Immunotoxin Therapy Before and After Surgery in Treating Patients With Recurrent Malignant Glioma
RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells. Immunotoxin therapy may be effective in treating malignant glioma.
PURPOSE: Phase I trial to study the effectiveness of immunotoxin therapy before and after surgery in treating patients who have recurrent malignant glioma.
|Brain and Central Nervous System Tumors||Biological: cintredekin besudotox Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy||Phase 1|
|Study Design:||Primary Purpose: Treatment|
|Official Title:||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|
|Study Start Date:||November 2001|
|Study Completion Date:||December 2009|
|Primary Completion Date:||January 2005 (Final data collection date for primary outcome measure)|
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00036972
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10021|
|Study Chair:||Lauren E. Abrey, MD||Memorial Sloan Kettering Cancer Center|