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

Memorial Sloan Kettering Cancer Center

Overview

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.

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

Purpose

TREATMENT

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Interventions

7-hydroxystaurosporineDRUG

fluorouracilDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Data from ClinicalTrials.gov

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