UCN-01, Fluorouracil, and Leucovorin in Treating Patients With Metastatic or Unresectable Solid Tumors

National Cancer Institute (NCI)

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Drug: 7-hydroxystaurosporine

Drug: fluorouracil

Drug: leucovorin calcium

Study type

Interventional

Funder types

NIH

Identifiers

NCT00042861

CDR0000069478

NCI-NAVY-01-04

NCI-02-C-0222

NCI-5535

Details and patient eligibility

About

RATIONALE: UCN-01 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining UCN-01 with chemotherapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining UCN-01, fluorouracil, and leucovorin in treating patients who have metastatic or unresectable solid tumors.

Full description

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.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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