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

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Completed 3 to 21 NCI PBTC-013 PBTC-013, NCT00074334

Objectives

Primary

1. 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.
2. Determine the toxic effects of this drug in these patients.
3. Determine the efficacy of this drug, in terms of post-infusion survival, in these patients.

Secondary

1. Determine the prevalence of epidermal growth factor receptor (EGFR) expression and phosphorylation (activity) in patients treated with this drug.
2. 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.
3. Determine the objective response rate in patients treated with this drug.
4. Determine the progression-free survival of patients treated with this drug.

Entry 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

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

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/mm³
• Platelet count at least 100,000/mm³*
• 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

Expected Enrollment

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

Outcomes

Survival at 1 year

Progression-free survival at 1 year
Response as measured by radiographic criteria

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 disease progression (yes or no).

• 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 followed by escalating concentrations of TP-38 until the maximum safe volume (MSV) and maximum tolerated infusion concentration (MTIC) are 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.

Patients are followed at 30 days, every 3 months for 1 year, and then every 6 months for at least 2 years.

Trial Contact Information

Trial Lead Organizations

Pediatric Brain Tumor Consortium

Roger Packer, MD, Protocol chair		Ph: 202-884-2120
Robert Keating, MD, Protocol co-chair		Ph: 202-884-3020

Registry Information
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
Trial Start Date		2004-05-04
Registered in ClinicalTrials.gov		NCT00074334
Date Submitted to PDQ		2003-11-06
Information Last Verified		2006-04-13
NCI Grant/Contract Number		CA81457

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