RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of phenylbutyrate in treating children who have recurrent or progressive cancer of the central nervous system.

Condition	Treatment or Intervention	Phase
Brain Cancer	Drug: phenylbutyrate  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES:

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

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.

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

Ages Eligible for Study:  2 Years   -   21 Years,  Genders Eligible for Study:  Both

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

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/mm^3*
• Platelet count at least 50,000/mm^3*
• 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

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

California
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94143-0128,  United States
District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2970,  United States
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States
Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104-4318,  United States
      Children's Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States
Texas
      Texas Children's Cancer Center, Houston,  Texas,  77030-2399,  United States

Study chairs or principal investigators

Susan Blaney, MD,  Study Chair,  Texas Children's Cancer Center   

Study ID Numbers:  CDR0000068163; TCCC-H-6321; TCCC-GCRC-0692; NCI-O1-C-0028; NCI-T98-0042
Record last reviewed:  April 2003
Last Updated:  October 13, 2004
Record first received:  September 11, 2000
ClinicalTrials.gov Identifier:  NCT00006238
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08