CWRU 1296: Biochemical and Pharmacokinetic Predictors of Colon Cancer Response to a Topoisomerase I Directed Treatment With Irinotecan
OBJECTIVES: I. Confirm the greater than 20% response rate to irinotecan in patients with
metastatic or recurrent colorectal cancer who have not receive prior chemotherapy for their
advanced disease. II. Characterize pharmacokinetic parameters of irinotecan and its
metabolite SN-38 and their relationship to response and toxic effect. III. Characterize
tumor samples for topoisomerase I activity, proliferative fraction (ki67 expression), and
p53 expression and determine whether clinical response is related to these tumor
characteristics in patient population. IV. Determine the in vitro inhibition of
topoisomerase I activity by irinotecan, SN-38, and other camptothecin analogs and evaluate
whether the degree of in vitro sensitivity to irinotecan and/or SN-38 is associated with
clinical response in these patients. VII. Determine the frequency of somatic mutations
following irinotecan and correlate this with pharmacologic parameters.
OUTLINE: Patients receive irinotecan IV at a starting dose weekly for 4 weeks followed by 2
weeks of rest. Treatment continues in the absence of disease progression or unacceptable
toxicity. Tumor status is reassessed every 12 weeks during study. Patients attaining a
complete response may receive additional courses of treatment. Patients are followed until
PROJECTED ACCRUAL: A total of 54 patients will be accrued into this study at a rate of 25
patients per year.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Effectiveness of irinotecan in treating patients who have metastatic or recurrent colorectal cancer.
Starting dose weekly for 4 weeks followed by 2 weeks of rest. Treatment continues in the absence of disease progression or unacceptable toxicity. Tumor status is reassessed every 12 weeks during study.
James KV Willson, MD
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
United States: Federal Government
|Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center||Cleveland, Ohio 44106-5065|
|Veterans Affairs Medical Center - Cleveland||Cleveland, Ohio 44106|