Amgen 386 for Recurrent Glioblastoma

Inclusion Criteria * Signed informed consent approved by the Institutional Review Board prior to participant entry * Age ≥ 18 years. * Karnofsky ≥ 70% * Participant must be able and willing to comply with study and/or follow-up procedures Participants must have histologically confirmed diagnosis of GBM patients with either grade III or IV malignant glioma are eligible to the Phase I portion of the study) and radiographic evidence of recurrence or disease progression (defined as either a greater than 25% increase in the largest bidimensional product of enhancement, a new enhancing lesion, or significant increase in T2 FLAIR) following prior therapy (i.e. chemotherapy, XRT, other investigational therapies). * No more than 2 prior episodes of progressive disease (patients with more than 2 prior episodes of progressive disease are eligible for the Cohort B, Phase I portion of this study) * An interval of at least 4 weeks (to start of study agent) between prior surgical resection or one week from stereotactic biopsy * An interval of at least 12 weeks (to start of study agent) from the end of prior radiotherapy unless there is a new area of enhancement consistent with recurrent tumor outside of the radiation field, or there is histological confirmation of unequivocal tumor progression * From the projected start of scheduled study treatment, the following time periods must have relapsed: 4 weeks (or 5 half lives, whichever is shorter) from any investigational agent, 4 weeks (or 5 half lives, whichever is shorter) from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies (or 5 half lives, whichever is shorter), or 4 weeks (or 5 half lives, whichever is shorter) from other anti-tumor therapies. * Participants must have recovered to a grade 0 or 1 from the toxic effects of prior therapy (with the exception of lymphopenia, which is common after therapy with temozolomide, and alopecia). * No evidence of hemorrhage on the baseline MRI or CT scan other than those that are ≤ grade 1 and either post-operative or stable on at least two consecutive scans. Clinical Labs - performed within 14 days prior to enrollment * Hematocrit ≥ 29%, ANC ≥ 1,000 cells/μl, platelets ≥ 100,000 cells/μl ; * Serum creatinine ≤ 1.5 mg/dl, serum SGOT and bilirubin ≤ 1.5 times upper limit of normal; * PTT or aPTT ≤ 1.5 times upper limit of normal and INR ≤ 1.5 * Calculated creatinine clearance ≥ 40 mL/min according to the Cockcroft-Gault formula OR per 24 hour urine collection * Urinary protein quantitative value of \< 30 mg/dL in urinalysis or \<1+ on dipstick, unless quantitative protein is \< 1000 mg in a 24 hour urine sample; * Participants of child-bearing potential who have not undergone a bilateral salpingo-oophorectomy and are sexually active must consent to use an accepted and highly effective non-hormonal method of contraception (i.e. double barrier method \[e.g., condom plus diaphragm\]) from signing the informed consent through 6 months after last dose of study drug. Exclusion Criteria: * Prior anti-angiogenic therapy targeting VEGF or VEGF receptor including prior bevacizumab. * Prior AMG 386 therapy or other molecules that inhibit the angiopoietins or Tie2 receptor. * Co-medication that may interfere with study results; e.g. immunosuppressive agents other than corticosteroids. * Active infection requiring intravenous antibiotics * Current or within 30 days prior to enrollment treatment with immune modulators such as systemic cyclosporine and tacrolimus. * Current us of warfarin sodium or any other Coumadin-derivative anticoagulant. Participant must be off Coumadin-derivative anticoagulants for at least seven days prior to starting study drug. ow molecular weight heparin is allowed. * Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than supportive care or epidemiologic studies. * Herbal preparations/medications are not allowed throughout the study. These herbal medications include, but are not limited to: St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, ginseng. Participants should stop using any herbal medications 7 days prior to first dose of study drug. * History of clinically significant bleeding within 6 months of enrollment * History of allergic reactions to bacterially produced proteins * Known hypersensitivity to any component of bevacizumab (cohort B only) * Known sensitivity to any of the products to be administered during dosing * History of venous or arterial thromboembolism within 12 months prior to enrollment. * Severe hepatic insufficiency (ongoing grade 3 or greater hepatic adverse events) or known active chronic hepatitis. * Inadequately controlled hypertension (defined as systolic blood pressure \>140 and/or diastolic blood pressure \> 90 mmHg). The use of anti-hypertensive medications to control hypertension is permitted. * Any prior history of hypertensive crisis or hypertensive encephalopathy * Clinically significant cardiovascular disease within 12 months prior to enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent. * 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 (including gastrointestinal), or bone fracture. * Any condition which in the investigator's opinion makes the subject unsuitable for study participation. * Pregnant (positive pregnancy test) or lactating. Refusal or inability to use highly effective means of contraception (men and women) in participants of child-bearing potential.