
• Participants must use a condom from signing ICF, during study intervention, and for 6 months after the last dose of study drug, with all sexual partners.

Exclusion Criteria:

• Participants with a history of MDS/AML or with features suggestive of MDS/AML
• Participants with any known predisposition to bleeding
• Any history of persisting (> 2 weeks) severe cytopenia
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD5305 and/or the assigned NHA.
• History of another primary malignancy, with exceptions
• Persistent toxicities (CTCAE Grade = 2) caused by previous anticancer therapy.
• Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention
• Cardiac criteria, including history of arrythmia and cardiovascular disease
• Any prior anticancer pharmacotherapy or surgery for metastatic prostate cancer, with

exceptions:

• Prior treatment within 14 days with blood product support or growth factor support.
• Participants who are unevaluable for both bone and soft tissue progression

Related Conditions & MeSH terms

• Hypersensitivity
• Metastatic Castration-Sensitive Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Saruparib
Oral
• Placebo
Oral
• Abiraterone Acetate
Oral
• Darolutamide
Oral
• Enzalutamide
Oral

Locations

Country	Name	City	State
Australia	Research Site	Chermside
Australia	Research Site	Darlinghurst
Australia	Research Site	Hyde Park
Australia	Research Site	Kurralta Park
Australia	Research Site	Melbourne
Australia	Research Site	Randwick
Australia	Research Site	South Brisbane
Austria	Research Site	Graz
Austria	Research Site	Innsbruck
Austria	Research Site	Krems an der Donau
Austria	Research Site	Linz
Austria	Research Site	Wien
Austria	Research Site	Wien
Belgium	Research Site	Charleroi
Belgium	Research Site	Gent
Belgium	Research Site	Kortrijk
Belgium	Research Site	Leuven
Brazil	Research Site	Curitiba
Brazil	Research Site	Pelotas
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Salvador
Brazil	Research Site	Sao Luis
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Canada	Research Site	Abbotsford	British Columbia
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Chicoutimi	Quebec
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Greenfield Park	Quebec
Canada	Research Site	Halifax	Nova Scotia
Canada	Research Site	Kelowna	British Columbia
Canada	Research Site	Kingston	Ontario
Canada	Research Site	London	Ontario
Canada	Research Site	Mississauga	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Newmarket	Ontario
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Saskatoon	Saskatchewan
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Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
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Chile	Research Site	Concepcion
Chile	Research Site	La Serena
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Temuco
Chile	Research Site	Viña del Mar
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changsha
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China	Research Site	Chongqing
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China	Research Site	Guangzhou
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China	Research Site	Jiaxing
China	Research Site	Jinan
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China	Research Site	Nantong
China	Research Site	Ningbo
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China	Research Site	Shenyang
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China	Research Site	Suining
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Finland	Research Site	Helsinki
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France	Research Site	Tours
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Korea, Republic of	Research Site	Daejeon
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon
Malaysia	Research Site	George Town
Malaysia	Research Site	Johor Bahru
Malaysia	Research Site	Kota Kinabalu
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuala Lumpur
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Netherlands	Research Site	Amsterdam
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Peru	Research Site	Arequipa
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Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Poland	Research Site	Bydgoszcz
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Poland	Research Site	Rzeszów
Poland	Research Site	Szczecin
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Poland	Research Site	Wroclaw
Poland	Research Site	Zory
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Spain	Research Site	Madrid
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Spain	Research Site	Sabadell
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Sweden	Research Site	Göteborg
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Taiwan	Research Site	Kaohsiung
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Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Chiang Mai
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Turkey	Research Site	Bornova-Izmir
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United Kingdom	Research Site	Truro
United States	Research Site	Albany	New York
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Annapolis	Maryland
United States	Research Site	Atlanta	Georgia
United States	Research Site	Bakersfield	California
United States	Research Site	Bala-Cynwyd	Pennsylvania
United States	Research Site	Baltimore	Maryland
United States	Research Site	Baltimore	Maryland
United States	Research Site	Belleville	New Jersey
United States	Research Site	Bethesda	Maryland
United States	Research Site	Billings	Montana
United States	Research Site	Bozeman	Montana
United States	Research Site	Brick	New Jersey
United States	Research Site	Bronx	New York
United States	Research Site	Camden	New Jersey
United States	Research Site	Chandler	Arizona
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cleveland	Ohio
United States	Research Site	Cleveland	Ohio
United States	Research Site	Cleveland	Ohio
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United States	Research Site	Columbus	Ohio
United States	Research Site	Dallas	Texas
United States	Research Site	Denton	Texas
United States	Research Site	Des Moines	Iowa
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United States	Research Site	Grand Rapids	Michigan
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United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Jacksonville	Florida
United States	Research Site	Jacksonville	Florida
United States	Research Site	Kansas City	Kansas
United States	Research Site	Lake Barrington	Illinois
United States	Research Site	Lakewood	Colorado
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lexington	Kentucky
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Montebello	California
United States	Research Site	Myrtle Beach	South Carolina
United States	Research Site	Nashville	Tennessee
United States	Research Site	New Haven	Connecticut
United States	Research Site	New Hyde Park	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Newark	Delaware
United States	Research Site	North Charleston	South Carolina
United States	Research Site	Norwich	Connecticut
United States	Research Site	Palm Bay	Florida
United States	Research Site	Pasadena	California
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Plano	Texas
United States	Research Site	Pomona	California
United States	Research Site	Portland	Oregon
United States	Research Site	Portland	Oregon
United States	Research Site	Providence	Rhode Island
United States	Research Site	Rio Rancho	New Mexico
United States	Research Site	Rochester	Minnesota
United States	Research Site	Sacramento	California
United States	Research Site	Saint George	Utah
United States	Research Site	Saint Petersburg	Florida
United States	Research Site	Salt Lake City	Utah
United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	San Francisco	California
United States	Research Site	Santa Barbara	California
United States	Research Site	Santa Monica	California
United States	Research Site	Santa Rosa	California
United States	Research Site	Scarborough	Maine
United States	Research Site	Shirley	New York
United States	Research Site	Shreveport	Louisiana
United States	Research Site	Sioux Falls	South Dakota
United States	Research Site	Spokane	Washington
United States	Research Site	Spokane Valley	Washington
United States	Research Site	Springdale	Arkansas
United States	Research Site	Sugar Land	Texas
United States	Research Site	Syracuse	New York
United States	Research Site	Tacoma	Washington
United States	Research Site	Tampa	Florida
United States	Research Site	Towson	Maryland
United States	Research Site	Troy	Michigan
United States	Research Site	Tucson	Arizona
United States	Research Site	Tyler	Texas
United States	Research Site	Voorhees	New Jersey
United States	Research Site	Wichita	Kansas
United States	Research Site	Wichita Falls	Texas
United States	Research Site	Winchester	Virginia
United States	Research Site	York	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  China,  Finland,  France,  Germany,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Netherlands,  Peru,  Poland,  Spain,  Sweden,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of TEAEs (treatment emergent adverse events), SAEs (serious adverse events), and AEs (adverse events) leading to dose modifications		up to approximately 90 months
Primary	Radiographic Progression-Free Survival (rPFS)	rPFS is defined as the time from randomisation to radiographic progression, as assessed by the investigator per RECIST 1.1 (soft tissue) and/or PCWG3 criteria (bone), or, death due to any cause.	up to approximately 50 months
Secondary	Overall Survival (OS)	OS is defined as the time from randomisation until the date of death due to any cause.	up to approximately 90 months
Secondary	Second Progression-Free Survival (PFS2)	Time from randomisation to PFS2 is defined as the time from randomisation to the earliest of progression (defined as radiographic progression, clinical progression, or PSA progression) after initiation of first subsequent treatment following the initial investigator-assessed progression or death.	up to approximately 90 months
Secondary	Time to First Subsequent Therapy or Death (TFST)	TFST is defined as the time from randomisation to the start date of the first subsequent anticancer therapy after discontinuation of randomised treatment, or death due to any cause.	up to approximately 90 months
Secondary	Symptomatic Skeletal Event-Free Survival (SSE-FS)	SSE-FS is defined as the time from randomisation to the earliest of the following: Use of radiation therapy to prevent or relieve skeletal symptoms.; Occurrence of new symptomatic pathological bone fractures (vertebral or non-vertebral).; Occurrence of spinal cord compression.; Orthopaedic surgical intervention for bone metastasis.; Death due to any cause.	up to approximately 90 months
Secondary	Time to the First Castration-Resistant Event (TTCR)	TTCR is defined as the time from randomisation to the first castration resistant event (radiographic disease progression per RECIST 1.1 [soft tissue] and/or PCWG3 criteria [bone], PSA progression per PCWG3, or SSE, PSA progression per PCWG3, or SSE), whichever occurs first, with castrate levels of testosterone (below 50 ng/dL).	up to approximately 90 months
Secondary	Time to Pain Progression (TTPP)	TTPP is defined as the time from randomisation to clinically meaningful pain progression based on a 2-point increase from baseline in the Brief Pain Inventory - Short Form (BPI-SF) Item 3 'worst pain in 24 hours' score and/or initiation of/increase in opioid analgesic use.	up to approximately 90 months
Secondary	Time To Deterioration in Urinary Symptoms (TTDUS)	TTDUS is defined as the time from randomisation to deterioration in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Prostate Questionnaire (Urinary Symptoms) (QLQPR25 [US]) subscale scores.	up to approximately 90 months
Secondary	Time to Deterioration in Fatigue (TTDF)	TTDF is defined as the time from randomisation to deterioration in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7A scores.	up to approximately 90 months
Secondary	Time to Deterioration in Physical Function (TTDPF)	TTDPF is defined as the time from randomisation to deterioration in PROMIS Physical Function Short Form 8C scores.	up to approximately 90 months
Secondary	Health-related Quality of Life (HrQoL)	Change from baseline in BPI-SF worst pain score, pain severity, and interference domain scores.	up to approximately 90 months
Secondary	BRCA and other HRR gene mutation status.		at screening
Secondary	Plasma concentrations of AZD5305		up to approximately 90 months
Secondary	Samples will be used to develop complementary or companion diagnostics by analyzing their performance characteristics and calculate their consistency with clinical trial assays used for enrolment onto the study.	Samples will be tested by a CDx to certify consistency with assays used in the study.	up to approximately 90 months
Secondary	PSA (prostate-specific antigen) undetectable rate at 6, 12 months	proportion of participants with undetectable PSA (< 0.2 ng/mL) for those with PSA = 0.2 ng/mL at baseline	up to approximately 90 months