Saruparib (AZD5305) vs Placebo in Men With Metastatic Castration-Sensitive Prostate Cancer Receiving Physician's Choice New Hormonal Agents (EvoPAR-PR01)

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ClinicalTrials.gov Identifier: NCT06120491

Recruitment Status : Recruiting

First Posted : November 7, 2023

Last Update Posted : April 26, 2024

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View this study on the modernized ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

AstraZeneca

Tracking Information

First Submitted Date ^ICMJE

October 17, 2023

First Posted Date ^ICMJE

November 7, 2023

Last Update Posted Date

April 26, 2024

Actual Study Start Date ^ICMJE

November 21, 2023

Estimated Primary Completion Date

January 11, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Radiographic Progression-Free Survival (rPFS) [ Time Frame: up to approximately 50 months ]

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.

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Current Secondary Outcome Measures ^ICMJE

Overall Survival (OS) [ Time Frame: up to approximately 90 months ]
OS is defined as the time from randomisation until the date of death due to any cause.
Second Progression-Free Survival (PFS2) [ Time Frame: up to approximately 90 months ]
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.
Time to First Subsequent Therapy or Death (TFST) [ Time Frame: up to approximately 90 months ]
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.
Symptomatic Skeletal Event-Free Survival (SSE-FS) [ Time Frame: up to approximately 90 months ]
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.
Time to the First Castration-Resistant Event (TTCR) [ Time Frame: up to approximately 90 months ]
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).
Time to Pain Progression (TTPP) [ Time Frame: up to approximately 90 months ]
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.
Time To Deterioration in Urinary Symptoms (TTDUS) [ Time Frame: up to approximately 90 months ]
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.
Time to Deterioration in Fatigue (TTDF) [ Time Frame: up to approximately 90 months ]
TTDF is defined as the time from randomisation to deterioration in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7A scores.
Time to Deterioration in Physical Function (TTDPF) [ Time Frame: up to approximately 90 months ]
TTDPF is defined as the time from randomisation to deterioration in PROMIS Physical Function Short Form 8C scores.
Health-related Quality of Life (HrQoL) [ Time Frame: up to approximately 90 months ]
Change from baseline in BPI-SF worst pain score, pain severity, and interference domain scores.
BRCA and other HRR gene mutation status. [ Time Frame: at screening ]
Plasma concentrations of AZD5305 [ Time Frame: up to approximately 90 months ]
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. [ Time Frame: up to approximately 90 months ]
Samples will be tested by a CDx to certify consistency with assays used in the study.
PSA (prostate-specific antigen) undetectable rate at 6, 12 months [ Time Frame: up to approximately 90 months ]
proportion of participants with undetectable PSA (< 0.2 ng/mL) for those with PSA ≥ 0.2 ng/mL at baseline

Original Secondary Outcome Measures ^ICMJE

Overall Survival (OS) [ Time Frame: up to approximately 90 months ]
OS is defined as the time from randomisation until the date of death due to any cause.
Second Progression-Free Survival (PFS2) [ Time Frame: up to approximately 90 months ]
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.
Time to First Subsequent Therapy or Death (TFST) [ Time Frame: up to approximately 90 months ]
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.
Symptomatic Skeletal Event-Free Survival (SSE-FS) [ Time Frame: up to approximately 90 months ]
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.
Time to the First Castration-Resistant Event (TTCR) [ Time Frame: up to approximately 90 months ]
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).
Time to Pain Progression (TTPP) [ Time Frame: up to approximately 90 months ]
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.
Time To Deterioration in Urinary Symptoms (TTDUS) [ Time Frame: up to approximately 90 months ]
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.
Time to Deterioration in Fatigue (TTDF) [ Time Frame: up to approximately 90 months ]
TTDF is defined as the time from randomisation to deterioration in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7A scores.
Time to Deterioration in Physical Function (TTDPF) [ Time Frame: up to approximately 90 months ]
TTDPF is defined as the time from randomisation to deterioration in PROMIS Physical Function Short Form 8C scores.
Health-related Quality of Life (HrQoL) [ Time Frame: up to approximately 90 months ]
Change from baseline in BPI-SF worst pain score, pain severity, and interference domain scores.
BRCA and other HRR gene mutation status. [ Time Frame: at screening ]
Plasma concentrations of AZD5305 and plasma PK parameters. [ Time Frame: up to approximately 90 months ]
To assess the PK of AZD5305.
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. [ Time Frame: up to approximately 90 months ]
Samples will be tested by a CDx to certify consistency with assays used in the study.
PSA (prostate-specific antigen) undetectable rate at 6, 12 months [ Time Frame: up to approximately 90 months ]
proportion of participants with undetectable PSA (< 0.2 ng/mL) for those with PSA ≥ 0.2 ng/mL at baseline

Current Other Pre-specified Outcome Measures

Number of TEAEs (treatment emergent adverse events), SAEs (serious adverse events), and AEs (adverse events) leading to dose modifications [ Time Frame: up to approximately 90 months ]

Original Other Pre-specified Outcome Measures

Same as current

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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)

Brief 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.

Detailed 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.

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 3

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

within each cohort (HRRm and non-HRRm), participants are randomised in 1:1 ratio to one of two treatment arms

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Double-blind

Primary Purpose: Treatment

Condition ^ICMJE

Metastatic Castration-Sensitive Prostate Cancer

Intervention ^ICMJE

Drug: Saruparib
Oral

Other Name: AZD5305
Drug: Placebo
Oral
Drug: Abiraterone Acetate
Oral

Other Name: Zytiga
Drug: Darolutamide
Oral

Other Name: Nubequa
Drug: Enzalutamide
Oral

Other Name: Xtandi

Study Arms ^ICMJE

Experimental: Arm 1: Saruparib (AZD5305) + Physician's Choice NHA
Saruparib (AZD5305) + physician's choice NHA (Abiraterone, Darolutamide, or Enzalutamide)
Interventions:
- Drug: Saruparib
- Drug: Abiraterone Acetate
- Drug: Darolutamide
- Drug: Enzalutamide
Placebo Comparator: Arm 2: Placebo + Physician's Choice NHA
Placebo + physician's choice NHA (Abiraterone, Darolutamide, or Enzalutamide)
Interventions:
- Drug: Placebo
- Drug: Abiraterone Acetate
- Drug: Darolutamide
- Drug: Enzalutamide

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

1800

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date ^ICMJE

April 30, 2031

Estimated Primary Completion Date

January 11, 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Sex/Gender ^ICMJE

Sexes Eligible for Study:	Male
Gender Based Eligibility:	Yes
Gender Eligibility Description:	Male participants

Ages ^ICMJE

18 Years to 130 Years (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact: AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Listed Location Countries ^ICMJE

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, United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT06120491

Other Study ID Numbers ^ICMJE

D9723C00001
2023-504214-30-00 ( Other Identifier: EU CT )

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

IPD Sharing Statement ^ICMJE

Plan to Share IPD:	Yes
Plan Description:	Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Supporting Materials:	Study Protocol
Supporting Materials:	Statistical Analysis Plan (SAP)
Time Frame:	AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria:	When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL:	https://astrazenecagroup-dt.pharmacm.com/DT/Home