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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
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Description
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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.

Condition or disease Intervention/treatment Phase
Metastatic Castration-Sensitive Prostate Cancer Drug: Saruparib Drug: Placebo Drug: Abiraterone Acetate Drug: Darolutamide Drug: Enzalutamide Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1800 participants
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
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)
Actual Study Start Date : November 21, 2023
Estimated Primary Completion Date : January 11, 2028
Estimated Study Completion Date : April 30, 2031

Resource links provided by the National Library of Medicine

Drug Information available for: Abiraterone

Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm 1: Saruparib (AZD5305) + Physician's Choice NHA
Saruparib (AZD5305) + physician's choice NHA (Abiraterone, Darolutamide, or Enzalutamide)
 Drug: Saruparib
Oral
Other Name: AZD5305

Drug: Abiraterone Acetate
Oral
Other Name: Zytiga

Drug: Darolutamide
Oral
Other Name: Nubequa

Drug: Enzalutamide
Oral
Other Name: Xtandi
Placebo Comparator: Arm 2: Placebo + Physician's Choice NHA
Placebo + physician's choice NHA (Abiraterone, Darolutamide, or Enzalutamide)
 Drug: Placebo
Oral

Drug: Abiraterone Acetate
Oral
Other Name: Zytiga

Drug: Darolutamide
Oral
Other Name: Nubequa

Drug: Enzalutamide
Oral
Other Name: Xtandi


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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).

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. BRCA and other HRR gene mutation status. [ Time Frame: at screening ]
  12. Plasma concentrations of AZD5305 [ Time Frame: up to approximately 90 months ]
  13. 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.

  14. 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


Other Outcome Measures:
  1. 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 ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Male participants
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06120491


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Kim Nguyen Chi, MD BC Cancer, Canada
Principal Investigator: Arun Azad, MD Peter MacCallum Cancer Centre, Australia
More Information
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT06120491    
Other Study ID Numbers: D9723C00001
2023-504214-30-00 ( Other Identifier: EU CT )
First Posted: November 7, 2023    Key Record Dates
Last Update Posted: April 26, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
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
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
AZD5305; HRRm; non-HRRm; mCSPC; Prostate Cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Hypersensitivity
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Genital Diseases
Urogenital Diseases
Prostatic Diseases
Male Urogenital Diseases
 Immune System Diseases
Abiraterone Acetate
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 Enzyme Inhibitors