TP-38 Toxin in Treating Young Patients With Recurrent or Progressive Supratentorial High-Grade Glioma - Full Text View

Sponsor:	Pediatric Brain Tumor Consortium
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier:	NCT00074334

Purpose

RATIONALE: The TP-38 toxin can locate tumor cells and kill them without harming normal cells. Giving TP-38 toxin directly into the tumor may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of TP-38 toxin administered directly into the brain and to see how well it works in treating young patients with recurrent or progressive supratentorial high-grade glioma.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Biological: TGFa-PE38 immunotoxin Procedure: conventional surgery	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Safety/Efficacy Study
Official Title:	A Phase I/II Study Of A Recombinant Chimeric Protein Composed Of Transforming Growth Factor (TGF)-a And A Mutated Pseudomonas Exotoxin Termed PE38 (TP-38) In Pediatric Patients With Recurrent Or Progressive Supratentorial High Grade Gliomas

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Pediatric Brain Tumor Consortium:

Primary Outcome Measures:

Maximum safe volume rate of TP-38 infused through three catheters (Stratum A) or through two catheters (Stratum B). [ Designated as safety issue: Yes ]
Maximum tolerated infusion concentration of TP-38 infused through three catheters (Stratum A) or through two catheters (Stratum B). [ Designated as safety issue: Yes ]
Toxicities of TP-38 [ Designated as safety issue: Yes ]
Post-infusion survival (phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:

EGFR expression and phosphorylation (activity) [ Designated as safety issue: No ]
Correlation of EGFR expression with tumor histology, tumor grade, tumor response (phase I and phase II) and survival and progression-free survival (phase II). [ Designated as safety issue: No ]
Post-infusion progression-free survival (phase II) [ Designated as safety issue: No ]
Objective response (phase II) [ Designated as safety issue: No ]

Enrollment:	3
Study Start Date:	May 2004
Study Completion Date:	June 2006
Primary Completion Date:	June 2006 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Phase I
- Determine the maximum safe volume rate and maximum tolerated infusion concentration of TGFa-PE38 toxin (TP-38) infused through 2 or 3 catheters in pediatric patients with recurrent or progressive supratentorial high-grade glioma.
- Describe the toxic effects of this drug in these patients.
Phase II
- Estimate the efficacy of this drug, in terms of post-infusion survival, in these patients.

Secondary

Phase I and II
- Determine the prevalence of epidermal growth factor receptor (EGFR) expression and phosphorylation (activity) in patients treated with this drug.
- Correlate EGFR expression with qualitative measures (e.g., histology, grade, and other tumor characteristics) and tumor response, survival, and progression-free survival in patients treated with this drug.
Phase II Only
- Estimate the objective response rate in patients treated with this drug.
- Estimate the progression-free survival of patients treated with this drug.

OUTLINE: This is a dose-escalation, multicenter study. Patients in the phase I portion of the study are stratified according to the number of successfully placed catheters (3 catheters vs 2 catheters). Patients in the phase II portion of the study are stratified according to time of recurrence of high-grade glioma (first vs second or greater) and by surgery extent (surgical resection vs stereotactic biopsy) for those with first recurrence only.

Phase I: Patients undergo stereotactic biopsy or resection of the tumor followed by intratumoral (or tumor bed) catheter placement for treatment infusion. Within 12-48 hours after intratumoral (or tumor bed) catheter placement, patients receive TGFa-PE38 toxin (TP-38) intratumorally through 2 or 3 catheters over 33 to 124 hours. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients (in each stratum) receive escalating volumes until the maximum safe volume (MSV) is determined. Cohorts of 3-6 patients (in each stratum) receive escalating concentrations at the MSV until the maximum tolerated infusion concentration (MTIC) is determined. The MSV and MTIC are defined as the volume and concentration preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Phase II: Patients receive treatment as in phase I at the MSV and MTIC.

Phase I patients are followed post catheter placement, daily during TP-38 infusion, at 30 days, and then every 2 months for 1 year. Phase II patients will be followed for an additional year.

PROJECTED ACCRUAL: A total of 6-105 patients (6-60 for phase I and 45 for phase II) will be accrued for this study.

Eligibility

Ages Eligible for Study:	3 Years to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed supratentorial malignant glioma
- Recurrent or progressive disease
Amenable to gross total resection, clinically indicated partial resection, or biopsy
Tumor must have a single solid portion at least 1 cm and no greater than 5 cm in maximum diameter
- No tumor crossing midline
  - Tumors invading the corpus callosum that do not extend beyond to midline or into the contralateral hemisphere allowed
- No more than 1 focus of tumor
- No tumors involving the brainstem or cerebellum
- No tumor dissemination (i.e., subependymal or leptomeningeal)
Must be on steroids ≥ 3 days prior to surgery
Must have received prior external beam radiotherapy (tumor dose at least 45 Gy) and completed therapy at least 8 weeks before study entry
No impending herniation, including midline shift greater than 0.5 cm
No requirement for immediate palliative treatment

PATIENT CHARACTERISTICS:

Age

3 to 21

Performance status

Karnofsky 60-100% (patients over 16 years of age) OR
Lansky 60-100% (patients age 16 and under)

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* NOTE: *Transfusion independent

Hepatic

ALT and AST less than 2.5 times upper limit of normal (ULN)
PT and PTT no greater than ULN

Renal

Creatinine less than 1.5 times normal OR
Glomerular filtration rate greater than 70 mL/min

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for at least 30 days after study participation
No uncontrolled seizures
No active infection requiring treatment
No unexplained febrile illness
No known or suspected allergies to local anesthetics
No systemic disease or other condition that may be associated with unacceptable anesthetic/operative risk and/or that would preclude study completion
No other malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

At least 8 weeks since prior hematopoietic stem cell transplantation

Chemotherapy

At least 6 months since prior polifeprosan 20 with carmustine implant (Gliadel® wafer)
At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas and 2 weeks for vincristine)
At least 2 weeks since prior non-cytotoxic chemotherapy
No other prior intracerebral chemotherapy
No concurrent chemotherapy

Endocrine therapy

Concurrent steroids allowed

Radiotherapy

See Disease Characteristics
No prior focal radiotherapy (e.g., gamma knife radiosurgery, stereotactic radiosurgery, or brachytherapy)
No concurrent radiotherapy

Surgery

Not specified

Other

Recovered from prior therapy
At least 4 weeks since prior anticancer investigational agents
No prior localized antitumor therapy for malignant glioma
No other concurrent investigational agent
No other concurrent anticancer (including alternative anticancer medicines/treatment) agent or therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00074334

Locations

United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, United States, 77030-2399

Sponsors and Collaborators

Pediatric Brain Tumor Consortium

National Cancer Institute (NCI)

Investigators

Study Chair:

Roger J. Packer, MD

Children's Research Institute

More Information

Additional Information:

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

No publications provided

Responsible Party:	Pediatric Brain Tumor Consortium ( James M. Boyett/PBTC Operations and Biostatistics Center Executive Director )
Study ID Numbers:	CDR0000344416, PBTC-013
Study First Received:	December 10, 2003
Last Updated:	October 20, 2009
ClinicalTrials.gov Identifier:	NCT00074334 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Pediatric Brain Tumor Consortium:

childhood high-grade cerebral astrocytoma
recurrent childhood cerebral astrocytoma
childhood oligodendroglioma

childhood supratentorial ependymoma
recurrent childhood ependymoma
recurrent childhood brain tumor

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Immunologic Factors
Physiological Effects of Drugs
Nervous System Diseases

Central Nervous System Neoplasms
Pharmacologic Actions
Immunotoxins
Nervous System Neoplasms

ClinicalTrials.gov processed this record on November 22, 2009