Evaluation of Safety and Feasibility of EUS-guided RFA for Solid Pancreatic Neoplasms

Pancreatic Cancer Clinical Trial

Official title:

Evaluation of Safety and Feasibility of Endoscopic Ultrasound (EUS)-Guided Radiofrequency Ablation (RFA) for Solid Pancreatic Neoplasms

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03435770
• Other study ID #: 2017/2702
• Status: Not yet recruiting
• Phase: N/A
• First received: February 10, 2018
• Last updated: February 17, 2018
• Start date: March 1, 2018
• Est. completion date: September 1, 2019

Study information

• Verified date: February 2018
• Source: Singapore General Hospital
• Contact: Yung Ka Chin, MBChB
• Phone: +6562223322
• Email: chin.yung.ka[@]singhealth.com.sg
• 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 neoplasm (pancreatic adenocarcinoma or neuroendocrine tumour). The ablation is performed using EUSRA needle and radio frequency waves under ultrasound imaging. The subject who will be recruited into this study are patients who are deemed as non-surgical candidates.

Description:

RFA causes tissue destruction through the application of a high frequency alternating current, generating local temperatures above 60°C and leading to coagulative necrosis. The technique has been widely used in many solid organ tumours and has been shown to result in 5-year survival rates comparable to surgery. The technique is currently the standard therapy in hepatocellular carcinoma and colorectal pulmonary metastasis particular in patients that are not suitable for surgery.

The application of RFA in the pancreas was first described in 1999. Thereafter, several studies performed in the porcine model demonstrated the feasibility of RFA under EUS guidance. In the first porcine study by Goldberg et al, RFA was applied through a modified 19 gauge Vilmann-type needle (GIP/MediGlobe, Grassau, Germany). The needles were electrically insulated with shrink tubing for all but the distal 1 to 1.5cm. 16 ablations were performed and the procedure resulted in hypodense foci of non-enhancing pancreas 1 to 2 days after ablation. Pathologic examination showed well demarcated spherical foci of coagulation necrosis measuring 8 to 12mm in size. One swine developed hyperlipasemia, a focal zone of pancreatitis and another with pancreatic fluid collection. 4 swine also suffered from thermal injury to the gastrointestinal wall caused by improper electrode placement.

Thereafter, 4 subsequent porcine studies also demonstrated the feasibility of RFA under EUS guidance with proprietary radiofrequency electrodes. In the most recent study, EUS-guided RFA was delivered by a novel 18-gauge RFA electrode and a VIVA RF generator (STARmed, Korea). RFA was applied to both the ex-vivo and in-vivo models to determine the optimum power settings and efficacy of the device. A power setting of 50 W for 6 minutes was shown to result in the most effective depth and size of ablation zone, whilst a higher power setting resulted in tissue charring and reduced the conductive coagulative necrosis effect. 10 swine then received EUS-guided RFA to the pancreas and the mean size of the ablated lesions were 23 +/- 6.9mm. None of the swine suffered from any adverse events and there were no significant changes in the serum levels of amylase and lipase, both before and after the procedures.

On the other hand, the experience of RFA in human pancreas is accumulating. Earlier studies using first generation percutaneous RFA probes applied intra-operatively to pancreatic carcinomas were associated with unacceptably high rates of mortality (0% - 25%) and morbidity (0% - 40%). Subsequently, human data on new generation EUS-guided RFA probes with improved design and outcomes have become available. 22 patients with locally advanced pancreatic ductal adenocarcinoma were treated the cryotherm probe (CTP) (ERBE Elektromedizin GmbH, Tübingen, Germany). The CTP was successfully applied in 16 patients (72.8%), amylase rose in 3 of 16 patients but none had clinical signs of pancreatitis. The median post ablation survival time was 6 months. In another 2 studies, the Habib RFA catheter was used (EMcision, United Kingdom). 7 patients with unresectable pancreatic ductal carcinoma and 8 patients with pancreatic neuroendocrine tumour and cystic tumours were treated with EUS-guided RFA. In patients suffering from pancreatic ductal carcinoma, post procedural imaging showed a decrease in size of the lesions in 2 patients and 1 patient suffered from mild pancreatitis. Whilst in patients with cystic neoplasms and neuroendocrine tumours, all showed complete resolution or reduction in size of the lesions. Only 2 patients suffered from abdominal pain that resolved spontaneously. On the other hand, RFA with the VIVA generator was applied in 6 patients with unresectable pancreatic adenocarcinoma. Two patients suffered from mild abdominal pain but no serious adverse events reported.

Thus, based on these preliminary results, we conclude that the new generation EUS-guided RFA probe is safe and feasible. The next stage in development with conduction of this study would involve recruitment of larger patient cohorts to further establish the efficacy and risk profile of the procedure.

HYPOTHESIS AND OBJECTIVES The aim of the current study is to perform a single center prospective study on EUS-guided radiofrequency ablation (RFA) of solid pancreatic neoplasms. We hypothesize that EUS-guided RFA is safe, feasible and effective for treating solid pancreatic neoplasms.

EXPECTED RIKS AND BENEFITS The expected risks for the patients include mild abdominal pain. The benefit may include RFA destroy the tumour cells via coagulative necrosis process hence providing some form of disease control. Besides, the current study could establish the safety and feasibility of EUS-guided RFA of solid pancreatic neoplasms. These results could provide insights as to whether the procedure is comparable to surgery for treatment of these lesions in the future.

STUDY POPULATION We aim to recruit 10 subjects over the period of 18 months. The subjects must have pancreatic neuroendocrine tumour or pancreatic ductal carcinoma that was unsuitable for surgery or not keen for surgery.

STUDY DESIGN AND PROCEDURES/METHODOLOGY The RFA system It consists of two components, a19-gauge RFA electrode and a VIVA combo RF generator. The total length of the electrode including the delivery system is 150 cm. The distal end of the electrode is needle-shaped and echogenic that allows EUS guided puncture of the target lesion. The active electrode tip is 1 cm in length. During ablation, the RF electrode is cooled and perfused internally with circulating chilled saline solution (0°C) delivered via a pump to maintain a constant temperature. A setting of 50W energy would be used for RFA and the duration of application is 10 seconds.

EUS-guided radiofrequency ablation This procedure is very similar to the standard technique of EUS-guided fine needle aspiration. The location and size of the lesion would be assessed for suitability of treatment. After locating the lesion, the RFA needle would be inserted to the centre of the lesion. RFA would then be initiated and hyperechoic interferences would be observed around the electrode signifying heating of the tissue. Post procedural, the site of needle entry would be inspected endoscopically to assess for presence of thermal injury to the gastrointestinal wall.

Follow-up protocol There will be clinic visit scheduled by both gastroenterologist and oncologist at two weeks after discharging from hospital to review participant's condition and to plan for further treatment. Follow-up phone call will be made at 1st week and 1st month after discharging from the ward to determine for any adverse event and whether they are attributable. When reporting complication rates, only definite and probably attributable events occurring within 30 days will be include.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: September 1, 2019
• Est. primary completion date: September 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 99 Years

Eligibility

Inclusion Criteria:

• Age 21 years-old or above

• Suffering from pancreatic neuroendocrine tumour or pancreatic ductal carcinoma that was confirmed by fine needle aspiration cytology

• Unsuitable for surgery, due to one (or more) of the following items:

• ASA score >/= III

• An alternative advanced malignancy

• Unsuitable for surgery upon expert's opinion for any other reason

• Individuals who are not keen for surgical resection

• Eligible for endoscopic intervention

• Written informed consent

Exclusion Criteria:

• Coagulopathy (international normalized ratio >1.5, partial thromboplastin time greater than twice that of control), platelet count <50,000x103/uL

• Pregnancy

• Patients with a poor mental condition or mental retardation, unable to understand the nature and possible consequences of the study

• Patients unwilling to undergo follow-up assessments

• Patients with liver cirrhosis, portal hypertension and/or gastric varices.

Related Conditions & MeSH terms

• Adenocarcinoma
• Neoplasms
• Neuroendocrine Tumors
• Pancreatic Adenocarcinoma
• Pancreatic Cancer
• Pancreatic Ductal Adenocarcinoma
• Pancreatic Neoplasms
• Pancreatic Neuroendocrine Tumor

Intervention

Device:
• EUSRA RFA needle
A 19-gauge RFA electrode and a RF generator with a electrode that is needle-shaped and echogenic that allows EUS guided puncture of the target lesion. The active electrode tip is 1 cm in length. During ablation, the RF electrode is cooled and perfused internally with circulating chilled saline solution (0°C) delivered via a pump to maintain a constant temperature. A setting of 50W energy would be used for RFA and the duration of application is 10 seconds. Sequential applications of up to 7 times per session are allowed for complete ablation of the lesions.

Locations

Country	Name	City	State
Singapore	Singapore General Hospital	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
Singapore General Hospital

Country where clinical trial is conducted

Singapore, 

References & Publications (25)

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Arcidiacono PG, Carrara S, Reni M, Petrone MC, Cappio S, Balzano G, Boemo C, Cereda S, Nicoletti R, Enderle MD, Neugebauer A, von Renteln D, Eickhoff A, Testoni PA. Feasibility and safety of EUS-guided cryothermal ablation in patients with locally advanced pancreatic cancer. Gastrointest Endosc. 2012 Dec;76(6):1142-51. doi: 10.1016/j.gie.2012.08.006. Epub 2012 Sep 26. — View Citation

Bai H, Huangz X, Jing L, Zeng Q, Han L. The effect of radiofrequency ablation vs. liver resection on survival outcome of colorectal liver metastases (CRLM): a meta-analysis. Hepatogastroenterology. 2015 Mar-Apr;62(138):373-7. Review. — 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

Carrara S, Arcidiacono PG, Albarello L, Addis A, Enderle MD, Boemo C, Neugebauer A, Campagnol M, Doglioni C, Testoni PA. Endoscopic ultrasound-guided application of a new internally gas-cooled radiofrequency ablation probe in the liver and spleen of an animal model: a preliminary study. Endoscopy. 2008 Sep;40(9):759-63. doi: 10.1055/s-2008-1077520. Epub 2008 Aug 13. — View Citation

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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

Goldberg SN, Mallery S, Gazelle GS, Brugge WR. EUS-guided radiofrequency ablation in the pancreas: results in a porcine model. Gastrointest Endosc. 1999 Sep;50(3):392-401. — View Citation

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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

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McGahan JP, Browning PD, Brock JM, Tesluk H. Hepatic ablation using radiofrequency electrocautery. Invest Radiol. 1990 Mar;25(3):267-70. — View Citation

Pai M, Senturk H, Lakhtakia S, Reddy DN, Cicinnati C, Kabar I, Beckebaum S, Jin Z, Wang D, Yang J, et al. Endoscopic Ultrasound Guided Radiofrequency Ablation (EUS-RFA) for Cystic Neoplasms and Neuroendocrine Tumours of the Pancreas. Gastrointest Endosc. 2013;77(5S): AB143-AB144

Qi X, Tang Y, An D, Bai M, Shi X, Wang J, Han G, Fan D. Radiofrequency ablation versus hepatic resection for small hepatocellular carcinoma: a meta-analysis of randomized controlled trials. J Clin Gastroenterol. 2014 May-Jun;48(5):450-7. doi: 10.1097/MCG.0000000000000008. Review. — View Citation

Rossi S, Fornari F, Pathies C, Buscarini L. Thermal lesions induced by 480 KHz localized current field in guinea pig and pig liver. Tumori. 1990 Feb 28;76(1):54-7. — View Citation

Smith SL, Jennings PE. Lung radiofrequency and microwave ablation: a review of indications, techniques and post-procedural imaging appearances. Br J Radiol. 2015 Feb;88(1046):20140598. doi: 10.1259/bjr.20140598. Epub 2014 Dec 3. Review. — 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

Spiliotis JD, Datsis AC, Michalopoulos NV, Kekelos SP, Vaxevanidou A, Rogdakis AG, Christopoulou AN. Radiofrequency ablation combined with palliative surgery may prolong survival of patients with advanced cancer of the pancreas. Langenbecks Arch Surg. 2007 Jan;392(1):55-60. Epub 2006 Nov 7. — View Citation

Varadarajulu S, Jhala NC, Drelichman ER. EUS-guided radiofrequency ablation with a prototype electrode array system in an animal model (with video). Gastrointest Endosc. 2009 Aug;70(2):372-6. doi: 10.1016/j.gie.2009.03.008. Epub 2009 Jun 26. — View Citation

Wu Y, Tang Z, Fang H, Gao S, Chen J, Wang Y, Yan H. High operative risk of cool-tip radiofrequency ablation for unresectable pancreatic head cancer. J Surg Oncol. 2006 Oct 1;94(5):392-5. — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To measure the technical success of EUS-guided RFA	It is defined as successful puncture of the pancreatic lesion with the RFA needle and completion of the ablation cycle.	18 months
Primary	To measure side effects and adverse event of EUS-guided RFA	Adverse events specific to RFA would be graded according to the lexicon of endoscopic adverse events (PB Cotton GIE 2010). Potential adverse events specific to RFA include: Post-RFA syndrome: Combination of flu like symptoms including fever, malaise, pain at the site of ablation, nausea, and/or vomiting and that no other septic source is identified.; Pancreatitis: Clinical presence of abdominal pain with an increase in amylase level >3 times above the normal serum amylase levels.; Pancreatic leak: The presence of an abdominal collection with an amylase level that is >3 times normal serum amylase levels.; Thermal injury: Coagulative necrosis occurring at the site of needle entry within the gastrointestinal tract with or without clinical sequelae.	18 months