Phase I trial to study the effectiveness of combining UCN-01 with carboplatin in treating patients who have advanced solid tumors. UCN-01 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining UCN-01 with carboplatin may kill more tumor cells.
PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose, dose limiting toxicity and other toxicities of UCN-01 when combined with carboplatin. II. Preliminarily evaluate the antitumor effect of the combination of carboplatin and UCN-01. III. Determine the pharmacokinetics of UCN-01 and carboplatin. OUTLINE: This is a dose-escalation study. Patients receive carboplatin IV over 1 hour followed by UCN-01 IV over 3 hours on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of carboplatin and UCN-01 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, United States
Maximum tolerated dose of UCN-01 when combined with carboplatin determined by dose-limiting toxicities graded according to NCI Common Toxicity Criteria (CTC)
Time frame: 21 days
Response rate
Reported with 95% confidence intervals.
Time frame: Up to 3 years
Survival
Estimated utilizing Kaplan-Meier analysis.
Time frame: From the date of first treatment until death or last follow up, assessed up to 3 years
Pharmacokinetics parameters of UCN-01
Will be determined using model independent and compartmental modeling methods. Will include, but not be limited too; the maximum plasma concentration (Cmax), area under the concentration versus time curve (AUC), terminal elimination half-life (t1/2), clearance (Cl), and volume of distribution (Vd).
Time frame: Prior to and at 0.5, 1, 2, and 3 hours after the start of the infusion and at 2, 4, 8, 24, 48 hours, and 7, and 21 days after the end of the infusion
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