Postoperative Evaluation of 5-FU by Bolus Injection vs. 5-FU by Prolonged Venous Infusion Prior to and Following Combined Prolonged Venous Infusion Plus Pelvic XRT vs. Bolus 5-FU Plus Leucovorin Plus Levamisole Prior to and Following Combined Pelvic XRT Plus Bolus 5-FU Plus Leucovorin in Patients With Rectal Cancer, Phase III
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,917
- 试验地点
- 37
- 主要终点
- Survival and Relapse-free survival
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known which treatment regimen is more effective for rectal cancer.
PURPOSE: Randomized phase III trial to compare the effectiveness of different regimens of combination chemotherapy plus radiation therapy in treating patients who have rectal cancer that has been surgically removed.
详细描述
OBJECTIVES: I. Compare the overall and relapse free survival of patients with stage II or III rectal cancer treated with one of the following three regimens: bolus injections of fluorouracil (5-FU) prior to and following pelvic irradiation plus protracted venous infusion (PVI) 5-FU radiosensitization vs PVI 5-FU prior to and following pelvic irradiation plus PVI 5-FU radiosensitization vs bolus 5-FU with leucovorin calcium and levamisole prior to and following pelvic irradiation. II. Describe relapse patterns and tolerance associated with these regimens in these patients.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to type of prior surgery (abdominoperineal resection vs anterior resection), nodal status (N0 vs N1 vs N2-3), depth of tumor invasion (T1-2 vs T3 vs T4a vs T4b), time from surgery to study entry (20-45 days vs 46-70 days), participating center, and performance status (0-1 vs 2). Patients are randomized to one of three treatment arms. Arm I: Patients receive fluorouracil (5-FU) IV on days 1-5 and 29-33. 5-FU is then given as a continuous infusion beginning on day 57 and continuing concurrently with radiotherapy for 5 weeks. Following a 28 day break from treatment patients receive 5-FU IV on days 1-5 of a 28 day course. Postradiotherapy treatment repeats for a total of 2 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive 5-FU IV continuously on days 1-42. 5-FU and radiotherapy are then administered as in arm II. Arm III: Patients receive leucovorin calcium (CF) IV followed by 5-FU IV on days 1-5 and 29-33. Patients also receive oral levamisole twice daily on days 1-3, 15-17, 29-31, and 43-45. CF IV and 5-FU IV are then given on days 57-60 and 85-88 concurrently with radiotherapy. Following a 28 day break from treatment patients receive CF IV and 5-FU IV on days 1-5 and 29-33 and oral levamisole twice daily on days 1-3, 15-17, 29-31, and 43-45 in the absence of disease progression or unacceptable toxicity. All patients receive radiotherapy 5 days per week for 5 weeks starting on day 57. Patients are followed every 4 months for 2 years, then every 6 months for 4 years, and then annually until death.
PROJECTED ACCRUAL: A total of 1,800 patients (600 per arm) will be accrued for this 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 —（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
Bolus 5-FU, Pelvic XRT + PVI 5-FU, Bolus 5-FU
Bolus 5-FU (fluorouracil) (500mg/m2/day on days 1-5, 29-33), Pelvic XRT + PVI 5-FU, Bolus 5-FU (450mg/m2/day for 5 days beginning 28 days after RT, for 2 cycles on days 1-5 of a 28 days cycle).
干预措施: fluorouracil (Drug)
Bolus 5-FU, Pelvic XRT + PVI 5-FU, Bolus 5-FU
Bolus 5-FU (fluorouracil) (500mg/m2/day on days 1-5, 29-33), Pelvic XRT + PVI 5-FU, Bolus 5-FU (450mg/m2/day for 5 days beginning 28 days after RT, for 2 cycles on days 1-5 of a 28 days cycle).
干预措施: radiation therapy (Radiation)
PVI 5-FU+Pelvic XRT+PVI 5-FU+PVI 5-FU
5-FU (fluorouracil) 300mg/m2/day for 42 days followed by 2 week interruption, Day 57 through XRT will receive 225mg/m2/day of 5-FU followed by 1 month interruption, 4 weeks after completion of XRT 1 8wk cycle of 5-FU 300mg/m2/day.
干预措施: fluorouracil (Drug)
PVI 5-FU+Pelvic XRT+PVI 5-FU+PVI 5-FU
5-FU (fluorouracil) 300mg/m2/day for 42 days followed by 2 week interruption, Day 57 through XRT will receive 225mg/m2/day of 5-FU followed by 1 month interruption, 4 weeks after completion of XRT 1 8wk cycle of 5-FU 300mg/m2/day.
干预措施: radiation therapy (Radiation)
Bol 5-FU+LV+LEV+Pel XRT+Bol 5-FU+LV Bol 5-FU + LV + LEV
5-FU (fluorouracil) 425/mg/m2/day Days 1-5,29-33; LV (leucovorin calcium) 20mg/m2/day Days 1-5,29-33; LEV (levamisole hydrochloride) 150mg/day (50mg TID) for 3 days every 14 days starting after each course of 5-FU. During RT: 5-FU and LV 4 days on wk 1 and wk 5 of RT. LV 20 mg/m2/day IV bolus within 2hrs after completion of that day's radiation therapy, for four days in each cycle. Followed immediately by 5- FU 400 mg/m2/day IV bolus. Treatment will be given on days 57 - 60 and 85 - 88.Treatment post-RT-chemotherapy 28 days after completion of RT consist of 5 days of chemotherapy in 28 day cycles. 5-FU, 380 mg/m2/day on days 1 - 5 and LV given at a dose of 20 mg/m2/day on days 1 - 5 with the 5-FU given immediately after the LV. For 2 post-radiation cycles on days 1 - 5 of a 28 day cycle. Levamisole will be given orally at a dose of 150 mg/day (50 mg tid) for 3 days every 14 days during the 1st 3 days of each cycle of 5-FU, and again 14 days after starting each course of 5-FU.
干预措施: fluorouracil (Drug)
Bol 5-FU+LV+LEV+Pel XRT+Bol 5-FU+LV Bol 5-FU + LV + LEV
5-FU (fluorouracil) 425/mg/m2/day Days 1-5,29-33; LV (leucovorin calcium) 20mg/m2/day Days 1-5,29-33; LEV (levamisole hydrochloride) 150mg/day (50mg TID) for 3 days every 14 days starting after each course of 5-FU. During RT: 5-FU and LV 4 days on wk 1 and wk 5 of RT. LV 20 mg/m2/day IV bolus within 2hrs after completion of that day's radiation therapy, for four days in each cycle. Followed immediately by 5- FU 400 mg/m2/day IV bolus. Treatment will be given on days 57 - 60 and 85 - 88.Treatment post-RT-chemotherapy 28 days after completion of RT consist of 5 days of chemotherapy in 28 day cycles. 5-FU, 380 mg/m2/day on days 1 - 5 and LV given at a dose of 20 mg/m2/day on days 1 - 5 with the 5-FU given immediately after the LV. For 2 post-radiation cycles on days 1 - 5 of a 28 day cycle. Levamisole will be given orally at a dose of 150 mg/day (50 mg tid) for 3 days every 14 days during the 1st 3 days of each cycle of 5-FU, and again 14 days after starting each course of 5-FU.
干预措施: leucovorin calcium (Drug)
Bol 5-FU+LV+LEV+Pel XRT+Bol 5-FU+LV Bol 5-FU + LV + LEV
5-FU (fluorouracil) 425/mg/m2/day Days 1-5,29-33; LV (leucovorin calcium) 20mg/m2/day Days 1-5,29-33; LEV (levamisole hydrochloride) 150mg/day (50mg TID) for 3 days every 14 days starting after each course of 5-FU. During RT: 5-FU and LV 4 days on wk 1 and wk 5 of RT. LV 20 mg/m2/day IV bolus within 2hrs after completion of that day's radiation therapy, for four days in each cycle. Followed immediately by 5- FU 400 mg/m2/day IV bolus. Treatment will be given on days 57 - 60 and 85 - 88.Treatment post-RT-chemotherapy 28 days after completion of RT consist of 5 days of chemotherapy in 28 day cycles. 5-FU, 380 mg/m2/day on days 1 - 5 and LV given at a dose of 20 mg/m2/day on days 1 - 5 with the 5-FU given immediately after the LV. For 2 post-radiation cycles on days 1 - 5 of a 28 day cycle. Levamisole will be given orally at a dose of 150 mg/day (50 mg tid) for 3 days every 14 days during the 1st 3 days of each cycle of 5-FU, and again 14 days after starting each course of 5-FU.
干预措施: levamisole hydrochloride (Drug)
Bol 5-FU+LV+LEV+Pel XRT+Bol 5-FU+LV Bol 5-FU + LV + LEV
5-FU (fluorouracil) 425/mg/m2/day Days 1-5,29-33; LV (leucovorin calcium) 20mg/m2/day Days 1-5,29-33; LEV (levamisole hydrochloride) 150mg/day (50mg TID) for 3 days every 14 days starting after each course of 5-FU. During RT: 5-FU and LV 4 days on wk 1 and wk 5 of RT. LV 20 mg/m2/day IV bolus within 2hrs after completion of that day's radiation therapy, for four days in each cycle. Followed immediately by 5- FU 400 mg/m2/day IV bolus. Treatment will be given on days 57 - 60 and 85 - 88.Treatment post-RT-chemotherapy 28 days after completion of RT consist of 5 days of chemotherapy in 28 day cycles. 5-FU, 380 mg/m2/day on days 1 - 5 and LV given at a dose of 20 mg/m2/day on days 1 - 5 with the 5-FU given immediately after the LV. For 2 post-radiation cycles on days 1 - 5 of a 28 day cycle. Levamisole will be given orally at a dose of 150 mg/day (50 mg tid) for 3 days every 14 days during the 1st 3 days of each cycle of 5-FU, and again 14 days after starting each course of 5-FU.
干预措施: radiation therapy (Radiation)
结局指标
主要结局
Survival and Relapse-free survival
时间窗: Until death
次要结局
未报告次要终点