A Pharmacodynamic Study of Metformin in Patients With Resectable Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Pancreatic tumor cell proliferation and apoptosis as measured by the percentage of cells Ki-67+, percentage of cells TUNEL+, and mitotic counts in tissue samples
研究概览
简要总结
This randomized clinical trial studies metformin hydrochloride in treating patients with pancreatic cancer that can be removed by surgery. Metformin hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. To determine the effect of escalating doses of metformin (metformin hydrochloride) given pre-operatively on pancreatic cancer cell proliferation and apoptosis.
SECONDARY OBJECTIVES:
I. To assess toxicity of escalating doses of metformin given pre-operatively in patients with resectable pancreatic carcinoma.
II. To measure the effect of metformin on the expression of phosphorylated acetyl-CoA carboxylase alpha (ACC), phosphorylated mechanistic target of rapamycin (serine/threonine kinase) (mTOR), and pancreatic cancer stem cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •Patients must have histologically or cytologically confirmed resectable pancreatic carcinoma; patients with pancreatic neuroendocrine tumors are not eligible
- •Patients must be previously untreated with chemotherapy or radiation therapy
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- •Patients must have surgical resection of the pancreas planned, with enrollment at least 7 days prior to surgery; patients with surgery scheduled > 15 days will not be excluded
- •Hemoglobin (Hg)A1C must be below 7%
- •Total bilirubin less than 1.5 X institutional upper limit of normal
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 X institutional upper limit of normal
- •Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
- •Serum creatinine within normal institutional limits
- •Alkaline phosphatase < 1.5 X institutional upper limit of normal
- •Subjects must have the ability to understand and be willing to provide written informed consent
排除标准
- •History of metformin use in the previous 3 months
- •Treatment with neoadjuvant chemotherapy or radiation therapy
- •History of allergic reactions attributed to metformin
- •Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Metabolic acidosis, acute or chronic, including ketoacidosis
- •Metastatic disease
研究组 & 干预措施
Group II (metformin hydrochloride)
Patients receive metformin hydrochloride PO BID for at least 7 days in the absence of disease progression or unacceptable toxicity.
干预措施: metformin hydrochloride (Drug)
Group II (metformin hydrochloride)
Patients receive metformin hydrochloride PO BID for at least 7 days in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Group III (metformin hydrochloride)
Patients receive metformin hydrochloride as in Group II.
干预措施: metformin hydrochloride (Drug)
Group III (metformin hydrochloride)
Patients receive metformin hydrochloride as in Group II.
干预措施: pharmacological study (Other)
结局指标
主要结局
Pancreatic tumor cell proliferation and apoptosis as measured by the percentage of cells Ki-67+, percentage of cells TUNEL+, and mitotic counts in tissue samples
时间窗: At time of surgery (after 7 days of treatment)
The difference between treatment groups will be compared using analysis of variance (ANOVA) (3 groups) followed by Tukey's pair-wise comparison procedure. Transformation may be applied (e.g. natural log) prior to analysis to better approximate normality.
次要结局
- Expression of pACC and pMTOR quantified by the mean fluorescence intensity (MFI) in tissue samples(At time of surgery (after 7 days of treatment))
- Percentage of pancreatic cancer stem cells in tissue samples(At time of surgery (after 7 days of treatment))
- Occurrence of grade 3 and 4 toxicities according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE; version 4.0)(Baseline to 30 days after treatment has been discontinued or after the date of surgery, whichever occurs first)