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

Pancreas Cancer Clinical Trial

Official title:

Phase II, Neoadjuvant Study of Parasympathetic Stimulation With Bethanechol in Combination With Gemcitabine and Nab-paclitaxel in Borderline Resectable Pancreatic Adenocarcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05241249
• Other study ID #: AAAT5285
• Status: Recruiting
• Phase: Phase 2
• Start date: February 1, 2022
• Est. completion date: January 2025

Study information

• Verified date: March 2024
• Source: Columbia University
• Contact: Research Nurse Navigator
• Phone: 212-342-5162
• Email: cancerclinicaltrials[@]cumc.columbia.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 37
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreas Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• Bethanechol
Study Drug: Bethanechol (generic), supplied as 50mg oral tablets. Subjects will take 2 tablets (100mg) twice daily. Medication should be taken 1 hour before meals in AM and PM. Medication will be purchased commercially and dispensed at the research pharmacy.
• Gemcitabine
Non-experimental. Chemotherapy will be administered on a day 1, 8 and 15 schedule with gemcitabine at a dose of 1000 mg/m2
• nab-paclitaxel
Non-experimental. Chemotherapy will be administered on a day 1, 8 and 15 schedule with nab-paclitaxel dose at 125 mg/m2

Locations

Country	Name	City	State
United States	Columbia University Medical Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Susan E. Bates

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	R0 resection rate	This rate will be analyzed in patients treated with bethanechol in combination with gemcitabine and nab-paclitaxel compared to historical R0 resection rates.	36 months
Secondary	Ki-67 expression in tumor cells	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.	36 months