Prostate Androgen Response Investigation Using a Stratification BIOmarker; Predicting Prostate Cancer Downstaging by Neoadjuvant Darolutamide With PCAI ImmunoScore (PARIS-BIO)
24 de mayo de 2026 actualizado por: 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.
Descripción general del estudio
Estado
Reclutamiento
Condiciones
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Intervencionista
Inscripción (Estimado)
100
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Estudio Contacto
- Nombre: Per H Vincent, MScEng, PhD
- Número de teléfono: +46(0)708239320
- Correo electrónico: per.vincent@regionstockholm.se
Copia de seguridad de contactos de estudio
- Nombre: Sara Göransson, PhD
- Número de teléfono: +46(0)812377000
- Correo electrónico: sara.goransson@regionstockholm.se
Ubicaciones de estudio
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Gothenburg, Suecia
- Reclutamiento
- Sahlgrenska University Hospital
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Contacto:
- Johan Stranne, MD, Professor
- Número de teléfono: +46(0)709558865
- Correo electrónico: johan.stranne@vgregion.se
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Investigador principal:
- Johan Stranne, MD, Professor
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Stockholm, Suecia, SE-17176
- Reclutamiento
- Karolinska University Hospital
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Contacto:
- Johan Björklund, MD, PhD
- Número de teléfono: +46(0)709583113
- Correo electrónico: johan.bjorklund@regionstockholm.se
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Contacto:
- Axel Möller, MD, PhD
- Número de teléfono: +46(0)706271734
- Correo electrónico: axel.moller@regionstockholm.se
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Investigador principal:
- Johan Björklund, MD, PhD
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
No
Descripción
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
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Otro
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Neoadjuvant Darolutamide
All participants receive Darolutamide 600 mg orally twice daily for 90-120 days prior to radical prostatectomy
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Neoadjuvant Darolutamide alone (without ADT) 2x300 mg orally twice daily is given to all study subjects for 90-120 days prior to prostatectomy.
Otros nombres:
Robot-assisted radical prostatectomy, with or without extirpation of pelvic lymph nodes according to clinician's choice in concordance with local guidelines
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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The association between the pre-treatment probability of treatment response given by PCAI ImmunoScore and the occurrence of minimal residual disease (MRD)
Periodo de tiempo: 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.
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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.
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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.
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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The association between PCAI ImmunoScore and pathologic complete response (pCR)
Periodo de tiempo: 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.
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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.
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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.
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Pathological T-stage (pT-stage)
Periodo de tiempo: Pathological T-stage will be ascertained shortly after radical prostatectomy (day 90-120)
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Staging of the tumor at final pathology
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Pathological T-stage will be ascertained shortly after radical prostatectomy (day 90-120)
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Residual tumor size
Periodo de tiempo: At the time of radical prostatectomy (day 90-120)
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Measurement of the largest cross-sectional dimensions (mm) of residual tumor
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At the time of radical prostatectomy (day 90-120)
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PSA Kinetics
Periodo de tiempo: Baseline, Day 30, Day 60, Day 90, and within 4 weeks after surgery
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Change in blood PSA concentration (ng/ml) during treatment
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Baseline, Day 30, Day 60, Day 90, and within 4 weeks after surgery
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Hormonal side effects
Periodo de tiempo: From baseline up to 12 months post-surgery
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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
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From baseline up to 12 months post-surgery
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Patient-reported urinary continence
Periodo de tiempo: Pre-surgery (day 80-119), 3 months post-surgery, 12 months post-surgery
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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
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Patient-reported erectile function
Periodo de tiempo: Pre-surgery (day 80-119), 3 months post-surgery, 12 months post-surgery
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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
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MRI tumor response
Periodo de tiempo: Pre-surgery (day 90-120)
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Change in tumor size and Extraprostatic Extension (EPE) score (Likert scale 1-5) on MRI compared to baseline MRI
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Pre-surgery (day 90-120)
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Peter N Wiklund, MD, Professor, Region Stockholm represented by Karolinska University Hospital
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
9 de noviembre de 2025
Finalización primaria (Estimado)
1 de junio de 2027
Finalización del estudio (Estimado)
1 de diciembre de 2030
Fechas de registro del estudio
Enviado por primera vez
12 de diciembre de 2025
Primero enviado que cumplió con los criterios de control de calidad
24 de mayo de 2026
Publicado por primera vez (Actual)
1 de junio de 2026
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
1 de junio de 2026
Última actualización enviada que cumplió con los criterios de control de calidad
24 de mayo de 2026
Última verificación
1 de noviembre de 2025
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades urogenitales
- Enfermedades Genitales
- Neoplasias Genitales Masculinas
- Neoplasias urogenitales
- Neoplasias por sitio
- Neoplasias
- Enfermedades Genitales Masculinas
- Enfermedades prostáticas
- Enfermedades urogenitales masculinas
- Neoplasias por tipo histológico
- Neoplasias Glandulares y Epiteliales
- Carcinoma
- Neoplasias prostáticas
- Adenocarcinoma
- darolutamida
Otros números de identificación del estudio
- 5.1.1-2025-027483
- 2025-520639-17-00 (Ctis)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
NO
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
producto fabricado y exportado desde los EE. UU.
No
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