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

Not Applicable

Not yet recruiting

• Conditions: Pancreatic Adenocarcinoma

• Registration Number: NCT06743386
• Lead Sponsor: French Society of Digestive Endoscopy

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-16
• Study First Submitted QC: 2024-12-18
• Last Update Submitted: 2024-12-18
• Study First Posted: 2024-12-19
• Last Update Posted: 2024-12-19
• Study Start: 2025-01
• Primary Completion: 2027-08
• Study Completion: 2027-08

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 30

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).

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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).

  3. 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.

  4. 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.

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

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

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

  8. 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.

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

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

Secondary Outcome Measures

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