A Randomized Phase II Study to Investigate the Deepness of Response of FOLFOXIRI Plus Cetuximab (Erbitux) Versus FOLFOXIRI Plus Bevacizumab as the First-line Therapy in Metastatic Colorectal Cancer Patients With RAS Wild-type Tumors: DEEPER
试验速览
- 阶段
- 2 期
- 入组人数
- 360
- 主要终点
- Best deepness of response
研究概览
简要总结
This study is to verify the advantage of FOLFOXIRI plus cetuximab over FOLFOXIRI plus bevacizumab as the first-line therapy in metastatic colorectal cancer patients with RAS wild-type tumors.
详细描述
This study is to verify the advantage of FOLFOXIRI plus cetuximab over FOLFOXIRI plus bevacizumab as the first-line therapy in metastatic colorectal cancer patients with RAS wild-type tumors. In this study the investigators employed deepness of response as a primary endpoint.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed colorectal cancer
- •RAS wild-type
- •Measurable lesion by RECIST (Ver.1.1)
- •No past history of chemotherapy in the case of unresectable primary lesion/distant metastasis/lymph node metastasis.In the case of recurrence, no treatment for the first recurrence lesion after operation
- •Eastern Cooperative Oncology Group (ECOG) Performance status 0-1.The case >=71 years is PS
- •Life expectancy of more than 6 months
- •Patients have enough organ function for study treatment within 14 days before enrollment;
- •White blood cell (WBC)>=3,000/mm3, <12,000/mm
- •Neu>=1,500/mm
- •Platelet count (PLT) >=10.0x104/mm
- •Hb>=9.0g/dL.
- •Total Bilirubin<=1.5x Upper Limited Normal (ULN)
- •aspartate aminotransferase (AST) <=2.5xULN.
- •alanine aminotransferase (ALT) <=2.5xULN.
- •Creatinine<=1.5xULN.
- •Proteinuria<=1+.
- •prothrombin time-international normalized ratio (PT-INR) <=1.5
- •Must be able to swallow tablets
- •Written informed consent
排除标准
- •Synchronous multiple malignancy or metachronous multiple malignancy within 5 years disease free interval
- •Lynch syndrome
- •Brain metastases
- •Infectious disease
- •Interstitial lung disease or pulmonary fibrosis
- •Comorbidity or history of serious heart failure
- •History of thromboembolic events
- •Cerebrovascular disease
- •History of hemoptysis/hematemesis
- •Uncontrolled hypertension (systolic BP>180mmHg, or diastolic BP>100mmHg)
- •Sensory alteration or paresthesia interfering with function
- •Large quantity of pleural, abdominal or cardiac effusion
- •Severe comorbidity (renal failure, liver failure, hypertension, etc)
- •Prior radiotherapy for primary and metastases leision
- •Men/women who are unwilling to avoid pregnancy
- •Women who are pregnant or breastfeeding
- •Women with a positive pregnancy test
- •History of severe allergy
- •HBsAg positive or active viral hepatitis
- •Administration of blood products/ Granulocyte-Colony Stimulating Factor (G-CSF), and blood transfusion within 14 days
- •Surgical procedure or such as skin-open biopsy, trauma surgery, or other more intensive surgery within 28 days
- •Systematic administration of antiplatelet drug or non steroid anti-inflammatory drugs (NSAIDs)
- •Diathesis of bleeding (history of hemoptysis, including cavitation and/or necrosis in lung metastasis confirmed by imaging), coagulopathy
- •History of gastrointestinal perforation within 1 year
- •Unhealed traumatic bone fracture
- •Uncontrolled diarrhea
- •History of organ recipient
- •Prior cetuximab/bevacizumab/Irinotecan/Oxaliplatin treatment (Adjuvant therapy by Oxaliplatin is excluded)
- •Administration of atazanavir sulfate
- •Ileus or bowel obstruction
- •Clinical diagnosis of Alzheimer's Disease
- •Insulin dependent diabetes
- •Thyroid disease
- •Any other cases who are regarded as inadequate for study enrollment by investigators
研究组 & 干预措施
FOLFOXIRI+Bmab
Patients in the FOLFOXIRI + Bmab group receive until 12 cycles of FOLFOXIRI plus bevacizumab, consisting of a 30-minute infusion of bevacizumab at a dose of 5 mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and bevacizumab every 14 days until disease progression.
干预措施: fluorouracil (Drug)
FOLFOXIRI+Bmab
Patients in the FOLFOXIRI + Bmab group receive until 12 cycles of FOLFOXIRI plus bevacizumab, consisting of a 30-minute infusion of bevacizumab at a dose of 5 mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and bevacizumab every 14 days until disease progression.
干预措施: Leucovorin (Drug)
FOLFOXIRI+Bmab
Patients in the FOLFOXIRI + Bmab group receive until 12 cycles of FOLFOXIRI plus bevacizumab, consisting of a 30-minute infusion of bevacizumab at a dose of 5 mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and bevacizumab every 14 days until disease progression.
干预措施: irinotecan (Drug)
FOLFOXIRI+Bmab
Patients in the FOLFOXIRI + Bmab group receive until 12 cycles of FOLFOXIRI plus bevacizumab, consisting of a 30-minute infusion of bevacizumab at a dose of 5 mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and bevacizumab every 14 days until disease progression.
干预措施: oxaliplatin (Drug)
FOLFOXIRI+Bmab
Patients in the FOLFOXIRI + Bmab group receive until 12 cycles of FOLFOXIRI plus bevacizumab, consisting of a 30-minute infusion of bevacizumab at a dose of 5 mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and bevacizumab every 14 days until disease progression.
干预措施: bevacizumab (Biological)
FOLFOXIRI+Cmab
Patients in the experimental group received until 12 cycles of FOLFOXIRI plus cetuximab, consisting of a 30-minute infusion of cetuximab first time at a dose of 400 mg per kilogram, after the second time at a dose of 250mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and cetuximab every 14 days until disease progression.
干预措施: fluorouracil (Drug)
FOLFOXIRI+Cmab
Patients in the experimental group received until 12 cycles of FOLFOXIRI plus cetuximab, consisting of a 30-minute infusion of cetuximab first time at a dose of 400 mg per kilogram, after the second time at a dose of 250mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and cetuximab every 14 days until disease progression.
干预措施: Leucovorin (Drug)
FOLFOXIRI+Cmab
Patients in the experimental group received until 12 cycles of FOLFOXIRI plus cetuximab, consisting of a 30-minute infusion of cetuximab first time at a dose of 400 mg per kilogram, after the second time at a dose of 250mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and cetuximab every 14 days until disease progression.
干预措施: irinotecan (Drug)
FOLFOXIRI+Cmab
Patients in the experimental group received until 12 cycles of FOLFOXIRI plus cetuximab, consisting of a 30-minute infusion of cetuximab first time at a dose of 400 mg per kilogram, after the second time at a dose of 250mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and cetuximab every 14 days until disease progression.
干预措施: oxaliplatin (Drug)
FOLFOXIRI+Cmab
Patients in the experimental group received until 12 cycles of FOLFOXIRI plus cetuximab, consisting of a 30-minute infusion of cetuximab first time at a dose of 400 mg per kilogram, after the second time at a dose of 250mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and cetuximab every 14 days until disease progression.
干预措施: cetuximab (Biological)
结局指标
主要结局
Best deepness of response
时间窗: up to 2 years
The maximum tumor shrinkage rates by Response Evaluation Criteria in Solid Tumors (RECIST) throughout the treatments
次要结局
- Early tumor shrinkage(at 8 weeks)
- Deepness of response(at 4 months)
- Response rate(up to 2 years)
- Progression free survival(up to 2 years)
- Number of adverse events(up to 2 years)
- Overall survival(up to 2 years)
- Rate of curatively resected metastatic lesion(up to 2 years)