AZD5305 vs Placebo in Men with Metastatic Castration-Sensitive Prostate Cancer Receiving Physician's Choice New Hormonal Agents.
- Conditions
- Metastatic Castration-Sensitive Prostate Cancer (mCSPC)MedDRA version: 21.0Level: LLTClassification code: 10001198Term: Adenocarcinoma of the prostate metastatic Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-504214-30-00
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Male
- Target Recruitment
- 1805
Male = 18 years of age., 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., 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 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., Cardiac criteria, including history of arrythmia and cardiovascular disease., Any prior anticancer pharmacotherapy or surgery for metastatic prostate cancer, with the following exceptions: a) = 4 months ADT for metastatic disease (per inclusion criterion 4). b) Radiation therapy (for example radiation therapy to the prostate for participants with low volume metastatic disease or palliative radiation therapy to treat symptoms resulting from metastatic disease). Radiation therapy needs to have been completed > 4 weeks prior to randomisation for wide field radiation therapy and > 2 weeks for limited field radiation therapy. Participants should have fully recovered from any clinically significant adverse events. c) Surgical therapy to treat symptoms from metastatic disease if it was completed at least 4 weeks prior to first day of dosing and participant fully recovered from any clinically significant AEs., Patients to whom the investigator's choice of NHA based on an individualised assessment, would be darolutamide + docetaxel combination will be excluded from the study., Prior treatment within 14 days with blood product support or growth factor support., Participants who are unevaluable for both bone and soft tissue progression., 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 the following exceptions: a) Adequately resected non-melanoma skin cancer. b) Curatively treated in situ disease. c) Malignancy treated with curative intent = 3 years before the first dose of study intervention, and with no known active disease during the intervening time period., 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To demonstrate superiority of AZD5305 + physician's choice NHA relative to placebo + physician's choice NHA by assessment of radiographic progression-free survival (rPFS).;Secondary Objective: To demonstrate superiority of AZD5305 + physician's choice NHA relative to placebo + physician's choice NHA by assessment of overall survival (OS) in participants with mCSPC in the BRCAm subpopulation within the HRRm cohort, in the HRRm cohort, and the non-HRRm cohort.;Primary end point(s): Radiographic progression-free survival, 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
Name Time Method Secondary end point(s):Overall Survival, defined as the time from the date of randomisation until death due to any cause.;Secondary end point(s):Time to Second Progression or Death (PFS2), defined as the time from randomisation to the earliest progression after initiation of first subsequent treatment following the initial investigator-assessed progression or death.;Secondary end point(s):Time to First Subsequent Therapy or Death (TFST), 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.;Secondary end point(s):Symptomatic Skeletal Event-free Survival.;Secondary end point(s):Time to Castration-Resistance (TTCR), defined as the time from randomisation to the first castration-resistant event.;Secondary end point(s):Clinical Outcome Assessments, including TTPP, TTDUS, TTDF, TTDPF, and HRQoL.