Pilot Study of EUS-Guided Radiofrequency and FOLFIRINOX in Advanced Pancreatic Cancer (RadioFAP ) (RadioFAP)

Pilot Study Evaluating the Combination of Endoscopic Ultrasound-Guided Radiofrequency and FOLFIRINOX in Locally Advanced Pancreatic Cancer

Pancreatic adenocarcinoma (PDAC) constitutes 90% of pancreatic tumors and is projected to become the second leading cause of cancer-related mortality in Europe by 2030. In France, its incidence doubled in men and tripled in women between 1982 and 2012. PDAC remains the digestive cancer with the poorest prognosis, with a five-year overall survival rate below 10% across all stages. Only surgical management with R0 resection (surgical margins free of cancer cells) offers a chance for cure or prolonged survival. However, surgery is feasible in only 15% of patients, as the disease is typically diagnosed at a late stage-locally advanced in 35% of cases or metastatic in 50%. Chemotherapy, specifically FOLFIRINOX, is the standard treatment for advanced cases, but resistance to chemotherapy poses a significant challenge. A key contributor to this resistance is the tumor stroma, which constitutes most of the tumor mass. This fibrous tissue acts as a mechanical barrier, restricting blood flow and potentially limiting the delivery of chemotherapy to cancer cells. The development of endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has shown promise in treating pancreatic neuroendocrine tumors (pNETs) and pancreatic cystic neoplasms, sparking interest in its potential for PDAC. Preliminary studies demonstrate the feasibility of radiofrequency in PDAC, showing increased blood flow around treated sites. Combining systemic chemotherapy with radiofrequency may enhance drug diffusion and improve treatment efficacy. Additionally, tumor thermoablation could stimulate an immune response, as observed in experimental and clinical research. This study aims to evaluate the feasibility of tumor destruction via radiofrequency ablation combined with FOLFIRINOX in improving progression-free survival for patients with PDAC.

Study Overview

• Status: Not yet recruiting
• Conditions: Pancreatic Adenocarcinoma
• Intervention / Treatment: Device: Therapeutic procedure combines EUS-Guided Radiofrequency Ablation (RFA)

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients over the age of 18
2. Patients with locally advanced, borderline resectable, or inoperable pancreatic adenocarcinoma, confirmed by histological or cytological tests and assessed through a multidisciplinary consultation.
3. Patients without evidence of metastases.
4. No prior anti-tumoral treatment.
5. World Health Organization (WHO) performance status ≤ 1.
6. Measurable tumor according to the RECIST v1.1 criteria: a tumor lesion with the largest diameter ≥ 20 mm using conventional imaging techniques or ≥ 10 mm using spiral CT scan.
7. Patient who has provided written consent.
8. Patient with no contraindications to general anesthesia.
9. Pancreatic tumor accessible via endoscopic ultrasound.
10. Patient enrolled in a social security program (beneficiary or dependent).

Exclusion Criteria:

• 1. Other types of non-ductal or solid pancreatic tumors, including endocrine tumors, acinar cell adenocarcinoma, cystadenocarcinoma, and malignant ampullary tumors.

  2. Presence of metastases. 3. Contraindication to treatment with 5FU, oxaliplatin, or irinotecan. 4. Patients with a tumor that could benefit from neoadjuvant treatment with radiochemotherapy or chemotherapy alone for secondary resection (decision by a multidisciplinary committee).

  5. Pre-existing neuropathy, Gilbert's disease, or known UGT1A1*28/*28 genotype. 6. Chronic inflammatory bowel disease. 7. Other concurrent cancers, or a history of cancer within the last 5 years, except for in situ cervical cancer that has been treated or a properly treated basal cell carcinoma or squamous cell carcinoma.

  8. Hereditary intolerance to fructose. 9. Individuals deprived of liberty or under guardianship. 10. Inability to follow up with the study due to geographical, social, or psychological reasons.

  11. Contraindication to echo-endoscopy-guided cytopuncture (coagulation disorders or previously operated stomach).

  12. Neutrophil count < 1500/mm³. 13. Platelet count < 70,000/mm³. 14. Patients are not effectively treated for neoplastic jaundice if present at diagnosis.

  15. Patient in an exclusion period or currently participating in another clinical research protocol.

  16. Patients are unable to understand or read the information/consent form. 17. Pregnant women or those wishing to become pregnant during the study period, or breastfeeding women.

  18. Patients with implanted pacemakers or implantable cardioverter-defibrillators (ICDs).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: EUS-Guided Radiofrequency Ablation (RFA); Therapeutic procedure that combines endoscopic ultrasound (EUS) with radiofrequency ablation technology according to the practices of the investigating center

Device: Therapeutic procedure combines EUS-Guided Radiofrequency Ablation (RFA); It will be performed under general anesthesia with intubation, using a sectorial probe echoendoscope to target pancreatic tumors. Prophylactic measures, including intrarectal Diclofenac and antibiotics, are used to prevent complications. A high-frequency monopolar electrode needle is inserted into the lesion under ultrasound guidance, avoiding critical structures like pancreatic and biliary ducts. Energy is delivered until specific safety parameters are met, with multiple applications to maximize tumor coverage. RFA sessions are scheduled before, midway, and after chemotherapy cycles, and progress is monitored with routine imaging. Post-procedure care includes fasting, pain management, and standard blood tests. Patients are typically discharged the day after the procedure if no complications occur. Further treatment plans, including continuation or modification of chemotherapy and RFA, are determined based on disease progression observed in follow-up scans.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The success rate of tumor destruction achieved using radiofrequency ablation (RFA) with a radiofrequency needle guided by endoscopic ultrasound (EUS), in combination with chemotherapy.	This rate will be defined as the ratio of satisfactory deliveries (without serious adverse events) to the total number of deliveries performed	2, 6, 9, 12, and18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival:	The time interval between the date of enrollment in the study and the point at which the disease progresses	2, 6, 9, 12, and18 months
Impact of radiofrequency tumor ablation combined with FOLFIRINOX on overall survival	Measured from study enrollment to date of death, regardless of cause	2, 6, 9, 12, and18 months
Impact of radiofrequency tumor ablation with FOLFIRINOX on quality of life	Assessed using the EORTC QLQ-C30 questionnaire	2, 6, 9, 12, and 18 months
Effect of radiofrequency ablation combined with FOLFIRINOX on secondary resectability	Assessed through regular CT scans (RECIST 1.1) to determine if initially unresectable tumors become resectable after RFA treatment	2, 6, 9, 12, and18 months
Pancreatic intratumoral radiofrequency technical success	Defined as successful EUS-RFA execution, including needle insertion and ablation feasibility	14 days before chemotherapy and at 2 and 4 months post-treatment.
RFA tolerance	Defined as the ratio of adverse events (AEs) to the total number of patients who underwent EUS-RFA	14 days before chemotherapy and at 2 and 4 months post-treatment.

Collaborators and Investigators

• Sponsor: French Society of Digestive Endoscopy

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: December 16, 2024
• First Submitted That Met QC Criteria: December 18, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: EUS-Guided Radiofrequency Ablation (RFA); Pancreatic Tumor Ablation; Minimally Invasive Tumor Treatment
• Other Study ID Numbers: SFED-159

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No