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

NCT00074334 | Terminated Phase 1 DMC

• 2 other identifiers: CDR0000344416PBTC-013
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

childhood high-grade cerebral astrocytoma; recurrent childhood cerebral astrocytoma; childhood oligodendroglioma; childhood supratentorial ependymoma; recurrent childhood ependymoma; recurrent childhood brain tumor

Outcome Measures

Primary Outcomes (4)

• Maximum safe volume rate of TP-38 infused through three catheters (Stratum A) or through two catheters (Stratum B).

• Maximum tolerated infusion concentration of TP-38 infused through three catheters (Stratum A) or through two catheters (Stratum B).

• Toxicities of TP-38

• Post-infusion survival (phase II)

Secondary Outcomes (4)

• EGFR expression and phosphorylation (activity)

• Correlation of EGFR expression with tumor histology, tumor grade, tumor response (phase I and phase II) and survival and progression-free survival (phase II).

• Post-infusion progression-free survival (phase II)

• Objective response (phase II)

Interventions

TGFa-PE38 immunotoxin BIOLOGICAL

conventional surgery PROCEDURE

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Pediatric Brain Tumor Consortium: lead
• National Cancer Institute (NCI): collaborator

Study Sites (8)

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104-4283, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital

Houston, Texas, 77030-2399, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Astrocytoma; Oligodendroglioma; Familial ependymoma

Interventions

transforming growth factor(alpha)-Pseudomonas aeruginosa exotoxin (38)

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Roger J. Packer, MD

  Children's National Research Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NETWORK

Study Record Dates

• First Submitted: December 10, 2003
• First Posted: December 11, 2003
• Study Start: May 1, 2004
• Primary Completion: June 1, 2006
• Study Completion: June 1, 2006
• Last Updated: October 21, 2009

Record last verified: 2009-10

Locations

US (8)