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

NCT00001565 | Completed Phase 1

• 2 other identifiers: 97005197-C-0051
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Brain Neoplasms; Neuroblastoma

Keywords

Brain Tumors; Differentiation; Maximally Tolerated Dose; Neuroblastoma; Phenylacetate

Interventions

phenylbutyrate DRUG

Eligibility Criteria

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

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

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

• Samid D, Shack S, Sherman LT. Phenylacetate: a novel nontoxic inducer of tumor cell differentiation. Cancer Res. 1992 Apr 1;52(7):1988-92.

  PMID: 1372534 BACKGROUND

MeSH Terms

Conditions

Brain Neoplasms; Neuroblastoma

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; 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

Intervention Hierarchy (Ancestors)

Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: December 10, 2002
• Study Start: December 1, 1996
• Study Completion: October 1, 2000
• Last Updated: March 4, 2008

Record last verified: 1999-11

Locations

US (1)