Metformin in Association to Chemoradiotherapy for the Neoadjuvant Treatment of Locally Advanced Rectal Cancer: a Randomized, Placebo-controlled Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Pathological Complete Response
研究概览
简要总结
A phase II, randomized study of placebo versus metformin in association to chemotherapy with capecitabine and radiation in the neoadjuvant treatment of locally advanced (T3-4N0M0 or TxN1-2M0) rectal carcinomas.
详细描述
NEOMETRE is a randomized, double blind trial aiming to evaluate the efficacy and tolerability of metformin in association to chemoradiotherapy for the preoperative treatment of locally advanced (T3-4N0M0 or TxN1-2M0) rectal carcinomas.
Patients eligible for this study will be submitted to neoadjuvant 3D radiotherapy with 50,4 Gray (Gy) divided in 25 applications, in association to capecitabine, 825mg/m2 bid for five days every week. The participants will be randomized to daily metformin or placebo during the chemoradiotherapy period. The primary end-point is pathological complete response. The secondary end-points are recurrence-free survival (RFS), disease-free survival (DFS), overall survival (OS), local recurrence rate, overall response rate, sphincter preservation rate, quality of life (QoL) and toxicity.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years or older;
- •biopsy proven poorly differentiated carcinoma or adenocarcinoma of the rectum;
- •lesions located within 12 cm of the anal verge (from colonoscopy assessment);
- •ability to tolerate oral treatment;
- •locally advanced tumor, classified by the presence of positive regional lymph nodes or primary tumor invasion beyond the serosa (T3 or T4), assessed by MRI;
- •eligibility for curative surgery (no distant metastasis or invasion of bony structures of the pelvis);
- •Performance Status (PS) Eastern Cooperative Oncology Group (ECOG) 0-2;
- •adequate hematologic functions (hemoglobin ≥ 10 g / dL [5.6 mmol / L]; neutrophil count ≥ 1,500 / mm3 and platelet count ≥ 100,000 / mm3), adequate renal function (serum creatinine less than 1.5 times the UNL) and adequate hepatic function (bilirubin less than 1.5 times the UNL; aspartate aminotransferase and alanine aminotransferase less than 2.5 times the UNL);
排除标准
- •known hypersensitivity to metformin or its excipients;
- •squamous carcinomas of the rectum or anal canal;
- •chronic treatment with corticosteroids or other immunosuppressive agents;
- •treatment with oral antidiabetic products;
- •distant metastasis at diagnosis or tumor invasion of pelvic bone structures that may proscribe curative intent surgery;
- •chronic or acute infections;
- •use of drugs under study up to four weeks prior to randomization;
- •pregnant or nursing patients;
- •prior radiotherapy to the pelvic region;
- •myocardial infarction up to six months prior to randomization, or uncontrolled ischemic heart disease;
- •congestive heart insufficiency New York Heart Association (NYHA) III-IV.
研究组 & 干预措施
Neoadjuvant capecitabine and metformin
- Capecitabine 825 mg/m2 bid D1-5, q7d, for five weeks;
- Metformin 2500mg/d for five weeks;
- 3D radiotherapy 50,4Gy divided in 25 fractions
干预措施: Radiotherapy (Radiation)
Neoadjuvant capecitabine and metformin
- Capecitabine 825 mg/m2 bid D1-5, q7d, for five weeks;
- Metformin 2500mg/d for five weeks;
- 3D radiotherapy 50,4Gy divided in 25 fractions
干预措施: Capecitabine (Drug)
Neoadjuvant capecitabine and metformin
- Capecitabine 825 mg/m2 bid D1-5, q7d, for five weeks;
- Metformin 2500mg/d for five weeks;
- 3D radiotherapy 50,4Gy divided in 25 fractions
干预措施: Metformin (Drug)
Neoadjuvant capecitabine and placebo
- Capecitabine 825 mg/m2 bid D1-5, q7d, for five weeks;
- Placebo 2500mg/d for five weeks;
- 3D radiotherapy 50,4Gy divided in 25 fractions
干预措施: Capecitabine (Drug)
Neoadjuvant capecitabine and placebo
- Capecitabine 825 mg/m2 bid D1-5, q7d, for five weeks;
- Placebo 2500mg/d for five weeks;
- 3D radiotherapy 50,4Gy divided in 25 fractions
干预措施: Radiotherapy (Radiation)
Neoadjuvant capecitabine and placebo
- Capecitabine 825 mg/m2 bid D1-5, q7d, for five weeks;
- Placebo 2500mg/d for five weeks;
- 3D radiotherapy 50,4Gy divided in 25 fractions
干预措施: Placebo (Drug)
结局指标
主要结局
Pathological Complete Response
时间窗: 8 to 16 weeks after neoadjuvant treatment completion
Pathological evaluation of the surgical specimen. Complete response will be defined as absence of neoplastic tissue upon pathological exam.
次要结局
- Sphincter Preservation Rate(8 to 16 weeks after neoadjuvant treatment completion)
- Local Recurrence Free Survival(up to 5 years)
- Local Recurrence Rate(up to 5 years)
- Overall Response Rate(4 to 6 weeks after neoadjuvant treatment completion)
- Toxicity will be assessed using National Cancer Institute Common Toxicity Criteria for Adverse Effects (NCI CTCAE) v4.03(up to 4 weeks after neoadjuvant treatment completion)
- Disease Free Survival(up to 5 years)
- Overall Survival(up to 5 years)
- Quality of Life(up to 20 weeks after neoadjuvant treatment completion)
研究者
Ligia Traldi Macedo
Clinical Oncology
University of Campinas, Brazil