Cetuximab Added to Capecitabine, Oxaliplatin and Bevacizumab in Patients With Previously Untreated Advanced Colorectal Carcinoma, a Randomised Phase III Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 750
- 试验地点
- 1
- 主要终点
- progression free survival
研究概览
简要总结
This is a study to assess the efficacy and safety of the addition of cetuximab to the combined regimen of capecitabine, oxaliplatin and bevacizumab in patients with previously untreated advanced colorectal carcinoma. It is an open, comparative study, comparing the effects of capecitabine, oxaliplatin and bevacizumab to those of the same regimen plus cetuximab.
Seven hundred fifty patients will be included. Treatment will continue until disease progression or serious toxicity and follow up will continue until death. It is anticipated that the addition of cetuximab will lead to an increase in progression free survival.
详细描述
Primary objective: To assess the efficacy, defined as progression-free survival (PFS), of adding cetuximab to capecitabine/oxaliplatin/bevacizumab for advanced CRC.
Secondary objectives: To assess tumour response (CR, PR or SD), response duration, overall survival, toxicity profile, quality of life, translational research.
Methodology: Open, randomised multicenter phase III study. The number of patients is 750.
Test products: All cycles will be administered q 3 weeks. Oxaliplatin will be discontinued after 6 cycles in both study arms. The dose of capecitabine will be increased to 1250 mg/m2 b.i.d. as of cycle 7.
Arm A: capecitabine 1000 mg/m2 orally b.i.d. on day 1-14 (1250 mg/m2 after 6 cycles), oxaliplatin 130 mg/m2 i.v. infusion on day 1 during 6 cycles, bevacizumab 7.5 mg/kg i.v. infusion on day 1.
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
- 否
入选标准
- •Histology and Staging Disease
- •Histologically proven advanced colorectal cancer (CRC); not amenable to curative surgery
- •Of Note: In case of a single metastasis, histological or cytological proof of colorectal carcinoma should be obtained prior to randomisation.
- •Unidimensionally measurable disease (>= 1 cm on spiral CT scan or >= 2 cm on chest X-ray; liver ultrasound not allowed). Index lesions should not be in a previously irradiated area. Serum carcinoembryonic antigen (CEA) may not be used as a parameter for disease evaluation.
- •In case of previous radiotherapy, at least one measurable lesion should be located outside the irradiated field.
- •General Conditions
- •Signed written informed consent
- •Age 18 years and above
- •World Health Organization (WHO) performance status 0-1
- •Adequate bone marrow function (white blood cell count [WBC] > 3.0 x 10^9/L, platelets > 100 x 10^9/L, hemoglobin [Hb] > 6 mmol/L)
- •Adequate hepatic function: total bilirubin < 2 x upper normal limit, aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) < 3 x upper normal limits (in case of liver metastases < 5 x upper normal limits)
- •Adequate renal function: serum creatinine < 1.5 x upper normal limit
- •Urinary protein excretion < 0.5 gram/24h
- •Expected adequacy of follow-up
排除标准
- •Prior chemotherapy for advanced disease; prior adjuvant chemotherapy is allowed provided that the last administration was given > 6 months prior to randomisation, and that patients have recovered from all toxic events related to adjuvant chemotherapy, and that safety evaluations during adjuvant chemotherapy do not present any risk for serious adverse events during the administration of protocol treatment.
- •Previous radiotherapy for rectal cancer or for symptomatic treatment of distant metastases is allowed, provided that at least one measurable lesion is located outside the irradiated field, irradiation has been completed for at least 4 weeks, and patients have recovered from all side effects.
- •Previous epidermal growth factor receptor (EGFR) targeting therapy
- •Sensory neuropathy > grade 1
- •Bleeding diathesis or coagulation disorders or the need for full-dose anticoagulation
- •Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the start of drug administration
- •Anticipated major surgical procedure during the course of the study
- •Serious non-healing wound or ulcer
- •Any condition preventing the intake or absorption of oral drugs
- •Significant cardiovascular disease (unstable angina pectoris, recent myocardial infarction < 12 months, uncontrolled hypertension, previous cerebrovascular disease)
- •Pregnancy or lactation
- •Patients (males/females) with reproductive potential not implementing adequate contraceptive measures
- •Central nervous system metastases (in asymptomatic patients no screening is required)
- •Serious active infections
- •Other serious concomitant diseases preventing the safe administration of study drugs or likely to interfere with the study assessments
- •Other malignancies in the past 5 years with the exception of adequately treated carcinoma in situ of the cervix or squamous or basal cell carcinoma of the skin
- •Concomitant treatments: concomitant (or within 4 weeks before randomisation) administration of any other experimental drug under investigation; concurrent treatment with any other anti-cancer therapy; full-dose anticoagulation
- •Continuous use of immunosuppressive agents
研究组 & 干预措施
1Capecitabine + bevacizumab + oxaliplatin + cetuximab
干预措施: 1Capecitabine + oxaliplatin + bevacizumab + cetuximab (Drug)
21Capecitabine + bevacizumab + oxaliplatin
干预措施: 21Capecitabine + bevacizumab + oxaliplatin (Drug)
结局指标
主要结局
progression free survival
时间窗: study duration
toxicity
时间窗: study duration
次要结局
- response duration(study duration)
- overall survival(study duration)
- quality of life(study duration)
- translational research(study duration)
- tumour response (complete response [CR], partial response [PR] or stable disease [SD])(study duration)