A Phase I Pharmacologic Trial Of Infusional UCN-01 Given With A Weekly Schedule Of 5-Fluorouracil And Leucovorin
- Determine the maximum tolerated dose of fluorouracil when given in combination with
UCN-01 and leucovorin calcium in patients with metastatic or unresectable solid tumors.
- Determine the clinical toxic effects of this regimen in these patients.
- Determine the pharmacokinetics of these drugs in these patients.
- Correlate, if possible, the pharmacokinetics of these drugs with clinical toxicity in
- Assess the pharmacodynamic effects of these drugs in these patients.
- Assess any clinical activity of this regimen in patients with measurable disease.
OUTLINE: This is a dose-escalation study of fluorouracil (5-FU).
Patients receive leucovorin calcium (CF) IV over 2 hours and 5-FU IV (at the midpoint of CF
administration) on day 1, followed by UCN-01 IV over 36-72 hours, on weeks 1-3. Courses
repeat every 4 weeks 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 preceding that at which at least 2 of 3
or 2 of 6 patients experience dose-limiting toxicity. The recommended phase II dose (RPIID)
is defined as the dose preceding the MTD. At least 6 additional patients are treated at the
PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study within 16 months.
Primary Purpose: Treatment
Jean L. Grem, MD
National Cancer Institute (NCI)
United States: Federal Government
|Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support||Bethesda, Maryland 20892-1182|