Clinical trial NCT00081289
Conditions: Colorectal Cancer
Keywords: stage III rectal cancer adenocarcinoma of the rectum stage II rectal cancer
Sponsor: Radiation Therapy Oncology Group
Start date: 2004-03-01; Completion date: 2016-12-01
Enrollment: 146 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Drugs used in chemotherapy work in 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. Chemoradiotherapy (combining chemotherapy with radiation therapy) before surgery may shrink the tumor so that it can be removed. Giving chemotherapy after surgery may kill any remaining tumor cells.

PURPOSE: This randomized phase II trial is studying two different regimens of neoadjuvant chemoradiotherapy and adjuvant chemotherapy and comparing how well they work in treating patients who are undergoing surgical resection for locally advanced rectal cancer.

Detailed description:
OBJECTIVES:

* Evaluate the pathologic complete response rate in patients with locally advanced rectal cancer undergoing surgical resection treated with 2 different regimens of neoadjuvant chemoradiotherapy and adjuvant chemotherapy.
* Evaluate the time to treatment failure and patterns of failure in patients treated with these regimens.
* Evaluate the incidence of hematologic and non-hematologic grade 3-4 toxicity (preoperatively, postoperatively, and overall) in patients treated with these regimens.
* Evaluate the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to clinical stage of tumor (T3 vs T4). Patients are randomized to 1 of 2 treatment arms.

Quality of life is assessed at baseline, within 1 week after completion of radiotherapy, within 1 week after completion of adjuvant chemotherapy (12 months), and then at 24 months.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Arms: arm 1: Patients receive neoadjuvant therapy comprising 45 Gy (1.8 Gy/fx) + 5.4 Gy boost (1.8 Gy/fx) radiation therapy (RT), oral capecitabine 1200mg/m\^2/day 5 days/week during RT, and irinotecan 50 mg/m\^2 IV for 1 hour days 1, 8, 22, 29. Surgery 4-8 weeks after RT. Postoperative chemotherapy beginning Day 1 postoperatively for nine 14-day cycles(folinic acid 400 mg/m\^2 over 2 hours Day 1; 5-fluorouracil bolus 400 mg/m\^2 IV push Day 1 plus 2400 mg/m\^2 IV continuous infusion over 46 hours, beginning Day 1; and oxaliplatin 85 mg/m\^2 IV over 2 hours Day 1) . arm 2: Patients receive neoadjuvant therapy comprising 45 Gy (1.8 Gy/fx) + 5.4 Gy boost (1.8 Gy/fx) radiation therapy (RT), oral capecitabine 1650mg/m\^2/day 5 days/week during RT, and oxaliplatin 50 mg/m\^2 IV for 2 hours days 1, 8, 15, 22, 29. Surgery 4-8 weeks after RT. Postoperative chemotherapy beginning Day 1 postoperatively for nine 14-day cycles(folinic acid 400 mg/m\^2 over 2 hours Day 1; 5-fluorouracil bolus 400 mg/m\^2 IV push Day 1 plus 2400 mg/m\^2 IV continuous infusion over 46 hours, beginning Day 1; and oxaliplatin 85 mg/m\^2 IV over 2 hours Day 1) .
Interventions: intervention 1: Radiation Therapy intervention 2: Capecitabine 1650 mg/m^2/day intervention 3: Capecitabine 1200 mg/m^2/day intervention 4: Irinotecan intervention 5: Oxaliplatin intervention 6: Surgery intervention 7: Folinic Acid intervention 8: Fluorouracil intervention 9: Oxaliplatin
Intervention descriptions: intervention 1: Pelvic radiation therapy given once daily 5 days a week for 6 weeks, 45 Gy in 25 fractions + boost of 5.4 Gy in 3 fractions for a total dose of 50.4 Gy. intervention 2: 825 mg/m\^2 q12 hours (1650 mg/m\^2/day) orally 5 days per week during radiotherapy. intervention 3: 600 mg/m\^2 q12 hours(1200 mg/m\^2/day) orally 5 days per week during radiotherapy. intervention 4: 50mg/m\^2 IV over 1 hour on days 1, 8, 22, and 29 intervention 5: 50mg/m\^2 IV over 2 hours on days 1, 8, 15, 22, and 29 intervention 6: All patients will undergo surgery four to eight weeks following the completion of radiation therapy. The choice of procedure abdominoperineal resection (APR), low anterior resection (LAR), or LAR/coloanal anastomosis is at the discretion of the surgeon. intervention 7: 400 mg/m\^2 IV over 2 hours Day 1 (postoperatively) ,every 14 days, for nine 14-day cycles. intervention 8: 5-fluorouracil bolus 400 mg/m\^2 IV push Day 1 (postoperatively), every 14 days, for nine 14-day cycles.

5-fluorouracil infusion 2400 mg/m\^2 IV continuous infusion over 46 hours, beginning day 1, every 14 days, for nine 14-day cycles. intervention 9: 85 mg/m\^2 IV over 2 hours Day 1 (postoperatively), every 14 days, for nine 14-day cycles.

Protocol documents: