Trial Information

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

OBJECTIVES:

- Determine the concentration of interleukin-13 PE38QQR immunotoxin that produces
histologic evidence of toxicity to tumor and the corresponding toxic effects of this
drug when administered via continuous intratumoral infusion prior to second resection
in patients with recurrent resectable supratentorial malignant glioma.

- Determine the toxic effects of this drug when administered via continuous peritumoral
infusion, at concentrations determined in objective I, after second resection in these
patients.

- Determine any toxic effects of increasing the duration of continuous peritumoral
infusion of this drug, at concentrations determined in objective II, after second
resection in these patients.

- Determine the time to progression and survival of patients treated with this regimen.

OUTLINE: This is a dose-escalation, multicenter study.

- Pre-resection therapy (initial cohorts of patients only): Patients undergo stereotactic
biopsy of brain tumor followed by stereotactic placement of 1 intratumoral catheter on
day 1. Patients with histologically confirmed malignant glioma receive interleukin-13
PE38QQR immunotoxin via continuous intratumoral infusion over 48 hours on days 2 and 3.

Cohorts of 3-6 patients receive escalating doses of pre-resection interleukin-13 PE38QQR
immunotoxin until the histologically effective concentration (HEC) is reached or maximum
tolerated dose (MTD) is determined. The HEC is defined by pathologic observations. The MTD
is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting
toxicity. After the HEC is reached or MTD is determined, up to 6 additional patients are
enrolled at selected dose levels to study safety and tolerability. Subsequent cohorts of
patients are not treated with a pre-resection infusion.

- Resection (all patients): Patients undergo maximal resection (en bloc, if feasible)
followed by placement of 2-3 peritumoral catheters (4 days after completion of
pre-resection infusion for the initial cohorts of patients and at study entry for
subsequent cohorts of patients).

- Post-resection therapy (all patients): Beginning on the second day after resection,
patients receive interleukin-13 PE38QQR immunotoxin via continuous peritumoral infusion
over 96 hours.

Cohorts of 3-6 patients receive escalating doses of interleukin-13 PE38QQR immunotoxin until
the previously-defined HEC is reached or MTD is determined, whichever occurs first. If
dose-escalation is stopped after HEC is reached, then three additional cohorts of patients
receive escalating durations (5, 6, or 7 days) of post-resection infusion. If dose
escalation is stopped after the MTD is determined, then the duration of post-resection
infusion is not escalated.

Patients are followed every 8 weeks.

PROJECTED ACCRUAL: A total of 25-50 patients will be accrued for this study.