Clinical trial NCT00268385 (phase 1, status: active, not recruiting)
Conditions: adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma, adult mixed glioma, recurrent adult brain neoplasm
ICD codes: C84.67, C84.77, C84.7A, C84.60, C84.70, C84.62, C84.66, C84.67, C84.77, C84.7A, C84.60, C84.70, C84.62, C84.66, C71.7, C71.9, C79.31, D33.0, D33.1, D33.2, D49.6
Drugs: temozolomide, vorinostat
SMILES: CSCC[C@H](N)C(O)=O, ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1
Eligibility criteria:

        Inclusion Criteria:

          -  Patients with histologically proven intracranial malignant glioma will be eligible for
             this protocol; malignant gliomas include glioblastoma multiforme (GBM), gliosarcoma
             (GS), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed
             oligoastrocytoma (AMO), or malignant astrocytoma NOS (not otherwise specified);
             patients will be eligible if the original histology was low-grade glioma and a
             subsequent histological diagnosis of a malignant glioma is made

          -  All patients must sign an informed consent indicating that they are aware of the
             investigational nature of this study; patients must have signed an authorization for
             the release of their protected health information; patients must be registered with
             the Adult Brain Tumor Consortium (ABTC) Central Office database prior to treatment
             with study drug

          -  Life expectancy > 8 weeks

          -  Karnofsky performance status of >= 60

          -  White blood cell (WBC) >= 3,000/mm^3

          -  Absolute neutrophil count (ANC) >= 1,500/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Hemoglobin >= 10 g/dL; eligibility level for hemoglobin may be reached by transfusion

          -  Serum glutamic oxaloacetic transaminase (SGOT) < 2 times upper limit of normal (ULN)

          -  Bilirubin < 2 times ULN

          -  If liver function tests are above the institutional upper limit of normal but < 2
             times institutional upper limit of normal, the decision to initiate temozolomide
             treatment should carefully consider the benefits and risks for the individual patient

          -  Creatinine < 1.5 mg/dL

          -  A scan should be performed within 14 days prior to registration and on a steroid dose
             that has been stable for at least 5 days; if the steroid dose is increased between the
             date of imaging and registration a new baseline magnetic resonance (MR)/computed
             tomography (CT) is required; the same type of scan, i.e., magnetic resonance imaging
             (MRI) or CT must be used throughout the period of protocol treatment for tumor
             measurement

          -  Patients must have an interval of greater than or equal to 3 weeks (21) days from the
             completion of radiation therapy to study entry

          -  Women of childbearing potential must have a negative beta-human chorionic gonadotropin
             (HCG) pregnancy test documented within 7 days prior to registration; should a woman
             become pregnant or suspect she is pregnant while participating in this study, she
             should inform her treating physician immediately

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of participation in the study

          -  Patients must be willing to participate in the pharmacokinetic studies

          -  ELIGIBILITY CRITERIA SPECIFIC FOR PATIENTS IN PART I OF THE STUDY

          -  Patients with either stable disease after radiation therapy or with progression are
             eligible (except if they have progressed on temozolomide; patients who have received
             prior treatment with temozolomide and have stable disease are eligible

          -  Patients with recurrent disease may have had treatment for any number of prior
             relapses; relapse is defined as progression following initial therapy (i.e. radiation
             +/- chemo if that was used as initial therapy)

          -  Patients must have recovered from the toxic effects of prior therapy: 28 days from any
             investigational agent, 28 days from prior cytotoxic therapy except 23 days from last
             dose of temozolomide for patients taking the standard 5 days every 28 day regimen of
             temozolomide, 14 days from vincristine, 42 days from nitrosoureas, 21 days from
             procarbazine administration, and 7 days for non-cytotoxic agents, e.g., interferon,
             tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count); any
             questions related to the definition of non-cytotoxic agents should be directed to the
             study chair

          -  Patients having undergone recent resection of recurrent or progressive tumor will be
             eligible as long as all of the following conditions apply:

               -  They have recovered from the effects of surgery

               -  Residual disease following resection is not mandated for eligibility into the
                  study; to best assess the extent of residual disease post-operatively, a CT/MRI
                  should be done no later than 96 hours in the immediate post-operative period or
                  at least 4 weeks post-operatively, within 14 days prior to registration; if the
                  96-hour scan is more than 14 days before registration, the scan needs to be
                  repeated; if the steroid dose is increased between the date of imaging and
                  registration, a new baseline MRI/CT is required on a stable steroid dosage for at
                  least 5 days

          -  Patients with prior therapy that included interstitial brachytherapy or stereotactic
             radiosurgery must have confirmation of true progressive disease rather than radiation
             necrosis based upon either positron emission tomography (PET) or thallium scanning, MR
             spectroscopy or surgical documentation of disease

          -  ELIGIBILITY CRITERIA SPECIFIC FOR PATIENTS IN PART II OF THE STUDY

          -  Only patients with stable disease after radiation therapy are eligible for part 2 of
             the study; patients with recurrent disease are ineligible

          -  The only prior therapy permitted for patients in part 2 of the study is concomitant
             temozolomide with radiation therapy or radiation therapy alone; patients that are
             stable on adjuvant temozolomide may also participate

          -  Patients with recurrent disease and prior chemotherapies (except concurrent or
             adjuvant temozolomide) will not be included in this part of the study

        Exclusion Criteria:

          -  Patients who have progressed on temozolomide are ineligible

          -  Patients must not have any significant medical illnesses that in the investigator's
             opinion cannot be adequately controlled with appropriate therapy or would compromise
             the patient's ability to tolerate this therapy; patients with a history of any other
             cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in
             complete remission and off of all therapy for that disease for a minimum of 3 years
             are ineligible

          -  Patients must not have active infection or serious intercurrent medical illness

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             the mother is treated with vorinostat (SAHA); potential risks may also apply to
             temozolomide

          -  Patients must not have any disease that will obscure toxicity or dangerously alter
             drug metabolism

          -  Patients who are known to be human immunodeficiency virus (HIV) positive and are
             receiving combination antiretroviral therapy are ineligible

          -  Patients may not be receiving any other investigational agents

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to vorinostat (SAHA) or other agents used in study

          -  Patients should not have taken valproic acid (another histone deacetylase inhibitor)
             for at least 2 weeks prior to enrollment