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NCT Number: NCT07617272

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

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.

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Key information

Conditions

Prostate Cancer (Adenocarcinoma) Adenocarcinoma Carcinoma Genital Diseases Genital Diseases, Male Genital Neoplasms, Male Male Urogenital Diseases Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Prostatic Diseases Prostatic Neoplasms Urogenital Diseases Urogenital Neoplasms

Age range

18 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2

Primary location

Sahlgrenska University Hospital, Gothenburg, Sweden

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Darolutamide

Drug

Neoadjuvant Darolutamide alone (without ADT) 2x300 mg orally twice daily is given to all study subjects for 90-120 days prior to prostatectomy.

Other names: Neoadjuvant ARPI, Nubeqa

radical prostatectomy

Procedure

Robot-assisted radical prostatectomy, with or without extirpation of pelvic lymph nodes according to clinician's choice in concordance with local guidelines

Other names: RALP, RARP, Robot-assisted prostatectomy

Primary outcomes

  1. The association between the pre-treatment probability of treatment response given by PCAI ImmunoScore and the occurrence of minimal residual disease (MRD)

    Time frame: 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.

    The primary outcome is the association between the pre-treatment PCAI ImmunoScore and the occurrence of minimal residual disease (MRD) after 90-120 days of neoadjuvant Darolutamide treatment. MRD is defined as < 0.05 cm3 residual tumour on final pathology after prostatectomy. The study endpoint MRD will be dichotomized into responder (if MRD is met) or non-responder (if MRD is not met) as input for the statistical data analysis. This classification (ground truth) will be tested in AUROC analysis against the calculated PCAI ImmunoScore-based probability p (0<p<1) of Darolutamide response. PCAI ImmunScore is calculated from RNA sequencing of tumor material from diagnostic (pre-treatment) biopsies. The collection of RNA and calculation of PCAI ImmunoScore will take place after the recruitment period. Sequencing will be performed in bulk once all samples have been collected. The objective is to assess the predictive value of the pre-treatment genomic biomarker for pathological response.

Secondary outcomes

  1. The association between PCAI ImmunoScore and pathologic complete response (pCR)

    Time frame: 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.

    The study endpoint pCR is defined as no residual tumour visible at final pathology and will be dichotomized into responder (if pCR is met) or non-responder (if pCR is not met) as input for the statistical data analysis. This classification (ground truth) will be tested in AUROC analysis against the calculated PCAI ImmunoScore-based probability p (0<p<1) (baseline model) of Darolutamide response. The extended model including the additional covariates will be tested equivalent to the baseline model.

  2. Pathological T-stage (pT-stage)

    Time frame: Pathological T-stage will be ascertained shortly after radical prostatectomy (day 90-120)

    Staging of the tumor at final pathology

  3. Residual tumor size

    Time frame: At the time of radical prostatectomy (day 90-120)

    Measurement of the largest cross-sectional dimensions (mm) of residual tumor

  4. PSA Kinetics

    Time frame: Baseline, Day 30, Day 60, Day 90, and within 4 weeks after surgery

    Change in blood PSA concentration (ng/ml) during treatment

  5. Hormonal side effects

    Time frame: From baseline up to 12 months post-surgery

    Incidence and severity of adverse events assessed by CTCAE v5.0 and patient-reported quality-of-life using the 26-question questionnaire Expanded Prostate cancer Index Composite (EPIC-26), where lower scores indicate worse outcome

  6. Patient-reported urinary continence

    Time frame: Pre-surgery (day 80-119), 3 months post-surgery, 12 months post-surgery

    Assessment of pre-and post-treatment urinary function using the Swedish national questionnaires (electronic patient-reported outcome measurements -ePROM "Symtom- och biverkningsenkät" that all patients undergoing prostate cancer treatment in Sweden routinely are invited to answer), where urinary continence is assessed using the question "How many protective pads do you use daily due to urine leakage?" The reply alternatives are:

    None Fewer than 1 per day About 1 per day About 2 per day About 3-4 per day About 5 or more per day

  7. Patient-reported erectile function

    Time frame: Pre-surgery (day 80-119), 3 months post-surgery, 12 months post-surgery

    Assessment of pre-and post-treatment erectile function using the Swedish national questionnaires (electronic patient-reported outcome measurements -ePROM "Symtom- och biverkningsenkät" that all patients undergoing prostate cancer treatment in Sweden routinely are invited to answer), where erectile function is assessed using the question "How would you describe your erection?" The reply alternatives are:

    No noticeable filling or firmness Some filling, but not sufficient for full function Moderate firmness Full firmness

  8. MRI tumor response

    Time frame: Pre-surgery (day 90-120)

    Change in tumor size and Extraprostatic Extension (EPE) score (Likert scale 1-5) on MRI compared to baseline MRI

Study contacts

Contact information is provided by the study sponsor or research team.

Per H Vincent, MScEng, PhD

CONTACT

[email protected]

+46(0)708239320

Sara Göransson, PhD

CONTACT

[email protected]

+46(0)812377000

Sponsors and collaborators

Lead sponsor

Region Stockholm

Other Gov

Collaborators

  • Bayer
  • European Union
  • OHMX.bio
  • Philips Intellectual Property & Standards
  • Sahlgrenska University Hospital

Registry information

Official study title

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

Acronym: PARIS-BIO

Important dates

Study start
2025
Primary completion
2027
Study completion
2030
First posted
Jun 1, 2026
Registry last updated
Jun 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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