Study to Determine the Maximum Tolerated Dose of Liposome-Encapsulated C-RAF Antisense Oligodeoxynucleotide (LErafAON) in Patients With Advanced Solid Tumors
OBJECTIVES: I. Determine the toxicity and MTD of LErafAON when given by weekly IV infusion
for 8 weeks in patients with advanced malignancies.
II. Characterize the plasma pharmacokinetics of LErafAON after IV infusion.
III. Document in vivo inhibition of Raf-1 protein by LErafAON.
IV. Detect anti-tumor effects of intravenous LErafAON.
PROTOCOL OUTLINE: This is a Phase I Maximum Tolerated Dose (MTD) study for patients with
recurrent solid tumor malignancies. Study medication will be administered by intravenous
infusion over at least 60 minutes, once per week, for 8 weeks. In the absence of
progression, patients may continue on weekly treatment. Pre-medications will be
administered prior to each dose of study medication. Patients will be followed for one
month after receiving the last dose of study medication. Patients with Complete Response
(CR), Partial Response (PR), or Stable Disease (SD) at the Week 8 disease assessment may
continue to receive study medication until disease progression (PD).
Cohorts of at least three patients will be entered at escalating dose-levels. Each cohort
will be observed for at least ten days after receiving the first dose of treatment before
additional patients are treated at a higher dose level. Patients will be followed for one
month after receiving the last dose of study medication. The study will stop when a maximum
tolerated dose (MTD) is identified. Dose escalation within a patient will not be allowed.
PROJECTED ACCRUAL: Estimated enrollment is 15-35 patients; 3 per dose level, expanded to 6
if DLT occurs.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Charles Rudin, M.D.
United States: Food and Drug Administration
|Temple University Cancer Center||Philadelphia, Pennsylvania 19140|
|Georgetown University||Washington, District of Columbia 20007-2197|
|University of Chicago Medical Center||Chicago, Illinois 60637|