Bortezomib, Temozolomide, and Regional Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma
Condition: Brain and Central Nervous System Tumors
MeSH terms: Glioblastoma; Nervous System Neoplasms; Gliosarcoma; Central Nervous System Neoplasms
Intervention: bortezomib + temozolomide+ radiation therapy
Intervention description: Patients will be treated with Bortezomib at 1.3 mg/m2 IV on days1,4,8,11,29,32,36 and 39 and Temozolomide on 75mg/m2 daily during radiation. External beam fractionated regional radiation will be given on consecutive week days at 200 centigray (cGy) daily doses to a total dose of 6000 cGy.
Intervention MeSH terms: Temozolomide; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: adult giant cell glioblastoma; adult glioblastoma; adult gliosarcoma

Summary:

      RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy,
      such as temozolomide, work in different ways to stop the growth of tumor cells, either by
      killing the cells or by stopping them from dividing. Radiation therapy uses high-energy
      x-rays to kill tumor cells. Giving bortezomib together with temozolomide and radiation
      therapy may kill more tumor cells and allow doctors to save the part of the body where the
      cancer started.

      PURPOSE: This phase II trial is studying the side effects and how well bortezomib works when
      given together with temozolomide and regional radiation therapy in treating patients with
      newly diagnosed glioblastoma multiforme or gliosarcoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must be >- 18 years old, with a life expectancy > 8 weeks

          -  Histologically confirmed intracranial glioblastoma multiforme (GBM) or gliosarcoma

          -  Must submit an unstained paraffin block or slides from surgical procedure

          -  Patients without prior treatment and with prior diagnosis of lower-grade gliomas that
             have been upgraded to GBM after repeated resection allowed

          -  At least 21 days since cranial MRI or contrast CT scan OR ≥ 96 hours since cranial MRI
             or contrast CT scan for patients who underwent surgical resection

          -  Measurable or assessable disease

          -  Voluntary written informed consent obtained before performance of any study related
             procedure not part of normal medical care.

          -  Karnofsky performance status > 60%

          -  White Blood Count (WBC) ≥ 3,000/mm^3

          -  absoulte neutrophil count(ANC) ≥ 1,500/mm^3

          -  Platelet count ≥ 100,000/mm^3

          -  Hemoglobin ≥ 10 g/dL (transfusion allowed)

          -  Bilirubin < 2.5 times upper limit of normal (ULN)

          -  serum glutamic-oxaloacetic transaminase (SGOT) < 2.5 times ULN

          -  Creatinine < 1.5 mg/dL

          -  Creatinine clearance ≥ 20 mL/minute

          -  Serum sodium > 130 mmol/L

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  Patients on Enzyme-Inducing Antiepileptic Drugs (EIAED) must be transitioned to non-
             EAIED for ≥ 2 weeks

          -  Concurrent full-dose warfarin or its equivalent (e.g., unfractionated and/or low
             molecular weight heparin) allowed

        Exclusion Criteria:

          -  peripheral neuropathy ≥ grade 2

          -  Myocardial infarction within the past 6 months

          -  New York Heart Association (NYHA) class III or IV heart failure

          -  Uncontrolled angina

          -  Severe uncontrolled ventricular arrhythmias

          -  Electrocardiographic evidence of acute ischemia or active conduction system
             abnormalities

          -  hypersensitivity to bortezomib, boron, or mannitol

          -  serious medical or psychiatric illness that would interfere with study participation
             including, but not limited to, any of the following:

          -  Ongoing or active infection requiring IV antibiotics

          -  Psychiatric illness and/or social situations that would limit compliance with study
             requirements

          -  Disorders associated with a significant immunocompromised state (e.g., HIV, systemic
             lupus erythematosus)

          -  history of stroke within the past 6 months

          -  other malignancy within the past 3 years except completely resected basal cell
             carcinoma or squamous cell carcinoma of the skin, an in situ malignancy (i.e.,
             cervical cancer), or low-risk prostate cancer after curative therapy

          -  significant medical illness that, in the investigator's opinion, cannot be adequately
             controlled with appropriate therapy or would compromise the patient's ability to
             tolerate this therapy

          -  disease that will obscure toxicity or dangerously alter drug metabolism

          -  viral hepatitis (HBV surface antigen positive) or active hepatitis C infection

          -  Prior or concurrent corticosteroids, automated external defibrillator, analgesics, and
             other drugs to treat symptoms or prevent complications allowed

          -  concurrent investigational drugs that must be stopped at least 4 months prior to
             therapy.

          -  prior radiotherapy to the brain

          -  prior cytotoxic or noncytotoxic drug therapy or experimental drug therapy (including
             chemotherapy, hormonal therapy, or immunotherapy) directed against the brain tumor

          -  prior polifeprosan 20 with carmustine implant (Gliadel wafer)

          -  concurrent stereotactic radiosurgery or brachytherapy

          -  concurrent sargramostim

          -  concurrent inducers of CYP450 3A4 (e.g., enzyme-inducing anti-epileptic drugs [EIAED])