Phase I and Pharmacokinetic Trial of Phenylbutyrate Given as a Continuous Infusion in Pediatric Patients With Refractory Malignancy
phenylbutyrate
Maladies du cerveau+14
+ Maladies du système nerveux central
+ Néoplasmes
Étude thérapeutique
Résumé
Date de début de l'étude : 1 décembre 1996
Date à laquelle le premier participant a commencé l'étude.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.
Protocole
Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.35 participants à inclure
Nombre total de participants que l'essai clinique vise à recruter.Traitement
Éligibilité
Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.Tout sexe
Le sexe biologique des participants éligibles à s'inscrire.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Conditions
Pathologie
Critères
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.
Centres d'étude
Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.Cette étude comporte 1 site
National Cancer Institute (NCI)
Bethesda, United StatesOuvrir National Cancer Institute (NCI) dans Google Maps