Valproic Acid in Treating Young Patients With Recurrent or Refractory Solid Tumors or CNS Tumors
Brain and Central Nervous System Tumors, Unspecified Childhood Solid Tumor, Protocol Specific
About this trial
This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring recurrent childhood brain stem glioma, recurrent childhood brain tumor, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma, recurrent childhood ependymoma, recurrent childhood medulloblastoma, recurrent childhood supratentorial primitive neuroectodermal tumor, unspecified childhood solid tumor, protocol specific, recurrent childhood visual pathway and hypothalamic glioma, childhood high-grade cerebral astrocytoma, childhood low-grade cerebral astrocytoma, childhood infratentorial ependymoma, childhood supratentorial ependymoma, childhood spinal cord neoplasm, childhood grade I meningioma, childhood grade II meningioma, childhood grade III meningioma, childhood craniopharyngioma, childhood central nervous system germ cell tumor
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed* malignant solid tumor, including CNS tumors, at original diagnosis or relapse Recurrent or refractory disease NOTE: *Histologic confirmation not required for intrinsic brain stem or optic pathway tumors Measurable or evaluable disease, defined by 1 of the following criteria: Any unidimensionally measurable lesion ≥ 10 mm by standard MRI or CT scan for either solid or CNS tumors At least 1 nonmeasurable lesion that is evaluable by nuclear medicine, immunocytochemistry, tumor markers, cerebrospinal fluid cytology, or other reliable measures No known curative therapy exists No documented tumor involvement in the bone marrow PATIENT CHARACTERISTICS: Age 2 to 21 Performance status* Lansky 50-100% (for patients ≤ 10 years of age) Karnofsky 50-100% (for patients > 10 years of age) Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,000/mm^3 Platelet count ≥ 100,000/mm^3 (transfusion independent) Hemoglobin ≥ 8.0 g/dL (transfusions allowed) Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) ALT ≤ 110 (ULN for this study is 45 U/L) Albumin ≥ 2 g/dL Renal Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR Creatinine based on age as follows: No greater than 0.8 mg/dL (for patients ≤ 5 years of age) No greater than 1.0 mg/dL (for patients 6 to 10 years of age) No greater than 1.2 mg/dL (for patients 11 to 15 years of age) No greater than 1.5 mg/dL (for patients over 15 years of age) Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Neurologic deficits in patients with CNS tumors must be stable for ≥ 1 week before study entry No uncontrolled infection No known urea cycle disorders or other metabolic disorders No other condition that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy Recovered from prior immunotherapy At least 7 days since prior hematopoietic growth factors that support platelet or WBC number or function At least 7 days since prior antineoplastic biologic agents At least 3 months since prior stem cell transplantation or rescue without total body irradiation No evidence of active graft vs host disease No other concurrent anticancer biologic therapy or immunotherapy Chemotherapy More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered No other concurrent anticancer chemotherapy Endocrine therapy Patients with CNS tumors must be on a stable or decreasing dose of dexamethasone for the past 7 days Radiotherapy See Biologic therapy Recovered from prior radiotherapy At least 6 months since prior total body irradiation, craniospinal radiotherapy, or radiotherapy to ≥ 50% of the pelvis At least 6 weeks since other prior substantial bone marrow radiotherapy At least 2 weeks since prior local palliative small port radiotherapy No concurrent anticancer radiotherapy Surgery Not specified Other No other concurrent investigational agents No other concurrent anticancer agents No other concurrent anticonvulsants Patients receiving valproic acid (VPA) before study entry must have a total trough VPA concentration < 100 mcg/mL within the past 7 days
Sites / Locations
- Children's Hospital of Orange County
- Stanford Comprehensive Cancer Center - Stanford
- Children's National Medical Center
- Children's Memorial Hospital - Chicago
- Indiana University Melvin and Bren Simon Cancer Center
- Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
- University of Minnesota Children's Hospital - Fairview
- Mayo Clinic Cancer Center
- Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
- SUNY Upstate Medical University Hospital
- Cincinnati Children's Hospital Medical Center
- Oregon Health & Science University Cancer Institute
- Children's Hospital of Philadelphia
- Baylor University Medical Center - Houston
- Children's Hospital and Regional Medical Center - Seattle
- Hospital for Sick Children
- Hopital Sainte Justine
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Treatment 1
Treatment 10
Treatment 20
VPA Target Trough Concentration 75-100 mcg/mL, week 1 VPA dose: 15 mg/kg/day, divided tid
VPA Target Trough Concentration 100-150 mcg/mL, week 1 VPA dose: 15 mg/kg/day, divided tid
VPA Target Trough Concentration 150-200 mcg/mL