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
7-hydroxystaurosporine
+ fluorouracil
Treatment Study
Summary
Study start date: July 1, 1999
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.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
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
Memorial Sloan-Kettering Cancer Center
New York, United StatesOpen Memorial Sloan-Kettering Cancer Center in Google Maps