Phase I Study to Determine the Maximum Tolerated Dose of LErafAON in Combination With Radiotherapy in Patients With Advanced Malignancies
OBJECTIVES: I. Determine the toxicity and MTD of LErafAON administered in daily I.V.
infusions, in combination with radiotherapy, to patients with advanced malignancies.
II. Characterize the plasma pharmacokinetics of LErafAON after IV infusion.
III. Assess in vivo inhibition of Raf-1 protein by LErafAON.
IV. Determine efficacy in radiated and non-radiated tumors.
PROTOCOL OUTLINE: This study is a traditional Phase I MTD study. Cohorts of at least three
patients will be entered at escalating dose-levels. Patients will receive daily IV
infusions of LErafAON for 2 weeks (total of 10 doses). Each cohort will be observed for at
least two weeks post treatment with study medication to allow for observation of toxicity
before the next cohort is enrolled. Dose escalation will proceed until the MTD is
identified. Dose escalation within a patient will not be allowed.
PROJECTED ACCRUAL: Up to 27 patients; at least 3 per dose level, expanded to 6 if
dose-limiting toxicity (DLT) occurs.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Anatoly Dritschilo, M.D.
United States: Food and Drug Administration
|Fox Chase Cancer Center||Philadelphia, Pennsylvania 19111|
|Temple University Cancer Center||Philadelphia, Pennsylvania 19140|
|Georgetown University||Washington, District of Columbia 20007-2197|
|University of Chicago Medical Center||Chicago, Illinois 60637|