A Phase I Pharmacodynamic Trial of SU5416 (NSC 696819)
OBJECTIVES: I. Determine the maximum target-inhibiting dose of SU5416 in patients with
advanced solid tumors. II. Determine the relationship between dose or plasma levels and the
clinical safety profile and antitumor effects of this treatment regimen in terms of
objective response, stabilization of disease, or progression-free survival in this patient
population. III. Evaluate the relationship between dose or plasma levels of SU5416
concentrations and the ability of this treatment regimen to reduce microvessel density and
induce apoptosis of endothelial and tumor cells in this patient population. IV. Determine
prognostic and surrogate serologic markers in these patients treated with this regimen. V.
Determine if pre and posttreatment plasma and serum levels of angiogenic growth factors,
basic fibroblast growth factor, and vascular endothelial cell growth factor are prognostic
in predicting patient response to this regimen. VI. Determine if elevated plasma levels of
endothelial cell specific proteins reflective of SU5416-induced endothelial damage and/or
apoptosis are useful surrogate markers in assessing response to this treatment regimen in
OUTLINE: This is a dose-deescalation study. Patients receive SU5416 IV over 1 hour twice
weekly for 4 weeks. Treatment continues in the absence of disease progression or
unacceptable toxicity. Cohorts of 6-12 patients receive deescalating doses of SU5416 until
the maximum target-inhibiting dose (MTID) is determined. The MTID is defined as the dose at
which patients experience no greater than grade 1 toxicity. Patients are followed every 3
PROJECTED ACCRUAL: Approximately 20-30 patients will be accrued for this study.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine the maximum target-inhibiting dose of SU5416 in patients with advanced solid tumors.
1 hour twice weekly for 4 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients followed every 3 months.
Afshin Dowlati, MD
Ireland Cancer Center
United States: Federal Government
|Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
|Cleveland, Ohio 44106-5065