Immunotoxin Therapy Before and After Surgery in Treating Patients With Recurrent Malignant Glioma - Full Text View

Sponsors and Collaborators:	Memorial Sloan-Kettering Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00036972

Purpose

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.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Biological: cintredekin besudotox Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy	Phase I

Study Type:	Interventional
Study Design:	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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Surgery

Drug Information available for: Cintredekin Besudotox

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

November 2001

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

Karnofsky 70-100%

Life expectancy:

Not specified

Hematopoietic:

Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00036972

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Lauren E. Abrey, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Kunwar S, Prados MD, Chang SM, Berger MS, Lang FF, Piepmeier JM, Sampson JH, Ram Z, Gutin PH, Gibbons RD, Aldape KD, Croteau DJ, Sherman JW, Puri RK; Cintredekin Besudotox Intraparenchymal Study Group. Direct intracerebral delivery of cintredekin besudotox (IL13-PE38QQR) in recurrent malignant glioma: a report by the Cintredekin Besudotox Intraparenchymal Study Group. J Clin Oncol. 2007 Mar 1;25(7):837-44.

Study ID Numbers:	CDR0000069345, MSKCC-01141, NEOPHARM-IL13PEI-002-R01, NCI-G02-2066
Study First Received:	May 13, 2002
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00036972 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent adult brain tumor
adult glioblastoma
adult anaplastic astrocytoma

adult mixed glioma
adult giant cell glioblastoma
adult gliosarcoma

Study placed in the following topic categories:

Glioblastoma
Astrocytoma
Adjuvants, Immunologic
Central Nervous System Neoplasms
Immunotoxins
Recurrence
Brain Neoplasms

Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Glioma
Gliosarcoma
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neuroectodermal Tumors
Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Nervous System Diseases

Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Glioma
Neoplasms, Neuroepithelial
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on July 02, 2009