Avastin in Combination With Temozolomide and Irinotecan for Unresectable or Multifocal Glioblastoma Multiformes and Gliosarcomas
- Patients must have histologically confirmed diagnosis of WHO grade IV primary
malignant glioma (glioblastoma multiforme or gliosarcoma). Patients will be
unresectable or have multifocal disease.
- Age > or = to 18 years and a life expectancy of >12 weeks.
- Evidence of measurable primary CNS neoplasm on contrast enhanced MRI.
- An interval of at least one week between prior biopsy or four weeks from surgical
resection and enrollment on this protocol.
- Karnofsky > or = to 60%.
- Hemoglobin > or = to 9g/dl, ANC > or = to 1,500 cells/microliter, platelets > or = to
- Serum creatinine ≤ 1.5 mg/dl, serum SGOT and direct bilirubin ≤ 1.5 times upper limit
of normal (if the total bilirubin is greater than or equal to 1.5 x the upper limit
of normal, then the direct bilirubin must be ≤ 1.5 x the upper limit of normal).
- Signed informed consent approved by the Institutional Review Board prior to patient
- If sexually active, patients will take contraceptive measures for the duration of the
- 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.
- 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.
Avastin-specific Exclusion Criteria:
- Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or
diastolic blood pressure > 100 mmHg on antihypertensive medications)
- Any 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
- History of stroke or transient ischemic attack within 6 months prior to study
- Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
- Symptomatic peripheral vascular disease
- Evidence of bleeding diathesis or coagulopathy
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to study enrollment 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, or intra-abdominal
abscess within 6 months prior to study enrollment
- Serious, non-healing wound, ulcer, or bone fracture
- Proteinuria at screening as demonstrated by either urine protein:creatinine (UPC)
ratio > or = to 1.0 at screening OR 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
- Known hypersensitivity to any component of Avastin
- Pregnant (positive pregnancy test) or lactating. Use of effective means of
contraception (men and women) in subjects of child-bearing potential