Metastatic Castration-Sensitive Prostate Cancer
Conditions
Keywords
AZD5305; Saruparib; HRRm; non-HRRm; mCSPC; Prostate Cancer
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.
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 (AZD5305) + physicians choice NHA.
Interventions
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Intervention model description
Within each cohort (HRRm and non-HRRm), participants are randomised in 1:1 ratio to one of two treatment arms
Eligibility
Sex/Gender
MALE
Age
18 Years to 130 Years
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 (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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Second Progression-Free Survival (PFS2) | 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. |
| Time to First Subsequent Therapy or Death (TFST) | 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. |
| Symptomatic Skeletal Event-Free Survival (SSE-FS) | 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. |
| Time to the First Castration-Resistant Event (TTCR) | 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). |
| Time to Pain Progression (TTPP) | 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. |
| Time To Deterioration in Urinary Symptoms (TTDUS) | 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. |
| Time to Deterioration in Physical Function (TTDPF) | 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. |
| Health-related Quality of Life (HrQoL) | Up to approximately 50 months | Change from baseline in BPI-SF worst pain score, pain severity, and interference domain scores. |
| BRCA, other HRR gene mutation and HRD status | At screening | — |
| Plasma concentrations of AZD5305 | Up to approximately 10 months | — |
| 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 50 months | Samples will be tested by a CDx to certify consistency with assays used in the study. |
| Assessment of PSA (prostate-specific antigen) in participants in mCSPC | 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 |
Countries
Australia, Austria, Belgium, Brazil, Canada, Chile, China, Finland, France, Germany, Hungary, India, Italy, Japan, Malaysia, Netherlands, Peru, Poland, Puerto Rico, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
PRINCIPAL_INVESTIGATORKim Nguyen Chi, MD
BC Cancer, Canada
PRINCIPAL_INVESTIGATORArun Azad, MD
Peter MacCallum Cancer Centre, Australia
Outcome results
None listed