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

Phase
Recruitment status
Active, not recruiting
Participants
Lead sponsor
Start date
Number of sites

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

Control arm
Registry reports results
Listing at source
Recruitment status
Active, not recruiting
Phase
Study type
Interventional

Completion date
First posted
Registry last updated
Primary completion date
Start date

Actual participants
Participants
Participant count basis
Protocol amendments
Randomisation ratio
Number of sites

Data monitoring committee
Registry sponsor category
Lead sponsor
Source registry
ClinicalTrials.gov

Registry ID
ClinicalTrials.gov ID
Registry record
Open registry record

Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Quadruple masking
Masking description
Double-blind
Masked roles
Participants, Care providers, Investigators, Outcome assessors
Sources for study design

  1. Radiographic Progression-Free Survival (rPFS)

    Timeframe: 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.

  1. Overall Survival (OS)

    Timeframe: 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)

    Timeframe: Up to approximately 50 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)

    Timeframe: Up to approximately 50 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)

    Timeframe: Up to approximately 50 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)

    Timeframe: Up to approximately 50 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)

    Timeframe: Up to approximately 50 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)

    Timeframe: Up to approximately 50 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 Physical Function (TTDPF)

    Timeframe: Up to approximately 50 months

    TTDPF is defined as the time from randomisation to deterioration in PROMIS Physical Function Short Form 8C scores, or death due to any cause.

  9. Health-related Quality of Life (HrQoL)

    Timeframe: Up to approximately 50 months

    Change from baseline in BPI-SF worst pain score, pain severity, and interference domain scores.

  10. BRCA, other HRR gene mutation and HRD status

    Timeframe: At screening

  11. Plasma concentrations of AZD5305

    Timeframe: Up to approximately 10 months

  12. 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.

    Timeframe: Up to approximately 50 months

    Samples will be tested by a CDx to certify consistency with assays used in the study.

  13. Assessment of PSA (prostate-specific antigen) in participants in mCSPC

    Timeframe: Up to approximately 50 months

    proportion of participants achieving a \>= 50% or \>=90% decrease in PSA from baseline; proportion of participants with undetectable PSA (\< 0.2 ng/mL); time to PSA progression

Sources for outcomes

Sex
Male
Age groups
Adults, Older adults
Minimum age
18 Years
Maximum age
130 Years
Healthy volunteers
No

  • 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.

  • Participants with a history of MDS/AML or with features suggestive of MDS/AML (as determined by prior diagnostic investigation). In case there is no clinical MDS/AML suspicion, no specific screening for MDS/AML (by BM/bone biopsy) is required.
  • 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 arrhythmia 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.
Sources for eligibility

  • Research SiteChandler, United States
  • Research SiteGilbert, United States
  • Research SitePhoenix, United States
  • Research SiteTucson, United States
  • Research SiteLittle Rock, United States
  • Research SiteSpringdale, United States
  • Research SiteBakersfield, United States
  • Research SiteFountain Valley, United States
  • Research SiteFullerton, United States
  • Research SiteLos Angeles, United States
  • Research SiteMontebello, United States
  • Research SiteSan Francisco, United States
  • Research SiteSanta Barbara, United States
  • Research SiteSanta Monica, United States
  • Research SiteSanta Rosa, United States
  • Research SiteGolden, United States
  • Research SiteLakewood, United States
  • Research SiteNew Haven, United States
  • Research SiteAtlanta, United States
  • Research SiteGlenview, United States
  • Research SiteLake Barrington, United States
  • Research SiteFort Wayne, United States
  • Research SiteIndianapolis, United States
  • Research SiteWestwood, United States
  • Research SiteShreveport, United States

And 297 more, listed on the interactive page.

Sources for sites

  • 2023
  • 2023-504214-30-00
Sources for references

Related records

Drugs (4)

Lead sponsors (1)

Conditions (1)

Targets (2)