Phase II, Neoadjuvant Study of Parasympathetic Stimulation With Bethanechol in Combination With Gemcitabine and Nab-paclitaxel in Borderline Resectable Pancreatic Adenocarcinoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- R0 resection rate
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pancreatic Ductal Adenocarcinoma
- •Plan for neoadjuvant chemotherapy
- •Available diagnostic tissue adequate for biomarker analysis
- •Ability to tolerate PO meds and comply with study procedures
排除标准
- •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.
研究组 & 干预措施
Bethanechol
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.
干预措施: Bethanechol (Drug)
Bethanechol
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.
干预措施: Gemcitabine (Drug)
Bethanechol
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.
干预措施: nab-paclitaxel (Drug)
结局指标
主要结局
R0 resection rate
时间窗: 36 months
This rate will be analyzed in patients treated with bethanechol in combination with gemcitabine and nab-paclitaxel compared to historical R0 resection rates.
次要结局
- Ki-67 expression in tumor cells(36 months)
研究者
Susan E. Bates
Associate Professor of Medicine
Columbia University