BIOEQUIVALENCE COMBINATION 776C85/5FU PILL & INDIVIDUAL 776C85 & 5FU PILL

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PURPOSE: This is a phase I, open-label, rising, multiple-dose study designed to characterize the safety profile and determine the maximally- tolerated dose and dose-limiting toxicity of SCH 66336 when administered orally to adult patients with advanced cancer. SCH 66336 is a potent, specific inhibitor of farnesyl protein transferase. This transferase is necessary for activation of ras proteins that when mutated are frequently found in human cancers. SCH 66336 thus represents a new class of antineoplastic compounds. It was developed by Schering Plough and has not yet been tested in humans. METHODS: Patients eligible for this phase I trial will be those with histologically confirmed solid tumor malignancies, without bone marrow involvement, for which no conventional therapies are available. No more than two prior chemotherapy regimens for advanced disease are permitted. At each dose level, subjects will receive a single-dose of SC 66336 followed by a 24 hour observation period (cycle l only). Subjects will then receive SC 66336 twice daily for 13 consecutive days. At each dose level, pharmacokinetic evaluations will be performed on day 1 and day 14. Patients will be housed on the Clinical Research Unit for monitoring and pharmacokinetics for their first dose and repeat pharmacokinetics on day 14. One patient each will be treated at each dose level until DLT is observed. If grade II toxicity (non-DLT) is observed during the first 28 days, an additional 2 subjects will be enrolled at that dose level. If one of three patients has non-DLT, then escalation will continue with one patient at each dose level. If 2 or 3 subjects have non-DLT, the dose escalation schedule will be changed to 3 subjects at each dose level. Patients may continue to take SC 66336 in the absence of disease progression (28-day cycles).