Vorinostat and Bortezomib in Treating Patients With Progressive, Recurrent Glioblastoma Multiforme
Condition: Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Tumor
MeSH terms: Glioblastoma; Gliosarcoma; Recurrence
Intervention: vorinostat; therapeutic conventional surgery; bortezomib
Intervention description: Given orally; Patient undergoes surgery; Given IV
Intervention MeSH terms: Bortezomib; Vorinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving vorinostat together with bortezomib works in
      treating patients with progressive, recurrent glioblastoma multiforme. Vorinostat and
      bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth. Giving vorinostat together with bortezomib may kill more tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed glioblastoma multiforme

               -  Gliosarcoma or other grade 4 astrocytoma variant (e.g., giant cell glioblastoma)
                  allowed

               -  Recurrent disease

          -  Must have evidence of tumor progression by MRI or CT scan after radiotherapy or after
             the most recent antitumor therapy

          -  Bidimensionally measurable or evaluable disease by MRI or CT scan

               -  Patients receiving corticosteroids must be on a fixed dose for at least 1 week
                  prior to baseline scan

          -  ECOG performance status 0-2

          -  WBC ≥ 3,000/mm³

          -  ANC ≥ 1,500/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Hemoglobin ≥ 9 g/dL

          -  Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

          -  AST ≤ 3 times ULN

          -  Creatinine normal

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for 6 months after the
             last dose of vorinostat

          -  Willing to provide mandatory correlative laboratory tissue samples

          -  Able to take oral medications

          -  No uncontrolled infection

          -  No known hypersensitivity to any of the components of vorinostat or bortezomib

          -  No myocardial infarction or unstable angina within the past 6 months

          -  No congestive heart failure requiring use of ongoing maintenance therapy or history of
             life-threatening ventricular arrhythmias

          -  No concurrent uncontrolled illness including, but not limited to, any of the
             following:

               -  Ongoing or active infection

               -  Psychiatric illness or social situation that would limit compliance with study
                  requirements

          -  No other active malignancy within the past 3 years except nonmelanoma skin cancer or
             carcinoma in situ of the cervix

          -  No comorbid systemic illness or other severe concurrent disease that, in the judgment
             of the investigator, would preclude study entry or significantly interfere with proper
             assessment of safety and toxicity of the prescribed study regimens

          -  Not immunocompromised

               -  Patients known to be HIV positive are eligible provided there is no clinical
                  evidence of an immunocompromised state

          -  No peripheral neuropathy ≥ grade 2

          -  No peripheral neuropathy with pain ≥ grade 1

          -  No congenital long QT syndrome

          -  No prolonged OTC interval (> 450 msec)

          -  No other concurrent anticancer therapy (other than hormonal therapy)

          -  At least 8 weeks since prior radiotherapy

          -  More than 6 weeks since prior stereotactic radiosurgery or interstitial brachytherapy,
             unless there is a separate lesion on MRI that is not part of the prior treatment field

          -  More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)

          -  No more than 1 prior chemotherapy regimen* for progressive/recurrent disease (stratum
             1)

               -  Patients in stratum 2 may have received any number of prior chemotherapy
                  regimens* for progressive/recurrent disease

          -  More than 2 weeks since prior small molecule cell cycle inhibitors

          -  More than 7 days since prior valproic acid

          -  More than 7 days since prior category I drugs that are generally accepted to have a
             risk of causing Torsades de Pointes including:

               -  Quinidine, procainamide, disopyramide

               -  Amiodarone, sotalol, ibutilide, dofetilide

               -  Erythromycin, clarithromycin

               -  Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide

               -  Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone,
                  halofantrine, levomethadyl, pentamidine, sparfloxacin,lidoflazine

          -  More than 4 weeks since prior bevacizumab

          -  No prior treatment with vorinostat or bortezomib

          -  No concurrent enzyme-inducing antiepileptic drugs (e.g., phenytoin,fosphenytoin,
             carbamazepine, phenobarbital, or primidone)

          -  No other concurrent potent CYP3A4 inducer (e.g., rifampin or St. John's wort)

          -  No other concurrent investigational therapy for the primary neoplasm