Combination Chemotherapy and Intensity-Modulated Radiation Therapy in Treating Patients Undergoing Surgery for Locally Advanced Rectal Cancer
Recruitment status was Active, not recruiting
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.
Drug: leucovorin calcium
Procedure: adjuvant therapy
Procedure: neoadjuvant therapy
Procedure: therapeutic conventional surgery
Radiation: 3-dimensional conformal radiation therapy
Radiation: intensity-modulated radiation therapy
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Evaluation of Preoperative Chemoradiotherapy Utilizing Intensity Modulated Radiation Therapy (IMRT) in Combination With Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer|
- Treatment-related gastrointestinal adverse events ≥ grade 2 per NCI CTCAE v. 3.0, occurring preoperatively [ Designated as safety issue: Yes ]
- Intensity-modulated radiotherapy (IMRT) feasibility [ Designated as safety issue: No ]
- Pathologic complete response rate [ Designated as safety issue: No ]
- All treatment-related adverse events per NCI CTCAE v3.0 preoperative, postoperative, and overall [ Designated as safety issue: Yes ]
- Patterns of failure (i.e., local, regional, and distant), including overall survival (death due to any cause) [ Designated as safety issue: No ]
- Correlation of pre- and post-treatment serum cytokines with adverse events and efficacy [ Designated as safety issue: No ]
- Rate of anterior posterior resections [ Designated as safety issue: No ]
|Study Start Date:||April 2008|
|Estimated Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
- 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.
- 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 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.
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|Study Chair:||Michael C. Garofalo, MD||University of Maryland Greenebaum Cancer Center|
|Investigator:||Adam C. Berger, MD||Kimmel Cancer Center (KCC)|
|Investigator:||Johanna Bendell, MD||Duke Cancer Institute|