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

Susan E. Bates

Status and phase: Enrolling; Phase 2

Conditions: Pancreas Cancer

Treatments: Drug: nab-paclitaxel; Drug: Gemcitabine; Drug: Bethanechol

Study type: Interventional

Funder types: Other

Identifiers

NCT05241249

AAAT5285

Details and patient eligibility

About

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.

Full 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.

Enrollment: 37 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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37 participants in 1 patient group

Bethanechol

Experimental group

Description:

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.

Treatment:

Drug: Bethanechol

Drug: Gemcitabine

Drug: nab-paclitaxel