Ph II Cilengitide Plus Bevacizumab for Recurrent Glioblastoma (GBM)

Inclusion Criteria: 1. Patients with histologically proven intracranial glioblastoma (GBM) will be eligible for this protocol. Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a glioblastoma is made. a) Central pathology review is required for study entry. Either H \& E stained slides from diagnosis or more recent tumor sampling OR unstained tumor sections must be submitted and reviewed by the study neuropathologist. b) A paraffin-embedded tumor block (preferred) or 15 unstained tumor section slides are required to be submitted at the time of registration. 2. All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must have signed an authorization for the release of their protected health information. Patients must be registered in the MD Anderson Cancer Center Office of Multicenter Clinical Research (OMCR) database prior to treatment with study drug. 3. Patients must be \>/= 18 years old. 4. Patients must have a Karnofsky performance status of \>/= 70 5. At the time of registration: Patients must have recovered from the toxic effects of prior therapy: \>/= 28 days from any investigational agent, \>/= 28 days from prior cytotoxic therapy (\>/= 7 days from prior daily administered \[i.e. metronomic\] cytotoxic agents) , \>/= 14 days from vincristine, \>/= 42 days from nitrosoureas, \>/= 21 days from procarbazine administration, and \>/= 7 days for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count). Any questions related to the definition of non-cytotoxic agents should be directed to the Study Chair. 6. Patients must have adequate bone marrow function (ANC \>/= 1,000/mm3, platelet count of \>/= 100,000/mm3, and hemoglobin \>/= 10 gm/dl), adequate liver function (SGOT \< 2.5 times ULN and bilirubin \< 2 times ULN), and adequate renal function (creatinine \< 1.5 times ULN) before starting therapy. These tests must be performed within 14 days prior to treatment start date. Eligibility level for hemoglobin may be reached by transfusion. 7. Patients must have shown unequivocal radiographic evidence for tumor progression by MRI or CT scan. A scan should be performed within 14 days prior to treatment start date and on a steroid dose that has been stable or decreasing for at least 5 days. If the steroid dose is increased between the date of imaging and registration a new baseline MR/CT is required. The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement. 8. Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply: a). They have recovered from the effects of surgery and are at least four weeks from craniotomy or at least 1 week from stereotactic biopsy. b). Residual disease following resection of recurrent GBM is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, a CT/ MRI should be done no later than 96 hours in the immediate post-operative period or at least 4 weeks post-operatively, within 14 days prior to treatment start date. If the 96-hour scan is more than 14 days before registration, the scan needs to be repeated. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days. 9. Patients must have failed prior radiation therapy and must have an interval of greater than or equal to 12 weeks from the completion of radiation therapy to study entry unless there is a new area of enhancement consistent with recurrent tumor outside of the radiation field, or there is histopathologic confirmation of recurrent tumor. 10. Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium scanning, MR spectroscopy or surgical/pathological documentation of disease. 11. Women of childbearing potential must have a negative B-HCG pregnancy test documented within 14 days prior to treatment start date. 12. Prothrombin time (PT)/international normalized ratio (INR) within normal limits and partial thromboplastin time (PTT) below upper limit of normal. 13. No evidence of hemorrhage on the baseline MRI or CT scan other than those that are stable grade 1. 14. Patients must be at first or second relapse. Relapse is defined as progression following initial therapy (i.e. radiation+/- chemo if that was used as initial therapy). The intent therefore is that patients have no more than 2 prior therapies (initial and treatment for 1 relapse). If the patient had a surgical resection for relapsed disease and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered as 1 relapse. For patients who had prior therapy for a low-grade glioma, the surgical diagnosis of a high-grade glioma will be considered the first relapse. Exclusion Criteria: 1. Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol. 2. History of coagulation disorder associated with bleeding or thrombotic events. 3. Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results, including legal incapacity or limited legal capacity. 4. Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids 5. Active infection requiring intravenous antibiotics 6. Requires anticoagulation therapy with vitamin K antagonists, heparin, or thrombin or factor X inhibitors. (Low molecular weight heparin is allowed) 7. Have had a diagnosis of another malignancy, unless the patient has been disease-free for at least 12 months following the completion of curative intent therapy, with the following exceptions: a). Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed. b). Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed. 8. Inability to comply with study and/or follow-up procedures; 9. Current or planned participation in an experimental therapeutic drug study; 10. Severe hepatic insufficiency (ongoing grade 3 or greater hepatic adverse events) or known active chronic hepatitis 11. Prior treatment with cilengitide, bevacizumab or other VEGF/VEGFR-targeting therapy. 12. Inadequately controlled hypertension (defined as systolic blood pressure \>150 and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications) 13. Any prior history of hypertensive crisis or hypertensive encephalopathy 14. New York Heart Association (NYHA) Grade II or greater congestive heart failure 15. History of myocardial infarction or unstable angina within 6 months prior to study enrollment 16. History of stroke or transient ischemic attack within 6 months prior to study enrollment 17. Significant vascular disease (e.g., aortic aneurysm, aortic dissection) 18. Symptomatic peripheral vascular disease 19. Evidence of bleeding diathesis or coagulopathy 20. 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 21. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment 22. History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess or endoscopically-proven ulcer (esophageal, gastric or duodenal) within 6 months prior to study enrollment 23. Serious, non-healing wound, ulcer, or bone fracture 24. Proteinuria at screening as demonstrated by either: a). Urine protein:creatinine (UPC) ratio \>/= 1.0 at screening OR b). 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). 25. Known hypersensitivity to any component of bevacizumab, Chinese hamster ovary cell products or other recombinant human or humanized antibodies. 26. Pregnant (positive pregnancy test) or lactating. Use of effective means of contraception (men and women) in subjects of child-bearing potential 27. Known hypersensitivity to cilengitide, other trial treatment(s) or diluents (when applicable), including placebo or other comparator drug(s).