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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00042861
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : April 30, 2015
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Unspecified Adult Solid Tumor, Protocol Specific Drug: 7-hydroxystaurosporine Drug: fluorouracil Drug: leucovorin calcium Phase 1

Detailed Description:


  • 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.

Study Type : Interventional  (Clinical Trial)
Primary Purpose: Treatment
Official Title: A Phase I Pharmacologic Trial Of Infusional UCN-01 Given With A Weekly Schedule Of 5-Fluorouracil And Leucovorin
Study Start Date : August 2002

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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



  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified


  • Absolute neutrophil count at least 1,500/mm3
  • Platelet count at least 100,000/mm3


  • Bilirubin no greater than 1.5 mg/dL
  • AST and ALT no greater than 3 times upper limit of normal


  • Creatinine no greater than 1.5 mg/dL OR
  • Creatinine clearance at least 60 mL/min


  • No known active coronary artery disease


  • No pulmonary dysfunction


  • 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


Biologic therapy

  • At least 4 weeks since prior immunotherapy and recovered
  • No concurrent cytokines during the first course of therapy


  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

  • No concurrent systemic corticosteroids


  • At least 2 weeks since prior radiotherapy and recovered
  • No prior pulmonary or mediastinal radiation exceeding 40 Gy


  • Recovered from prior surgery


  • No other concurrent investigational agents
  • No concurrent cimetidine
  • No concurrent sorivudine or brivudine

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00042861

United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
National Cancer Institute (NCI)
Study Chair: Jean L. Grem, MD National Cancer Institute (NCI) Identifier: NCT00042861     History of Changes
Obsolete Identifiers: NCT00039637
Other Study ID Numbers: CDR0000069478
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: April 30, 2015
Last Verified: April 2003

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protective Agents
Protein Kinase Inhibitors
Enzyme Inhibitors