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

Alternate Title

Phenylbutyrate in Treating Children With Refractory Cancers

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 2 to 21 NCI TCCC-T96-0044 NCI-T96-0044O, T96-0044

Objectives

I.  Determine the maximum tolerated dose of phenylbutyrate given as a 
continuous infusion in children with refractory tumor.

II.  Determine the dose-limiting toxic effects and the incidence and severity 
of other toxic effects associated with phenylbutyrate.

III.  Study the pharmacokinetics of phenylbutyrate.

IV.  Determine the steady-state plasma concentrations of phenylbutyrate and 
its metabolite, phenylacetate, and attempt to correlate these plasma 
concentrations with clinical toxicity.

Entry Criteria

Disease Characteristics:

Histologically confirmed tumor that is refractory to standard therapy or for
which no standard or potentially curative therapy exists
 Including patients with neurofibromatosis type I or II with progressive
  inoperable plexiform neurofibromas that have the potential to cause
   significant morbidity
 Requirement for histologic verification may be waived for brain stem glioma

The following are allowed but render patient inevaluable for hematologic
toxicity:
 Histologic evidence of bone marrow involvement
 History of bone marrow transplant or extensive radiotherapy (e.g.,
  craniospinal radiotherapy or fields encompassing a region larger than the
   hemipelvis)

Prior/Concurrent Therapy:

At least 3 weeks since myelosuppressive therapy unless specified  

Biologic therapy:
 See Disease Characteristics
 Must have recovered from prior biologic therapy

Chemotherapy:
 No concurrent dexamethasone unless dose stable or decreasing for at least 2
  weeks prior to study entry
 At least 6 weeks since nitrosoureas
 Must have recovered from any other prior chemotherapy

Endocrine therapy:
 Must have recovered from prior endocrine therapy

Radiotherapy:
 See Disease Characteristics
 At least 6 weeks since prior radiotherapy

Surgery:
 Not specified

Patient Characteristics:

Age:
 2 to 21

Performance status:
 ECOG 0-2

Life expectancy:
 At least 8 weeks

Hematopoietic:
 Absolute granulocyte count at least 1,500/mm3
 Platelet count at least 100,000/mm3
 Hemoglobin at least 8.0 g/dL
  (Exempt from above criteria if bone marrow (BM) involvement by tumor or
    history of either BM transplantation or extensive radiotherapy)

Hepatic:
 Bilirubin no greater than 2.0 mg/dL
 ALT less than twice normal

Renal:
 Creatinine no greater than 1.5 mg/dL OR
 Creatinine clearance at least 60 mL/min per square meter

Other:
 No significant systemic illness
 No amino aciduria or organic acidemia
 No grade 2 or worse neurocortical toxicity (i.e., moderate somnolence,
  agitation)
 Not pregnant or nursing

Expected Enrollment

Approximately 15-20 patients will be accrued for this study within 1 year.

Outline

This is a dose escalation study.

Patients receive phenylbutyrate IV over 30 minutes on the first course only to 
determine pharmacokinetic parameters.  This is followed 24 hours later by 
phenylbutyrate administered by continuous infusion. Courses repeat every 28 
days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating continuous infusion doses of 
phenylbutyrate until the maximum tolerated dose (MTD) is determined.  

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