MedPath

Stimulation With Bethanechol in Combination With Gemcitabine and Nab-paclitaxel in Pancreatic Adenocarcinoma

Phase 2
Recruiting
Conditions
Pancreas Cancer
Interventions
Registration Number
NCT05241249
Lead Sponsor
Susan E. Bates
Brief Summary

The primary objective of this study is to assess the impact of bethanechol therapy on R0 resection rates. The safety objective will be assessment of the safety and tolerability of bethanechol in combination with gemcitabine and nab-paclitaxel. The exploratory objective will be to evaluate genomic biomarkers associated with parasympathetic stimulation in pancreatic cancer, and the ability to reduce tumor growth rate.

Detailed Description

The purpose of this study is to determine whether the drug, bethanechol, could potentially be used in combination with chemotherapy regimen gemcitabine and nab-paclitaxel and surgery to decrease the chance of the cancer coming back after it is removed. Animal models have shown that treatment with bethanechol can inhibit cancer growth and spread. The chemotherapy regimen nab-paclitaxel for use in combination with gemcitabine to treat patients with metastatic pancreatic cancer is FDA approved. Although bethanechol is FDA approved, in this study its use is experimental. The aim of the study is to show that the medication is easy to tolerate and that it shows signs of slowing cancer cell growth. The investigators hypothesize that treatment with bethanechol will alter nerve conduction within tumors by stimulating the parasympathetic nervous system and reduce tumor proliferation, decrease CD44+ expression in cancer cells, decrease tumor growth rate resulting in an improved R0 resection rate.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
37
Inclusion Criteria
  • Pancreatic Ductal Adenocarcinoma
  • Plan for neoadjuvant chemotherapy
  • Available diagnostic tissue adequate for biomarker analysis
  • Ability to tolerate PO meds and comply with study procedures
Exclusion Criteria
  • Metastatic disease
  • Evidence of GI obstruction
  • Baseline bradycardia (HR<55) or hypotension (systolic blood pressure<90)
  • Use of acetylcholinesterase inhibitors
  • Medical conditions including: hyperthyroidism, active/symptomatic coronary artery disease, seizure disorder, peptic ulcer disease.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Bethanecholnab-paclitaxelPatients with borderline resectable pancreatic cancer and no contraindication to bethanechol therapy will receive bethanechol on day 1 and continue until 2 days prior to scheduled surgery for a minimum of 2 months.
BethanecholBethanecholPatients with borderline resectable pancreatic cancer and no contraindication to bethanechol therapy will receive bethanechol on day 1 and continue until 2 days prior to scheduled surgery for a minimum of 2 months.
BethanecholGemcitabinePatients with borderline resectable pancreatic cancer and no contraindication to bethanechol therapy will receive bethanechol on day 1 and continue until 2 days prior to scheduled surgery for a minimum of 2 months.
Primary Outcome Measures
NameTimeMethod
R0 resection rate36 months

This rate will be analyzed in patients treated with bethanechol in combination with gemcitabine and nab-paclitaxel compared to historical R0 resection rates.

Secondary Outcome Measures
NameTimeMethod
Ki-67 expression in tumor cells36 months

This is to measure cell proliferation by Ki-67 expression in tumor cells, to quantify the change in tumor growth and alterations in inflammatory cytokines and immune profiles.

Trial Locations

Locations (1)

Columbia University Medical Center

🇺🇸

New York, New York, United States

© Copyright 2025. All Rights Reserved by MedPath