A Phase I, Open Label Multiple Dose, Safety and Pharmacokinetic Study of Intravenously Administered Humanized Anti-VEGF Monoclonal Antibody (HuMV833) to Patients With Relapsed or Refractory Solid Tumors
OBJECTIVES: I. Determine the preliminary tolerability and safety of monoclonal antibody VEGF
(MOAB VEGF) in patients with relapsed or refractory progressive solid tumors. II. Determine
the optimum biologically active dose of MOAB VEGF for further evaluation based on
exploratory methods. III. Determine the maximum tolerated dose of MOAB VEGF in these
patients. IV. Determine a safe dose of MOAB VEGF for further clinical studies. V. Determine
the dose limiting toxicity and pharmacokinetics of this regimen in these patients. VI.
Determine the response rate in patients treated with this regimen.
OUTLINE: This is a dose escalation, multicenter study. Patients receive monoclonal antibody
VEGF (MOAB VEGF) IV over 1 hour on days 1, 15, 22, and 29. Patients with partial response
(PR), complete response (CR), or stable disease (SD) after completion of the fourth dose may
receive weekly infusions for up to 6 months in the absence of disease progression or
unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of MOAB VEGF until
the maximum tolerated dose (MTD) and optimum biologically active dose (OBAD) are determined.
The MTD is defined as the dose at which 1 of 6 patients experiences dose limiting toxicity.
The OBAD is defined as the dose at which vascular endothelial growth factor is optimally
inhibited. Patients with PR, CR, or SD are evaluated every 6 weeks until disease progression
or initiation of another treatment. Patients who discontinue treatment prematurely due to
toxicity are followed weekly until resolution of any associated toxicity. Patients who
discontinue treatment after the fourth dose of MOAB VEGF for any reason other than toxicity
are followed every month for up to 6 months.
PROJECTED ACCRUAL: A maximum of 25 patients will be accrued for this study.
Primary Purpose: Treatment
Gordon Jayson, MD
Christie Hospital NHS Foundation Trust
United States: Federal Government