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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: 7-hydroxystaurosporine
* Drug: fluorouracil


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: 7-hydroxystaurosporine|nan|
|Drug: fluorouracil|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific