Phase I Study to Assess the Histologic Effect and Safety of Pre-Operative and Post-Operative Infusions of IL13-PE38QQR Cytotoxin in Patients With Recurrent Resectable Supratentorial Malignant Glioma
I. Determine the concentration of IL13-PE38QQR that produces histologic evidence of toxicity
to tumor, and the corresponding drug toxicity, following a 2-day continuous infusion into
recurrent malignant glioma prior to surgical resection.
II. Determine the toxicity of IL13-PE38QQR administered as a 4-day continuous infusion via
catheters into brain adjacent to tumor resection site, after surgical resection, at
concentrations up to the selected concentration.
III. Determine the toxicity of increasing duration of continuous infusion of IL13- PE38QQR
via catheters into brain adjacent to tumor resection site, after surgical resection, at the
IV. Determine the feasibility and safety of IL13-PE38QQR administration following
post-operative placement of stereotaxic catheters 2 days after tumor resection, utilizing a
post-operative imaging study for planning of catheter placement. A 4-day continuous infusion
at the MTD is planned.
V. Describe the time to progression and survival of patients treated with IL13-PE38QQR.
PROTOCOL OUTLINE: This study is designed to determine two dose levels. The first is defined
as the histologically effective concentration (HEC) when the agent is administered prior to
tumor resection. The second is defined using safety and tolerability of study drug
administered after tumor resection at doses up to the HEC. Safety and tolerability of
increasing duration of infusion after tumor resection will then be assessed.
Patient cohorts will be treated at escalating pre-resection dose-levels until a stopping
criterion for the pre-surgery dose is met, holding the post-resection dose constant at the
starting level. Stopping criteria for dose escalation of the pre-surgery infusion are
determination of the HEC or the maximum tolerated dose (MTD).
Subsequent cohorts will be treated only post-operatively at escalating dose levels until a
stopping criterion for the post-surgery dose is met. Stopping criteria for dose escalation
of the post-surgery infusion are reaching the HEC determined for the pre-operative infusion
or determination of the MTD. After the HEC is reached, subsequent cohorts will be treated
with post-operative infusions of increasing duration at the HEC until the maximum duration
defined in the study is reached or an MTD is defined. (If an MTD has already detected,
duration will not be escalated.)
After the stage of the study evaluating escalation of infusion duration has completed, the
study will expand to evaluate post-operative placement of catheters after tumor resection.
This stage of the study will assess the feasibility and safety of stereotaxic placement of
catheters 2 days after tumor resection using a post-operative imaging study for planning.
Patients will receive a 96 hour post-resection infusion at the MTD.
Cohorts of at least three patients will be entered at each dose level. Each cohort will be
observed for at least thirty days after completion of administration of study drug to allow
for observation of toxicity before the next cohort is enrolled.
PROJECTED ACCRUAL: Depends on number of dose-levels, estimated at 25-50 patients.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
United States: Food and Drug Administration
|MD Anderson Cancer Center||Houston, Texas 77030-4096|
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|University of California San Francisco||San Francisco, California 941104206|
|Yale University||New Haven, Connecticut 06520|