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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00001565
Recruitment Status : Completed
First Posted : December 10, 2002
Last Update Posted : March 4, 2008
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

This is a pharmacokinetic trial. Patients receive phenylbutyrate through a central venous catheter for each 28 day cycle. The first several days of drug administration should be inpatient. Cycles may be repeated if there is no tumor progression or dose limiting toxicities (DLT). There are no breaks between cycles.

Once a minimum of 3 patients have completed at least 4 weeks of therapy without DLT, new patients will be entered at the next dose level.

Condition or disease Intervention/treatment Phase
Brain Neoplasms Neuroblastoma Drug: phenylbutyrate Phase 1

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Enrollment : 35 participants
Primary Purpose: Treatment
Official Title: Phase I and Pharmacokinetic Trial of Phenylbutyrate Given as a Continuous Infusion in Pediatric Patients With Refractory Malignancy
Study Start Date : December 1996
Study Completion Date : October 2000

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.


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.


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.


Bilirubin no greater than 2 mg/Dl.

SGPT less than 2 times normal.


Creatinine no greater than 1.5 mg/Dl OR

Creatinine clearance at least 60 Ml/min/square meter.


No systemic illness.

Not pregnant or nursing.

No amino acidurias or organic acidemias.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00001565

United States, Maryland
National Cancer Institute (NCI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)

Publications: Identifier: NCT00001565     History of Changes
Other Study ID Numbers: 970051
First Posted: December 10, 2002    Key Record Dates
Last Update Posted: March 4, 2008
Last Verified: November 1999

Keywords provided by National Institutes of Health Clinical Center (CC):
Brain Tumors
Maximally Tolerated Dose

Additional relevant MeSH terms:
Brain Neoplasms
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
4-phenylbutyric acid
Antineoplastic Agents