Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Gastrointestinal Agents

All Drugs and Chemicals

Pancrelipase

Pancreatin

Bethanechol

Muscarinic Agonists

Cholinergic Agents

Neurotransmitter Agents

Patients with pancreatic adenocarcinoma will receive bethanechol prior to pancreatic surgery

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.

Research Nurse Navigator

Susan Bates, MD

Susan E Bates, MD

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.

Pancreatic ductal adenocarcinoma (PDA) is one of the most difficult cancers and, unlike other common cancers, annual deaths from PDA are rising. During the year 2017, it was estimated that 53,670 people would be diagnosed with PDA and approximately 43,090 people would die in the U.S. Despite recent advances, cytotoxic chemotherapy for PDA has been disappointing with response rates of 20-30% for the most active regimens and little activity for targeted therapies. Even among the small subset of patients who are suitable for surgical resection at the time of diagnosis, complete resection is followed by recurrence in \>90% of patients without further systemic therapy, with a median time to recurrence of 6.9 months. Thus all PDA patients require systemic chemotherapy and more effective regimens are urgently needed.

The purpose of this study is to determine whether the drug, bethanechol, could potentially be used in combination with surgery to decrease the chance of cancer coming back after it is removed. Bethanechol is a medication that is approved by the FDA and regulates the parasympathetic nervous system. It is used to treat dry mouth and for patients who have difficulty urinating. It has been used to manage the side effects of chemotherapy drugs. The investigators planned this study in pancreatic cancer because animal models have shown that treatment with bethanechol can inhibit cancer growth and spread. People with pancreatic cancer localized to a small area usually undergo surgery to remove the tumor. The study is designed to investigate that the medication is easy to tolerate and that it shows signs of slowing cancer cell growth.

.

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

Bethanechol Prior to Pancreatic Surgery

Phase 1 Window of Opportunity Study of Parasympathetic Stimulation With Bethanechol in Localized Pancreatic Adenocarcinoma Prior to Surgery

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.

Subjects will be contacted every week (+/- 3 days) after the start of treatment to approximately 28 days after surgery.

Columbia University

Professor of Medicine at Columbia University Medical Ctr

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Patients 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.

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.

Non-experimental. Chemotherapy will be administered on a day 1, 8 and 15 schedule with gemcitabine at a dose of 1000 mg/m2

Non-experimental. Chemotherapy will be administered on a day 1, 8 and 15 schedule with nab-paclitaxel dose at 125 mg/m2

nab-paclitaxel

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.

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.

This is a Phase IIA study evaluating short term parasympathetic activation with fixed dose bethanechol in subjects with pancreatic cancer who should proceed to surgery after 4 -6 months of chemotherapy.

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

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

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

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Bethanechol Prior to Pancreatic Surgery	NCT03572283	Pancreas Cancer	Bethanechol	18 Years -	Columbia University
Bethanechol Prior to Pancreatic Surgery	NCT03572283	Pancreas Cancer	Bethanechol	18 Years -	Columbia University
Stimulation With Bethanechol in Combination With Gemcitabine and Nab-paclitaxel in Pancreatic Adenocarcinoma	NCT05241249	Pancreas Cancer	Bethanechol Gemcitabine nab-paclitaxel	18 Years -	Columbia University
Stimulation With Bethanechol in Combination With Gemcitabine and Nab-paclitaxel in Pancreatic Adenocarcinoma	NCT05241249	Pancreas Cancer	Bethanechol Gemcitabine nab-paclitaxel	18 Years -	Columbia University

Spots Global Cancer Trial Database for parasympathetic