A Phase I Trial of Sarcosinamide Nitrosourea (SarCNU) in Patients With Solid Tumors

PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of an oral formulation of SarCNU given on an every 4th day times three schedule (days 1, 5, 9). II. Establish an appropriate oral dose of SarCNU for phase II clinical trials. III. Identify the dose-limiting toxicities (DLTs) of SarCNU. IV. Determine the oral bioavailability of SarCNU. V. Characterize the plasma pharmacokinetics of SarCNU. SECONDARY OBJECTIVES: I. Determine whether SarCNU undergoes metabolic N-demethylation to generate reactive isocyanate species that have been implicated in BCNU pulmonary toxicity. II. Evaluate response to treatment with SarCNU in patients with measurable or evaluable disease. III. Attempt to establish pharmacodynamic relationships for response and/or toxicity. OUTLINE: This is a dose-escalation study. Patients receive oral sarcosinamide nitrosourea (SarCNU) on days 1, 5, and 9. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SarCNU 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. Patients are followed at 4-5 weeks posttreatment.