A Phase I Investigation of Carboxyamido-triazole (CAI) Modulated by Ketoconozole In Patients With Advanced Malignancies
I. Determine the maximum tolerated dose of carboxyamidotriazole (CAI) in combination with
ketoconazole in patients with advanced malignancies.
II. Evaluate the toxic effects, safety, and efficacy of CAI in combination with
III. Determine the modulatory effects of ketoconazole on the pharmacokinetic profile of CAI.
IV. Determine a pharmacodynamic model for CAI and ketoconazole with respect to potential
gastrointestinal, hematologic, and neurotoxicities.
OUTLINE: This is a dose escalation study.
Patients receive oral carboxyamidotriazole (CAI) as a test dose on day 1. Patients receive
oral ketoconazole on day 7, followed by CAI plus ketoconazole on day 8. CAI and ketoconazole
are administered in combination on day 1 and days 3-28 of the first course. Ketoconazole is
administered alone on day 2 of the first course. Subsequent courses begin at 28 day
intervals in the absence of disease progression or unacceptable toxic effects. Cohorts of 3
patients are evaluated at each dose level prior to dose escalation. If one of three patients
within a cohort experiences dose limiting toxicity (DLT), that dose level is expanded to
incorporate six patients. If two or more patients experience DLT, the next lower dose is
declared to be the maximum tolerated dose.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Mark J. Ratain, MD
University of Chicago
United States: Food and Drug Administration
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