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

Alternate Title

Phenylbutyrate in Treating Children With Progressive or Recurrent Cancer of the Central Nervous System

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 2 to 21 NCI TCCC-H-6321 TCCC-GCRC-0692, NCI-O1-C-0028, NCI-T98-0042, NCT00006238, T98-0042

Objectives

1. Determine the therapeutic efficacy of phenylbutyrate in terms of response rate and time to progression in children with recurrent or progressive CNS malignancy.
2. Determine the toxicity of this regimen in these patients.
3. Determine the correlation between serum steady state phenylbutyrate levels and response or toxicity in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed recurrent or progressive brain tumor after radiotherapy, chemotherapy, or bone marrow transplantation
  • High grade glioma (anaplastic astrocytoma or glioblastoma multiforme)
  • Brain stem glioma
  • Medulloblastoma or primitive neuroectodermal tumors present in supratentorial or posterior fossa
  • Other



• Histological confirmation waived in brain stem tumors



• Patients previously treated with radiosurgery require a biopsy, PET scan or NMR spectroscopy



• Measurable disease by CT or MRI imaging that clearly demonstrates recurrent or progressive nature of the lesion



• Histologic evidence of bone marrow involvement allowed

Prior/Concurrent Therapy:

Biologic therapy:

• See Disease Characteristics
• Recovered from toxic effects of prior immunotherapy
• Prior bone marrow transplantation allowed
• No concurrent prophylactic hematopoietic growth factors except for neutropenia or documented infection

Chemotherapy:

• See Disease Characteristics
• At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)
• Recovered from prior chemotherapy
• No other concurrent chemotherapy

Endocrine therapy:

• If receiving dexamethasone must be on stable or decreasing dose for 2 weeks prior to study

Radiotherapy:

• See Disease Characteristics
• Recovered from prior radiotherapy
• More than 8 weeks since prior radiotherapy to evaluable lesion
• More than 4 months since prior radiosurgery to evaluable lesion
• Prior extensive radiotherapy (i.e., craniospinal radiotherapy or field encompassing region greater than hemipelvis) allowed

Surgery:

• See Disease Characteristics
• See Radiotherapy

Other:

• No other concurrent investigational agents
• Concurrent electrolyte supplements to maintain electrolyte levels allowed

Patient Characteristics:

Age:

• 2 to 21

Performance status:

• Lansky 50-100% (10 and under)
• Karnofsky 50-100% (over 10)

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm³*
• Platelet count at least 50,000/mm³*
• Hemoglobin at least 8.0 g/dL*

 [Note: *Transfusion allowed]

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGPT no greater than 2 times normal

Renal:

• Creatinine normal for age

  OR

• Creatinine clearance at least 70 mL/min

Other:

• No other concurrent significant systemic illness (e.g., infection)
• No significant electrolyte abnormalities
• No amino acidurias or organic acidemias
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study

Expected Enrollment

A maximum of 120 patients (approximately 9-24 evaluable patients per stratum) will be accrued for this study within 2 years.

Outline

This is a multicenter study. Patients are stratified according to tumor histology (high grade glioma (anaplastic astrocytoma or glioblastoma multiforme) vs brain stem glioma vs medulloblastoma or primitive neuroectodermal tumors vs other).

Patients receive phenylbutyrate IV continuously on days 1-28. Treatment continues every 4 weeks for up to a maximum of 12 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed at 1 week.

Trial Contact Information

Trial Lead Organizations

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

Susan Blaney, MD, Protocol chair		Ph: 832-822-1482 Email: sblaney@txccc.org

Registry Information
Official Title		Phase II Trial of Phenylbutyrate Given as a Continuous Infusion in Pediatric Patients with Progressive or Recurrent CNS Malignancy
Trial Start Date		2000-11-09
Registered in ClinicalTrials.gov		NCT00006238
Date Submitted to PDQ		2000-07-24
Information Last Verified		2003-04-01
NCI Grant/Contract Number		CA82744