Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
Conditions
Keywords
Saruparib, HRRm, non-HRRm, mHSPC, Prostate Cancer, AZD5305, PSA>0.2ng/ml, Androgen pathway modulation sensitive (APMS), Castration sensitive, Metastatic prostate cancer, Hormone sensitive prostate cancer, PARPi, Docetaxel, PSMA-directed 177Lutetium
Brief summary
The primary objective of this study is to measure efficacy of saruparib + physician's choice of ARPI compared with placebo + ARPI in men with metastatic hormone-sensitive prostate cancer (mHSPC) who have previously received docetaxel chemotherapy or a prostate-specific membrane antigen (PSMA)-directed lutetium-177 radioligand therapy with no evidence of disease progression and PSA ≥ 0.2 ng/mL.
Interventions
DRUGSaruparib
Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone)
OTHERPlacebo
Arm 2: Placebo + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone)
DRUGEnzalutamide
Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone) Arm 2: Placebo + Physician's Choice ARPI
DRUGDarolutamide
Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone) Arm 2: Placebo + Physician's Choice ARPI
DRUGAbiraterone
Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone) Arm 2: Placebo + Physician's Choice ARPI
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant must be ≥ 18 at the time of signing the informed consent. * Histologically documented diagnosis of prostate adenocarcinoma that is de novo or recurrent and hormone-sensitive. * Metastatic disease confirmed prior to initiation of previous treatment with docetaxel or Lu-PSMA-containing regimens for mHSPC. * Previous treatment with docetaxel (IV, Q3w)- or Lu-PSMA (IV, Q6w) with last dose within past 6 months. * Participants must have the following: * Must be receiving ADT with a GnRH analogue or has undergone bilateral orchiectomy. * Had no evidence of disease progression * Had all toxicities related to docetaxel- or Lu-PSMA-containing treatment (except for alopecia and peripheral neuropathy) resolved to CTCAE Grade 1 or lower. * PSA ≥ 0.2 ng/mL within 14 days prior to randomization. * Serum testosterone \< 1.7 nmol/L or 50 ng/dL. * Palliative radiotherapy for symptoms management will be permitted and is to be completed at least 4 weeks prior to randomization for wide field radiation therapy and at least 2 weeks prior to randomization for limited field radiation therapy. * Provision of a FFPE tumor tissue sample and a blood sample (for ctDNA). * Confirmed HRRm, HRD and PTEN status. * Adequate organ and bone marrow function. * Minimum life expectancy of 6 months. * Male, assigned at birth, inclusive of all gender identities. * Contraceptive use by participants or participant partners should be consistent with local regulations. * Capable of giving signed informed consent. * \- -
Exclusion criteria
* Hypersensitivity to saruparib, ARPI or any excipients of these products or any contraindication or restriction based on the local label. * Any history of persisting (\> 2 weeks) severe cytopenia due to any cause (eg, ANC\< 0.5 × 10\^9/L or platelets \< 50 × 10\^9/L) * Any known predisposition to bleeding (eg, active peptic ulceration, recent \[within6 months\] hemorrhagic stroke, proliferative diabetic retinopathy. * Spinal cord compression or brain metastases unless asymptomatic and stable. * History of MDS/AML or with features suggestive of MDS/AML * History of another primary malignancy, with some exceptions. * Any chronic gastrointestinal diseases or conditions including inability to swallow the formulated product that would preclude adequate absorption of any study drug. * History of seizure or predispose to seizure, including any history of loss of consciousness or transient ischemic attack within 12 months of enrolment. * Serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. * Major surgical procedure or significant traumatic injury within 4 weeks of the first dose or an anticipated need for major surgery during the study. * Switched ARPI agent in previous treatment for mHSPC due to disease progression. Note: if the ARPI agent was switched due to any reason other than disease progression and switch was prior to ICF signature, participants will be eligible. * Any prior treatment with a PARPi or platinum chemotherapy. * \- -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic progression-free survival (rPFS) | Up to approximately 56 months | Radiographic PFS (rPFS) is the primary endpoint of this study, defined as the time from randomization 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 80 months | OS is defined as the time from the date of randomization until death due to any cause. |
| Radiographic progression-free survival (rPFS) | Up to approximately 56 months | Radiographic PFS (rPFS) is the primary endpoint of this study, defined as the time from randomization 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. |
| Time to Second Progression or Death (PFS2) | Up to approximately 56 months | PFS2 is defined as the time from randomization to the earliest progression (defined as radiographic progression, clinical progression, or PSA progression) after initiation of first subsequent treatment following the initial investigator-assessed progression or death (ie, date of PFS2 event or censoring - date of randomization + 1). |
| Time to First Subsequent Therapy or Death (TFST) | Up to approximately 56 months | TFST is defined as the time from randomization to the start date of the first subsequent anticancer therapy after discontinuation of randomized treatment, or death due to any cause (ie, date of first subsequent cancer therapy or death - date of randomization + 1). |
| Symptomatic Skeletal Event-free Survival (SSE-FS) | Up to approximately 56 months | SSE-FS is defined as the time from the date of randomization 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). Radiographic documentation is required. A pathological fracture, as determined by investigator, is defined as associated with low or no trauma and deemed to have occurred at a site of bone metastasis. * Occurrence of spinal cord compression. Radiographic documentation is required. * Orthopedic surgical intervention for bone metastasis. * Death due to any cause. |
| Time to Castration Resistance (TTCR) | Up to approximately 56 months | TTCR is defined as the time from randomization to the first castration-resistant event (radiographic disease progression, PSA progression per PCWG3, or SSE, whichever occurs first, with castrate levels of testosterone below 50 ng/dL). |
| Time to PSA progression | Up to approximately 56 months | Time to PSA progression, defined as the time from randomization to PSA progression per PCWG3 criteria. |
| Time to deterioration in physical function (TTDPF) | Up to approximately 56 months | TTDPF is defined as the time from randomization to deterioration in PROMIS SF-PF scores. |
| Time to pain progression (TTPP) | Up to approximately 56 months | TTPP is defined as the time from randomization to clinically meaningful pain progression based on a 2-point increase from baseline in the BPI-SF Item 3 'worst pain in 24 hours' score and/or initiation of/increase in opioid analgesic use. |
| Brief Pain Inventory - Short Form (BPI-SF) | Up to approximately 56 months | Change from baseline in BPI-SF worst pain score, pain severity and interference domain scores. |
| Time to deterioration in urinary symptoms (TTDUS) | Up to approximately 56 months | TTDUS is defined as the time from randomization to deterioration in the EORTC QLQ-PR25(US) subscale scores. |
| Plasma concentrations of AZD5305 | Day 1 of Cycle 1, Cycle 2 and Cycle 3 (each cycle is of 28 days) | To assess PK of AZD5305 in plasma |
Countries
Canada
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed