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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат Gemcitabine
  Non-experimental. Chemotherapy will be administered on a day 1, 8 and 15 schedule with gemcitabine at a dose of 1000 mg/m2
• Препарат nab-paclitaxel
  Non-experimental. Chemotherapy will be administered on a day 1, 8 and 15 schedule with nab-paclitaxel dose at 125 mg/m2

Первичные конечные точки

• R0 resection rate [Срок оценки: 36 months]

Вторичные конечные точки (1)

• Ki-67 expression in tumor cells [Срок оценки: 36 months]

Критерии участия

Критерии включения

• Pancreatic Ductal Adenocarcinoma
• Plan for neoadjuvant chemotherapy
• Available diagnostic tissue adequate for biomarker analysis
• Ability to tolerate PO meds and comply with study procedures

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Другое

Центры проведения

США · 1 центр

• Columbia University Medical Center — New York

Идентификаторы

NCT: NCT05241249 · AAAT5285

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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