Deze pagina is automatisch vertaald en de nauwkeurigheid van de vertaling kan niet worden gegarandeerd. Raadpleeg de Engelse versie voor een brontekst.

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

24 mei 2026 bijgewerkt door: Region Stockholm

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

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.

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Geschat)

100

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Contact Back-up

Studie Locaties

  • Zweden
      • Gothenburg, Zweden
        • Werving
        • Sahlgrenska University Hospital
        • Contact:
        • Hoofdonderzoeker:
          • Johan Stranne, MD, Professor
      • Stockholm, Zweden, SE-17176

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Ander
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Neoadjuvant Darolutamide
All participants receive Darolutamide 600 mg orally twice daily for 90-120 days prior to radical prostatectomy
Geneesmiddel: Darolutamide
Neoadjuvant Darolutamide alone (without ADT) 2x300 mg orally twice daily is given to all study subjects for 90-120 days prior to prostatectomy.
Andere namen:
  • Nubeqa
  • Neoadjuvant ARPI
Procedure: Radical prostatectomy
Robot-assisted radical prostatectomy, with or without extirpation of pelvic lymph nodes according to clinician's choice in concordance with local guidelines
Andere namen:
  • RALP
  • RARP
  • Robot-assisted prostatectomy

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
The association between the pre-treatment probability of treatment response given by PCAI ImmunoScore and the occurrence of minimal residual disease (MRD)
Tijdsspanne: 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.
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.

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
The association between PCAI ImmunoScore and pathologic complete response (pCR)
Tijdsspanne: 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.
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)
Tijdsspanne: Pathological T-stage will be ascertained shortly after radical prostatectomy (day 90-120)
Staging of the tumor at final pathology
Pathological T-stage will be ascertained shortly after radical prostatectomy (day 90-120)
Residual tumor size
Tijdsspanne: At the time of radical prostatectomy (day 90-120)
Measurement of the largest cross-sectional dimensions (mm) of residual tumor
At the time of radical prostatectomy (day 90-120)
PSA Kinetics
Tijdsspanne: Baseline, Day 30, Day 60, Day 90, and within 4 weeks after surgery
Change in blood PSA concentration (ng/ml) during treatment
Baseline, Day 30, Day 60, Day 90, and within 4 weeks after surgery
Hormonal side effects
Tijdsspanne: 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
From baseline up to 12 months post-surgery
Patient-reported urinary continence
Tijdsspanne: 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
Pre-surgery (day 80-119), 3 months post-surgery, 12 months post-surgery
Patient-reported erectile function
Tijdsspanne: 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
Pre-surgery (day 80-119), 3 months post-surgery, 12 months post-surgery
MRI tumor response
Tijdsspanne: Pre-surgery (day 90-120)
Change in tumor size and Extraprostatic Extension (EPE) score (Likert scale 1-5) on MRI compared to baseline MRI
Pre-surgery (day 90-120)

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Region Stockholm

Medewerkers

Bayer
Sahlgrenska University Hospital
Philips Intellectual Property & Standards
OHMX.bio
Innovative Health Initiative - European Union

Onderzoekers

  • Hoofdonderzoeker: Peter N Wiklund, MD, Professor, Region Stockholm represented by Karolinska University Hospital

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

9 november 2025

Primaire voltooiing (Geschat)

1 juni 2027

Studie voltooiing (Geschat)

1 december 2030

Studieregistratiedata

Eerst ingediend

12 december 2025

Eerst ingediend dat voldeed aan de QC-criteria

24 mei 2026

Eerst geplaatst (Werkelijk)

1 juni 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

1 juni 2026

Laatste update ingediend die voldeed aan QC-criteria

24 mei 2026

Laatst geverifieerd

1 november 2025

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 5.1.1-2025-027483
  • 2025-520639-17-00 (Ctis)

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

product vervaardigd in en geëxporteerd uit de V.S.

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

Abonneren