Safety and Efficacy of an Ablation Catheter for the Treatment of Pancreatic Premalignant Cyctic Lesions.

Pancreatic Cancer Clinical Trial

— yes  

Official title:

A Prospective, Open Label Study: Safety and Efficacy of a New Ablation Catheter RFA (Radiofrequency Under EUS) Developed by TAEWOONG Company for the Treatment of Pancreatic Premalignant and Early Malignant Cyctic Lesions.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03417843
• Other study ID #: 0090-17-EMC
• Status: Not yet recruiting
• Phase: N/A
• First received: January 17, 2018
• Last updated: February 11, 2018
• Start date: February 2018
• Est. completion date: February 2021

Study information

• Verified date: February 2018
• Source: HaEmek Medical Center, Israel
• Contact: Stanislav Bezobchuk, doctor
• Phone: 04-6495552
• Email: Stanislavbe[@]clalit.org.il
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to evaluate the safety and efficacy of new ablation catheter developed by MEDICAL TAEWOONG for the treatment of pancreatic premalignant and early malignant cystic lesion. The ablation is performed using EUSRA needle and radiofrequncy waves under ultrasound imaging. The method will be exaimened on patients who are candidates for surgical intervention and to examine the ability of the method to serve as an alternative to surgical intervention.

Description:

In recent years, local and non-invasive intervention methods have been attempted to eliminate or at least reduce the growth of pancreatic lesions. Over the past two years there has been considerable but not successful experience in ablation (burning) of lesions by direct alcohol injection and / or other drugs into the cyst through the EUS. To date, treatment has been performed in three groups of patients in a clinical trial and has shown clinical success from 33% to 70%. However, it should be noted that there is a large incidence of treatment failure and also complications such as pancreatitis.

An interesting alternative to surgical intervention is the local destruction of the cyst by radio waves ENDOSCOPIC RADIOFREQUENCY (RF). This is a familiar local method that works by releasing heat that causes necrosis and disappearance of the lesion.High efficacy and high safety profile were reported for this method; 90% of the cases showed disappearance of of metaplasia by the follow-up of 5 years and 80% disappearance of dysplasia (both early and advanced) followed by two and a half years.

In addition, in recent years EMCISION has developed a catheter called ENDO HBP HABIB. It is a thin RF probe that can be inserted through work channels of all types of endoscopes and cholangioscopes. The depth of the penetration of heat and energy intensity is in accordance with the resistance of the tissue being treated, and the device operates under the computerized control of an ultrasound device with high resolution. This method showed success in short-term follow-up in preliminary research.The technical difficulty of this therapeutic method is related to the limitation of the ability to position itself precisely by inserting the catheter through the EUS needle.In order to overcome the difficulty of operating HABIB PROBE, MEDICAL TAEWOONG, recognized worldwide and Israel as an advanced endoscopic equipment company, developed in cooperation with STARMED an RF needle called EUSRA, which works in conjunction with a VIVO COMBO generator. The function of the generator is to provide up to 200 watts of energy to activate the electrode. The needle can be directly inserted into the pancreas lesion while controlling EUS. At the tip of the needle is a probe that releases the energy at 50W for 10 seconds or 40W until the white bubbles appear in a sonographic image.In recent years, two cases of successful treatment have been reported. In both cases, treatment of neuroendocrine cancer showed good initial results. The first study was performed on a 76-year-old patient with a neuroendocrine tumor.CT performed about one month after the procedure showed complete disappearance of the lesion without any complications. The second study was performed in six patients with an average age of 62. The average diameter of lesion was 3.8 cm. The procedure was successful when two patients felt abdominal pain followed. There were no bleeding events and pancreatitis.This year, a multicenter study was conducted in France in patients with neuroendocrine tumors and cystic lesions in the pancreas, testing the safety and initial efficacy of the method and monitoring for up to 12 months. The study was conducted in a group of 30 patients.In 6 patients with endocrine tumors there was complete disappearance of the lesions, in 3 patients there was a decrease in the diameter of the lesions by more than 50% and in one patient the treatment failed. In 7 of 8 patients with cystic tumors, walled nadies disappeared and in 5 out of 10 patients cystic tumors disappeared. Prophylactic treatment of antibiotics and NSAIDs (anti-inflammatory drugs) and empty the cyst fluid before the procedure led to a dramatic reduction in complications (3.5%). Three patients experienced mild abdominal pain without signs of inflammation successfully treated with paracetamol. (study not yet published).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: February 2021
• Est. primary completion date: February 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Patients aged 18-85

• Patients who agreed to join study and signed an informed consent letter

• Patients with IPMN pancreas cystic tumor with a diameter greater than 30 mm and with secondary branches.

• Patients with a tissue component within the cystic lesion

• Patients with atypical cells in cytology, regardless of the size of the lesion and regardless of the contents of the cyst

• Patients with a lesion of less than 30 mm diameter showing rapid changes in size (15 mm increments followed by 6 months)

• Patients with a consistent increase in CEA level within the cyst.

• Patients with cystinus cystadenoma of any size with suspicious signs such as thickening of the cyst wall, calcification of the cyst wall, irregularity of the cyst wall, tissue content within the cyst, the presence of atypical cells within the cyst in cytology.

• Symptomatic patients (pain defined as related to the lesion)

• Asymptomatic patients with a normal cyst greater than 40 mm in diameter.

• Patients referred for surgical treatment (after the multidisciplinary committee (gastroenterologists, surgeons and pathologists / cytologists) has approved the diagnosis and indication of therapeutic intervention (as is customary) but not suitable for surgery due to high risk of anesthesia (ASAIV) or severe anatomy due to repeat surgery or patients who do not agree to undergo surgical intervention (these are most patients)

• Patients with low anesthetic risk: ASA 1-3.

• Women who are not pregnant during recruitment, and women of childbearing age who take birth control during the study.

Exclusion Criteria:

• Patients with clear evidence of invasive tumor development within the lesion (both candidates and not candidates for continued surgical treatment).

• Patients with severe coagulation disorders (PT, elongated PTT)

• Patients with platelet counts less than 75000

• Patients taking anticoagulants that can not be stopped temporarily

• Patients with pacemakers

• Patients with dilatation pages

• Patients who take clopidogrel in situations that do not allow temporary cessation of the drug.

• Patients with hight anesthetic risk(ASA4 group).

• Patients belonging to groups: pregnant women, nursing patients, and demineral patients.

• Women of childbearing age who do not take birth control.

• Patients who are unable to express informed consent.

Related Conditions & MeSH terms

• Neuroendocrine Tumors
• Pancreatic Cancer
• Pancreatic Cancer Stage
• Pancreatic Cyst
• Pancreatic Neoplasms
• Pancreatic Neuroendocrine Tumor
• Precancerous Conditions

Intervention

Device:
• EUSRA RF electrode
At the tip of the needle there is a probe that releases the peripheral energy in a continuous and continuous manner. The method is a long 50W power release for 10 seconds or 40W until white bubbles appear in a sonographic image. Materials that come into contact with the body: electrode and grounding surfaces

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
HaEmek Medical Center, Israel

References & Publications (20)

Armellini E, Crinò SF, Ballarè M, Occhipinti P. Endoscopic ultrasound-guided radiofrequency ablation of a pancreatic neuroendocrine tumor. Endoscopy. 2015;47 Suppl 1 UCTN:E600-1. doi: 10.1055/s-0034-1393677. Epub 2015 Dec 15. — View Citation

Brugge WR, Lewandrowski K, Lee-Lewandrowski E, Centeno BA, Szydlo T, Regan S, del Castillo CF, Warshaw AL. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology. 2004 May;126(5):1330-6. — View Citation

Cho YK, Kim JK, Kim MY, Rhim H, Han JK. Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies. Hepatology. 2009 Feb;49(2):453-9. doi: 10.1002/hep.22648. Review. — View Citation

DeWitt J, McGreevy K, Schmidt CM, Brugge WR. EUS-guided ethanol versus saline solution lavage for pancreatic cysts: a randomized, double-blind study. Gastrointest Endosc. 2009 Oct;70(4):710-23. doi: 10.1016/j.gie.2009.03.1173. Epub 2009 Jul 4. — View Citation

Dolak W, Schreiber F, Schwaighofer H, Gschwantler M, Plieschnegger W, Ziachehabi A, Mayer A, Kramer L, Kopecky A, Schrutka-Kölbl C, Wolkersdörfer G, Madl C, Berr F, Trauner M, Püspök A; Austrian Biliary RFA Study Group. Endoscopic radiofrequency ablation for malignant biliary obstruction: a nationwide retrospective study of 84 consecutive applications. Surg Endosc. 2014 Mar;28(3):854-60. doi: 10.1007/s00464-013-3232-9. Epub 2013 Oct 3. — View Citation

Fleischer DE, Overholt BF, Sharma VK, Reymunde A, Kimmey MB, Chuttani R, Chang KJ, Muthasamy R, Lightdale CJ, Santiago N, Pleskow DK, Dean PJ, Wang KK. Endoscopic radiofrequency ablation for Barrett's esophagus: 5-year outcomes from a prospective multicenter trial. Endoscopy. 2010 Oct;42(10):781-9. doi: 10.1055/s-0030-1255779. Epub 2010 Sep 20. — View Citation

Gan SI, Thompson CC, Lauwers GY, Bounds BC, Brugge WR. Ethanol lavage of pancreatic cystic lesions: initial pilot study. Gastrointest Endosc. 2005 May;61(6):746-52. — View Citation

Hammel P. [Incidental pancreatic tumors: diagnosis and management]. Gastroenterol Clin Biol. 2002 Aug-Sep;26(8-9):700-8. Review. French. — View Citation

Itoi T, Isayama H, Sofuni A, Itokawa F, Tamura M, Watanabe Y, Moriyasu F, Kahaleh M, Habib N, Nagao T, Yokoyama T, Kasuya K, Kawakami H. Evaluation of effects of a novel endoscopically applied radiofrequency ablation biliary catheter using an ex-vivo pig liver. J Hepatobiliary Pancreat Sci. 2012 Sep;19(5):543-7. doi: 10.1007/s00534-011-0465-7. — 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

Matsumoto T, Aramaki M, Yada K, Hirano S, Himeno Y, Shibata K, Kawano K, Kitano S. Optimal management of the branch duct type intraductal papillary mucinous neoplasms of the pancreas. J Clin Gastroenterol. 2003 Mar;36(3):261-5. — View Citation

Monga A, Gupta R, Ramchandani M, Rao GV, Santosh D, Reddy DN. Endoscopic radiofrequency ablation of cholangiocarcinoma: new palliative treatment modality (with videos). Gastrointest Endosc. 2011 Oct;74(4):935-7. doi: 10.1016/j.gie.2010.10.018. Epub 2010 Dec 18. — View Citation

Oh HC, Seo DW, Lee TY, Kim JY, Lee SS, Lee SK, Kim MH. New treatment for cystic tumors of the pancreas: EUS-guided ethanol lavage with paclitaxel injection. Gastrointest Endosc. 2008 Apr;67(4):636-42. doi: 10.1016/j.gie.2007.09.038. Epub 2008 Feb 11. — View Citation

Okabayashi T, Kobayashi M, Nishimori I, Sugimoto T, Namikawa T, Okamoto K, Okamoto N, Kosaki T, Onishi S, Araki K. Clinicopathological features and medical management of intraductal papillary mucinous neoplasms. J Gastroenterol Hepatol. 2006 Feb;21(2):462-7. — View Citation

Prat F, Lafon C, De Lima DM, Theilliere Y, Fritsch J, Pelletier G, Buffet C, Cathignol D. Endoscopic treatment of cholangiocarcinoma and carcinoma of the duodenal papilla by intraductal high-intensity US: Results of a pilot study. Gastrointest Endosc. 2002 Dec;56(6):909-15. — View Citation

Preliminary data of first RFA results of Multicentre study in France (not published). Oral presentation RFA course , Marseille 05.2017.

Shaheen NJ, Sharma P, Overholt BF, Wolfsen HC, Sampliner RE, Wang KK, Galanko JA, Bronner MP, Goldblum JR, Bennett AE, Jobe BA, Eisen GM, Fennerty MB, Hunter JG, Fleischer DE, Sharma VK, Hawes RH, Hoffman BJ, Rothstein RI, Gordon SR, Mashimo H, Chang KJ, Muthusamy VR, Edmundowicz SA, Spechler SJ, Siddiqui AA, Souza RF, Infantolino A, Falk GW, Kimmey MB, Madanick RD, Chak A, Lightdale CJ. Radiofrequency ablation in Barrett's esophagus with dysplasia. N Engl J Med. 2009 May 28;360(22):2277-88. doi: 10.1056/NEJMoa0808145. — View Citation

Song TJ, Seo DW, Lakhtakia S, Reddy N, Oh DW, Park DH, Lee SS, Lee SK, Kim MH. Initial experience of EUS-guided radiofrequency ablation of unresectable pancreatic cancer. Gastrointest Endosc. 2016 Feb;83(2):440-3. doi: 10.1016/j.gie.2015.08.048. Epub 2015 Sep 4. — View Citation

Steel AW, Postgate AJ, Khorsandi S, Nicholls J, Jiao L, Vlavianos P, Habib N, Westaby D. Endoscopically applied radiofrequency ablation appears to be safe in the treatment of malignant biliary obstruction. Gastrointest Endosc. 2011 Jan;73(1):149-53. doi: 10.1016/j.gie.2010.09.031. — View Citation

Zacharoulis D, Lazoura O, Rountas C, Katsimboulas M, Mantzianas G, Tzovaras G, Habib N. Experimental animal study of a novel radiofrequency endovascular occlusion device. Am J Surg. 2011 Jul;202(1):103-9. doi: 10.1016/j.amjsurg.2010.08.031. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse and serious adverse events	The number of subjects with post EUS-RFA-related adverse events including: Fever >38C (will be measured in celcius)	up to one month post-procedure
Primary	Incidence of adverse and serious adverse events	The number of subjects with post EUS-RFA-related adverse events including: Pancreatitis as measured by an increase of at least 3 times in serum amylase (units/liter) in the initial 72 hours post-procedure	up to 72 hours post-procedure
Primary	Incidence of adverse and serious adverse events	The number of subjects with post EUS-RFA-related adverse events including: Hemorrhage as measured by need for transfusion of packed red blood cells	up to 72 hours post-procedure
Primary	Incidence of adverse and serious adverse events	The number of subjects with post EUS-RFA-related adverse events including: Perforation as confirmed by abdominal CT	up to 72 hours post-procedure
Primary	Incidence of adverse and serious adverse events	The number of subjects with post EUS-RFA-related adverse events including: Mortality	up to 12 months post-procedure
Secondary	Absolute disappearance incidence or reduction in lesion size	Direct measuring of lesion diameter and area (in milimeter and milimeter^2 respectively) during the 12-month blind follow-up by EUS, CT and MRI .	up to 12 months post-procedure (3, 6 and 12 months post-procedure)
Secondary	Absolute disappearance incidence or reduction in lesion size	disappearance of mural nodule inside cyst follow-up by EUS, CT and MRI .	up to 12 months post-procedure (3, 6 and 12 months post-procedure)
Secondary	Technical efficiency of the method	To examine the technical efficiency of the method by estimating the frequency of success in performing the operation according to the protocol, without any mishaps and deviations from the original protocol.	during the procedure