Feasibility Trial of EUS-PCA in IPMN Pancreatic Cysts

Single-arm Intervention Trial of the Feasibility of Endoscopic Ultrasound-guided Pancreatic Cyst Chemoablation (EUS-PCA) Using Gemcitabine and Paclitaxel for Intraductal Papillary Mucinous Neoplasms (IPMN) in Two New Zealand Tertiary Interventional Endoscopy Centres

The goal of this single-arm intervention trial is to determine the feasibility of implementing endoscopic ultrasound-guided pancreatic cyst chemoablation (EUS-PCA) using gemcitabine and paclitaxel for intraductal papillary mucinous neoplasms (IPMN) in two New Zealand tertiary interventional endoscopy centres.

Study Overview

• Status: Not yet recruiting
• Conditions: Intraductal Papillary Mucinous Neoplasm of Pancreas
• Intervention / Treatment: Procedure: Endoscopic ultrasound-guided pancreatic cyst chemoablation (EUS-PCA) using gemcitabine and paclitaxel

Detailed Description

Early detection and treatment of pancreatic premalignant lesions, most commonly IPMN, may be the best current strategy to prevent invasive pancreatic cancer. The rates of IPMN progression to invasive cancer range from 7 to 25% at 10 years, depending on risk characteristics. The feasibility and safety of EUS-PCA has been demonstrated in studies, including smaller randomised trials, totaling about 140 participants. EUS-PCA with the chemotherapy drugs being used in this trial has been implemented in several major international centres due to its potential for the minimally-invasive prevention of invasive pancreatic cancer, though it has never been compared to surgery in a clinical trial.

This single-arm intervention trial will evaluate the feasibility of implementing endoscopic ultrasound-guided pancreatic cyst ablation (EUS-PCA) for IPMN in interventional endoscopy units in two New Zealand tertiary centres. Doing so in a clinical trial is consistent with the recommendation of an international expert panel to implement EUS-PCA in the context of a research trial.

A previous US trial reported a complete response rate at 12 months of 59%, with response maintained or further improved at 3 years. Of those with complete response, >95% of patients had not relapsed a median of 6 years after EUS-PCA. About 8% of patients in this trial underwent surgery for persistent cysts.

The trial will recruit patients with concerning IPMN features, for whom a multidisciplinary meeting recommends EUS-PCA as a treatment option. This patient group would usually be recommended to have surgery, but many patients decline surgery due to its high morbidity and significant mortality rates or are not candidates for this due to comorbidities or other issues. If EUS-PCA is successful, then it may ablate these precancerous lesions, treat patients who are not fit for surgery and reduce the incidence of invasive pancreatic adenocarcinoma. This is likely to reduce inequity for Māori, who are at higher risk of being ineligible for surgery for these lesions. While this is a small trial, we will also aim to recruit 50% Māori to further address inequity of opportunity and health outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eibhlin Corrigan; Phone Number: +64 (0)9 923 9643; Email: eibhlin.corrigan@auckland.ac.nz
• Study Contact Backup: Name: Sarah Benge; Phone Number: +64276045647; Email: s.benge@auckland.ac.nz

Study Locations

• New Zealand
  • Auckland, New Zealand
    • Te Whatu Ora Waitematā
    • Contact: Eibhlin Corrigan; Email: eibhlin.corrigan@auckland.ac.nz
  • Hamilton, New Zealand
    • Te Whatu Ora Waikato
    • Contact: Eibhlin Corrigan; Email: eibhlin.corrigan@auckland.ac.nz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Radiological diagnosis of branch duct IPMN.
• Cyst size of 3cm or worrying growth on serial imaging.
• Suitable to undergo endoscopy under deep sedation or general anaesthesia.
• Willing and able to comply with all trial requirements, including treatment, timing and/or nature of required assessments.
• Signed, written informed consent.

Exclusion Criteria:

• Presence of known or suspected pancreatic cancer or pathologic lymphadenopathy.

• Radiological diagnosis of IPMN with any of the following:

  1. Main pancreatic duct dilation of >10 mm
  2. Cytology with high grade dysplasia or "suspicious for malignancy"
  3. Common bile duct obstruction causing jaundice
  4. Septated cysts with > 4 compartments
  5. Epithelial type mural nodules (> 2mm)
  6. Lesions with thick wall/septation (> 2mm)
  7. High-grade communication with the main pancreatic duct
  8. Previous aspiration failure due to excessive cyst fluid viscosity

• Clinically significant laboratory abnormalities

  1. INR >= 1.7
  2. APTT > 80 secs
  3. Platelet count < 100 x 10E9/L
  4. ALT > 500 U/L
  5. Total bilirubin > 25 umol/L
• Evidence of pancreatitis within the last 6 months.
• History of hypersensitivity to gemcitabine or paclitaxel.
• Concurrent illness that may jeopardise the ability of the patient to safely undergo the procedures outlined in this protocol.
• Any medical condition that would, at the discretion of the investigator, interfere with the completion of and/or participation in the protocol.
• Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the trial protocol and follow-up schedule, including alcohol dependence or drug abuse.
• Pregnancy, lactation, or inadequate contraception.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single-arm; Gemcitabine 19 mg per 1 ml of estimated cyst fluid + paclitaxel 3 mg per 1 ml of estimated cyst fluid + 0.9% sodium chloride solution, given as a single administration	Procedure: Endoscopic ultrasound-guided pancreatic cyst chemoablation (EUS-PCA) using gemcitabine and paclitaxel; EUS-PCA using gemcitabine and paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients in whom EUS-PCA was completed as planned.	The proportion of patients in whom the cyst was aspirated and injected with the chemotherapy solution as intended, determined by the interventional endoscopist.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The IPMN complete response rate in the injected lesion(s) on imaging 3 months post-EUS-PCA.	The proportion with a complete response (CR) in the injected lesion on imaging 3 months after EUS-PCA a) in all recruited patients, and b) in those in whom EUS-PCA was successfully completed.; The proportion with CR at 3 months in Māori and non-Māori.; The safety of EUS-PCA in the first 30 days post-procedure.; The additional resource use required for this procedure compared to EUS and cyst aspiration alone.; Cyst characteristics according to radiological features and amylase, CEA, viscosity, and cytology from cyst fluid.	2 years

Collaborators and Investigators

• Sponsor: University of Auckland, New Zealand
• Collaborators: North Shore Hospital, New Zealand; Waikato Hospital; Gut Cancer Foundation, New Zealand
• Investigators: Study Chair: Michael B Jameson, PhD, University of Auckland, New Zealand

Study record dates

Study Major Dates

• Study Start (Estimated): May 31, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: November 20, 2023
• First Submitted That Met QC Criteria: November 30, 2023
• First Posted (Actual): December 8, 2023

Study Record Updates

• Last Update Posted (Actual): April 23, 2025
• Last Update Submitted That Met QC Criteria: April 21, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms, Glandular and Epithelial; Cysts; Neoplasms; Pancreatic Neoplasms; Pancreatic Cyst; Neoplasms, Cystic, Mucinous, and Serous; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Gemcitabine; Paclitaxel
• Other Study ID Numbers: CTNZ-2022-06

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No