Prostate Androgen Response Investigation Using a Stratification BIOmarker; Predicting Prostate Cancer Downstaging by Neoadjuvant Darolutamide With PCAI ImmunoScore

Официальное название

PARIS-BIO - Prostate Androgen Response Investigation Using a Stratification BIOmarker; Predicting Prostate Cancer Downstaging by Neoadjuvant Darolutamide With PCAI ImmunoScore in a Non-randomised Open Label Prospective Trial

Обзор

The PARIS-BIO study evaluates whether a novel genomic biomarker, the PCAI ImmunoScore, can predict the response to neoadjuvant treatment with Darolutamide in patients with high-risk localized or locally advanced prostate cancer. Patients will receive Darolutamide monotherapy for 90-120 days prior to radical prostatectomy. The study aims to validate if the biomarker can identify patients who achieve Minimal Residual Disease (MRD) at the time of surgery.

Подробное описание

High-risk prostate cancer patients are at risk for recurrence after local therapy. The presence of micro-metastatic disease, undetectable by conventional imaging, likely contributes to the poor prognosis. Neoadjuvant hormonal therapy, particularly with the advent of ARPIs like Darolutamide, has shown promise, but patient selection remains crucial for optimizing outcomes. This Phase II, single-arm, open-label trial investigates the predictive value of the PCAI ImmunoScore, a gene expression signature derived from diagnostic biopsies.

100 participants with high-risk prostate cancer scheduled for radical prostatectomy will be enrolled. They will receive Darolutamide (600 mg twice daily) for a period of 90 to 120 days. MRI imaging will be performed between day 90 and 120 prior to surgery. Radical prostatectomy is performed within the same window.

The primary analysis compares the pre-treatment biomarker score with the pathological response (Minimal Residual Disease) observed in the surgical specimen. Secondary analyses include MRI response, PSA kinetics, and patient-reported functional outcomes.

Вмешательства

• Препарат Darolutamide
  Neoadjuvant Darolutamide alone (without ADT) 2x300 mg orally twice daily is given to all study subjects for 90-120 days prior to prostatectomy.
• Процедура Radical prostatectomy
  Robot-assisted radical prostatectomy, with or without extirpation of pelvic lymph nodes according to clinician's choice in concordance with local guidelines

Первичные конечные точки

• The association between the pre-treatment probability of treatment response given by PCAI ImmunoScore and the occurrence of minimal residual disease (MRD) [Срок оценки: MRD is ascertained shortly after radical prostatectomy (day 90-120). PCAI ImmunoScore will be ascertained after bulk sequencing of all samples, tentatively 1 year after surgery of the 100th study subject. The association will be calculated thereafter.]

Вторичные конечные точки (8)

• The association between PCAI ImmunoScore and pathologic complete response (pCR) [Срок оценки: pCR is ascertained shortly after radical prostatectomy (day 90-120). PCAI ImmunoScore will be ascertained after bulk sequencing of all samples, tentatively 1 year after surgery of the 100th study subject. The association will be calculated thereafter.]
• Pathological T-stage (pT-stage) [Срок оценки: Pathological T-stage will be ascertained shortly after radical prostatectomy (day 90-120)]
• Residual tumor size [Срок оценки: At the time of radical prostatectomy (day 90-120)]
• PSA Kinetics [Срок оценки: Baseline, Day 30, Day 60, Day 90, and within 4 weeks after surgery]
• Hormonal side effects [Срок оценки: From baseline up to 12 months post-surgery]
• Patient-reported urinary continence [Срок оценки: Pre-surgery (day 80-119), 3 months post-surgery, 12 months post-surgery]
• Patient-reported erectile function [Срок оценки: Pre-surgery (day 80-119), 3 months post-surgery, 12 months post-surgery]
• MRI tumor response [Срок оценки: Pre-surgery (day 90-120)]

Критерии участия

Критерии включения

• Biopsy-confirmed high-risk prostate cancer defined as: Global ISUP score > 3 with any MRI PI-RADS score OR Global ISUP score = 3 with MRI PI-RADS score = 5
• Candidate for radical prostatectomy
• Clinical prostate MRI not older than 3 months at screening
• ECOG performance status score of 0 or 1
• Able to receive Darolutamide for 90-120 days
• Signed informed consent form
• Willingness to use contraception if sexually active

Критерии исключения

• Metastatic (M1) or node-positive (N2) disease
• Prior treatment with androgen receptor antagonists
• Prior treatment with gonadotropin-releasing hormone (GnRH)
• History of prior systemic or local therapy for prostate cancer (including radiation and focal therapy)
• Major surgery <4 weeks prior to inclusion

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Другое

Центры проведения

Швеция · 2 центра

• Sahlgrenska University Hospital — Gothenburg
• Karolinska University Hospital — Stockholm

Идентификаторы

NCT: NCT07617272 · 5.1.1-2025-027483 · 2025-520639-17-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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