Upfront EUS CGN/CPN vs Conventional Step up Approach for Inoperable Painful Pancreatic Cancer

Study Overview
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Brief Summary
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Patients with unresectable pancreatic cancer are often demoralized by intractable, persistent and incapacitating pain. It must be managed aggressively and strong opioids are recommended as the mainstay of treatment. However, patients develop opioid-related adverse effects. EUS-guided celiac plexus neurolysis (CPN) and celiac ganglion neurolysis (CGN) has been shown to provide high efficacy for pain control. The optimal timing, however, is in debate.

Official Title
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Upfront Endoscopic Ultrasound-guided Celiac Ganglion Neurolysis Versus Conventional Step-up Approach for Patients With Painful, Inoperable Pancreatic Cancer

Conditions
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Pancreatic Cancer Non-resectable, Tumor Pancreas, Pain Cancer

Intervention / Treatment
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* Procedure: EUS-guided coeliac ganglion neurolysis / celiac plexus neurolysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 18 years old Diagnosed to have inoperable pancreatic cancer Presence of tumor pain (centrally located, constant, with no other obvious cause) with a VAS >= 3 Karnofsky performance status >= 60 Planned for EUS examination and/or biopsy of the pancreatic tumor Exclusion Criteria: Allergy to bupivacaine, or alcohol Potentially operable after neoadjuvant therapy Expected survival of less than 3 months Patient who is already on opioids for pain control Previous percutaneous or EUS-guided CGN/ CPN Recurrent pancreatic tumors after operation Uncorrectable coagulopathy Inability or unwillingness to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 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: Patient will be randomly assigned in a 1:1 ratio to either the upfront EUS-guided CGN/CPN approach or to the conventional step-up approach at the time of EUS. Site-specific block randomization will be performed via an online web-based randomization program with a concealed, fixed block size.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: EUS-guided coeliac ganglion neurolysis / celiac plexus neurolysis<br>Patient would undergo a EUS diagnostic procedure with or without a biopsy. Patient would be blinded to the group they were assigned. The procedure will be performed with a linear array echoendoscope (EUS) under conscious sedation or monitored anaesthesia care. For cases in which celiac ganglia could not be visualized, EUS-guided coeliac plexus neurolysis (CPN) will be performed. | Procedure: EUS-guided coeliac ganglion neurolysis / celiac plexus neurolysis<br>* The EUS scope was first inserted into the stomach, and the coeliac trunk was visualized by scanning from the lesser curve of the gastric body. After visualization, the scope was rotated clockwise, enabling visualization and identification of the left adrenal gland. The coeliac ganglia are often seen to the left of the coeliac artery, between the aorta and the left adrenal gland, at the level between the coeliac artery and the left adrenal artery. They are also visualized cephalad to the coeliac artery in some cases. Hypoechoic nodular structures linked by hypoechoic threads residing in the periphery of this region were defined as the coeliac ganglia . A 19G or 22G needle was used for puncture of the CGN. After confirming the lack of backflow of blood with aspiration, a mixture of 5ml of 0.25-0.5% bupivacaine and 5ml absolute alcohol was injected. For cases in which celiac ganglia could not be visualized, EUS-guided coeliac plexus neurolysis (CPN) will be performed.<br>|
| Active Comparator: Conventional step-up approach<br>Patient would undergo a EUS diagnostic procedure with or without a biopsy. Patient would be blinded to the group they were assigned. The concept of the conventional step-up approach is to follow ESMO clinical practice guidelines for cancer pain. In case of inadequate pain control, the analgesics will be stepped up according to the guidelines. After 4 weeks, if patient's VAS score more than 7 or VAS score fails to improve by 20% despite optimal oral analgesics, patients are given the option of EUS-guided CGN/ CPN. | Procedure: EUS-guided coeliac ganglion neurolysis / celiac plexus neurolysis<br>* The EUS scope was first inserted into the stomach, and the coeliac trunk was visualized by scanning from the lesser curve of the gastric body. After visualization, the scope was rotated clockwise, enabling visualization and identification of the left adrenal gland. The coeliac ganglia are often seen to the left of the coeliac artery, between the aorta and the left adrenal gland, at the level between the coeliac artery and the left adrenal artery. They are also visualized cephalad to the coeliac artery in some cases. Hypoechoic nodular structures linked by hypoechoic threads residing in the periphery of this region were defined as the coeliac ganglia . A 19G or 22G needle was used for puncture of the CGN. After confirming the lack of backflow of blood with aspiration, a mixture of 5ml of 0.25-0.5% bupivacaine and 5ml absolute alcohol was injected. For cases in which celiac ganglia could not be visualized, EUS-guided coeliac plexus neurolysis (CPN) will be performed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The mean change in VAS pain score at 3 months | The mean change in VAS pain score at 3 months when compared to baseline (pre-procedure) between upfront EUS group and conventional step-up group | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The mean percentage and absolute change in VAS pain score at 1 month | The mean percentage and absolute change in VAS pain score at 1 month when compared to baseline (pre-procedure) | 1 month | 
| The mean percentage in VAS pain score at 3 month | The mean percentage in VAS pain score at 3 month when compared to baseline (pre-procedure) | 3 months | 
| Short form McGill Pain Questionnaire-2 | The absolute and mean percentage change in Short form McGill Pain Questionnaire-2 | 3 months | 
| Brief Pain Inventory | The absolute and mean percentage change in Brief Pain Inventory | 3 months | 
| Morphine equivalent (MEQ) consumption | Absolute use and percentage change of morphine (expressed in morphine equivalent (MEQ) consumption) when compared to baseline | 3 months | 
| Common opioid-related adverse effects | Common opioid-related adverse effects including nausea, pruritus, constipation and drowsiness will be recorded | 3 months | 
| Quality of life | Changes of the score in quality of life (EORTC QLQ-C30) | 3 months | 
| Karnofsky performance status | Karnofsky performance status at baseline, 4 weeks, 8 weeks and 12 weeks | 12 weeks | 
| Adverse events from the EUS-guided CGN/CPN | Adverse events from the EUS-guided CGN/CPN will be recorded | 7 days | 
| Breakthrough visits | Breakthrough visits in between the 4 weeks | 4 weeks | 
| Need for and timing EUS-guided CGN/CPN for the conventional group | Need for and timing EUS-guided CGN/CPN for the conventional group will be recorded | 3months | 
| Overall survival | Date of death will be recorded | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tumor pain, Pancreatic Cancer Non-resectable, endoscopic ultrasound-guided celiac ganglion neurolysis