Bethanechol Prior to Pancreatic Surgery

NCT03572283 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: AAAR6735
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to assess the impact of bethanechol therapy on tumor activity by looking at biomarkers of proliferation, inflammation, and stem cell markers in post-treatment specimens compared to pre-treatment specimens and compared to other patients who were not treated with bethanechol prior to surgery. The investigators hypothesize that treatment with bethanechol will alter nerve conduction within tumors by stimulating the parasympathetic nervous system and reduce tumor proliferation, reduce macrophage activation, reduce tumor necrosis factor (TNF) alpha, and decrease human cluster of differentiation 44 (CD44) protein cancer stem cells. The safety objective is to assess the safety and tolerability of short course bethanechol prior to surgery and the impact of this treatment on immediate surgical outcomes. The investigators will assess all treatment-related toxicities with an emphasis on GI side effects and evaluate the impact of therapy on surgical delays or immediate post-op complications. All subjects will be contacted 1 week after beginning therapy to assess toxicity including GI specific toxicity and followed for safety for 30 days following completion of study medication. The investigators hypothesize that treatment for a minimum of 1 week will be tolerable in this selected patient population and will not interfere with progression to surgery or lead to increased surgical complications.

Conditions

Pancreas Cancer

Keywords

Pancreas; pancreatic adenocarcinoma; adenocarcinoma; bethanechol; parasympathetic

Outcome Measures

Primary Outcomes (1)

• Change in cell proliferation by Ki-67 expression in tumor cells

  Individual tumor tissues will be evaluated, comparing pre-treatment and post-treatment samples. Percentage of change in proliferation/staining and standard deviation will be analyzed and calculated.

  Baseline, 28 days after surgery

Secondary Outcomes (1)

• Number of Adverse Events

  Baseline, 28 days after surgery

Study Arms (1)

Bethanechol

EXPERIMENTAL

Patients with pancreatic adenocarcinoma will receive bethanechol prior to pancreatic surgery

Drug: Bethanechol

Interventions

Bethanechol DRUG

Supplied as 50mg oral tablets. Take 2 tablets (total 100mg) twice daily from day 1 for a minimum of 1 week and a maximum of 4 weeks (or 2 days prior to scheduled surgery). Medication should be taken 1 hour before meals in the morning and the evening. Although bethanechol is FDA approved, in this study its use is experimental.

Also known as: Bethanechol chloride tablet

Bethanechol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Age ≥18 years of age on the day of signing informed consent.
• Have histologically or cytologically confirmed the diagnosis of resectable pancreatic ductal adenocarcinoma or be willing to undergo a biopsy with confirmed pathology prior to starting therapy.
• Have a predicted life expectancy of greater than 3 months.
• Have a performance status of 0 or 1 using the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale within 3 days of the first dose of study drug.
• Have a negative urine or serum pregnancy test within 7 days prior to receiving the first dose of study medication (Cycle 1, Day 1) (female subjects of childbearing potential). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

You may not qualify if:

• Has received prior chemotherapy or radiotherapy for a current episode of pancreatic adenocarcinoma.
• Is currently using an acetylcholinesterase inhibitor or a beta-blocker.
• Has active peptic ulcer disease as defined by documented peptic ulcer and symptoms uncontrolled with oral medication.
• Has a known hypersensitivity or allergy to bethanechol.
• Has uncontrolled hyperthyroidism, defined as clinical hyperthyroidism uncontrolled by oral medication.
• Has bradycardia with resting heart rate \< 50 beats per minute.
• Has chronic hypotension with resting systolic blood pressure \< 90 mmHg.
• Has symptomatic coronary artery disease, such as angina or symptoms of claudication
• Has vasomotor instability.
• Has seizure disorder or required anti-seizure medication for seizure prevention within 5 years prior to study entry.
• Has a history of Parkinson's disease.
• Has bronchial asthma.
• Has a history of recent urinary bladder surgery within 12 months of study entry.
• Has a history of gastrointestinal resection and anastomosis within 12 months of study entry.
• Has a history of current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Adenocarcinoma

Interventions

Bethanechol

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Bethanechol Compounds; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Onium Compounds

Study Officials

• Susan E Bates, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine at Columbia University Medical Ctr

Model Details: Phase 0 study to assess the impact of bethanechol on pancreatic cancer biomarkers

Study Record Dates

• First Submitted: May 8, 2018
• First Posted: June 28, 2018
• Study Start: April 8, 2018
• Primary Completion: July 25, 2023
• Study Completion: August 24, 2023
• Last Updated: June 5, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)