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.
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
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)
Single group
Darolutamide
DrugNeoadjuvant Darolutamide alone (without ADT) 2x300 mg orally twice daily is given to all study subjects for 90-120 days prior to prostatectomy.
Radical prostatectomy
Procedure/SurgeryRobot-assisted radical prostatectomy, with or without extirpation of pelvic lymph nodes according to clinician's choice in concordance with local guidelines
The association between the pre-treatment probability of treatment response given by PCAI ImmunoScore and the occurrence of minimal residual disease (MRD)
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.
The association between PCAI ImmunoScore and pathologic complete response (pCR)
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.
Pathological T-stage (pT-stage)
Staging of the tumor at final pathology
Residual tumor size
Measurement of the largest cross-sectional dimensions (mm) of residual tumor
PSA Kinetics
Change in blood PSA concentration (ng/ml) during treatment
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Region Stockholm
Lead sponsor
Sahlgrenska University Hospital
Collaborator
Philips Intellectual Property & Standards
Collaborator
OHMX.bio
Collaborator
Innovative Health Initiative - European Union
Collaborator
Bayer
Collaborator
