Trial Information

A Phase I - Part B Multiple Dose Trial of Phenethyl Isothiocyanate

OBJECTIVES: I. Determine the maximum tolerated dose of oral phenethyl isothiocyanate in
smokers. II. Measure the steady state pharmacokinetics of phenethyl isothiocyanate required
to maintain a steady state of this substance during the hours of
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) exposure in these patients. III. Obtain
preliminary data on the perturbation of NNK metabolism by phenethyl isothiocyanate in these
patients.

OUTLINE: Patients complete a questionnaire containing a smoking and dietary log to assess
cigarette and cruciferous vegetable consumption. Patients receive phenethyl isothiocyanate
orally 4 times a day for 30 days. Cohorts of 3-6 patients receive escalating doses of
phenethyl isothiocyanate until the maximum tolerated dose (MTD) is determined. The MTD is
defined as the dose preceding that at which 2 of 6 patients experience dose limiting
toxicities. Patients are followed on days 35, 36, and 43.

PROJECTED ACCRUAL: A total of 15-27 patients will be accrued for this study over 4-6 months.