Prostate Androgen Response Investigation Using a Stratification BIOmarker; Predicting Prostate Cancer Downstaging by Neoadjuvant Darolutamide With PCAI ImmunoScore (PARIS-BIO)

Region Stockholm

Status and phase: Enrolling; Phase 2

Conditions: Prostate Cancer (Adenocarcinoma)

Treatments: Procedure: Radical prostatectomy; Drug: Darolutamide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07617272

5.1.1-2025-027483

2025-520639-17-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 100 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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100 participants in 1 patient group

Neoadjuvant Darolutamide

Experimental group

Description:

All participants receive Darolutamide 600 mg orally twice daily for 90-120 days prior to radical prostatectomy

Treatment:

Drug: Darolutamide

Procedure: Radical prostatectomy