Clinical Trial Finder

Inclusion Criteria:

• - Patients must have recurrent histologically confirmed diagnosis of WHO grade IV malignant glioma (glioblastoma multiforme or gliosarcoma) with no more than 3 prior progressions.

• - Age ≥ 18 years.

• - Karnofsky ≥ 60%.

• - An interval of at least 4 weeks between either prior tumor biopsy or prior major surgical procedure and study enrollment.

• - Bi-dimensionally measurable disease as assessed by magnetic resonance imaging.

• - Hemoglobin ≥9.0 g/dl, ANC ≥1500 cells/µl, Platelets ≥125,000 cells/µl (without transfusion within 14 days before enrollment).

• - Serum creatinine < 1.5 mg/dl, bilirubin < 1.5 times upper limit of normal, and serum SGOT (AST) and SGPT (ALT) < 2.5 times upper limit of normal.

• - For patients on corticosteroids, they must be on a stable 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 active 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.

• - Baseline ECG with QTc > 0.45 second.

• - Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids.

• - Thrombosis or vascular ischemic events within the last twelve months, such as deep venous thrombosis, pulmonary embolism, transient ischemic attack, cerebral infarction, or myocardial infarction.

• - Active infection requiring IV antibiotics 7 days before enrollment.

• - History of central nervous system bleeding as defined by stroke or intraocular bleed (including embolic stroke) within 6 months before enrollment.

• - Evidence of acute intracranial hemorrhage; except for subjects with stable grade 1 hemorrhage.

• - Less than 12 weeks from radiation therapy, unless progressive disease outside of the radiation field or 2 consecutive scans or histopathologic confirmation.

• - Treated previously with any c-Met or HGF targeted therapy.

• - Treated previously with VEGF or VEGFR therapies, including antibodies and tyrosine kinase inhibitors.

• - Treated with thalidomide or tamoxifen within 1 week before enrollment unless the patient has recovered from the toxic effects of such therapy.

• - Treated with immunotherapeutic agents, vaccines, or MAb therapy within 4 weeks before enrollment unless the patient has recovered from the toxic effects of such therapy.

• - Treated with alkylating agents within 4 weeks before enrollment or if the patient has been treated with daily or metronomic chemotherapy unless the patient has recovered from the toxic effects of such therapy.

• - Treated with chemotherapy (non-alkylating agents) within 2 weeks before enrollment unless the patient has recovered from the toxic effects of such therapy.

• - Less than 4 weeks after surgical resection of the brain tumor or less than 2 weeks after stereotactic biopsy before enrollment unless the patient has recovered from acute side effects of such procedures except for neurological effects.

• - Plans to receive surgery, radiation therapy or other elective surgeries during the course of the study.

• - Concurrent severe and/or uncontrolled medical disease (e.g. uncontrolled diabetes, congestive cardiac failure, myocardial infarction within 6 months before enrollment) that could compromise participation in the study.

• - Concurrent or prior (within 7 days of enrollment) anticoagulation therapy, except: Use of low dose coumadin-type anticoagulants (≤ 2 mg PO QD) low molecular weight heparins (LMWH), e.g. Enoxaparin sodium (Lovenox) and unfractionated heparin for prophylaxis against central venous catheter thrombosis is allowed.

• - Grade 2 or greater peripheral edema or effusion (pleural, pericardial, or ascites).

• - Inability to comply with study and/or follow-up procedure.

• - Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study.

Avastin-Specific Exclusion Criteria.Subjects meeting any of the following criteria are ineligible for study entry:

• - Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg 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, the day protocol therapy starts.

• - 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 (≥ 1/2 teaspoon of bright red blood per episode) within 28 days 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.

• - Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1.

• - Serious, non-healing wound, active ulcer or untreated bone fracture.

• - Proteinuria as defined by ≥ +1 on urinalysis dipstick.

• - Known hypersensitivity to any component of Avastin.

• - Pregnant (positive pregnancy test) or lactation.

Arms

Experimental: AMG 102 with Avastin

Avastin will be administered as a continuous intravenous infusion at 10 mg/kg prior to AMG 102, which will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg. Subjects will receive infusions every 2 weeks.

Interventions

Drug: - AMG 102

AMG 102 will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg every 2 weeks over 60 or 30 minutes.

Drug: - Avastin

Avastin will be administered as a continuous intravenous infusion at 10 mg/kg every 2 weeks (6-week study cycle) over 60 or 30 minutes. Avastin will be given prior to AMG 102.