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

Sponsor
AstraZeneca (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT06120491
Collaborator
(none)
1,800
Enrollment
193
Locations
2
Arms
89.1
Anticipated Duration (Months)
9.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The intention of the study is to demonstrate superiority of 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
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 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 AZD5305 + physicians choice NHA.

Study Design

Study Type:
Interventional
Anticipated 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 armswithin 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 AZD5305 in Combination With Physician's Choice New Hormonal Agents in Patients With HRRm and Non-HRRm Metastatic Castration-Sensitive Prostate Cancer (EvoPAR-Prostate01)
Anticipated Study Start Date :
Nov 24, 2023
Anticipated Primary Completion Date :
Jan 14, 2028
Anticipated Study Completion Date :
Apr 28, 2031

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm 1: AZD5305 + Physician's Choice NHA

AZD5305 + physician's choice NHA (Abiraterone, Darolutamide, or Enzalutamide)

Drug: AZD5305
Oral

Drug: Abiraterone Acetate
Oral
Other Names:
  • Zytiga

    • Drug: Darolutamide
    Oral
    Other Names:
  • Nubequa

    • Drug: Enzalutamide
    Oral
    Other Names:
  • 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 Names:
  • Zytiga

    • Drug: Darolutamide
    Oral
    Other Names:
  • Nubequa

    • Drug: Enzalutamide
    Oral
    Other Names:
  • Xtandi

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Radiographic Progression-Free Survival (rPFS) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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. [at screening]

    12. Plasma concentrations of AZD5305 and plasma PK parameters. [up to approximately 90 months]

      To assess the PK of AZD5305.

    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. [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 [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 [up to approximately 90 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 130 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 Research Site Tucson Arizona United States 85741
    2 Research Site Fayetteville Arkansas United States 72703
    3 Research Site Los Angeles California United States 90073
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    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    • Principal Investigator: Kim Nguyen Chi, MD, BC Cancer, Canada
    • Principal Investigator: Arun Azad, MD, Peter MacCallum Cancer Centre, Australia

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT06120491
    Other Study ID Numbers:
    • D9723C00001
    • 2023-504214-30-00
    First Posted:
    Nov 7, 2023
    Last Update Posted:
    Nov 7, 2023
    Last Verified:
    Oct 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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:
    Prostatic Neoplasms
    Hypersensitivity
    Abiraterone Acetate

    Study Results

    No Results Posted as of Nov 7, 2023