Phase I and Pharmacokinetic Trial of Phenylbutyrate Given as a Continuous Infusion in Pediatric Patients With Refractory Malignancy

Launched by NATIONAL CANCER INSTITUTE (NCI) · Dec 9, 2002

Keywords

ClinConnect Summary

Phenylbutyrate is an aromatic fatty acid that is converted to phenylacetate in vivo by mitochondrial beta-oxidation to phenylacetate. Preclinical studies have shown that continuous exposure to phenylacetate or phenylbutyrate can induce tumor cytostasis and differentiation in a wide variety of cell lines including malignant gliomas and neuroblastomas. However, phenylbutyrate has been shown to be a more potent differentiating agent than phenylacetate in a variety of tumor cell lines. In addition, phenylbutyrate appears to have molecular activities that are distinct from phenylacetate. The obj...

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Eligibility criteria

• Disease Characteristics:
• • Histologically proven cancer that is refractory to standard therapy.
• • Patients with neurofibromatosis having progressive inoperable plexiform neurofibromas with potential to cause significant morbidity are eligible.
• • Patients with brainstem gliomas histology may have histology requirements waived.
• • Patients without prior therapy are eligible if they have diseases with no available standard therapy.
• • Patients with evidence of bone marrow involvement by tumor, or a history of either bone marrow transplantation or extensive radiotherapy will be eligible, but inevaluable for hematologic toxicities.
• • Patients with greater than grade 2 neurocortical toxicity will be excluded.
• PRIOR/CONCURRENT THERAPY:
• • Biologic Therapy: No concurrent hematopoietic growth factor.
• • Chemotherapy: No chemotherapy within 3 weeks of study.
• • No nitrosoursea within 6 weeks of study.
• • No concurrent chemotherapy allowed.
• • Must be on stable or decreasing dose of dexamethasone within 2 weeks of study.
• • Endocrine Therapy: Not specified.
• • Radiotherapy: No radiotherapy within 6 weeks of study.
• • Surgery: Not specified.
• Other:
• • Patient must be recovered from toxic effects of all prior therapy.
• • Concurrent antibiotic therapy when appropriate.
• Patient Characteristics:
• • Age: 2 to 21.
• • Performance Status: ECOG 0-2.
• • Life Expectancy: At least 8 weeks.
• Hematopoietic (hematologic requirements below do not apply to patients with histologically confirmed bone marrow involvement or history of either bone marrow transplantation or extensive radiotherapy; these patients are inevaluable for hematologic toxicity):
• • Absolute granulocyte count (AGC) at least 1500/mm3.
• • Platelet count at least 100,000/mm3.
• • Hemoglobin at least 8 g/dL.
• Hepatic:
• • Bilirubin no greater than 2 mg/Dl.
• • SGPT less than 2 times normal.
• Renal:
• • Creatinine no greater than 1.5 mg/Dl OR
• • Creatinine clearance at least 60 Ml/min/square meter.
• Other:
• • No systemic illness.
• • Not pregnant or nursing.
• • No amino acidurias or organic acidemias.