Randomized Phase 3 Study on the Optimization of Bevacizumab With mFOLFOX/mOXXEL in the Treatment of Patients With Metastatic Colorectal Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 230
- 试验地点
- 1
- 主要终点
- Objective Response Rate
研究概览
简要总结
The purpose of this study is to evaluate if giving bevacizumab prior to chemotherapy compared to giving bevacizumab at the same time as chemotherapy improves patient overall response to treatment.
详细描述
OBELICS is a two-arm phase 3 trial comparing in mCRC patients (1:1): concurrent administration of bevacizumab in combination with modified FOLFOX-6 regimen (mFOLFOX-6) or modified OXXEL regimen (mOXXEL), in which bevacizumab is administered the same day as oxaliplatin, (standard arm); and sequential administration of bevacizumab with the same chemotherapeutic regimens, in which bevacizumab is administered 4 days before oxaliplatin at each cycle (experimental arm) Oxaliplatin regimen (mFOLFOX/mOXXEL) is chosen according to local clinical practice at the beginning of the study.
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
- •Histological diagnosis of colorectal adenoma carcinoma
- •Stage IV disease
- •Presence of at least one measurable target lesion (according to RECIST), and not previously radiated.
- •Age ≥ 18 e ≤ 75 years
- •ECOG Performance status 0-1
- •Life expectancy >3 months
- •Adequate recovery from surgery, with at least 28 days from surgery to date of pre-study biopsy.
- •Adequate contraception for male and female patients of child bearing potential
- •informed consent
排除标准
- •More than one previous line of therapy for metastatic disease
- •Prior treatment with bevacizumab or oxaliplatin (previous treatment with irinotecan,, cetuximab, fluoropyrimidine, folic acid are permitted)
- •Primary tumor that is stenosing and/or that infiltrates the entire thickness of the intestinal wall
- •Regular use of NSAIDs or aspirin
- •Bleeding disorders or coagulopathy
- •Concurrent anticoagulant therapy
- •Suspected or cerebral metastases (to verify in the presence of symptoms)
- •Neutrophils < 2000 / mm3, platelets < 100,000 / mm3, hemoglobin < 9g/dl
- •Creatinine > 1.5 times the upper normal limit
- •GOT and/or GPT > 2.5 times the upper normal limit, bilirubin > 1.5 times the upper normal limit in absence of liver metastases
- •GOT and/or GPT > 5 times the upper normal limit, bilirubin > 3 times the upper normal limit in presence of liver metastases
- •Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal and squamous cell carcinoma or cervical cancer in situ
- •Congestive heart failure, ischemic coronary events within past 12 months, uncontrolled cardiac arrhythmia
- •Uncontrolled hypertension
- •Active or uncontrolled infection
- •Any concomitant condition that, in the investigator's opinion, would contraindicate the use of any of the study drugs
- •Pregnancy or lactation
- •Central nervous system disorders or peripheral neuropathy > grade 1 (CTCAE v. 4.0)
- •Inability to comply with follow up procedures of the study
研究组 & 干预措施
bevacizumab before chemotherapy
Bevacizumab administered 4 days before each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL)
干预措施: Bevacizumab (Drug)
bevacizumab before chemotherapy
Bevacizumab administered 4 days before each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL)
干预措施: Oxaliplatin (Drug)
bevacizumab before chemotherapy
Bevacizumab administered 4 days before each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL)
干预措施: levo-folinic acid (Drug)
bevacizumab before chemotherapy
Bevacizumab administered 4 days before each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL)
干预措施: 5-fluorouracil (Drug)
bevacizumab before chemotherapy
Bevacizumab administered 4 days before each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL)
干预措施: Capecitabine (Drug)
bevacizumab with chemotherapy
Bevacizumab administered on the first day of each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL)
干预措施: Bevacizumab (Drug)
bevacizumab with chemotherapy
Bevacizumab administered on the first day of each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL)
干预措施: Oxaliplatin (Drug)
bevacizumab with chemotherapy
Bevacizumab administered on the first day of each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL)
干预措施: levo-folinic acid (Drug)
bevacizumab with chemotherapy
Bevacizumab administered on the first day of each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL)
干预措施: 5-fluorouracil (Drug)
bevacizumab with chemotherapy
Bevacizumab administered on the first day of each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL)
干预措施: Capecitabine (Drug)
结局指标
主要结局
Objective Response Rate
时间窗: Objective response was assessed by computed tomographic scan or other appropriate imaging at weeks 12 and 24 from randomization, and every 3 months thereafter, assessed up to 90 months.
Objective response rate (ORR), according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, was the primary end point and was defined as the number of complete plus partial responses divided by the number of enrolled patients. Per RECIST v 1.1 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
次要结局
- Disease Control Rate(At weeks 12 and 24 from randomization and every 3 months thereafter, assessed up to 90 months)
- Overall Survival(assessed up to 90 months)
- Progression-free Survival (PFS)(assessed up to 90 months)
- Toxic Effects(up to 4 weeks after the end of the treatment)