EUS-guided Laser Ablation in Pancreatic Adenocarcinoma

Study Overview
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Brief Summary
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This study evaluates the possibility of performing local therapy for PDAC using laser ablation of the tumor under ultrasonography (EUS) guidance. Safety of the procedure as well as post procedural quality of life will be also evaluated.

Detailed Description
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Pancreatic adenocarcinoma (PDAC) is projected to be the second cause of cancer death in Western societies within a decade. Management include chemotherapy and/or radiation therapy, while resectable disease is possible only in 15% of cases. Despite these therapeutic approaches, the survival rate of unresectable pancreatic cancer remains disappointing. Recently, there is a growing interest in the development of alternative therapeutic approaches, which can work in parallel with standard chemoradiation therapy. These methods include intra-lesion injection/instillation of antitumoral agents performed through a laparoscopic approach, or percutaneously or under endoscopic ultrasound (EUS) guidance and tumor volume reduction procedures using ablative techniques. In this context laser ablation has been reported to be effective in inducing coagulative necrosis of the tumour in absence of major adverse events. However, the available studies on the matter are limited by small sample size, lack of extended follow up and informations about the possibility to ablate the entire tumour mass.

Official Title
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EUS-guided Laser Complete Ablation of Advanced Pancreatic Ductal Adenocarcinoma: a Feasibility Study

Conditions
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Pancreatic Adenocarcinoma, Pancreas Cancer

Intervention / Treatment
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* Device: EUS-guided laser ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological diagnosis of pancreatic ductal adenocarcinoma Unresectable advanced, non-metastatic Stage III tumor Stable disease without regression or progression after 6 months of chemotherapeutic treatment Locally progressive disease after chemiotherapy, without evidence of metastases Age >18 and <80 years Willing to be followed up c/o the Fondazione Policlinico A. Gemelli University Hospital Signed informed consent Exclusion Criteria: Stage I, Stage II, Stage IV disease Absolute contraindications to general anesthesia or deep sedation Absolute contraindications to perform digestive endoscopy Known bleeding disorder that cannot be sufficiently corrected with co-fact or fresh frozen plasma (FFP) Use of anticoagulants that cannot be discontinued International Normalized Ratio (INR) >1.5 or platelet count <50.000 Pregnancy or lactation Unable to sigh informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EUS-guided laser ablation<br>Laser ablation will be performed using a 1064-nm wavelength laser with the insertion of a 300-μm optical fiber through a 22-gauge needle under endoscopic ultrasonography guidance. | Device: EUS-guided laser ablation<br>* EUS-guided LA will be performed with an endoscopic ultrasound guided approach using a 1064-nm wavelength laser with the insertion of a 300-μm optical fiber through a 22-gauge flexible needle that is inserted in the working channel of the echoendoscope.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor necrosis induction by EUS-guided laser ablation (LA) - Number of patients with necrosis of the tumor | Number of patients with necrosis of the tumor, as demonstrated by the involution of the pancreatic mass on CT scan performed after one month from the treatment | at 1 month from the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of early and late adverse events after EUS-guided laser ablation (LA) | Percentage of early and late adverse events. Early adverse events will be those occurring during the procedure up to the first week after the ablation treatment. Late adverse events will be defined as any adverse event potentially related to the procedure occurring at the site of the primary tumor within 3 months after EUS LA treatment. Adverse events will be considered major if they prevent completion of the scheduled procedure and/or resulted in prolongation of hospital stay, another therapeutic procedure (needing sedation/anesthesia), or subsequent medical consultation. Any potential adverse event such as pancreatitis, burns of the gastric or duodenal walls, bowel injury, or peritonitis will be recorded and graded according to the above-mentioned classification. | at 7 days and 3 months from the intervention | 
| Disease response to EUS-guided laser ablation (LA) | Correlation between RNA markers evaluated by TaqMan RNA assay in serum and treatment response | From date of treatment, every 4 months, assessed until death or up to 2 years | 
| Post-procedural quality of life | Change from baseline in quality of life (QOL) scores after treatment evaluated by using the European Organization for Research and Treatment core quality of life questionnaire (EORTC QLQ-C30), version 3.0. EORTC QLQ-C30 questionnaire evaluates 5 functions physical,role,cognitive, emotional, and social), 9 symptoms (fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation, diarrhea, and financial difficulties) and the global health status. Questions regarding functions and symptoms are scored 1 to 4, with higher values representing a worse outcomes. Questions regarding global health status are scored 1 to 7, with higher values representing better outcomes. | From date of enrollment (baseline), every 2 months, assessed until death or up to 2 years | 
| Progression-free-survival (PFS) | PFS defined as the time from the date of trial entry until disease progression or relapse. | From date of enrollment assessed until death or up to 2 years | 
| Overall survival | Overall survival defined as the length of time (in days) between the treatment date and the date of death. | From date of enrollment assessed until death or up to 2 years |