A Phase II Feasibility Translational Research Trial of Induction Chemotherapy Followed by Concomitant Chemoradiation in Patients With Clinical T4 Rectal Cancer
- Determine the feasibility of obtaining a pre-treatment determination of intratumoral
molecular markers (TS, DPD, and ERCC-1) for use in selection of the appropriate regimen
for induction cytotoxic combination chemotherapy in patients with cT3-4 rectal
- Determine the response probability (unconfirmed, complete and partial) in patients
treated with targeted induction cytotoxic chemotherapy.
- Determine the toxicity of targeted induction cytotoxic chemotherapy and
chemoradiotherapy in these patients.
- Determine the response probability in these patients treated with chemoradiotherapy.
OUTLINE: This is a multicenter study.
- Induction chemotherapy: Patients are assigned to 1 of 3 treatment groups based on
molecular analysis of the pretreatment tumor specimen.
- Group I (lower likelihood of resistance to a fluorouracil-based regimen): Patients
receive irinotecan IV over 90 minutes and leucovorin calcium IV over 2 hours on
day 1 and fluorouracil IV over 46 hours beginning on day 1.
- Group II (higher likelihood of resistance to a fluorouracil-based regimen):
Patients receive oxaliplatin IV over 2 hours and irinotecan IV over 90 minutes on
- Group III (high likelihood of sensitivity to oxaliplatin and fluorouracil
therapy): Patients receive oxaliplatin IV over 90 minutes and leucovorin calcium
IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1.
Treatment in all groups repeats every 2 weeks for 4 courses in the absence of disease
progression or unacceptable toxicity.
Patients are evaluated for response approximately 2 weeks after the completion of induction
chemotherapy. Patients with stable disease or better receive chemoradiotherapy.
- Chemoradiotherapy: Beginning approximately 3 weeks after the completion of induction
chemotherapy, patients receive oral capecitabine twice daily continuously for 5 weeks
and concurrent radiotherapy once daily 5 days a week for 5 weeks.
After chemoradiotherapy, patients may undergo attempted surgical resection at the discretion
of the treating physician.
Patients are followed every 3 months for 1 year and then every 6 months for 2 years.
PROJECTED ACCRUAL: A total of 10-65 patients will be accrued for this study.
Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Response (confirmed and unconfirmed response, complete response, partial response)
Charles R. Thomas, MD
University of Texas Health Science Center at San Antonio
United States: Federal Government