Saruparib in Combination With Physician's Choice of ARPI in Patients With mHSPC Previously Treated With Docetaxel or 177Lu-PSMA Therapy Without Disease Progression and PSA ≥ 0.2 ng/mL (EvoPAR-PR05)

Официальное название

A Randomized, Double-Blind, Placebo-Controlled, 2-Cohort, Phase III Study of Saruparib Combined With Physician's Choice of Androgen Receptor Pathway Inhibitor in Patients With Metastatic Hormone-Sensitive Prostate Cancer, Previously Treated With Docetaxel or PSMA-directed 177Lutetium-Containing Therapy Without Disease Progression, and With Prostate-Specific Antigen ≥ 0.2 ng/mL: EvoPAR-Prostate05

Обзор

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.

Вмешательства

• Препарат Saruparib
  Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone)
• Другое Placebo
  Arm 2: Placebo + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone)
• Препарат Enzalutamide
  Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone) Arm 2: Placebo + Physician's Choice ARPI
• Препарат Darolutamide
  Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone) Arm 2: Placebo + Physician's Choice ARPI
• Препарат Abiraterone
  Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone) Arm 2: Placebo + Physician's Choice ARPI

Первичные конечные точки

• Radiographic progression-free survival (rPFS) [Срок оценки: Up to approximately 56 months]

Вторичные конечные точки (12)

• Overall Survival (OS) [Срок оценки: Up to approximately 80 months]
• Radiographic progression-free survival (rPFS) [Срок оценки: Up to approximately 56 months]
• Time to Second Progression or Death (PFS2) [Срок оценки: Up to approximately 56 months]
• Time to First Subsequent Therapy or Death (TFST) [Срок оценки: Up to approximately 56 months]
• Symptomatic Skeletal Event-free Survival (SSE-FS) [Срок оценки: Up to approximately 56 months]
• Time to Castration Resistance (TTCR) [Срок оценки: Up to approximately 56 months]
• Time to PSA progression [Срок оценки: Up to approximately 56 months]
• Time to deterioration in physical function (TTDPF) [Срок оценки: Up to approximately 56 months]
• Time to pain progression (TTPP) [Срок оценки: Up to approximately 56 months]
• Brief Pain Inventory - Short Form (BPI-SF) [Срок оценки: Up to approximately 56 months]
• Time to deterioration in urinary symptoms (TTDUS) [Срок оценки: Up to approximately 56 months]
• Plasma concentrations of AZD5305 [Срок оценки: Day 1 of Cycle 1, Cycle 2 and Cycle 3 (each cycle is of 28 days)]

Критерии участия

Критерии включения

• 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.
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Критерии исключения

• 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.
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Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Канада · 2 центра

• Research Site — Ottawa
• Research Site — Montreal

Идентификаторы

NCT: NCT07711002 · D972DC00001 · 2026-526275-38-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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