Phase I-II Study of Fluorouracil in Combination With Phenylbutyrate, Indomethacin and Recombinant Human Interferon-Gamma in Advanced Colorectal Cancer
I. To determine in a Phase I study the toxicity of flurouracil (FU) when given in escalating
doses in combination with fixed doses of phenlylbutyrate (PB), indomethacin and recombinant
human interferon-gamma (rhIFNg) to patients with advanced colorectal cancer.
II. To determine in a Phase II study the efficacy of FU in combination with PB, indomethacin
and rhIFNg in patients with advanced colorectal cancer.
OUTLINE: This is a dose-escalation study of fluorouracil (5-FU).
Phase I: Patients receive 5-FU IV over 24 hours on day 1; phenylbutyrate IV over 120 hours
and oral indomethacin daily on days 2-6; and interferon gamma subcutaneously on days 2, 4,
and 6. Courses repeat weekly in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of 5-FU until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose at which less than 2 of 6 patients
experience dose-limiting toxicity (DLT).
Phase II :Patients receive 5-FU, phenylbutyrate, indomethacin, and interferon gamma as in
phase I at the MTD.
Patients are followed for survival.
PROJECTED ACCRUAL: A maximum of 24 patients will be accrued for the phase I portion of this
study and approximately 46 patients will be accrued for the phase II portion of this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Toxicity of flurouracil (FU) when given in escalating doses in combination with fixed doses of phenlylbutyrate (PB), indomethacin and recombinant human interferon-gamma (rhIFNg) to patients with advanced colorectal cancer (Phase I)
Mount Sinai School of Medicine
United States: Food and Drug Administration
|Mount Sinai Medical Center
|New York, New York 10029