Open-label, Multicenter, Phase II Study Of First-line Biweekly Irinotecan, Oxaliplatin And Infusional 5-FU/LV (FOLFOXIRI) In Combination With Bevacizumab In Patients With Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 57
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
This is a single-arm, open-label, multicentre phase II study evaluating the safety and efficacy of the combination of the G.O.N.O. FOLFOXIRI regimen with bevacizumab as first-line treatment of metastatic colorectal cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed colorectal adenocarcinoma
- •Unresectable and measurable metastatic disease (RECIST criteria)
- •Male or female, aged > 18 years and ≤ 75 years
- •ECOG Performance Status (PS) < 2 if aged < 71 years
- •ECOG PS = 0 if aged 71-75 years
- •Life expectancy of more than 3 months
- •Adequate haematological function: ANC ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L, Hb ≥ 9 g/dL
- •INR ≤ 1.5 and aPTT ≤ 1.5 x ULN within 7 days prior to starting study treatment
- •Adequate liver function: serum bilirubin ≤ 1.5 x ULN; alkaline phosphatase and transaminases ≤ 2.5 x ULN (in case of liver metastases < 5 x ULN)
- •Serum Creatinine ≤ 1.5 x ULN
- •Urine dipstick for proteinuria < 2+. If urine dipstick is ≥ 2+, 24- hour urine must demonstrate ≤ 1 g of protein in 24 hours
- •Previous adjuvant chemotherapy is allowed if more than 12 months have elapsed between the end of adjuvant therapy and first relapse
- •At least 6 weeks from prior radiotherapy and 4 weeks from surgery
排除标准
- •Prior palliative chemotherapy
- •Prior treatment with bevacizumab
- •Bowel obstruction (or subobstruction)
- •History of inflammatory enteropathy or extensive intestinal resection (> hemicolectomy or extensive small intestine resection with chronic diarrhea)
- •Symptomatic peripheral neuropathy > 2 grade NCIC-CTG criteria
- •Presence or history of CNS metastasis
- •Active uncontrolled infections
- •Active disseminated intravascular coagulation
- •Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to treatment, or anticipation of the need for major surgery during the course of the study
- •Central Venous Access Device (CVAD) for chemotherapy administration inserted within 2 days prior to study treatment start
- •Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin cancer or in situ carcinoma of the cervix
- •Clinically significant cardiovascular disease, for example cerebrovascular accidents (CVA) (≤ 6 months before treatment start), myocardial infarction (≤ 6 months before treatment start), unstable angina, NYHA ≥ grade 2 chronic heart failure (CHF), uncontrolled arrhythmia
- •Uncontrolled hypertension
- •24-hour urine protein > 1 g if dipstick > 2+
- •History of thromboembolic or hemorrhagic events within 6 months prior to treatment
- •Evidence of bleeding diathesis or coagulopathy
- •Serious, non healing wound/ulcer or serious bone fracture
- •No therapeutic anticoagulation or antiplatelet agents or NSAID with anti-platelet activity (aspirin ≤ 325 mg/day allowed)
- •Pregnancy or lactation
- •Fertile women (< 2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception
研究组 & 干预措施
FOLFOXIRI plus bevacizumab
BEVACIZUMAB 5 mg/Kg i.v. followed by IRINOTECAN 165 mg/sqm i.v. over 1 hr followed by OXALIPLATIN 85 mg/sqm i.v. over 2 hr concomitantly with l-LV 200 mg/sqm over 2 hrs followed by 5FU 3.200 mg/sqm c.i. over 48 hrs starting on day 1. Cycles repeated every 2 weeks
干预措施: Bevacizumab (Drug)
FOLFOXIRI plus bevacizumab
BEVACIZUMAB 5 mg/Kg i.v. followed by IRINOTECAN 165 mg/sqm i.v. over 1 hr followed by OXALIPLATIN 85 mg/sqm i.v. over 2 hr concomitantly with l-LV 200 mg/sqm over 2 hrs followed by 5FU 3.200 mg/sqm c.i. over 48 hrs starting on day 1. Cycles repeated every 2 weeks
干预措施: Irinotecan (Drug)
FOLFOXIRI plus bevacizumab
BEVACIZUMAB 5 mg/Kg i.v. followed by IRINOTECAN 165 mg/sqm i.v. over 1 hr followed by OXALIPLATIN 85 mg/sqm i.v. over 2 hr concomitantly with l-LV 200 mg/sqm over 2 hrs followed by 5FU 3.200 mg/sqm c.i. over 48 hrs starting on day 1. Cycles repeated every 2 weeks
干预措施: Oxaliplatin (Drug)
FOLFOXIRI plus bevacizumab
BEVACIZUMAB 5 mg/Kg i.v. followed by IRINOTECAN 165 mg/sqm i.v. over 1 hr followed by OXALIPLATIN 85 mg/sqm i.v. over 2 hr concomitantly with l-LV 200 mg/sqm over 2 hrs followed by 5FU 3.200 mg/sqm c.i. over 48 hrs starting on day 1. Cycles repeated every 2 weeks
干预措施: 5-fluorouracil/leucovorin (Drug)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: PFS rate at 10 months from study entry
PFS was calculated from the day of treatment start to the first observation of disease progression or death from any cause.
次要结局
- Response rate (RR)(2007-2010)
- Overall survival (OS)(2007-2010)
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability(2007-2010)
- Evaluation of potential surrogate markers predictive of bevacizumab activity(2007-2010)