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A Phase I Pharmacologic Trial Of Infusional UCN-01 Given With A Weekly Schedule Of 5-Fluorouracil And Leucovorin


Phase 1
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

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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 SupportBethesda, Maryland  20892-1182