A Phase II, Randomized, Double-blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of the Combination of Gemcitabine and Metformin in Treating Patients With Pancreatic Cancer After Curative Resection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Recurrence-free survival at one year after curative resection
研究概览
简要总结
Pancreatic cancer represents the most lethal of the common malignancies with a 5-year survival rate of less than 5%. For patients who are eligible for potentially curative resection, despite mortality and morbidity rates after surgery have improved, the recurrence rate is up to 85% within 2 years. Data from clinical trials indicate that adjuvant chemotherapy enhances 5-year survival to ~25% for patients who have undergone surgery to remove their tumor; and gemcitabine is the standard regimen of chemotherapy. Metformin is the first-line treatment for type 2 diabetes mellitus. Literatures reported that metformin might inhibit tumor growth by blocking some enzymes needed for cell growth. Some retrospective studies have revealed that diabetic patients taking metformin were less likely to develop pancreatic cancer. Additionally, pancreatic cancer patients treated with metformin showed a better survival than those without metformin. In this study, the researchers intend to investigate the activity and safety of the combination of gemcitabine and metformin in treating patients with pancreatic cancer that have removed by surgery.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed content obtained prior to treatment
- •Age ≥ 18 years and ≤ 80 years
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Patients must have histologically confirmed pancreatic adenocarcinoma (or any mixed pathology if adenocarcinoma is predominant) after curative resection (R0). The pathological staging does not exceed the stage IIB.
- •No tumor lesions are seen by abdominal and thoracic CT scan 4~8 weeks after surgery, and no serious adverse events are occurred during this period
- •The expected survival after surgery ≥ 6 months
- •White blood cell (WBC) ≥ 3 × 10^9/L; Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L; Platelets (PLT) ≥ 100 × 10^9/L; Hemoglobin (Hgb) ≥ 9 g/dL
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]/ alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) ≤ 2.5 × institutional upper limit of normal (ULN); Total bilirubin (TBIL) ≤ ULN; Creatinine (CRE) ≤ 1.5 × ULN
- •Prothrombin time (PT) and international normalized ratio (INR) ≤ 1.5 × ULN
- •Patients with diabetes (diagnosed after surgery) are eligible for this trial; all diabetic patients who are enrolled on this study should discuss the need to change their diabetes management regimen with their primary care physician or endocrinologist prior to enrollment
- •Diabetic patients who are on metformin are eligible as long as they have been on metformin for less than 6 months (estimated 6 months or less duration of metformin therapy from start of metformin to enrollment on study)
排除标准
- •Active second primary malignancy or history of second primary malignancy within the last 3 years
- •Patients who have received any form of anti-tumor therapy before surgery, including chemotherapy, radiotherapy, interventional chemoembolization, radiofrequency ablation, and molecular targeted therapy
- •Use of any other investigational agents
- •Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, internal hemorrhage, pancreatic leakage, bile leakage, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •History of allergic reactions attributed to compounds of similar chemical or biological composition to metformin or gemcitabine
- •Current use of metformin for more than 6 months prior to enrollment on study
- •Metabolic acidosis, acute or chronic, including ketoacidosis
- •Pregnant or nursing women
- •Human immunodeficiency virus (HIV)-positive patients
- •Patients who are unwilling or unable to comply with study procedures
研究组 & 干预措施
gemcitabine + placebo
gemcitabine at 1000 mg/m^2 on days 1, 8, and 15; placebo at 2 g on days 1-28
干预措施: Gemcitabine (Drug)
gemcitabine + placebo
gemcitabine at 1000 mg/m^2 on days 1, 8, and 15; placebo at 2 g on days 1-28
干预措施: placebo (Drug)
gemcitabine + metformin
gemcitabine at 1000 mg/m^2 on days 1, 8, and 15; metformin at 2 g on days 1-28
干预措施: Gemcitabine (Drug)
gemcitabine + metformin
gemcitabine at 1000 mg/m^2 on days 1, 8, and 15; metformin at 2 g on days 1-28
干预措施: Metformin (Drug)
结局指标
主要结局
Recurrence-free survival at one year after curative resection
时间窗: From date of randomization (after curative resection) until the date of first documented recurrence or date of death from any cause, whichever came first, assessed 2 months during therapy and 3 months thereafter up to 24 months
To evaluate the therapeutic efficacy of gemcitabine chemotherapy with versus without metformin hydrochloride in terms of recurrence-free survival in patients with pancreatic cancer at one year after curative resection. Computed tomography (CT) scan
次要结局
- Overall survival after curative resection(From date of randomization (after curative resection) until the date of death from any cause, assessed one month during therapy and 3 months thereafter up to 24 months)
- Quality of life score after curative resection(One month during therapy and 3 months thereafter up to 24 months)
- Number of grade 3 and 4 toxicities according to NCI CTCAE version 4.0(One week during therapy and 3 months thereafter up to 24 months)
研究者
Xian-Jun Yu
M.D., Ph.D.
Fudan University