Gliadel, XRT, Temodar, Avastin Followed by Avastin, Temodar for Newly Diagnosed Glioblastoma Multiforme (GBM)
Condition: Glioblastoma Multiforme; Gliosarcoma
MeSH terms: Glioblastoma; Gliosarcoma
Intervention: Gliadel; Radiation Therapy; Avastin; Temodar
Intervention description: Patients will have 1-8 wafers of Gliadel inserted at the time of surgical resection.; At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy.; Avastin (10 mg/kg) will be given every 14 days, and will begin a minimum of 42 days post-operatively.
Beginning two to three weeks after the last radiation therapy, but not greater than eight weeks, subjects will be treated with Avastin (10mg/m2) every 14 days.; At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy and daily Temodar (75mg/m2) for 6.5 weeks of the radiation. In addition, beginning 2-3 weeks after the last radiation therapy, but not greater than 8 weeks, patients will be treated with 5 day Temodar (200 mg/ m2).
Intervention MeSH terms: Bevacizumab; Temozolomide; Carmustine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: glioblastoma multiforme; gliosarcoma; malignant glioma; glioma; Gliadel; carmustine wafers; Avastin; bevacizumab; Temodar; temozolomide; Pro00025180; Desjardins; Duke; Preston Robert Tisch Brain Tumor Center

Summary:

      The purpose of this study is to determine the safety and effectiveness of Gliadel wafers at
      the time of surgery, followed by the combination of radiation, Temodar, and Avastin, and then
      the combination of Avastin and Temodar, after radiation is complete, on malignant brain
      tumors.

      About six weeks after surgery, subjects will begin standard radiation therapy, a fixed dose
      of Avastin every 2 weeks, and daily Temodar for the six and a half weeks of radiation.
      Beginning 2-3 weeks after the last radiation therapy, subjects will be given the same fixed
      dose of Avastin intravenously (through the vein) every 14 days. They will also be given a
      higher dose of oral Temodar to take daily the first 5 days of each 28-day study cycle.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a MRI consistent with a WHO grade IV primary malignant glioma
             (glioblastoma multiforme or gliosarcoma), and be candidates for surgical resection
             with Gliadel wafer placement. Patients have to be within 6 weeks of the last major
             surgical procedure.

          -  Age ≥ 18 years

          -  Candidates for Gliadel

          -  If a prior procedure was done, an interval of at least 2 weeks and not > 8 weeks
             between prior major surgical procedure and study enrollment

          -  No prior radiotherapy or chemotherapy for a brain tumor

          -  Karnofsky > 60%

          -  Hemoglobin ≥ 9.0 g/dl, ANC ≥ 1,500 cells/microliters, platelets ≥ 125,000
             cells/microliters

          -  Serum creatinine ≤ 1.5 mg/dl, serum SGOT and bilirubin ≤ 1.5 times upper limit of
             normal.

          -  Signed informed consent approved by the Institutional Review Board

          -  If sexually active, patients must agree to use appropriate contraceptive measures for
             the duration of the study and for 6 months afterwards as stated in the informed
             consent.

        Exclusion Criteria:

          -  Pregnancy or breast feeding.

          -  Co-medication that may interfere with study results; e.g. immuno-suppressive agents
             other than corticosteroids.

          -  Active infection requiring IV antibiotics.

          -  Prior treatment with radiotherapy or chemotherapy for a brain tumor, irrespective of
             the grade of the tumor.

          -  Evidence of > grade 1 CNS hemorrhage on baseline MRI or CT scan.

          -  Prior treatment with Avastin for any condition

          -  Prior, unrelated malignancy requiring active treatment with the exception cervical
             carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the
             skin

        Avastin-Specific Exclusion Criteria:

          -  Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or
             diastolic blood pressure > 100 mmHg)

          -  Prior history of hypertensive crisis or hypertensive encephalopathy

          -  New York Heart Association (NYHA) Grade II or greater congestive heart failure

          -  History of myocardial infarction or unstable angina within 6 months prior to study
             enrollment

          -  History of stroke or transient ischemic attack within 6 months prior to study
             enrollment

          -  Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or
             recent peripheral arterial thrombosis) within 6 months prior to study enrollment

          -  History of hemoptysis (≥ ½ teaspoon of bright red blood per episode) within 1 month
             prior to study enrollment

          -  Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic
             anticoagulation)

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to the first Avastin infusion or anticipation of need for major surgical
             procedure during the course of the study

          -  Core biopsy or other minor surgical procedure, excluding placement of a vascular
             access device, within 7 days prior to study enrollment

          -  History of abdominal fistula, gastrointestinal perforation within 6 months prior to
             study enrollment

          -  Serious, non-healing wound, active ulcer, or untreated bone fracture

          -  Proteinuria at screening as demonstrated by urine dipstick for proteinuria ≥ 2+
             (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should
             undergo a 24-hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to
             be eligible).

          -  Known hypersensitivity to any component of Avastin

          -  Pregnant (positive pregnancy test) or lactation. Use of effective means of
             contraception (men and women) in subjects of child-bearing potential