Fluorouracil Plus UCN-01 in Treating Patients With Advanced or Refractory Solid Tumors

June 20, 2013 updated by: Memorial Sloan Kettering Cancer Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 1999

Primary Completion (Actual)

September 1, 2002

Study Completion (Actual)

September 1, 2002

Study Registration Dates

First Submitted

December 10, 1999

First Submitted That Met QC Criteria

May 7, 2003

First Posted (Estimate)

May 8, 2003

Study Record Updates

Last Update Posted (Estimate)

June 21, 2013

Last Update Submitted That Met QC Criteria

June 20, 2013

Last Verified

June 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 99-024
  • CDR0000067256 (Registry Identifier: PDQ (Physician Data Query))
  • NCI-T99-0037

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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