FOLFOX and Bevacizumab With or Without Irinotecan in First-line Treatment for Metastatic Colorectal Cancer. A Randomized Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 250
- 试验地点
- 51
- 主要终点
- progression free survival rate
研究概览
简要总结
The primary objective of this study is to evaluate the efficacy of Irinotecan in combination with FOLFOX+Bevacizumab versus FOLFOX+Bevacizumab alone in the first-line treatment of patients with metastatic colorectal cancer.
详细描述
5-Fluorouracil and oxaliplatin (FOLFOX-Regimen) in combination with bevacizumab is regarded as standard first-line treatment in metastatic colorectal cancer [Saltz et al., 2008]. Current studies established the role of the FOLFOXIRI regimen [Souglakos et al., 2006, Falcone et al., 2007]. A further intensification of the therapy seems feasible yielding response rates up to 84% and a disease control rate up to 100% [Falcone, 2008, Santomaggio, 2009, Masi, 2010]. This trial evaluates the activity of an intensified first-line therapy for metastatic colorectal cancer compared to standard treatment.
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
- 是
入选标准
- •Patients with histologically confirmed diagnosis of stage IV (UICC) colorectal cancer (primary tumor may be present)
- •Patients with at least one measurable lesion, with size > 1 cm (RECIST v1.1)
- •ECOG Performance status ≤ 2 (ECOG 2, only if tumor related)
- •Patients, who are able to tolerate intensive first lien treatment as judged by the investigator
- •Life expectancy > 3 months
- •Age ≥ 18 years
- •Haematologic function: ANC ≥ 1.5 x 109/L, platelets ≥ 100 x109/L, hemoglobin
- •9 g/dl or 5.59 mmol/l
- •Patients not receiving therapeutic anticoagulation must have an INR < 1.5 ULN and aPTT < 1.5 ULN within 7 days prior to registration. The use of full dose anticoagulants is allowed as long as the INR or aPTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least two weeks at the time of registration.
- •Adequate liver function as measured by serum transaminases (AST & ALT) ≤ 2.5 x ULN (in case of liver metastases < 5 x ULN) and total bilirubin ≤ 1.5 x ULN
- •Adequate renal function: Serum creatinine ≤ 1.5 x ULN
- •Signed, written informed consent
排除标准
- •Patients with histologically confirmed diagnosis of stage IV (UICC) colorectal cancer (primary tumor may be present)
- •Patients with at least one measurable lesion, with size > 1 cm (RECIST v1.1)
- •ECOG Performance status ≤ 2 (ECOG 2, only if tumor related)
- •Patients, who are able to tolerate intensive first lien treatment as judged by the investigator
- •Life expectancy > 3 months
- •Age ≥ 18 years
- •Haematologic function: ANC ≥ 1.5 x 109/L, platelets ≥ 100 x109/L, hemoglobin
- •9 g/dl or 5.59 mmol/l
- •Patients not receiving therapeutic anticoagulation must have an INR < 1.5 ULN and aPTT < 1.5 ULN within 7 days prior to registration. The use of full dose anticoagulants is allowed as long as the INR or aPTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least two weeks at the time of registration.
- •Adequate liver function as measured by serum transaminases (AST & ALT) ≤ 2.5 x ULN (in case of liver metastases < 5 x ULN) and total bilirubin ≤ 1.5 x ULN
- •Adequate renal function: Serum creatinine ≤ 1.5 x ULN
- •Signed, written informed consent
研究组 & 干预措施
FOLFOX+Bevacizumab
bevacizumab at a dose of 5 mg/kg iv over 30 to 90 min (day 1) oxaliplatin at a dose of 85 mg/m2 iv over two hours (day 1) I-LV at a dose of 200 mg/m2 iv over two hours (day 1) 5-FU at a dose of 3200 mg/ m2 iv over 48 hours (day 1-3)
干预措施: Oxaliplatin, 5FU/LV, Bevacizumab (Drug)
FOLFOX+Bevacizumab+Irinotecan
bevacizumab at a dose of 5 mg/kg iv over 30 to 90 min (day 1) irinotecan at a dose of 165 mg/m2 iv over two hours (day 1) oxaliplatin at a dose of 85 mg/m2 iv over two hours (day 1) I-LV at a dose of 200 mg/m2 iv over two hours (day 1) 5-FU at a dose of 3200 mg/ m2 iv over 48 hours (day 1-3)
干预措施: 5FU/LV, Oxaliplatin, Bevacizumab, Irinotecan (Drug)
结局指标
主要结局
progression free survival rate
时间窗: 9 months after first study drug administration
次要结局
- Progression free survival rate(until progression of disease for a maximum of two years after end of treatment)
- Overall survival(until death for a maximum of two years after end of treatment)
- Adverse events(18 months after the date of last study drug administration)
- Quality of Life evaluated by questionnaire(Until end of treatment (maximum 2 years after first study drug administration))
- tumour response according to RECIST v 1.1(until progression of disease for a maximum of two years after end of treatment)
- Secondary resection rate(for a maximum of two years after end of treatment)
研究者
Hans-Joachim Schmoll, MD
MD
Martin-Luther-Universität Halle-Wittenberg