Tissue Pharmacokinetics of Intraoperative Gemcitabine in Resectable Adenocarcinoma of the Pancreas
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Gemcitabine DNA Levels in Human Pancreatic Cancer Tissue
研究概览
简要总结
The goal of this clinical research study is to learn if gemcitabine can enter pancreas cancer cells, to measure the amount of it that may enter the cells, and for biomarker testing. Biomarkers may be related to participant's reaction to the study drug.
详细描述
The Study Drugs:
Gemcitabine is a drug used to treat pancreatic cancer. However, there are no studies that show that gemcitabine is able to enter pancreatic cancer cells.
Losartan is a drug that lowers blood pressure. It also may increase the amount of gemcitabine that reaches the cancer cells. Participant may be asked to take this drug before participant's surgery.
Before Surgery:
If participant is found to be eligible and participant agrees to take part in this study, the following tests will be done before participant's surgery:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Cytologic or histologic proof of adenocarcinoma of the pancreas is required. Patients with Islet cell tumors are not eligible.
- •Patients do not have known metastases.
- •Patients must have potentially resectable pancreatic cancer and have agreed to undergo surgical resection at M D Anderson Cancer Center. They will have undergone staging (physical examination, chest x-ray, contrast enhanced CT or MRI (if CT contraindicated) and/or angiogram to determine resectability. Potentially resectable is defined as:No extra-pancreatic disease; No evidence (on CT/MRI) of tumor extension to the celiac axis or SMA; No evidence (CT/MRI or angiogram) of occlusion of the SMV or SMPV confluence.
- •Patients with a Karnofsky performance status greater than 70 are eligible.
- •There will be no upper age restriction. Patients less than 18 years of age are excluded from the protocol because adenocarcinoma of the pancreas is rarely seen in the pediatric population.
- •Adequate renal, and bone marrow function: Leukocytes >= 3,000/uL; Absolute neutrophil count >= 1,500/uL; Platelets >= 100,000/Ul; Serum creatinine <= 2.0 mg/dL.
- •Adequate Hepatic function (endoscopic or percutaneous drainage as needed): Total bilirubin < = 3 X institutional upper limits of normal (ULN); AST (SGOT)/ALT (SGPT) <= 5 X institutional ULN.
- •Patients must have no fever or evidence of infection or other coexisting medical condition that would preclude administration of gemcitabine. Patients with uncontrolled congestive heart failure, unstable angina and myocardial infarction within 3 months will be excluded.
- •Patient is not pregnant. Women of childbearing potential (defined as those who have not undergone a hysterectomy or who have not been postmenopausal for at least 24 consecutive months) must agree to practice adequate contraception and to refrain from breast-feeding, as specified in the informed consent.
- •Patients must sign a study-specific consent form.
排除标准
- •Patient has received preoperative chemotherapy and/or radiation.
- •Major cardiovascular or pulmonary comorbidity that precludes use of general anesthesia.
- •Identification of metastatic disease.
- •Inability to comply with study and/or follow-up procedures.
- •Patients < 18 years of age.
研究组 & 干预措施
Intraoperative Gemcitabine
Gemcitabine administered by the anesthesiologist as a dose of 1,000mg/m2 at a fixed dose rate of 10mg/m2/min. Drug infusion started 100 minutes prior to complete gross tumor removal in order to have drug administration complete at tumor removal.
干预措施: Gemcitabine (Drug)
Intraoperative Gemcitabine + Losartan
Losartan 50 mg by mouth daily for one week and 50 to 100 mg of Losartan by mouth daily for at least 1 week and at most 3 weeks prior to surgical resection.
Gemcitabine administered by the anesthesiologist as a dose of 1,000mg/m2 at a fixed dose rate of 10mg/m2/min. Drug infusion started 100 minutes prior to complete gross tumor removal in order to have drug administration complete at tumor removal.
干预措施: Gemcitabine (Drug)
Intraoperative Gemcitabine + Losartan
Losartan 50 mg by mouth daily for one week and 50 to 100 mg of Losartan by mouth daily for at least 1 week and at most 3 weeks prior to surgical resection.
Gemcitabine administered by the anesthesiologist as a dose of 1,000mg/m2 at a fixed dose rate of 10mg/m2/min. Drug infusion started 100 minutes prior to complete gross tumor removal in order to have drug administration complete at tumor removal.
干预措施: Losartan (Drug)
结局指标
主要结局
Gemcitabine DNA Levels in Human Pancreatic Cancer Tissue
时间窗: Before surgery, participants followed 30 days post surgery
CT scans analyzed, mapping 3 to 4 areas of pancreatic tumor based on differential enhancement patterns within the tumors, where each selected region is uniform within 5-10 HU at each phase of the CT. Each region will comprise no more than 33% of the greatest size of the tumor. Model parameters for each region plugged into the predictive equations for YVmax, YTmax, R0, and AUC.
Intratumoral Gemcitabine Levels in Human Pancreatic Cancer Tissue
时间窗: Collection during surgery, participants followed 30 days post surgery
Pharmacokinetic (PK) Testing of up to 10 blood samples (about 1 tablespoon each time) drawn during surgery starting before gemcitabine infusion and at end of surgery. Blood samples used to measure levels of gemcitabine in blood at the different time points.
次要结局
- Effect of Losartan on Gemcitabine DNA Incorporation Human Pancreatic Cancer Tissue(Before surgery, participants followed 30 days post surgery)