A Phase I Pharmacologic Trial Of Infusional UCN-01 Given With A Weekly Schedule Of 5-Fluorouracil And Leucovorin
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I Pharmacologic Trial Of Infusional UCN-01 Given With A Weekly Schedule Of 5-Fluorouracil And Leucovorin
OBJECTIVES:
- 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
these patients.
- 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
RPIID.
PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study within 16 months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed solid tumor that is metastatic or unresectable and for which
no standard curative or palliative measures exist or are effective
- No brain metastases or primary CNS malignancy
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count at least 1,500/mm3
- Platelet count at least 100,000/mm3
Hepatic
- Bilirubin no greater than 1.5 mg/dL
- AST and ALT no greater than 3 times upper limit of normal
Renal
- Creatinine no greater than 1.5 mg/dL OR
- Creatinine clearance at least 60 mL/min
Cardiovascular
- No known active coronary artery disease
Pulmonary
- No pulmonary dysfunction
Other
- HIV negative
- No history of unusually severe and/or prolonged toxicity during prior therapy with
fluorouracil (5-FU) or 5-FU prodrugs
- No diabetes mellitus requiring insulin or oral hypoglycemic therapy
- No ongoing or active infection requiring IV antibiotics
- No other serious concurrent medical illness that would preclude study
- No psychiatric illness or social situations that would preclude study
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- At least 4 weeks since prior immunotherapy and recovered
- No concurrent cytokines during the first course of therapy
Chemotherapy
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and
recovered
Endocrine therapy
- No concurrent systemic corticosteroids
Radiotherapy
- At least 2 weeks since prior radiotherapy and recovered
- No prior pulmonary or mediastinal radiation exceeding 40 Gy
Surgery
- Recovered from prior surgery
Other
- No other concurrent investigational agents
- No concurrent cimetidine
- No concurrent sorivudine or brivudine
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Jean L. Grem, MD
Investigator Role:
Study Chair
Investigator Affiliation:
National Cancer Institute (NCI)
Authority:
United States: Federal Government
Study ID:
CDR0000069478
NCT ID:
NCT00042861
Start Date:
August 2002
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
Name | Location |
|---|---|
| Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support | Bethesda, Maryland 20892-1182 |
