Health Condition 1: C61- Malignant neoplasm of prostate
Conditions
Interventions
Intervention1: Experimental Arm: both HRRm cohort and non HRRm Cohort
Saruparib mg + physicianâ??s choice NHA: during the treatment period, participants will receive Saruparib 60 mg orally once daily
Sponsors
AstraZeneca AB
AstraZeneca Pharma India Ltd
Eligibility
Inclusion criteria
Inclusion criteria: Inclusion criteria Type of Participant and Disease Characteristics 1 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. 2 Metastatic disease as documented by the investigator prior to randomisation, with clear evidence of 1 bone lesion (defined as one lesion with positive uptake on bone scan) and/or 1 soft tissue lesion (measurable and/or non-measurable) that can be accurately assessed at baseline and is suitable for repeated assessment with CT and/or MRI. Participants with metastatic disease identified by PSMA-PET only, will not be eligible. Participants with disease limited to regional pelvic lymph nodes only are not eligible. 3 Participant is receiving ADT with a GnRH analogue or has undergone bilateral orchiectomy starting 14 days and 4 months prior to randomisation with no radiographic evidence of disease progression or rising PSA levels prior to first day of dosing. Participant must remain on ADT throughout the study and be a candidate for treatment with an NHA. Combination with first generation AR antagonists to counter testosterone flare is permitted until randomisation. Note: Due to the interaction between relugolix and enzalutamide, this combination of ADT and NHA is not allowed. Relugolix is otherwise permitted. 4 ECOG performance status of 0 or 1 with no deterioration over the 2 weeks prior to randomisation. 5 Minimum life expectancy of 6 months. 6 Type of Participant and Disease Characteristics: 7. Provision of a FFPE tumour tissue sample and a blood sample (for ctDNA) as specified in the Laboratory Manual and designated Diagnostic Testing Manuals (refer to Section 8.8 and to Table 5). 8. B. Participants will be considered eligible for the Non-HRRm Cohort if no gene mutation (in any of BRCA1, BRCA2, ATM, CDK12, PALB2, RAD51B, RAD51C, RAD51D, and BARD1) is detected in tumor tissue and ctDNA test and a participant must have a non-HRRm tumour tissue test result. Participants without both a valid non-HRRm tumour tissue and ctDNA are not eligible for randomisation into the Non-HRRm Cohort. For details see Table 5 .
Exclusion criteria
Exclusion criteria: Exclusion criteria Medical Conditions 1 Participants with a history of MDS AML or with features suggestive of MDS AML as determined by prior diagnostic investigation. Specific screening for MDS AML is not required. 2 Participants with any known predisposition to bleeding eg, active peptic ulceration, recent within 6 months haemorrhagic stroke, proliferative diabetic retinopathy. 3 Any history of persisting 2 weeks severe cytopenia due to any cause eg, absolute neutrophil count 0.5 109 L or platelets 50 109 L 4 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. 5 History of another primary malignancy, with the following exceptions: Adequately resected non-melanoma skin cancer. Curatively treated in situ disease. 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. 6 Persistent toxicities CTCAE Grade 2 caused by previous anticancer therapy. Participants with side effects that are not reasonably expected to affect the safety of the participant on study intervention in the opinion of the investigator eg, ADT-related side effects may be included if agreed with the Study Clinical Lead 7 Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention. A minimum of 2 weeks must have elapsed between the end of brain radiotherapy and signing the main study ICF. 8 Any of the following cardiac criteria: Mean resting corrected QT interval QTcF 470 milliseconds obtained from triplicate ECGs and averaged, recorded 5 minutes apart. Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives. 9 History of arrhythmia multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, which is symptomatic or requires treatment CTCAE Grade 3, symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted upon discussion with the AstraZeneca study physician 10 Other cardiovascular disease as defined by any of the following: Symptomatic heart failure as defined by New York Heart Association class 2. Acute coronary syndrome/acute myocardial infarction, unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention or coronary artery bypass grafting within 6 months prior to randomisation. Cardiomyopathy of any aetiology Presence of clinically significant valvular heart disease. Left ventricular ejection fraction 50% measured by echocardiogram or MUGA scan at screening or based on assessment performed within 6 months prior to randomisation. Transient ischaemic attack, or stroke within 6 months prior to randomisation. Participants with symptomatic hypotension at screening. Uncontrolled hypertension despite medical management. 11 Evidence of active and uncontrolled hepatitis B and/or hepatitis C. Screeni
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To demonstrate superiority of Saruparib + physicianâ??s choice NHA relative to placebo + physicianâ??s choice NHA by assessment of radiographic progression-free survivalTimepoint: 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 The analysis will include all randomised participants in the relevant subpopulation/cohort as randomised. All events will be included regardless of whether the participant withdraws from therapy, receives another anticancer therapy, or clinically progresses prior to RECIST 1.1 (soft tissue) and/or PCWG3 criteria (bone). | — |
Secondary
| Measure | Time frame |
|---|---|
| To demonstrate the effectiveness of AZD5305 physicians choice NHA relative to placebo physicians choice NHA by assessment of time to deterioration in urinary symptoms TTDUS in participants with mCSPCTimepoint: 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 QLQ PR25 US subscale scores.The analysis will include all randomised participants in the relevant subpopulationcohort as randomised. All events will be included, regardless of progression status.The measure of interest is the HR of TTDUS;To demonstrate the effectiveness of AZD5305 physicians choice NHA relative to placebo physicians choice NHA by assessment of time to deterioration in fatigue TTDF in participants with mCSPCTimepoint: TTDF is defined as the time from randomisation to deterioration in Patient Reported Outcomes Measurement Information System PROMIS Fatigue Short Form 7A scores.The analysis will include all randomised participants in the relevant subpopulation cohort as randomised. All events will be included, regardless of progression status.The measure of interest is the HR of TTDF;To demonstrate the effectiveness of AZD5305 physicians choice NHA relative to placebo physicians choice NHA by assessment of time to deterioration in physical function TTDPF in participants with mCSPCTimepoint: TTDPF is defined as the time from randomisation to deterioration in PROMIS Physical Function Short Form 8C scores.The analysis will include all randomised participants in the relevant subpopulation cohort as randomised. All events will be included, regardless of progression status.The measure of interest is the HR of TTDPF;Future exploratory research into factors that may influence development of cancer and/or response to treatment, may be performed on the collected and stored archival tumour samples, blood samples and their derivativesTimepoint: This may include: Analys | — |
Countries
Australia, Austria, Belgium, Brazil, Canada, Chile, China, Finland, France, Germany, Hungary, India, Italy, Japan, Malaysia, Netherlands, Peru, Poland, Republic of Korea, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom
Contacts
Public ContactMr Sandeep AV
AstraZeneca Pharma India Ltd
Outcome results
None listed