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

This study has been terminated.
(Drug company withdrawal of support for investigational agent in this indication.)
Sponsor:
Collaborator:
Information provided by:
Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier:
NCT00074334
First received: December 10, 2003
Last updated: October 20, 2009
Last verified: October 2009
  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 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
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:


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)
  Show Detailed Description

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Investigators
Study Chair: Roger J. Packer, MD Children's Research Institute
  More Information

No publications provided

Responsible Party: James M. Boyett/PBTC Operations and Biostatistics Center Executive Director, Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier: NCT00074334     History of Changes
Other Study ID Numbers: CDR0000344416, PBTC-013
Study First Received: December 10, 2003
Last Updated: October 20, 2009
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:
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Nervous System Diseases
Immunotoxins
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 14, 2014