A Phase 1, Open-Label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of Kevetrin (Thioureidobutyronitrile) Administered Intravenously, in Patients With Advanced Solid Tumors

Kevetrin was found to be effective in pre-clinical studies of human xenograft tumor models and was reasonably well-tolerated at therapeutic doses in the non-clinical animal studies. Kevetrin was also effective in multi-drug resistant tumor models; therefore, Kevetrin has the potential to treat tumors that have become resistant to standard chemotherapy. This trial will determine tolerance in humans and, possibly, efficacy with a Phase I, open-label, dose-escalation, safety, pharmacokinetic, and pharmacodynamic study of Kevetrin, in adult patients with solid tumors. The primary objectives are the following: To determine the maximum tolerated dose (MTD) of Kevetrin. To determine the dose limiting toxicities (DLT) of Kevetrin. To establish a safe dose level of Kevetrin that can be used for future studies. The secondary objectives are to determine the following: The pharmacokinetics of Kevetrin in humans. Observe for evidence of antitumor activity following administration of Kevetrin. If Kevetrin induces changes in the biomarker p21 in peripheral blood lymphocytes. If there is a pharmacodynamic relationship between the plasma concentrations of Kevetrin and a clinical or cellular effect. During each 4 week cycle, each patient will receive three weekly doses of Kevetrin given as a 1 hour intravenous infusion followed by a 1 week off-treatment period. Following each dose, each patient will be monitored. If the patients have acceptable safety and tolerance, Kevetrin will be given once weekly for a total of 3 weeks. During each cycle patients will be evaluated for safety, tolerance, and Dose-Limiting Toxicity (DLT) that occur during a cycle.