Clinical trial NCT00613080
Conditions: Colorectal Cancer
Keywords: stage III rectal cancer adenocarcinoma of the rectum
Sponsor: Radiation Therapy Oncology Group
Start date: 2008-04-01; Completion date: 2016-12-01
Enrollment: 79 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying the side effects and how well giving combination chemotherapy together with intensity-modulated radiation therapy works in treating patients undergoing surgery for locally advanced rectal cancer.

Detailed description:
OBJECTIVES:

Primary

* To determine whether the incidence of neoadjuvant acute gastrointestinal toxicity (grade ≥ 2) associated with neoadjuvant chemoradiotherapy is reduced by inverse-planned intensity-modulated radiotherapy (IMRT)-based radiation treatment when compared with conventionally delivered radiotherapy, as was utilized in the capecitabine and oxaliplatin arm of RTOG-0247 (NCT00081289).

Secondary

* To evaluate the feasibility of performing IMRT in a cooperative group setting for the treatment of rectal cancer.
* To estimate the incidence of all toxicity (hematologic and non-hematologic) associated with protocol treatment in the neoadjuvant period, the adjuvant period, and overall.
* To estimate the pathologic complete response rate following neoadjuvant IMRT-based chemoradiotherapy.
* To estimate the time to treatment failure and patterns of failure.
* To correlate pre- and post-treatment levels of serum cytokines with symptoms during and pathological outcomes following neoadjuvant chemoradiotherapy for rectal cancer.
* To evaluate the rate of abdominoperineal resections.

OUTLINE: This is a multicenter study.

* Chemoradiotherapy: Patients undergo inverse-planned intensity-modulated radiotherapy to the pelvis once daily, 5 days a week, for 5 weeks (total of 45 Gy) and a 3-dimensional conformal radiotherapy boost to gross disease once daily for 3 days (total of 45 Gy). Beginning on the first day of radiotherapy and continuing through completion of radiotherapy, patients receive oral capecitabine twice daily, 5 days a week, for 5 weeks and oxaliplatin IV over 2 hours on days 1, 8, 15, 22, 29.
* Surgery: Within 4-8 weeks after completion of chemoradiotherapy, patients undergo resection of the rectal tumor.
* Adjuvant chemotherapy: Beginning 4-8 weeks after surgery, patients with completely resected disease and negative surgical margins receive leucovorin calcium IV over 2 hours and oxaliplatin IV over 2 hours on day 1 and fluorouracil IV bolus on day 1 and fluorouracil IV infusion continuously over 46 hours beginning on day 1 . Treatment repeats every 14 days for up to 9 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months after the start of treatment for 2 years, every 6 months for years 3-5, and then annually thereafter.

Arms: arm 1: Radiation therapy (intensity modulated radiation therapy \[IMRT\] + three dimensional conformal radiation therapy \[3D-CRT\]) + neoadjuvant chemotherapy (capecitabine and oxaliplatin) followed by resection and postoperative chemotherapy (FOLFOX)
Interventions: intervention 1: capecitabine intervention 2: oxaliplatin intervention 3: resection intervention 4: radiation therapy intervention 5: FOLFOX
Intervention descriptions: intervention 1: 1650 mg/m\^2/day orally 5 days/week during radiotherapy. intervention 2: None intervention 3: All patients undergo surgery 4 to 8 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 4: Pelvic intensity modulated radiation therapy (IMRT): 45 Gy in 25 fx Three dimensional conformal radiation therapy (3D-CRT) boost: 5.4 Gy in 3 fx to total dose of 50.4 Gy in 28 fx intervention 5: Postoperative chemotherapy is administered to all patients who have a complete resection of rectal cancer with negative surgical margins and begins within 4-8 weeks following surgical resection, consisting of a total of 9 14-day cycles. Oxaliplatin 85 mg/m\^2, IV over 2 hours, day 1.

Leucovorin 400 mg/m\^2, IV over 2 hours, day 1. 5-fluorouracil bolus 400 mg/m\^2, IV push, day 1. 5-fluorouracil infusion 2400 mg/m\^2, IV continuous infusion over 46 hours, day 1.

Protocol documents: