Trial Information

Phase II Randomized Placebo-Controlled Double-Blinded Study With 5-FU vs. 5-FU With IM862 With Cross-Over to CPT-11 vs. CPT-11 With IM862

OBJECTIVES: I. Compare the efficacy of fluorouracil with or without IM-862 in terms of
progression free survival in patients with previously untreated or recurrent metastatic
adenocarcinoma of the colon or rectum. II. Determine the toxicity of IM-862 and fluorouracil
in these patients. III. Determine the efficacy of IM-862 in combination with irinotecan in
terms of progression free survival in patients who have disease progression after receiving
fluorouracil. IV. Obtain preliminary data on molecular markers of response and time to
progression by determining levels of genes involved in adhesion, angiogenesis, apoptosis,
and drug resistance prior to and during chemotherapy. V. Determine the molecular correlates
for response and time to progression through analysis of serum and urine markers of
angiogenesis, such as vascular endothelial growth factor and fibroblast growth factor, in
patients treated with IM-862 in combination with fluorouracil or irinotecan. VI. Compare the
quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, double blind, placebo controlled, crossover study. Patients
are randomized to one of two treatment arms: Arm I: Patients receive fluorouracil IV
continuously on days 1-21 and IM-862 intranasally three times daily on days 1-28. Courses
repeat every 4 weeks in the absence of disease progression. Patients who develop disease
progression are taken off fluorouracil and IM-862, and then receive irinotecan IV over 90
minutes weekly for 4 weeks. Courses repeat every 6 weeks in the absence of disease
progression. Arm II: Patients receive fluorouracil as in arm I and placebo intranasally
three times daily on days 1-28. Courses repeat every 4 weeks in the absence of disease
progression. Patients who develop disease progression are taken off fluorouracil and
placebo, and then receive irinotecan and IM-862 as in arm I on days 1-42. Courses repeat
every 6 weeks in the absence of disease progression. Quality of life is assessed prior to
study, and then prior to every course during study. Patients are followed for a minimum of 6
months.

PROJECTED ACCRUAL: A total of 66 patients (33 per arm) will be accrued for this study within
26-27 months.