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Fluorouracil Plus UCN-01 in Treating Patients With Advanced or Refractory Solid Tumors
This study has been completed.
First Received: December 10, 1999   Last Updated: July 23, 2008   History of Changes
Sponsor: Memorial Sloan-Kettering Cancer Center
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00004059
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. UCN-01 may increase the effectiveness of a chemotherapy drug by making tumor cells more sensitive to the drug.

PURPOSE: Phase I trial to study the effectiveness of fluorouracil plus UCN-01 in treating patients who have advanced or refractory solid tumors.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: 7-hydroxystaurosporine
Drug: fluorouracil
Phase I

Study Type: Interventional
Study Design: Treatment
Official Title: A Phase I Study of the Cyclin-Dependent Kinase (CDK)/Protein Kinase C (PKC) Inhibitor UCN-01 (NSC 638850) in Combination With 5-Fluorouracil in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: July 1999
Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose, dose limiting toxicity, and toxicity profile of fluorouracil with UCN-01 in patients with advanced or refractory solid tumors.
  • Assess the clinical pharmacokinetics of this regimen and correlate with observed toxicities in these patients.
  • Obtain preliminary data on the therapeutic activity of this regimen in these patients.

OUTLINE: This is a dose escalation study of fluorouracil.

Patients receive fluorouracil IV over 24 hours on days 1, 8, 15, and 22. Patients receive an initial dose of UCN-01 IV over 72 hours beginning on day 2 during course 1 and then maintenance UCN-01 IV over 36 hours beginning on day 2 during subsequent courses. Treatment repeats every 4 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of fluorouracil until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity.

PROJECTED ACCRUAL: Approximately 6-48 patients will be accrued for this study within approximately 14 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed solid tumor that is refractory to standard therapy or for which no standard therapy exists
  • Measurable or evaluable disease
  • No CNS metastasis or primary CNS malignancy

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • Karnofsky 60-100%

Life expectancy:

  • Not specified

Hematopoietic:

  • WBC greater than 3,500/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

  • Bilirubin no greater than 1.5 mg/dL
  • SGOT and SGPT no greater than 2.5 times upper limit of normal

Renal:

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

Cardiovascular:

  • No history of coronary artery disease documented by prior myocardial infarction, angiography, or coronary-artery bypass grafting
  • No cardiac arrhythmias or congestive heart failure within the past 6 months
  • Stable atrial fibrillation on standard treatment allowed at discretion of investigator

Pulmonary:

  • DLCO at least 60% of predicted

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 2 months after study
  • No active serious or uncontrolled infection
  • HIV negative
  • No diabetes
  • No other medical condition that would preclude study

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics

Biologic therapy:

  • At least 4 weeks since prior immunotherapy and recovered

Chemotherapy:

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

Endocrine therapy:

  • Not specified

Radiotherapy:

  • No prior mediastinal radiotherapy
  • At least 4 weeks since prior radiotherapy and recovered

Surgery:

  • Not specified

Other:

  • No concurrent anticonvulsant medications
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00004059

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Study Chair: Gary K. Schwartz, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000067256, MSKCC-9924, NCI-T99-0037
Study First Received: December 10, 1999
Last Updated: July 23, 2008
ClinicalTrials.gov Identifier: NCT00004059     History of Changes
Health Authority: United States: Federal Government

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

Additional relevant MeSH terms:
Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
7-hydroxystaurosporine
Protein Kinase Inhibitors
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Fluorouracil
Therapeutic Uses
Staurosporine

ClinicalTrials.gov processed this record on November 09, 2009