SU5416, a novel antiangiogenesis agent, has been shown to be a potent and selective inhibitor
of the tyrosine kinase activity of FlK-1 (a downstream effector of VEGF) in vitro and to
inhibit the growth of endothelial cells. Since VEGF mRNA levels and vessel counts in tumor
tissues have been shown to be inversely related to prognosis in ovarian cancer, SU5416 may
prove to be a useful agent in this disease. Platinum agents currently provide the most
effective treatment for ovarian cancer. However, ovarian cancer often becomes refractory to
platinum therapy, leaving the patient with a poor prognosis. This is a phase I study designed
to: a) determine a dose level of carboplatin to use in combination with an established dose
of SU5416 for treatment of patients with platinum-refractory ovarian cancer, b) assess the
side effect profile of SU5416 and carboplatin combination therapy, c) characterize any
alterations in SU5416 pharmacokinetic and pharmacodynamic parameters when given in
combination with carboplatin, d) characterize carboplatin pharmacokinetic and pharmacodynamic
parameters when given in combination with SU5416, e) do exploratory studies to assess the
effect of SU5416 on platinum-DNA adduct levels, f) do exploratory studies to assess any
alterations in ERCC1 mRNA levels when carboplatin is administered with SU5416, and g) obtain
preliminary evidence of the ability of SU5416 to reverse platinum resistance in patients with
platinum-refractory ovarian carcinoma.