EUS-guided Laser Ablation in Pancreatic Adenocarcinoma

Pancreas Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03784417
• Other study ID #: EUS-LASER
• Status: Terminated
• Phase: N/A
• Start date: October 15, 2019
• Est. completion date: December 15, 2021

Study information

• Verified date: February 2022
• Source: Catholic University of the Sacred Heart
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: December 15, 2021
• Est. primary completion date: December 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreas Cancer
• Pancreatic Adenocarcinoma
• Pancreatic Neoplasms

Intervention

Device:
• EUS-guided laser ablation
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.

Locations

Country	Name	City	State
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Roma	RM
Italy	Universita' Cattolica del Sacro Cuore	Rome

Sponsors (1)

Lead Sponsor	Collaborator
Catholic University of the Sacred Heart

Country where clinical trial is conducted

Italy, 

References & Publications (14)

Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993 Mar 3;85(5):365-76. — View Citation

Carrara S, Arcidiacono PG, Albarello L, Addis A, Enderle MD, Boemo C, Campagnol M, Ambrosi A, Doglioni C, Testoni PA. Endoscopic ultrasound-guided application of a new hybrid cryotherm probe in porcine pancreas: a preliminary study. Endoscopy. 2008 Apr;40(4):321-6. doi: 10.1055/s-2007-995595. — View Citation

Di Matteo F, Martino M, Rea R, Pandolfi M, Rabitti C, Masselli GM, Silvestri S, Pacella CM, Papini E, Panzera F, Valeri S, Coppola R, Costamagna G. EUS-guided Nd:YAG laser ablation of normal pancreatic tissue: a pilot study in a pig model. Gastrointest Endosc. 2010 Aug;72(2):358-63. doi: 10.1016/j.gie.2010.02.027. Epub 2010 Jun 11. — View Citation

Di Matteo F, Picconi F, Martino M, Pandolfi M, Pacella CM, Schena E, Costamagna G. Endoscopic ultrasound-guided Nd:YAG laser ablation of recurrent pancreatic neuroendocrine tumor: a promising revolution? Endoscopy. 2014;46 Suppl 1 UCTN:E380-1. doi: 10.1055/s-0034-1377376. Epub 2014 Sep 25. — View Citation

Di Matteo FM, Saccomandi P, Martino M, Pandolfi M, Pizzicannella M, Balassone V, Schena E, Pacella CM, Silvestri S, Costamagna G. Feasibility of EUS-guided Nd:YAG laser ablation of unresectable pancreatic adenocarcinoma. Gastrointest Endosc. 2018 Jul;88(1):168-174.e1. doi: 10.1016/j.gie.2018.02.007. Epub 2018 Feb 13. — View Citation

Francica G, Petrolati A, Di Stasio E, Pacella S, Stasi R, Pacella CM. Effectiveness, safety, and local progression after percutaneous laser ablation for hepatocellular carcinoma nodules up to 4 cm are not affected by tumor location. AJR Am J Roentgenol. 2012 Dec;199(6):1393-401. doi: 10.2214/AJR.11.7850. — View Citation

Girelli R, Frigerio I, Giardino A, Regi P, Gobbo S, Malleo G, Salvia R, Bassi C. Results of 100 pancreatic radiofrequency ablations in the context of a multimodal strategy for stage III ductal adenocarcinoma. Langenbecks Arch Surg. 2013 Jan;398(1):63-9. doi: 10.1007/s00423-012-1011-z. Epub 2012 Sep 29. — View Citation

Girelli R, Frigerio I, Salvia R, Barbi E, Tinazzi Martini P, Bassi C. Feasibility and safety of radiofrequency ablation for locally advanced pancreatic cancer. Br J Surg. 2010 Feb;97(2):220-5. doi: 10.1002/bjs.6800. — View Citation

Gordon-Dseagu VL, Devesa SS, Goggins M, Stolzenberg-Solomon R. Pancreatic cancer incidence trends: evidence from the Surveillance, Epidemiology and End Results (SEER) population-based data. Int J Epidemiol. 2018 Apr 1;47(2):427-439. doi: 10.1093/ije/dyx232. — View Citation

Gress TM, Lausser L, Schirra LR, Ortmüller L, Diels R, Kong B, Michalski CW, Hackert T, Strobel O, Giese NA, Schenk M, Lawlor RT, Scarpa A, Kestler HA, Buchholz M. Combined microRNA and mRNA microfluidic TaqMan array cards for the diagnosis of malignancy of multiple types of pancreatico-biliary tumors in fine-needle aspiration material. Oncotarget. 2017 Nov 21;8(64):108223-108237. doi: 10.18632/oncotarget.22601. eCollection 2017 Dec 8. — View Citation

Han J, Chang KJ. Endoscopic Ultrasound-Guided Direct Intervention for Solid Pancreatic Tumors. Clin Endosc. 2017 Mar;50(2):126-137. doi: 10.5946/ce.2017.034. Epub 2017 Mar 30. Review. — View Citation

Kim HJ, Seo DW, Hassanuddin A, Kim SH, Chae HJ, Jang JW, Park DH, Lee SS, Lee SK, Kim MH. EUS-guided radiofrequency ablation of the porcine pancreas. Gastrointest Endosc. 2012 Nov;76(5):1039-43. doi: 10.1016/j.gie.2012.07.015. — View Citation

Lakhtakia S, Seo DW. Endoscopic ultrasonography-guided tumor ablation. Dig Endosc. 2017 May;29(4):486-494. doi: 10.1111/den.12833. Epub 2017 Mar 16. Review. — View Citation

Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med. 2014 Nov 27;371(22):2140-1. doi: 10.1056/NEJMc1412266. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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