A Study of Gliadel Followed by Avastin + Irinotecan for Glioblastoma Multiforme (GBM)
Condition: Malignant Glioma; Glioblastoma Multiforme; Gliosarcoma
MeSH terms: Glioblastoma; Glioma; Gliosarcoma
Intervention: Gliadel/Avastin/CPT-11
Intervention MeSH terms: Bevacizumab; Irinotecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Malignant glioma; Glioblastoma multiforme; GBM; Gliosarcoma; Gliadel; Carmustine; Irinotecan; CPT-11; Camptosar; Avastin; Bevacizumab

Summary:

      The primary objective of the study is to use 24 week survival to assess the efficacy of the
      combination of Gliadel followed by Avastin and irinotecan in the treatment of grade IV
      malignant glioma patients following surgical resection. The secondary objectives are to
      determine the progression-free survival following the combination of Gliadel followed by
      Avastin and irinotecan and to describe the toxicity of Gliadel followed by Avastin and
      irinotecan.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed diagnosis of WHO grade IV primary
             malignant glioma (glioblastoma multiforme or gliosarcoma). Patients have to be able to
             undergo a GTR.

          -  Age > or = 18 years

          -  Evidence of a unilateral, single focus of measurable central nervous system (CNS)
             neoplasm on contrast-enhanced MRI, unless medically contraindicated (CT scan will then
             be used)

          -  Patients must have < or = 2 disease progressions

          -  An interval of at least 4 weeks from the end of prior radiotherapy or one week from
             the end of a cycle of chemotherapy and enrollment on this protocol

          -  Karnofsky > or = 70%

          -  Hemoglobin > or = 9.0 g/dl, absolute neutrophil count (ANC) > or = 1,500
             cells/microliters, platelets > or = 125,000 cells/microliters

          -  Serum creatinine < or = 1.5 mg/dl, serum glutamic-oxaloacetic transaminase (SGOT) and
             bilirubin < or = 1.5 times upper limit of normal

          -  Patients on corticosteroids must have been on a stable dose for 1 week prior to entry,
             if clinically possible, and the dose should not be escalated over entry dose level

          -  If patient received chemotherapy or investigational agent as part of their prior
             therapy, the patient must recover from all toxicities (> or = Grade 1) prior to
             enrollment on this protocol

          -  Signed informed consent approved by the Institutional Review Board

          -  No evidence of CNS hemorrhage on the baseline MRI or CT scans

          -  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. Women of childbearing potential must have a negative
             serum pregnancy test within 72 hours prior to treatment administration

          -  Multifocal disease

          -  Prior treatment with Gliadel

          -  Prior treatment with CPT-11 or Avastin

          -  Prior stereotactic radiosurgery or brachytherapy

          -  Co-medication that may interfere with study results; e.g. immuno-suppressive agents
             other than corticosteroids

          -  Active infection requiring IV antibiotics

          -  Acute or chronic renal insufficiency (a glomerular filtration rate (GFR) <30
             mL/min/1.73m2) or acute renal insufficiency of any severity due to hepato-renal
             syndrome or in the peri-operative liver transplantation period

          -  Inability, in the opinion of the study investigator, to comply with study and/or
             follow-up procedures

          -  Current, recent (within 4 weeks of the first infusion of this study), or planned
             participation in an experimental drug study other than a Genentech-sponsored Avastin
             cancer study

          -  Life expectancy of less than 12 weeks

          -  Active malignancy, other than superficial basal cell and superficial squamous (skin)
             cell, or carcinoma in situ of the cervix within last five years

          -  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 Day 1

          -  History of stroke or transient ischemic attack within 6 months prior to Day 1

          -  Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or
             recent peripheral arterial thrombosis) within 6 months prior to Day 1

          -  History of hemoptysis (> or = 1/2 teaspoon of bright red blood per episode) within 1
             month prior to Day 1

          -  Evidence of bleeding diathesis or significant coagulopathy (in the absence of
             therapeutic anticoagulation)

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to Day 1 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 Day 1

          -  History of abdominal fistula, gastrointestinal perforation within 6 months prior to
             Day 1

          -  Serious, non-healing wound, active ulcer, or untreated bone fracture

          -  Proteinuria at screening as demonstrated by urinalysis (urine protein)

          -  Known hypersensitivity to any component of Avastin

          -  Pregnancy (positive pregnancy test) or lactation. Use of effective means of
             contraception (men and women) in subjects of child-bearing potential