vorinostat and radiation therapy followed by maintenance therapy with vorinostat in treating younger patients with newly diagnosed diffuse intrinsic pontine glioma

Conditions: Anaplastic Astrocytoma; Anaplastic Oligoastrocytoma; Diffuse Intrinsic Pontine Glioma; Gliosarcoma

Summary: this phase i/ii trial studies the side effects and best dose of vorinostat and to see how well it works when given together with radiation therapy followed by maintenance therapy with vorinostat in treating younger patients with newly diagnosed diffuse intrinsic pontine glioma (a brainstem tumor). vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. radiation therapy uses high-energy x-rays to kill tumor cells. giving vorinostat together with radiation therapy may kill more tumor cells.

primary objectives: l. to estimate the maximum tolerated dose (mtd) or recommend a phase 2 dose of vorinostat given concurrently with radiation in children with newly diagnosed diffuse intrinsic pontine glioma (dipg). ii. to define and describe the toxicities of vorinostat given concurrently with radiation in children with newly diagnosed dipg. iii. to determine, in the context of this phase i/ii trial, the anti-tumor activity of combining vorinostat with radiation, followed by maintenance vorinostat for twelve courses, in children with newly diagnosed dipg, as measured by 12-month event-free survival (efs) and overall survival (os). iv. to determine the toxicities of vorinostat for 12 additional courses after completion of vorinostat and radiation. secondary objectives: i. to measure non-homologous end-joining (nhej) activity in peripheral blood mononuclear cells (pbmcs) before treatment, at 2 weeks after starting vorinostat and radiation, and at the end of radiation. ii. to measure histone deacetylase 2 (hdac2) levels and assess histone acetylation in pbmcs before treatment, at 2 weeks after starting vorinostat and radiation, and at the end of radiation. iii. to quantify deoxyribonucleic acid (dna) repair proteins from the nhej and homologous recombination repair (hhr) pathways in tumors by either western analysis or immunohistochemistry, if paraffin-embedded tumor is available. outline: this is a phase i, dose-escalation study of vorinostat followed by a phase ii study. patients receive vorinostat orally (po) on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. patients undergo 3-dimensional (3d) conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. patients then receive maintenance therapy comprising vorinostat po on days 1-28. treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. after completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months.

Eligibility criteria:
inclusion criteria: * patients with newly diagnosed diffuse intrinsic pontine gliomas (dipgs), defined as tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the pons, are eligible without histologic confirmation; patients with brainstem tumors that do not meet these criteria or not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors are biopsied and proven to be an anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, or anaplastic mixed glioma; patients with juvenile pilocytic astrocytoma, fibrillary astrocytoma, gangliogliomas, or other mixed gliomas without anaplasia are not eligible; patients with disseminated disease are not eligible, and magnetic resonance imaging (mri) of spine must be performed if disseminated disease is suspected by the treating physician * karnofsky \>= 50% for patients \> 16 years of age and lansky \>= 50 for patients =\< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score * patients must not have received any prior treatment except dexamethasone and/or surgery * peripheral absolute neutrophil count (anc) \>= 1000/ul * platelet count \>= 100,000/ul (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment) * hemoglobin \>= 8.0 g/dl (may receive red blood cell \[rbc\] transfusions) * creatinine clearance or radioisotope glomerular filtration rate (gfr) \>= 70ml/min/1.73 m\^2 or a serum creatinine based on age/gender as follows: * 0.8 mg/dl (3 to \< 6 years of age) * 1 mg/dl (6 to \< 10 years of age) * 1.2 mg/dl (10 to \< 13 years of age) * 1.5 mg/dl (male) or 1.4 mg/dl (female) (13 to \< 16 years of age) * 1.7 mg/dl (male) or 1.4 mg/dl (female) (\>= 16 years of age) * bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (uln) for age * serum glutamate pyruvate transaminase (sgpt) (alanine aminotransferase \[alt\]) =\< 110 u/l; for the purpose of this study, the uln for sgpt (alt) is 45 u/l * serum albumin \>= 2 g/dl * patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants (with the exception of valproic acid) and seizures are well controlled * patients must be able to swallow capsules or liquids; patients dependent on nasogastric (ng) tube feeding are not permitted to receive protocol therapy * enrollment must be no later than 28 days after the date of radiographic diagnosis or surgery, whichever is the later date exclusion criteria: * pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method * growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment * patients who are currently receiving another investigational drug are not eligible * patients who are currently receiving other anti-cancer agents are not eligible * patients must not currently be receiving enzyme inducing anticonvulsants * patients on valproic acid must discontinue valproic acid for at least 2 weeks before starting protocol therapy * patients receiving coumadin, heparin, low-molecular weight heparin, or any other anti-coagulants are not eligible for study entry * patients receiving acetylsalicylic acid (asa) (\> 81 mg/day), non-steroidal anti-inflammatory drugs, clopidogrel (plavix), dipyridamole (persantine), or any other drug that inhibits platelet function are not eligible for study entry * patients who have an uncontrolled infection are not eligible * patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible