Trial Comparing EUS-guided Radiofrequency Ablation vs. EUS-guided Celiac Plexus Neurolysis

Study Overview
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Brief Summary
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Pancreatic cancer is the second most common gastrointestinal malignancy. Abdominal discomfort is a main symptom in patients with pancreatic cancer. Approximately 75% have pain at diagnosis and over 90% in advanced stages. Pain control is an important part of the plan of care for patients with pancreatic cancer.. The celiac plexus is a group of nerves that supply organs in the abdomen. EUS-guided celiac plexus neurolysis (EUS-CPN) has been widely used for pain management in patients with pancreatic cancer. Radiofrequency ablation of celiac ganglia or celiac plexus (EUS-RFA) is also being performed to alleviate abdominal pain in pancreatic cancer patients. However currently no comparative studies exist comparing EUS-CPN with EUS-RFA. The purpose of the study is to compare EUS-CPN with EUS-RFA for pain management in pancreatic patients, in order to determine which technique is better at improving pain in pancreatic cancer patients.

Detailed Description
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Pancreatic cancer is the second most common gastrointestinal malignancy and fourth leading cause of cancer mortality. The incidence in the US is estimated at 8.8 per 100,000 population with 30,000 new cases diagnosed annually. The prognosis of unresectable pancreatic cancer is poor; overall 1 and 5-year survivals do not exceed 20 and 4%, respectively. For the minority of patients (15%) who are resectable at diagnosis, the median survival is 10-20 months, with 5-year survival of 10-25%. Abdominal discomfort is a predominant symptom in patients with pancreatic cancer. Approximately 75% have pain at diagnosis and over 90% in advanced stages. Therefore a major aspect of palliation is provision of adequate pain control. The standard approach to pain management is based on the World Health Organization (WHO) 3-step ladder, beginning with non-opioid analgesics (e.g. non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen), followed by weak opioids and then finally strong opioids as necessary. Virtually all patients require escalating doses of opioids during their disease. Adjuvant therapies, including other medications (e.g. trazodone, tricyclic anti-depressants, and bisphosphonates), palliative radionucleotides, external beam radiation, or chemotherapy may also be useful for symptomatic control. In the last 10 years, EUS-guided celiac plexus neurolysis (EUS-CPN) has been widely practiced for alleviation of pain in patients with pancreatic cancer and has been shown to be effective. At our institution, radiofrequency ablation (EUS-RFA), which involves ablation of celiac ganglia or celiac plexus using a radiofrequency catheter, is being performed to alleviate abdominal pain in pancreatic cancer patients. However currently no comparative studies exist comparing EUS-CPN with EUS-RFA for pain alleviation in pancreatic cancer patients. In this randomized trial, the investigators will be comparing EUS-CPN with EUS-RFA for pain alleviation in pancreatic patients, in order to determine which technique is better at improving pain in pancreatic cancer patients.

Official Title
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Randomized Trial Comparing Endoscopic Ultrasound-guided Radiofrequency Ablation vs.Endoscopic Ultrasound-guided Celiac Plexus Neurolysis in the Alleviation of Abdominal Pain in Patients With Pancreatic Cancer

Conditions
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Pancreatic Carcinoma Metastatic, Pancreatic Adenocarcinoma, Pancreatic Neoplasms, Pancreatic Cancer, Pancreatic Cancer, Adult

Intervention / Treatment
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* Other: Celiac Plexus Neurolysis
* Other: Radiofrequency Ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 19 years The subject is capable of understanding and complying with protocol requirements. The subject is able to understand and willing to sign an informed consent form prior to the initiation of any study procedures. Abdominal pain typical for pancreatic cancer Cross-sectional imaging findings consistent with pancreatic cancer Pancreatic cancer confirmed by EUS-FNA in patients referred for suspected pancreatic cancer OR Patients with known diagnosis of pancreatic cancer Inoperable pancreatic cancer as determined during EUS or prior CT Exclusion Criteria: Age <19 years Unable to obtain consent for the procedure from the patient Unable to safely undergo EUS for any reason Irreversible coagulopathy (Prothrombin time > 18 secs, platelet count < 50,000/ml) Previous CPN or other neurolytic block that could affect pancreatic cancer-related pain or had implanted epidural or intrathecal analgesic therapy Another cause for abdominal pain such as pseudocyst, ulcer or other intraabdominal disorder Pregnant women will be excluded. This will be confirmed by self-report. Pregnancy in females of childbearing potential will be determined by routine preoperative urine or serum Human Chorionic Gonadotropin (HCG) testing.

Ages Eligible for Study
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Minimum Age: 19 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will randomized to either a group that receives Celiac Plexus Neurolysis or Radiofrequency Ablation.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Celiac Plexus Neurolysis<br>CPN will be undertaken at the celiac space which is located between the aorta and the celiac artery origin. A 22 or 19-gauge Fine Needle Aspiration (FNA) needle is used, and its tip is placed slightly anterior and cephalic to the origin of the celiac artery. Aspiration is first performed using a syringe to ensure that vascular puncture has not occurred. 10 mL Bupivacaine is injected first, followed by 20 mL of 98% alcohol. | Other: Celiac Plexus Neurolysis<br>* This intervention involves accessing the Celiac Plexus Nerve via endoscopic guided ultrasound and then injecting the nerve bundle with bupivacaine.<br>|
| Active Comparator: Radiofrequency Ablation<br>Once the celiac ganglia are identified on EUS, a 19-gauge FNA needle is inserted into the center of the ganglion or area of celiac plexus under EUS guidance. The radiofrequency (RF) probe (EMcision, Montreal, Canada) is advanced through the FNA needle. Radiofrequency ablation is performed via the probe for 90 seconds, followed by a 90 second rest and repeated as required. | Other: Radiofrequency Ablation<br>* Radiofrequency ablation is performed via the probe for 90 seconds, followed by a 90 second rest. This is repeated until the entire ganglion becomes hyperechoic on EUS.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject assessment of abdominal pain | Abdominal pain will be assessed with pain scores from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Pancreatic Cancer module (QLQ-PAN26). The questionnaire has 26 questions with scoring ranging from a minimum of 26 to a maximum of 104. The higher the score, the worse the subject's quality of life rating. | Baseline to 4 week follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject assessment of Quality of Life. | Quality of life (QOL) as assessed by the quality of life instrument: the Functional Assessment of Cancer Therapy, Pancreatic Cancer (FACT-PA) (i.e. QLQ-30 and PAN-26) | Baseline; 2 week follow up; 4 week follow up | 
| Narcotic Use | Subjects will be asked about their medication usage to manage pain and the answers will be documented. | Initial visit; 2 week follow up; 4 week follow up | 
| Crossover to alternate technique | Cross-over to the alternate technique due to inadequate response to the original technique (defined as < 50% decrease in VAS score post-original technique). | 48 hours post procedure; 2 week follow up; 4 week follow up | 
| Adverse effects, and endoscopic adverse events | Information regarding complications if any, that the subject may have experienced, which can include hypotension, diarrhea, neuropathic pain, paraplegia and endoscopic adverse events | 48 hours post procedure; 2 week follow up; 4 week follow up | 
| Survival rate | Information regarding if the subject is alive or deceased. | 2 week follow up; 4 week follow up | 
| Pain per the VAS tool. | Abdominal pain will be assessed with a standardized 11-point continous visual analog pain scale (with 0 equaling no pain, 5 moderate pain and 10 worst pain ever. | Baseline; 48 hour post procedure; 2 week follow up; 4 week follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endoscopic ultrasound, celiac plexus neurolysis, radiofrequency ablation, pancreatic cancer