NCT02295930已完成2 期
Induction Chemotherapy With Folfoxiri Plus Cetuximab and Maintenance With Cetuximab or Bevacizumab Therapy in Unresectable Kras Wild-type Metastatic Colorectal Cancer Patients
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 143
- 试验地点
- 22
- 主要终点
- 10 months-progression free rate (10m-PFR)
研究概览
简要总结
This is a phase II randomized study of 4-months induction first-line chemotherapy with FOLFOXIRI + cetuximab followed by maintenance with cetuximab or bevacizumab in patients affected by KRAS wild type (wt) mCRC.
详细描述
The aim of the study is to obtain a rapid disease control with the therapy and the maximum tumoral shrinkage, and than to treat patient with less intensive maintenance to inhibit tumoral regrowth.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed colorectal adenocarcinoma;
- •Availability of formalin-fixed paraffin embedded tumor block from primary and/or metastasis;
- •KRAS wild-type status of primary colorectal cancer or related metastasis;
- •Unresectable and measurable metastatic disease according to RECIST criteria;
- •Male or female, aged > 18 years and < 75 years;
- •ECOG 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;
- •Adequate liver and renal 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;
- •Previous adjuvant chemotherapy containing oxaliplatin is allowed if more than 12 months have elapsed between the end of adjuvant therapy and first relapse;
- •Previous adjuvant chemotherapy with fluoropyrimidine monotherapy is allowed if more than 6 months have elapsed between the end of adjuvant and first relapse;
- •At least 6 weeks from prior extended radiotherapy and 4 weeks from surgery;
- •Written informed consent to experimental treatment and KRAS analysis.
排除标准
- •Prior palliative chemotherapy;
- •Prior treatment with EGFR or VEGF inhibitors;
- •Symptomatic peripheral neuropathy > 2 grade NCIC-CTG criteria;
- •Presence or history of CNS metastasis;
- •Active uncontrolled infections; active disseminated intravascular coagulation;
- •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: cerebrovascular accidents or myocardial infarction ≤ 12 months before treatment start, unstable angina, NYHA ≥ grade 2 chronic heart failure, uncontrolled arrhythmia, uncontrolled hypertension;
- •Serious, non-healing wound, ulcer, or bone fracture;
- •Evidence of bleeding diathesis or coagulopathy;
- •Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start;
- •Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes or chronic, daily treatment with high-dose aspirin (>325 mg/day);
- •Subtotal colectomy, malabsorption syndrome and chronic inflammatory bowel disease (i.e. ulcerative colitis, Chron syndrome);
- •Fertile women (<2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception.
- •Psychiatric disorder precluding understanding of information on trial related topics,
- •Serious underlying medical condition (judged by the investigator) which could impair the ability of the patient to participate in the trial (e.g. uncontrolled diabetes mellitus, active autoimmune disease)
- •Concurrent treatment with other experimental drugs or other anti-cancer therapy; treatment in a clinical trial within 30 days prior to trial entry
- •Definite contraindications for the use of corticosteroids and antihistamines as premedication
- •Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs
- •Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies
- •Pregnancy
- •Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
- •Medical or psychological condition which, in the opinion of the investigator, would not permit the patient to complete the study or sign meaningful informed consent
研究组 & 干预措施
folfoxiri+cetuximab+surgery+cetuximab
Experimental
Induction FOLFOXIRI plus cetuximab will consist of:
- CETUXIMAB 500 mg/sqm IV over 1-h* , day 1 followed by
- IRINOTECAN 130 mg/sqm IV over 1-h, day 1 followed by
- OXALIPLATIN 85 mg/sqm IV over 2-h, day 1 concomitantly with
- l-LV 200 mg/sqm IV over 2-h, day 1 followed by
- 5-FLUOROURACIL 2400 mg/sqm IV 48-h continuous infusion, starting on day 1 repeated every 2 weeks for 8 cycles.
Surgical revaluation will be performed after the induction phase (8 cycles).
Patients deemed unsuitable for surgery will received maintenance treatment as follows:
•CETUXIMAB 500 mg/sqm IV over 60-min, day 1 repeated every 2 weeks until PD, patient's refusal, unacceptable toxicity or consent withdrawal.
干预措施: folfoxiri+cetuximab+surgery+cetuximab (Other)
folfoxiri+cetuximab+surgery+bevacizumab
Experimental
Induction FOLFOXIRI plus cetuximab will consist of:
- CETUXIMAB 500 mg/sqm IV over 1-h* , day 1 followed by
- IRINOTECAN 130 mg/sqm IV over 1-h, day 1 followed by
- OXALIPLATIN 85 mg/sqm IV over 2-h, day 1 concomitantly with
- l-LV 200 mg/sqm IV over 2-h, day 1 followed by
- 5-FLUOROURACIL 2400 mg/sqm IV 48-h continuous infusion, starting on day 1 repeated every 2 weeks for 8 cycles.
Surgical revaluation will be performed after the induction phase (8 cycles).
Patients deemed unsuitable for surgery will received maintenance treatment as follows:
•BEVACIZUMAB 5 mg/kg IV over 30-min, day 1 repeated every 2 weeks until PD, patient's refusal, unacceptable toxicity or consent withdrawal.
干预措施: folfoxiri+cetuximab+surgery+bevacizumab (Other)
结局指标
主要结局
10 months-progression free rate (10m-PFR)
时间窗: up to 10 months
10m-PFR is defined as the proportion of patients free from disease progression 10 months after randomization, relative to the total of enrolled patients. Patients whose disease status cannot be evaluated within 11 months after randomization and patients lost to follow up or dead within 10 months after randomization will be considered as progressed for the purpose of the primary endpoint analyses.
次要结局
- Best overall response rate(every 8 weeks, up to 60 months)
- 10 month resection rate(within 10 months after randomization)
- Time to strategy failure(from randomization, up to 60 months)
- Time to 2nd progressive disease(from randomization, up to 60 months)
- Progression free survival (PFS)(from randomization to first documentation of objective disease progression or death, up to 60 months)
- Overall survival (OS)(as the time from randomization to the date of death, up to 60 months)
- Toxicity rate(during the induction and the maintenance phases of treatment)
- Overall toxicity rate(during the induction and the maintenance phases of treatment)
研究者
研究点 (22)
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