Clinical trial NCT01076530 (phase 1, status: completed)
Conditions: childhood atypical teratoid/rhabdoid tumor, childhood central nervous system choriocarcinoma, childhood central nervous system embryonal tumor, childhood central nervous system germinoma, childhood central nervous system mixed germ cell tumor, childhood central nervous system teratoma, childhood central nervous system yolk sac tumor, childhood choroid plexus tumor, childhood craniopharyngioma, childhood ependymoblastoma, childhood grade i meningioma, childhood grade ii meningioma, childhood grade iii meningioma, childhood high-grade cerebellar astrocytoma, childhood high-grade cerebral astrocytoma, childhood infratentorial ependymoma, childhood low-grade cerebellar astrocytoma, childhood low-grade cerebral astrocytoma, childhood medulloepithelioma, childhood mixed glioma, childhood oligodendroglioma, childhood supratentorial ependymoma, extra-adrenal paraganglioma, recurrent childhood brain stem glioma, recurrent childhood central nervous system embryonal tumor, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma, recurrent childhood ependymoma, recurrent childhood medulloblastoma, recurrent childhood pineoblastoma, recurrent childhood spinal cord neoplasm, recurrent childhood subependymal giant cell astrocytoma, recurrent childhood supratentorial primitive neuroectodermal tumor, recurrent childhood visual pathway and hypothalamic glioma
ICD codes: K22.711, K31.A22, R85.613, R87.613, R87.623, R85.611, R87.611, K22.711, K31.A22, R85.613, R87.613, R87.623, R85.611, R87.611, G46.4, G11.2, G11.10, G11.19, G11.3, G32.81, I66.3, G47.13, J01.41, K11.22, K12.0, N96, F33.8, G03.2, E23.3
Drugs: vorinostat, temozolomide
SMILES: ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1, CSCC[C@H](N)C(O)=O
Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed CNS malignancy at original diagnosis or relapse

               -  Histologic confirmation not required for patients with intrinsic brain stem
                  tumors, optic pathway gliomas, or pineal tumors provided CSF or serum tumor
                  markers, including alpha-fetoprotein orbeta-HCG, are elevated

               -  Recurrent or refractory spinal cord tumors allowed

          -  Measurable or evaluable disease

          -  No known curative therapy or therapy proven to prolong survival with an acceptable
             quality of life

          -  Karnofsky performance status (PS) 50-100% (for patients > 16 years of age) OR Lansky
             PS 50-100% (for patients ≤ 16 years of age)

               -  Neurological deficits must have been relatively stable for ≥ 1 week before study
                  entry

               -  Patients unable to walk due to paralysis, but who are up in a wheelchair, are
                  considered ambulatory for the purpose of assessing performance status

          -  ANC ≥ 1,000/μL

          -  Platelet count ≥ 100,000/μL (transfusion independent, defined as no platelet
             transfusion within the past 7 days)

          -  Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)

          -  Creatinine clearance or radioisotope GFR ≥ 70mL/min OR maximum serum creatinine based
             on age and/or gender as follows:

               -  0.6 mg/dL (1 year of age)

               -  0.8 mg/dL (2 to 5 years of age)

               -  1.0 mg/dL (6 to 9 years of age)

               -  1.2 mg/dL (10 to 12 years of age)

               -  1.5 mg/dL (males) or 1.4 mg/dL (females) (13 to 15 years of age)

               -  1.7 mg/dL (males) or 1.4 mg/dL (females) (≥ 16 years of age)

          -  Bilirubin ≤ 1.5 times upper limit of normal

          -  ALT ≤ 110 U/L

          -  Serum albumin ≥ 2 g/dL

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  Able to swallow capsules or liquid

          -  Seizure disorder allowed provided it is well controlled with nonenzyme-inducing
             anticonvulsants

          -  No pre-existing QTc ≥ 450 msec

          -  No uncontrolled infection

          -  No patients who, in the opinion of the investigator, may not be able to comply with
             the safety monitoring requirements of study

          -  Fully recovered from prior chemotherapy, immunotherapy, or radiotherapy

          -  More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea)

          -  At least 7 days since prior hematopoietic growth factors

          -  At least 7 days since prior biologic agent (antineoplastic agent)

          -  At least 7 days or 3 half-lives, whichever is longer, since prior monoclonal
             antibodies

          -  More than 2 weeks since prior local palliative radiotherapy (small port)

          -  At least 6 months since prior total-body radiotherapy (TBI), craniospinal
             radiotherapy, or radiotherapy to ≥ 50% of the pelvis

          -  At least 6 weeks since other prior substantial bone marrow radiotherapy

          -  At least 3 months since prior stem cell transplantation or rescue (without TBI)

               -  No evidence of active graft-vs-host disease

          -  At least 2 weeks since prior valproic acid

          -  No prior vorinostat

          -  Prior temozolomide allowed provided there was no progressive disease during or within
             1 month after completion of treatment

          -  Concurrent corticosteroids allowed provided patient has been on a stable or decreasing
             dose for ≥ 7 days before study entry

          -  No other concurrent investigational drugs

          -  No other concurrent anticancer agents, including chemotherapy, radiotherapy,
             immunotherapy, or biologic therapy

          -  No concurrent enzyme-inducing anticonvulsants