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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

35 participants

Study Classification

INTERVENTIONAL

Study Start Date

1996-12-31

Study Completion Date

2000-10-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Phenylbutyrate to Treat Children With Progressive or Recurrent Brain Tumors

NCT00006450

Brain Tumor

COMPLETED PHASE2

Fenretinide in Treating Children With Solid Tumors

NCT00003191

Neuroblastoma Unspecified Childhood Solid Tumor, Protocol Specific

COMPLETED PHASE1

Phenylacetate in Treating Children With Recurrent or Progressive Brain Tumors

NCT00003241

Brain and Central Nervous System Tumors

COMPLETED PHASE2

Fenretinide in Treating Children With Recurrent or Resistant Neuroblastoma

NCT00053326

Recurrent Neuroblastoma

COMPLETED PHASE2

N2004-03: Intravenous Fenretinide in Treating Young Patients With Recurrent or Resistant Neuroblastoma

NCT00646230

Neuroblastoma

COMPLETED PHASE1

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Brain Neoplasms Neuroblastoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Primary Study Purpose

TREATMENT

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

phenylbutyrate

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

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.

Eligible Sex

ALL

Accepts Healthy Volunteers

No