Clinical Trial Finder

Inclusion Criteria:

• - 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 Central Nervous System (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, absolute neutrophil count (ANC) > or = to 1,500 cells/microliter, platelets > or = to 125,000 cells/microliter.

• - Serum creatinine ≤ 1.5 mg/dl, serum serum glutamic oxaloacetic transaminase (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 entry.

• - If sexually active, patients will take contraceptive measures for the duration of the treatments.

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.

• - 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 enrollment.

• - History of stroke or transient ischemic attack within 6 months prior to study enrollment.

• - 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 eligible).

• - 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

Arms

Experimental: Avastin in combination with temozolomide and irinotecan

Avastin 10 mg/kg every 14 days. Temozolomide 200 mg/m2 daily x 5 days in a 28-day cycle. Irinotecan dose depends on whether the patient is on an enzyme-inducing antiepileptic drug (EIAED). EIAED 340 mg/m2 every other week and no EIAED 125 mg/m2 every other week. Irinotecan dose also depends on if the patient has the UGT 1A1 polymorphism (7/7). If so, they do not metabolize the irinotecan normally, so these patients will start out at a two dose level reduction. EIAED starting dose will be 275 mg/m2 and no EIAED starting dose will be 75 mg/ m2.

Interventions

Drug: - Avastin

Avastin, by intravenous infusion, 10 mg/kg every 14 days

Drug: - Temozolomide

Oral temozolomide at 200 mg/m2 daily for 5 days

Drug: - Irinotecan

Irinotecan, by intravenous infusion, every other week (dose dependent upon if taking enzyme-inducing anti-epileptic drugs or if a blood test indicates the patient has the UGT 1A1 polymorphism)