Phase I and Pharmacokinetic Trial of Phenylbutyrate Given as a Continuous Infusion in Pediatric Patients With Refractory Malignancy
phenylbutyrate
Brain Diseases+14
+ Central Nervous System Diseases
+ Neoplasms
Treatment Study
Summary
Study start date: December 1, 1996
Actual date on which the first participant was enrolled.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 objective of this trial is to determine the maximum tolerated dose and the toxicities of phenylbutyrate administered as a continuous intravenous infusion for 28 days. In addition, the pharmacokinetics of phenylbutyrate and its metabolite, phenylacetate, will be studied using both model-dependent and model-independent parameters.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.35 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
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.
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
National Cancer Institute (NCI)
Bethesda, United StatesOpen National Cancer Institute (NCI) in Google Maps