Oxaliplatin, Capecitabine, and Radiation Therapy in Treating Patients With Locally Advanced Cancer of the Rectum
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, 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. Oxaliplatin and capecitabine may make tumor cells more sensitive to radiation therapy and may kill more tumor cells. Giving chemotherapy with radiation therapy before surgery may shrink the tumor so that it can be removed.
PURPOSE: This phase I/II trial is studying the side effects and best dose of oxaliplatin and capecitabine when given together with radiation therapy and to see how well they work in treating patients who are undergoing surgery for locally advanced cancer of the rectum. NOTE: *The phase I portion of this trial closed 06/2005. The best dose of oxaliplatin and capecitabine has been determined.
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Radiation: radiation therapy
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Weekly Intravenous Oxaliplatin in Combination With Oral Daily Capecitabine and Radiation Therapy in the Neoadjuvant Treatment of Rectal Cancer|
- Complete pathological response rate at time of surgery [ Time Frame: Time of surgery ] [ Designated as safety issue: No ]
- Disease-free survival, safety, and overall survival at 5 years [ Time Frame: Continuous ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2003|
|Study Completion Date:||May 2010|
|Primary Completion Date:||May 2007 (Final data collection date for primary outcome measure)|
- Determine the maximum tolerated dose of neoadjuvant oxaliplatin and capecitabine when combined with radiotherapy in patients with locally advanced adenocarcinoma of the rectum. (Phase I closed to accrual as of 06/2005.)
- Determine the rate of complete pathological response in patients treated with this regimen.
- Determine the overall survival of patients treated with this regimen.
- Determine the rate of local and overall failure in patients treated with this regimen.
- Determine the utility of TS, TP, DPD, ERCC-1, and apoptosis to predict response in patients treated with this regimen.
- Determine the rate of pathologic down-staging in patients treated with this regimen.
- Determine the safety and toxicity of this regimen in these patients.
- Determine the rate of sphincter-saving rectal surgery in patients treated with this regimen who had been deemed candidates for abdominoperineal resection at diagnosis.
OUTLINE: This is a multicenter, phase I (phase I closed to accrual as of 06/2005), dose-escalation study of oxaliplatin and capecitabine followed by a phase II study.
- Phase I (closed to accrual as of 06/2005): Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks and receive oral capecitabine twice daily on days radiotherapy is administered. Beginning on day 1 of radiotherapy, patients also receive oxaliplatin IV over 2 hours on days 1, 8, 15, 22, and 29.
Cohorts of 3-6 patients receive escalating doses of oxaliplatin and capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients undergo radiotherapy and receive capecitabine and oxaliplatin as in phase I at the MTD.
All patients undergo curative-intent surgery 6-8 weeks after the completion of chemoradiotherapy.
Patients are followed every 3 months for 3 years and then every 6 months for 2 years.
PROJECTED ACCRUAL: A total of 31-40 patients (6-15 for phase I [phase I closed to accrual as of 06/2005] and 25 for phase II) will be accrued for this study within 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00086931
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263-0001|
|Study Chair:||Marwan Fakih, MD||Roswell Park Cancer Institute|