Avastin in Combination With Radiation (XRT) & Temozolomide, Followed by Avastin, Temozolomide and Irinotecan for Glioblastoma (GBM) and Gliosarcomas
Condition: Glioblastoma; Gliosarcoma; Brain Tumor
MeSH terms: Glioblastoma; Brain Neoplasms; Gliosarcoma
Intervention: Avastin; Temozolomide; Radiation Therapy (XRT); Irinotecan
Intervention description: Avastin will be administered 10 mg/kg every other week beginning a minimum of 28 days after last major surgical procedure, open biopsy, or significant traumatic injury. Following completion of XRT, patients will receive treatment that includes 6 cycles of Avastin, beginning a minimum of 14 days after last XRT.; Daily temozolomide 75 mg/m2/day for 6.5 weeks of radiation treatment. Following completion of XRT, patients will receive treatment including temozolomide 200 mg/m2/day on the 1st 5 days of each 28-day cycle.; Treatment with standard XRT (radiation) for 6.5 weeks.; Following completion of XRT, patients will receive 6 cycles of treatment that includes irinotecan. Beginning a minimum of 14 days after last XRT, the irinotecan dose will depend on whether the patient is on enzyme-inducing antiepileptic drugs (EIAED). (EIAED:340 mg/m2 every other week, non-EIAED: 125 mg/m2.)
Intervention MeSH terms: Bevacizumab; Irinotecan; Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 125.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Avastin; Bevacizumab; Temozolomide; Temodar; Irinotecan; Camptosar; GBM; Glioblastoma Multiforme; Gliosarcoma; Brain tumor; Glioma; New GBM; Newly diagnosed GBM or gliosarcoma malignant brain tumor

Summary:

      Primary objective: To use overall survival to assess the efficacy of the combination of
      radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan
      in the treatment of grade IV malignant glioma patients following surgical resection.

      Secondary objective: To determine the progression-free survival following the combination of
      radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and
      irinotecan.

      Exploratory Objective: To explore the relationship between biomarkers and outcome (overall
      survival and progression-free survival) among patients with grade IV malignant glioma treated
      with radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and
      irinotecan.

      To describe the toxicity of radiation therapy,temozolomide and Avastin followed by Avastin,
      temozolomide, and irinotecan.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed diagnosis of World Health Organization
             (WHO) grade IV primary malignant glioma (glioblastoma multiforme or gliosarcoma).
             Patients have to be within 4 weeks of the last major surgical procedure.

          -  Age > 18 years.

          -  An interval of at least 2 weeks and not > 6 weeks between prior major surgical
             procedure and study enrollment.

          -  No prior radiotherapy or chemotherapy for a brain tumor

          -  Karnofsky ≥ 60 percent.

          -  Hemoglobin ≥ 9.0 g/deciliter (dl), absolute neutrophil count (ANC) ≥ 1,500 cells/
             microliter, platelets ≥ 125,000 cells/microliter.

          -  Serum creatinine ≤ 1.5 mg/dl, serum serum glutamic-oxaloacetic transaminase (SGOT) and
             bilirubin ≤ 1.5 times upper limit of normal (ULN).

          -  For patients on corticosteroids, they must be on a stable or decreasing dose for 1
             week prior to entry, and the dose should not be escalated over entry dose level, if
             clinically possible.

          -  Signed informed consent approved by the Institutional Review Board

          -  No evidence of > grade 1 central nervous system (CNS) hemorrhage on the baseline MRI
             or CT scan.

          -  If sexually active, patients will take contraceptive measures for the duration of
             treatment 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 intravenous (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 on CT scan.

        Avastin-Specific Concerns:

        Subjects meeting any of the following criteria are ineligible for study entry:

          -  Current, recent (within 4 weeks of the first infusion of this study), or planned
             participation in an experimental drug study

          -  Blood pressure of 150/100 mmHg

          -  Unstable angina

          -  New York Heart Association (NYHA) Grade II or greater 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 (prothrombin time (PT) or partial thromboplastin time (PTT) >1.5x normal
             or a history of > three grade 2 or greater hemorrhages)

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to first Avastin infusion during XRT/Temodar or anticipation of need for major
             surgical procedure during the course of the study

          -  Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
             prior to first Avastin infusion during XRT/Temodar

          -  Pregnant (positive pregnancy test) or lactating

          -  Urine protein >1.0 + at screening

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to first Avastin infusion during XRT/Temodar

          -  Serious, non-healing wound, ulcer, or bone fractures.

          -  Inability to comply with study and/or follow-up procedures.