A Trial Using Transcriptomic Signatures to Personalize Neoadjuvant Chemotherapy (NAC) for Patients With Resectable Borderline Pancreatic Adenocarcinoma (PDAC) (PRODIGE 104 B)
A Multicenter Randomized Phase II Trial Using Transcriptomic Signatures to Personalize Neoadjuvant Chemotherapy (NAC) for Patients With Resectable Borderline Pancreatic Adenocarcinoma (PDAC)
Pancreatic cancer exhibits significant heterogeneity, which poses a major challenge in selecting the best treatment for patients from the very beginning of care. Modern oncology recognizes the use of companion biomarkers to guide targeted therapy or immune checkpoint inhibitors. However, with regard to chemotherapy-which has long been the cornerstone of cancer treatment and remains crucial for most cancers-few predictive tests are available to guide the choice between monotherapy and combination chemotherapy.
Patients included in the PRODIGE 104 B - NEOPREDICT study will be those for whom the GEM transcriptomic signature is negative. This population will be treated according to the standard strategy and will be followed clinically and biologically to describe and identify the characteristics specific to this subgroup, and to compare the usual prognostic factors of this population with those of the GEM-positive population included in the parallel PRODIGE 104 A - NEOPREDICT study
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
Transcriptomic Signature for Patient Stratification and Prediction of Chemotherapy Sensitivity Transcriptomic signatures, derived from RNA-sequencing, capture unique patterns of gene expression that reflect the molecular phenotype of a tumor and can indicate its potential sensitivity or resistance to chemotherapeutic agents. Over the past decade, several molecular classifications of PDAC have been established (Collisson, Moffitt, Bailey), consistently distinguishing two major tumor subtypes: basal-like (poor prognosis) and classical (better prognosis). While these classifications provide strong prognostic information, they have not reliably predicted chemotherapy response in clinical practice.
Recent advances from the Dusetti/Iovanna research group have led to the development of robust transcriptomic signatures capable of predicting sensitivity to gemcitabine, irinotecan, 5-FU, oxaliplatin, and paclitaxel. These signatures-collectively referred to as Pancreas-View-were generated using preclinical models (PDX, organoids, primary cultures) and have been clinically validated, notably the gemcitabine-sensitivity signature in two retrospective cohorts and in the prospective PRODIGE 24 trial. Importantly, these signatures can be performed on FFPE-derived RNA with minimal material and rapid turnaround, making them compatible with real-world decision-making in the neoadjuvant setting.
Position of the Study Within Current Knowledge Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease due to late diagnosis, limited actionable biomarkers, and the modest efficacy of targeted and immunotherapeutic approaches. Its incidence is rising in Western countries, and without improved strategies, PDAC is projected to become the second leading cause of cancer-related death by 2040.
Borderline-resectable PDAC accounts for approximately 20% of cases and typically requires complex multidisciplinary management. Neoadjuvant chemotherapy (NAC)-now an international standard in BR-PDAC-offers several advantages: improved R0 resection rates, treatment of occult micrometastatic disease, and avoidance of futile surgery in rapidly progressing tumors.
Two main NAC regimens are currently used: mFOLFIRINOX and Gemcitabine + Nab-Paclitaxel. However, comparative studies in non-metastatic PDAC have not demonstrated a clear superiority of one regimen over the other, though their toxicity profiles differ substantially. As a result, selecting the optimal chemotherapy strategy remains challenging.
There is therefore a strong need for predictive biomarkers capable of guiding neoadjuvant regimen selection. The NEOPREDICT program positions itself directly within this unmet clinical need, evaluating the use of a transcriptomic gemcitabine-sensitivity signature to personalize treatment.
Tipo de estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: PAKRADOUNI
- Número de teléfono: +33 4 91 22 37 78
- Correo electrónico: drci.up@ipc.unicancer.fr
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- Borderline-resectable pancreatic ductal adenocarcinoma (BR-PDAC) as defined by the National Comprehensive Cancer Network (NCCN) v2.2025 criteria, identified on contrast-enhanced CT scan and reviewed by a local multidisciplinary pancreatic expert board including at least a medical oncologist / onco-gastroenterologist, a pancreatic surgeon, and an expert pancreatic radiologist. No central review required.
- WHO Performance Status 0-1.
- Histologically confirmed pancreatic ductal adenocarcinoma, including histological variants.
- Patient included-but not randomized-in the PRODIGE 104 A NEOPREDICT study due to a negative gemcitabine sensitivity signature (GEM-).
- Negative gemcitabine transcriptomic signature (test centrally performed in PRODIGE 104 A NEOPREDICT).
- No prior chemotherapy or radiotherapy for pancreatic cancer, and no previous definitive pancreatic cancer resection (except one cycle of mFOLFIRINOX administered while awaiting the signature result).
- Age > 18 years and < 80 years, with the possibility to include patients aged 75-80 if a standardized geriatric assessment confirms eligibility for the study chemotherapy regimen.
- Ability and willingness to comply with protocol requirements during the entire study period (treatment, scheduled visits, clinical and biological examinations, follow-up).
- Patient's non-opposition to participation in the study.
- Affiliation to the French national health insurance system.
Exclusion Criteria:
- Strictly resectable or locally advanced PDAC according to NCCN criteria.
- Distant metastases, including inter-aortocaval lymph nodes.
- Any condition contraindicating the use of irinotecan, oxaliplatin, or 5-FU.
- Complete dihydropyrimidine dehydrogenase (DPD) deficiency.
- Any uncontrolled or unstable medical condition within the past 6 months (e.g., hepatic, renal, respiratory, or cardiac insufficiency).
- Another concomitant malignancy or history of cancer within the past 3 years, except for adequately treated carcinoma in situ of the cervix or basal/squamous cell skin carcinoma.
- Pregnancy or breastfeeding.
- Patients under legal protection, guardianship, curatorship, or under judicial/administrative protection.
- Patients receiving psychiatric care or unable to provide consent.
- Inability to comply with medical follow-up for geographical, social, or psychological reasons.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- 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: single arm - mFOLFIRINOX
Patients GEM- with BR-PDAC receiving standard mFOLFIRINOX according to clinical guidelines.
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Patients with borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) who are negative for the gemcitabine sensitivity transcriptomic signature (GEM-) receive neoadjuvant mFOLFIRINOX chemotherapy as standard of care.
This observational cohort follows patients prospectively without modifying routine management.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Primary Outcome Measure
Periodo de tiempo: From treatment initiation through 1 year
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Event-Free Survival is defined as the time from the start of treatment to the occurrence of any of the following events:
Participants without an event will be censored at the date of last follow-up. |
From treatment initiation through 1 year
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Objective Response Rate (ORR)
Periodo de tiempo: During neoadjuvant chemotherapy (up to 16 weeks)
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Percentage of participants achieving a complete response or partial response per RECIST 1.1 criteria.
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During neoadjuvant chemotherapy (up to 16 weeks)
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Overall Survival (OS)
Periodo de tiempo: From treatment initiation through study completion (up to 18 months)
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Time from start of treatment to death from any cause.
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From treatment initiation through study completion (up to 18 months)
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Progression-Free Survival (PFS)
Periodo de tiempo: From treatment initiation through study completion (up to 18 months)
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For non-operated patients: time from treatment initiation to disease progression or death from any cause.
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From treatment initiation through study completion (up to 18 months)
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Recurrence-Free Survival (RFS)
Periodo de tiempo: From treatment initiation through study completion (up to 18 months)
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For operated patients: time from treatment initiation to first local or metastatic recurrence or death.
|
From treatment initiation through study completion (up to 18 months)
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Disease Control Rate (DCR)
Periodo de tiempo: During neoadjuvant chemotherapy (up to 16 weeks)
|
Percentage of patients achieving complete response, partial response, or stable disease.
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During neoadjuvant chemotherapy (up to 16 weeks)
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Tumor Regression Grade (TRG)
Periodo de tiempo: At time of surgery
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Pathologic tumor response assessed using Ryan's simplified Tumor Regression Grade (TRG 1-3) on the resected primary tumor.
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At time of surgery
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Postoperative Complications (Clavien-Dindo Classification)
Periodo de tiempo: Within 60 days after surgery
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Postoperative complications graded from I to V according to Clavien-Dindo.
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Within 60 days after surgery
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Time to Recurrence (TTR)
Periodo de tiempo: Up to 18 months
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Time from treatment initiation to first recurrence (local or metastatic) or death related to cancer.
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Up to 18 months
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Quality of Life (EORTC QLQ-C30 )
Periodo de tiempo: From baseline through study completion (up to 18 months)
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Change over time in the Global Health Status/Quality of Life scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30).
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From baseline through study completion (up to 18 months)
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Completion Rate of Neoadjuvant Chemotherapy (NAC)
Periodo de tiempo: End of the 4-month NAC period
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Percentage of participants who completed all 8 cycles of mFOLFIRINOX (regardless of dose modifications).
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End of the 4-month NAC period
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Adverse Events and Toxicities (NCI-CTCAE v5.0)
Periodo de tiempo: Before each chemotherapy cycle (Weeks 0-16)
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Incidence and severity of treatment-related toxicities graded according to NCI-CTCAE v5.0.
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Before each chemotherapy cycle (Weeks 0-16)
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ime to First Deterioration in Global Health Status
Periodo de tiempo: From treatment initiation through study completion (up to 18 months)
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Time to first deterioration of more than 5 points from baseline in the EORTC QLQ-C30 global health status score.
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From treatment initiation through study completion (up to 18 months)
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Pancreatic Cancer-Specific Quality of Life (EORTC QLQ-PAN26)
Periodo de tiempo: From baseline through study completion (up to 18 months)
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Change over time in symptom and functional scores assessed using the EORTC QLQ-PAN26 pancreatic
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From baseline through study completion (up to 18 months)
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Otros números de identificación del estudio
- PRODIGE 104 B-NEOPREDICT-IPC 2
Plan de datos de participantes individuales (IPD)
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Información sobre medicamentos y dispositivos, documentos del estudio
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