Phenylbutyrate to Treat Children With Progressive or Recurrent Brain Tumors

NCT00006450 | Completed Phase 2

• 2 other identifiers: 01002801-C-0028
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the safety and effectiveness of treating brain tumors in children with a continuous infusion of phenylbutyrate. A breakdown product of this drug, phenylacetate, is normally found in low concentrations in the blood. At much higher concentrations, phenylbutyrate and phenylacetate are active against cancer in animals. Patients between 2 and 21 years old with a brain tumor that has progressed or recurred after radiation or chemotherapy, including bone marrow transplant, may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood tests, magnetic resonance imaging (MRI) or computerized tomography (CT) of the head and, if needed, a spinal fluid test and bone marrow test. Study participants will have a continuous infusion of phenylbutyrate for two 28-day cycles-every day, 24 hours a day, 7 days a week. The medicine will be infused through a thin tube (catheter) placed in a large vein in the upper chest, delivered through a portable infusion pump. Patients will be hospitalized for at least 3 days when the treatment begins. If there are no side effects at that time, the infusions can continue on an outpatient basis. The patient or care giver will receive the medicine in 4-day supplies and will be taught how to change the bag and tubing daily for drug administration, as well as how to use the infusion pump. Patients will be monitored with weekly blood tests to look for side effects and measure blood levels of phenylbutyrate. They will have a physical examination at least once a week. At the end of the second 28-day cycle, patients will have a CT or MRI scan to evaluate the tumor's response to treatment. Patients whose tumor has grown will stop treatment and come off the study. Those whose tumor has remained stable or shrunk may continue phenylbutyrate as long as the treatment is beneficial and there are no serious side effects. CT or MRI scans will be done after every 2 cycles (or sooner if needed) to evaluate the treatment. Patients with certain tumor types (medulloblastoma, PNET, ependymoma, malignant germ cell tumor and pineoblastoma) or who have symptoms that indicate there might be tumor along the spinal cord may have a spinal tap. For this procedure, the patient lies on the side and a needle is inserted between two vertebrae (bones of the spine) in the lower back, into the cerebrospinal fluid space. A sample of fluid is drawn for testing for cancer cells. If the tumor has spread through the spinal fluid, a spinal tap will be done every other cycle (every 2 months) to monitor the effects of therapy.

Conditions

Brain Tumor

Keywords

Children; Brain; Maturation; Phenylacetate; Differentiation

Interventions

Phenylbutyrate DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: Patients must be between 2 and 21 years old.
• Histologic diagnosis: Previously treated brain tumor patients with any histologic diagnosis who have recurrent or progressive disease after radiation or chemotherapy, including bone marrow transplant. For patients with brainstem tumors the requirement for histologic verification may be waived. However, for patients with brainstem tumors treated with hyperfractionated radiotherapy a biopsy, a PET scan or NMR spectroscopy is strongly recommended prior to study entry to rule out radionecrosis as a possible cause of MRI changes. A biopsy, PET scan, or NMR spectroscopy is required for patients treated with radiosurgery prior to study entry.
• Phenylbutyrate will be studied within each of the following disease strata as defined by the initial tumor histology:
• High grade glioma (anaplastic astrocytoma or glioblastoma multiforme)
• Brainstem glioma
• Medulloblastoma or primitive neuroectodermal tumors (PNET) present in the supratentorial or posterior fossa locations.
• Other
• Radiologic evaluation: (must be obtained within two weeks prior to starting therapy) Patients must have a CT or MRI imaging studies documenting the measurable lesion(s) that clearly demonstrates the recurrent or progressive nature of the lesion(s).
• Recovery from prior therapy:
• Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and must be without significant systemic illness (e.g. Infection).
• Patients must not have received myelosuppressive chemotherapy within 3 weeks (six weeks if prior nitrosourea) of entry onto this protocol.
• Evaluable lesions must not have had any radiotherapy within 8 weeks, or radiosurgery within 4 months of the start of this protocol.
• Patients receiving dexamethasone must be on a stable or decreasing dose during the 2 weeks prior to study entry.
• Life Expectancy: Patients must have a life expectancy of at least 8 weeks.
• Performance status: For patients older than or equal to 10 years the Karnofsky performance score must be 50 percent or greater. For children younger than 10 years, the Lansky score must be 50 percent or greater. Patients who are unable to walk because of paralysis, but who are up in a wheel chair will be considered ambulatory for the purpose of calculating the performance score.

You may not qualify if:

• Women of childbearing potential who are pregnant or lactating.
• Patients with significant systemic illness.
• Patients with amino acidurias or organic acidemias.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Cancer Institute (NCI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Samid D, Shack S, Myers CE. Selective growth arrest and phenotypic reversion of prostate cancer cells in vitro by nontoxic pharmacological concentrations of phenylacetate. J Clin Invest. 1993 May;91(5):2288-95. doi: 10.1172/JCI116457.

  PMID: 8486788 BACKGROUND

• Samid D, Ram Z, Hudgins WR, Shack S, Liu L, Walbridge S, Oldfield EH, Myers CE. Selective activity of phenylacetate against malignant gliomas: resemblance to fetal brain damage in phenylketonuria. Cancer Res. 1994 Feb 15;54(4):891-5.

  PMID: 8313377 BACKGROUND

• Liu L, Shack S, Stetler-Stevenson WG, Hudgins WR, Samid D. Differentiation of cultured human melanoma cells induced by the aromatic fatty acids phenylacetate and phenylbutyrate. J Invest Dermatol. 1994 Sep;103(3):335-40. doi: 10.1111/1523-1747.ep12394874.

  PMID: 8077698 BACKGROUND

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Phenylbutyrates

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 7, 2000
• First Posted: November 8, 2000
• Study Start: November 1, 2000
• Study Completion: July 1, 2002
• Last Updated: March 4, 2008

Record last verified: 2002-07

Locations

US (1)