A Phase II Trial Of Irinotecan /5-FU/ Leucovorin Or Oxaliplatin /5-FU / Leucovorin With And Without Cetuximab (C225) For Patients With Untreated Metastatic Adenocarcinoma Of The Colon or Rectum
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 238
- 试验地点
- 77
- 主要终点
- Overall survival
研究概览
简要总结
This is a randomized phase II study trial that has served as a screening trial to test the increased efficacy of chemotherapy + cetuximab versus chemotherapy alone among patients with untreated, advanced or metastatic colon cancer regardless of tumor status with respect to EGFR.
详细描述
CALGB 80203 was activated on December 15, 2003. In February 2004, based on the results of the randomized trial of IFL +/- cetuximab showing a significant improvement in overall survival with cetuximab, cetuximab was approved by the FDA for use as front-line therapy for patients with metastatic colon cancer. In response to this action, the Data Safety and Monitoring Board recommended closure of CALGB 80203. CALGB 80203 was subsequently closed to accrual in January 2005 with 238 of the originally targeted 2200 patients enrolled. A final decision was to "replace" CALGB 80203 with a three-treatment arm randomized trial of chemotherapy (FOLFOX or FOLFIRI) with and without cetuximab and/or bevacizumab. The protocol was amended to allow analysis of the data from CALGB 80203 as a randomized phase II trial and reporting of the results.
Patients were stratified according to prior adjuvant chemotherapy (yes vs no) and prior pelvic radiation (yes vs no). Patients must have completed any major surgery or radiotherapy (eg, chest or bone palliative RT or pelvic RT) ≥ 4 weeks from registration and completed any minor surgery ≥ 2 weeks from registration. Patients must have fully recovered from the procedure and/or radiotherapy. Patients must have initiated treatment within 7 days of registration. Patients were randomized to 1 of 4 treatment arms, please see a description of the treatment regimens in the "Arms" section. In addition, patients received concomitant and supportive therapy as appropriate per the protocol.
OBJECTIVES:
Primary
- To determine if the addition of C225 to FOLFIRI or FOLFOX chemotherapy prolongs survival of patients with untreated, advanced or metastatic colorectal cancer.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm A: FOLFIRI
Patients receive irinotecan 180 mg/m^2 over 90 minutes on day 1, then leucovorin 400 mg/m^2 over 2 hours followed by 5FU 400 mg/m^2 IV bolus injection then 5FU 2400 mg/m^2 continuous IV infusion over 46-48 hours repeated every 2 weeks. One cycle of therapy is 8 weeks.
干预措施: 5-FU (Drug)
Arm A: FOLFIRI
Patients receive irinotecan 180 mg/m^2 over 90 minutes on day 1, then leucovorin 400 mg/m^2 over 2 hours followed by 5FU 400 mg/m^2 IV bolus injection then 5FU 2400 mg/m^2 continuous IV infusion over 46-48 hours repeated every 2 weeks. One cycle of therapy is 8 weeks.
干预措施: irinotecan (Drug)
Arm A: FOLFIRI
Patients receive irinotecan 180 mg/m^2 over 90 minutes on day 1, then leucovorin 400 mg/m^2 over 2 hours followed by 5FU 400 mg/m^2 IV bolus injection then 5FU 2400 mg/m^2 continuous IV infusion over 46-48 hours repeated every 2 weeks. One cycle of therapy is 8 weeks.
干预措施: leucovorin (Drug)
Arm B: FOLFIRI + C225
Patients receive irinotecan 180 mg/m^2 over 90 minutes, then leucovorin 400 mg/m^2 IV over 2 hours followed by 5FU 400 mg/m^2 IV bolus injection then 5FU 2400 mg/m^2 continuous IV infusion over 46-48 hours repeated every 2 weeks. Patients also receive cetuximab 400 mg/m^2 IV over 120 minutes day 1, then 250 mg/m^2 IV over 60 minutes weekly. All patients must be premedicated with diphenhydramine hydrochloride 50 mg (or a similar agent) IV prior to the first dose of cetuximab in an effort to prevent a hypersensitivity reaction. Premedication is recommended prior to subsequent doses, but at the Investigator's discretion the dose of diphenhydramine (or a similar agent) may be reduced.
干预措施: cetuximab (Drug)
Arm B: FOLFIRI + C225
Patients receive irinotecan 180 mg/m^2 over 90 minutes, then leucovorin 400 mg/m^2 IV over 2 hours followed by 5FU 400 mg/m^2 IV bolus injection then 5FU 2400 mg/m^2 continuous IV infusion over 46-48 hours repeated every 2 weeks. Patients also receive cetuximab 400 mg/m^2 IV over 120 minutes day 1, then 250 mg/m^2 IV over 60 minutes weekly. All patients must be premedicated with diphenhydramine hydrochloride 50 mg (or a similar agent) IV prior to the first dose of cetuximab in an effort to prevent a hypersensitivity reaction. Premedication is recommended prior to subsequent doses, but at the Investigator's discretion the dose of diphenhydramine (or a similar agent) may be reduced.
干预措施: 5-FU (Drug)
Arm B: FOLFIRI + C225
Patients receive irinotecan 180 mg/m^2 over 90 minutes, then leucovorin 400 mg/m^2 IV over 2 hours followed by 5FU 400 mg/m^2 IV bolus injection then 5FU 2400 mg/m^2 continuous IV infusion over 46-48 hours repeated every 2 weeks. Patients also receive cetuximab 400 mg/m^2 IV over 120 minutes day 1, then 250 mg/m^2 IV over 60 minutes weekly. All patients must be premedicated with diphenhydramine hydrochloride 50 mg (or a similar agent) IV prior to the first dose of cetuximab in an effort to prevent a hypersensitivity reaction. Premedication is recommended prior to subsequent doses, but at the Investigator's discretion the dose of diphenhydramine (or a similar agent) may be reduced.
干预措施: irinotecan (Drug)
Arm B: FOLFIRI + C225
Patients receive irinotecan 180 mg/m^2 over 90 minutes, then leucovorin 400 mg/m^2 IV over 2 hours followed by 5FU 400 mg/m^2 IV bolus injection then 5FU 2400 mg/m^2 continuous IV infusion over 46-48 hours repeated every 2 weeks. Patients also receive cetuximab 400 mg/m^2 IV over 120 minutes day 1, then 250 mg/m^2 IV over 60 minutes weekly. All patients must be premedicated with diphenhydramine hydrochloride 50 mg (or a similar agent) IV prior to the first dose of cetuximab in an effort to prevent a hypersensitivity reaction. Premedication is recommended prior to subsequent doses, but at the Investigator's discretion the dose of diphenhydramine (or a similar agent) may be reduced.
干预措施: leucovorin (Drug)
Arm C: FOLFOX
Patients receive oxaliplatin 85 mg/m^2 IV infused over 120 minutes, then leucovorin 400 mg/m^2 IV over 2 hours followed by 5 FU 400 mg/m^2 IV bolus injection then 5 FU 2400 mg/m^2 continuous IV infusion over 46-48 hours every 2 weeks.
干预措施: 5-FU (Drug)
Arm C: FOLFOX
Patients receive oxaliplatin 85 mg/m^2 IV infused over 120 minutes, then leucovorin 400 mg/m^2 IV over 2 hours followed by 5 FU 400 mg/m^2 IV bolus injection then 5 FU 2400 mg/m^2 continuous IV infusion over 46-48 hours every 2 weeks.
干预措施: leucovorin (Drug)
Arm C: FOLFOX
Patients receive oxaliplatin 85 mg/m^2 IV infused over 120 minutes, then leucovorin 400 mg/m^2 IV over 2 hours followed by 5 FU 400 mg/m^2 IV bolus injection then 5 FU 2400 mg/m^2 continuous IV infusion over 46-48 hours every 2 weeks.
干预措施: oxaliplatin (Drug)
Arm D: FOLFOX + C225
Patients receive oxaliplatin 85 mg/m^2 IV infused over 120 minutes, then leucovorin 400 mg/m^2 over 2 hours followed by 5 FU 400 mg/m^2 IV bolus injection then 5 FU 2400 mg/m^2 continuous IV infusion over 46-48 hours every 2 weeks. Patients also receive cetuximab 400 mg/m^2 IV over 120 minutes day 1, then 250 mg/m^2 IV over 60 minutes weekly. All patients must be premedicated with diphenhydramine hydrochloride 50 mg (or a similar agent) IV prior to the first dose of cetuximab in an effort to prevent a hypersensitivity reaction. Premedication is recommended prior to subsequent doses, but at the Investigator's discretion the dose of diphenhydramine (or a similar agent) may be reduced.
干预措施: cetuximab (Drug)
Arm D: FOLFOX + C225
Patients receive oxaliplatin 85 mg/m^2 IV infused over 120 minutes, then leucovorin 400 mg/m^2 over 2 hours followed by 5 FU 400 mg/m^2 IV bolus injection then 5 FU 2400 mg/m^2 continuous IV infusion over 46-48 hours every 2 weeks. Patients also receive cetuximab 400 mg/m^2 IV over 120 minutes day 1, then 250 mg/m^2 IV over 60 minutes weekly. All patients must be premedicated with diphenhydramine hydrochloride 50 mg (or a similar agent) IV prior to the first dose of cetuximab in an effort to prevent a hypersensitivity reaction. Premedication is recommended prior to subsequent doses, but at the Investigator's discretion the dose of diphenhydramine (or a similar agent) may be reduced.
干预措施: 5-FU (Drug)
Arm D: FOLFOX + C225
Patients receive oxaliplatin 85 mg/m^2 IV infused over 120 minutes, then leucovorin 400 mg/m^2 over 2 hours followed by 5 FU 400 mg/m^2 IV bolus injection then 5 FU 2400 mg/m^2 continuous IV infusion over 46-48 hours every 2 weeks. Patients also receive cetuximab 400 mg/m^2 IV over 120 minutes day 1, then 250 mg/m^2 IV over 60 minutes weekly. All patients must be premedicated with diphenhydramine hydrochloride 50 mg (or a similar agent) IV prior to the first dose of cetuximab in an effort to prevent a hypersensitivity reaction. Premedication is recommended prior to subsequent doses, but at the Investigator's discretion the dose of diphenhydramine (or a similar agent) may be reduced.
干预措施: leucovorin (Drug)
Arm D: FOLFOX + C225
Patients receive oxaliplatin 85 mg/m^2 IV infused over 120 minutes, then leucovorin 400 mg/m^2 over 2 hours followed by 5 FU 400 mg/m^2 IV bolus injection then 5 FU 2400 mg/m^2 continuous IV infusion over 46-48 hours every 2 weeks. Patients also receive cetuximab 400 mg/m^2 IV over 120 minutes day 1, then 250 mg/m^2 IV over 60 minutes weekly. All patients must be premedicated with diphenhydramine hydrochloride 50 mg (or a similar agent) IV prior to the first dose of cetuximab in an effort to prevent a hypersensitivity reaction. Premedication is recommended prior to subsequent doses, but at the Investigator's discretion the dose of diphenhydramine (or a similar agent) may be reduced.
干预措施: oxaliplatin (Drug)
结局指标
主要结局
Overall survival
时间窗: Up to 3 years of follow up
次要结局
- Progression-free survival(Up to 18 months of follow up)
- Partial response(Up to 18 months of follow up)
- Complete response(Up to 18 months of follow up)
- Proportion of patients experiencing ≥ Grade 3 ANC(Up to 30 days post-treatment)
- Percent of total dose administered(Up to 30 days post-treatment)
- Proportion of patients experiencing ≥ Grade 3 diarrhea(Up to 30 days post-treatment)
- Proportion of patients experiencing ≥ Grade 4 toxicity on each cetuximab treatment arm(Up to 30 days post-treatment)