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
- 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
- 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
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.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Complete pathological response rate at time of surgery
Time of surgery
Marwan Fakih, MD
Roswell Park Cancer Institute
United States: Food and Drug Administration
|Roswell Park Cancer Institute||Buffalo, New York 14263|