Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Immunotoxin Therapy Before and After Surgery in Treating Patients With Recurrent Malignant Glioma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over NCI, Pharmaceutical / Industry MSKCC-01141 NEOPHARM-IL13PEI-002-R01, NCI-G02-2066, NCT00036972

Objectives

1. 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.
2. 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.
3. 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.
4. Determine the time to progression and survival of patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed supratentorial malignant glioma (grade 3 or 4)
  • Anaplastic astrocytoma
  • Glioblastoma multiforme
  • Mixed oligoastrocytoma
  • Malignant astrocytoma, not otherwise specified



• Prior first resection of brain tumor



• Prior cranial radiotherapy with tumor dose of at least 48 Gy



• Radiographic evidence of recurrent or progressive supratentorial tumor
  • In patients who have received external beam radiotherapy or localized radiotherapy (e.g., gamma-knife or brachytherapy) within the past 12 weeks, progression must be confirmed by metabolic imaging (magnetic resonance spectroscopy or positron-emission tomography)



• Must be a candidate for second resection



• No signs of impending herniation



• No midline shift greater than 1 cm



• No multifocal disease or subependymal tumor spread

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior cytotoxic therapy (2 weeks for vincristine or 6 weeks for nitrosoureas)

Endocrine therapy:

• Concurrent steroids allowed
• No tapering of steroids during or immediately after study infusion

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy

Surgery:

• See Disease Characteristics

Other:

• Recovered from prior therapy
• At least 4 weeks since prior investigational agents
• At least 2 weeks since prior non-cytotoxic agents
• No other concurrent antitumor therapy

Patient Characteristics:

Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• Hemoglobin at least 9 g/dL

Hepatic:

• PT and PTT no greater than upper limit of normal

Renal:

• Not specified

Other:

• No uncontrolled seizures
• No other neurologic condition that would interfere with study evaluation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 60 days after study

Expected Enrollment

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

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.

Kunwar S, Prados MD, Chang SM, et al.: Direct intracerebral delivery of cintredekin besudotox (IL13-PE38QQR) in recurrent malignant glioma: a report by the Cintredekin Besudotox Intraparenchymal Study Group. J Clin Oncol 25 (7): 837-44, 2007.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Lauren Abrey, MD, Protocol chair		Ph: 212-639-5122; 800-525-2225 Email: abreyl@mskcc.org

Registry Information
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
Trial Start Date		2001-11-27
Registered in ClinicalTrials.gov		NCT00036972
Date Submitted to PDQ		2002-03-25
Information Last Verified		2004-07-16
NCI Grant/Contract Number		P30-CA08748

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