Phase II Avastin + Bortezomib for Patients With Recurrent Malignant Glioma
Condition: Glioblastoma; Gliosarcoma
MeSH terms: Glioblastoma; Glioma; Gliosarcoma
Intervention: Avastin; Bortezomib
Intervention description: Avastin was administered intravenously at the dose 15 mg/kg every 3 weeks.; Bortezomib was administered on days 1, 4, 8, 11, 22, 25, 29, & 32 of a 42-day cycle. Bortezomib was 1.7 mg/m2 for patients not taking EIAEDs & 2.5 mg/m2 for patients taking EIAEDs.
Intervention MeSH terms: Bevacizumab; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 56.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Glioblastoma; Gliosarcoma; Glioblastoma multiforme; Recurrent malignant glioma; GBM; Recurrent GBM; Malignant glioma; Brain tumor; Avastin; Bevacizumab; Bortezomib; Velcade

Summary:

      Primary Objective To estimate 6-month progression free survival probability of patients with
      recurrent glioblastoma multiforme treated with bortezomib plus Avastin. This efficacy
      assessment will be made separately among patients on enzyme-inducing anti-epileptic drugs and
      non enzyme-inducing anti-epileptic drugs.

      Secondary Objectives To evaluate safety & tolerability of bortezomib plus Avastin among
      patients with recurrent malignant glioma.

      To evaluate radiographic response, progression free survival & overall survival of patients
      with recurrent malignant glioma treated with bortezomib plus Avastin
    

Eligibility criteria:

        Inclusion Criteria:

        Patients have histologically confirmed diagnosis of recurrent/progressive WHO grade IV
        malignant glioma (MG)

          -  Age >18 yrs

          -  No prior treatment with bortezomib, & no Avastin in last 3 months, not allowed to have
             progressed to Avastin regimen. No history of > or equal to grade 2 CNS hemorrhage or
             grade 3 or higher toxicities while on Avastin

          -  At least 6 weeks from surgical resection, 4 weeks from end of radiotherapy &
             enrollment in this study

          -  Karnofsky Performance Status (KPS) > or equal to 70%

          -  Hemoglobin (Hgb) > or = to 9 g/deciliter (dL), absolute neutrophil count (ANC) > or =
             to 1,500 cells/microliter, platelets > or = to 125,000 cells/microliter;

          -  Serum creatinine <1.5 mg/dL, serum glutamic oxalocetic transaminase (SGOT) & bilirubin
             <1.5 x upper limit of normal

          -  Signed informed consent approved by IRB;

          -  If sexually active, patients must agree to take contraceptive measures for duration of
             treatments

          -  May have had up to 3 biological therapies (such as tyrosine kinase inhibitors,
             topoisomerase I or II inhibitors, or rapamycin)

        Exclusion Criteria:

          -  Gr 2 or greater peripheral neuropathy at time of study enrollment

          -  No prior taxanes, as it predisposes to sensory neuropathy

          -  Co-medication that may interfere with study results, e.g. immuno-suppressive agents
             other than corticosteroids

          -  Greater than 3 prior recurrences

          -  Evidence of CNS hemorrhage on baseline MRI on CT scan (except for grade 1 hemorrhage
             that has been stable for at least 3 months)

          -  History of thrombotic or hemorrhagic stroke or myocardial infarction within 6 months

          -  Requires therapeutic anti-coagulation

          -  At least 4 weeks from Day 0 of prior monthly chemotherapy (at least 6 weeks if a
             nitrosourea). At least 1 week from last dose of daily chemotherapy (such as metronomic
             temozolomide, cytoxan) or targeted therapies administered daily (such as gleevec,
             tarceva)

          -  Pregnancy or breast feeding

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection requiring IV antibiotics & psychiatric illness/social situations that would
             limit compliance with study requirements, or disorders associated with significant
             immunocompromised state

          -  Patients with another primary malignancy that has required treatment within past year.

        Avastin-Specific Concerns:

          -  Any prior history of hypertensive crisis or hypertensive encephalopathy

          -  Systolic blood pressure (BP) > 150 mmHg or diastolic BP > 100 mmHg

          -  Unstable angina

          -  New York Heart Association Gr II or > congestive heart failure

          -  History of myocardial infarction within 6 months

          -  History of stroke within 6 months

          -  Clinically significant peripheral vascular disease

          -  Evidence of bleeding diathesis, coagulopathy as documented by an elevated prothrombin
             time (PT), partial thromboplastin time (PTT)/bleeding time

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to Day 0, anticipation of need for major surgical procedure during course of
             study

          -  Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
             prior to Day 0

          -  Urine protein: creatinine ratio > or = to 1.0 at screening

          -  History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6
             months prior to Day 0

          -  Serious, non-healing wound, ulcer, or bone fracture

          -  Known hypersensitivity to any component of Avastin

          -  Inability to comply with study and/or follow-up procedures