Bevacizumab With or Without Anti-Endoglin Monoclonal Antibody TRC105 in Treating Patients With Recurrent Glioblastoma Multiforme
Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma, Adult Giant Cell Glioblastoma
About this trial
This is an interventional treatment trial for Adult Anaplastic Astrocytoma
Eligibility Criteria
Inclusion Criteria:
- Histological confirmation of grade 3 or 4 glioma, including astrocytoma, oligodendroglioma, and mixed gliomas, as determined by pre-registration central pathology review (Phase I)
- Histological confirmation of glioblastoma multiforme (grade 4 astrocytoma) as determined by pre-registration central pathology review; note: gliosarcomas and other grade 4 astrocytoma variants (e.g., giant cell) are eligible; glioblastoma (GBM) with oligodendroglial features are NOT PERMITTED in this study if they are 1p19q co-deleted; sites submitting GBM with oligodendroglial features will be asked to provide results of 1p/19q co-deletion status (Phase II)
- Evidence of tumor progression by MRI or computed tomography (CT) scan following radiation therapy or following the most recent anti-tumor therapy; note: patients who have had surgical treatment at recurrence are eligible if they had a resection with measurable or non-measurable residual disease on postoperative imaging or if there is imaging evidence of disease progression as compared to the first postoperative scan
- Measurable or evaluable disease by gadolinium MRI or contrast CT scan; note: patients who have had a gross total resection (GTR) are eligible on the basis of evaluable disease
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
- Absolute neutrophil count (ANC) >= 1,500/mm^3
- Platelet count >= 100,000/mm^3
- White blood cells (WBC) >= 3,000/mL
- Hemoglobin >= 10.0 g/dL; note: this level may be reached by transfusion
- Total bilirubin =< institutional upper limit of normal (ULN)
- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2 x ULN
- Creatinine =< ULN
- Life expectancy >= 12 weeks
- Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
- Urine protein creatinine (UPC) ratio < 1; note: urine protein must be screened by urine analysis for UPC ratio; for UPC ratio >= 1.0, 24-hour urine protein must be obtained and the level should be < 1,000 mg for registration
- Fixed or decreasing dose of corticosteroids (or no corticosteroids) >= 7 days prior to registration
- Calculated glomerular filtration rate (GFR) must be >= 60 ml/min; GFR will be calculated as needed per institutional guidelines
- Any number of prior chemotherapy regimens for recurrent disease (Phase I); =< 1 chemotherapy or other non-antiangiogenic regimen for recurrent disease (Phase II)
- Last dose of bevacizumab >= 2 weeks prior to registration (Phase I); note: for the phase II study only, prior exposure to bevacizumab is not allowed
- Surgery >= 4 weeks prior to registration
- Completion of radiation therapy >= 12 weeks prior to registration and prior chemotherapy >= 4 weeks prior to registration (>= 6 weeks from nitrosourea-containing regimens)
- Small molecular cell cycle inhibitors >= 2 weeks from registration
- Ability to provide informed written consent
- Ability to complete questionnaire(s) by themselves or with assistance
- Willing to return to enrolling institution for follow-up
- Willing to discontinue use of medications that inhibit platelet function >= 10 days prior to registration; aspirin at doses greater than 325 mg/day must be discontinued >= 10 days prior to registration and avoided through the study; note: nonsteroidal anti-inflammatory drug (NSAID) medications are recommended in place of aspirin; if NSAIDs or aspirin are used, histamine (H)-2 blockers and proton pump inhibitor (PPI) medications are recommended
- Willing to provide mandatory blood and tissue samples for correlative research purposes (Phase I and II)
Exclusion Criteria:
Any of the following:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception throughout the duration of the study and for at least 6 months after treatment has ended
- Prior hypersensitivity to bevacizumab or toxicity requiring discontinuation of bevacizumab (Phase I)
- Any prior exposure to any VEGF or VEGF inhibitor including, but not limited to, bevacizumab, cediranib, vandetanib, sunitinib, pazopanib, aflibercept, or sorafenib (Phase II)
- Prior hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies (Phase I and II)
- Prior hypersensitivity to triptan derivatives (Phase I and II)
- Other active malignancy =< 3 years prior to registration; exceptions: non-melanotic skin cancer or carcinoma-in-situ of the cervix; note: if there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer
- Uncontrolled infection
- Immunocompromised patients or patients known to be human immunodeficiency virus (HIV) positive and currently receiving combination antiretroviral therapy; patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the prescribed regimens
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
- History of hypertensive crisis or hypertensive encephalopathy
Clinically significant cardiovascular disease defined as follows:
- Inadequately controlled hypertension (i.e., systolic blood pressure [SBP] > 160 mm Hg and/or diastolic blood pressure [DBP] > 90 mm Hg despite antihypertensive therapy)
- History of cerebrovascular accident (CVA) within 6 months
- Myocardial infarction or unstable angina within 6 months
- New York Heart Association classification II, III, or IV cardiovascular disease
- Serious and inadequately controlled cardiac arrhythmia
- Significant vascular disease (i.e., aortic aneurysm, history of aortic dissection)
- Clinically significant peripheral vascular disease
- Evidence or history of bleeding diathesis (greater than normal risk of bleeding, i.e., hereditary hemorrhagic telangiectasia type I or HHT-1) or coagulopathy in the absence of therapeutic anti-coagulation or any hemorrhage/bleeding event > grade 3 within 4 weeks prior to registration; note: patients with full-dose anticoagulants are eligible provided the patient has been on a stable dose for at least 2 weeks of low molecular weight heparin; therapeutic Coumadin and aspirin doses > 325 mg daily are not allowed
- Receiving any other investigational agent that would be considered as a treatment for the primary neoplasm
- Prior treatment with TRC105
- Serious or non-healing wound, active ulcer, or untreated bone fracture
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess =< 6 months prior to registration
History of invasive procedures defined as follows:
- Major surgical procedure, open biopsy, or significant traumatic injury =< 28 days prior to registration
- Anticipation of need for major surgical procedures during the study
- Core biopsy =< 7 days prior to registration
- History of significant vascular disease (i.e., aortic aneurysm requiring surgical repair, or recent peripheral arterial thrombosis) within 6 months prior to registration
Sites / Locations
- University of Arkansas for Medical Sciences
- Saint Jude Medical Center
- Saint Joseph Hospital - Orange
- Sharp Memorial Hospital
- UCSF Medical Center-Mount Zion
- UCSF Medical Center-Parnassus
- Greenwich Hospital
- Smilow Cancer Hospital Care Center at Saint Francis
- Stamford Hospital/Bennett Cancer Center
- Beebe Medical Center
- Christiana Gynecologic Oncology LLC
- Delaware Clinical and Laboratory Physicians PA
- Helen F Graham Cancer Center
- Medical Oncology Hematology Consultants PA
- Regional Hematology and Oncology PA
- Christiana Care Health System-Christiana Hospital
- Beebe Health Campus
- Nanticoke Memorial Hospital
- Christiana Care Health System-Wilmington Hospital
- Mayo Clinic in Florida
- Mount Sinai Medical Center
- Florida Hospital Orlando
- Saint Alphonsus Cancer Care Center-Boise
- Kootenai Medical Center
- Kootenai Cancer Center
- Kootenai Cancer Clinic
- Saint Joseph Medical Center
- Illinois CancerCare-Bloomington
- Illinois CancerCare-Canton
- Memorial Hospital of Carbondale
- Illinois CancerCare-Carthage
- Centralia Oncology Clinic
- Northwestern University
- Cancer Care Center of Decatur
- Decatur Memorial Hospital
- Crossroads Cancer Center
- Illinois CancerCare-Eureka
- NorthShore University HealthSystem-Evanston Hospital
- Illinois CancerCare-Galesburg
- Western Illinois Cancer Treatment Center
- NorthShore University HealthSystem-Glenbrook Hospital
- Hematology Oncology Associates of Illinois-Highland Park
- NorthShore University HealthSystem-Highland Park Hospital
- Presence Saint Mary's Hospital
- Illinois CancerCare-Kewanee Clinic
- NorthShore Hematology Oncology-Libertyville
- Illinois CancerCare-Macomb
- Garneau, Stewart C MD (UIA Investigator)
- Spector, David MD (UIA Investigator)
- Trinity Medical Center
- Illinois Cancer Specialists-Niles
- Illinois CancerCare-Ottawa Clinic
- Radiation Oncology of Northern Illinois
- Illinois CancerCare-Pekin
- OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
- Methodist Medical Center of Illinois
- Illinois CancerCare-Peoria
- OSF Saint Francis Radiation Oncology at Peoria Cancer Center
- OSF Saint Francis Medical Center
- Illinois CancerCare-Peru
- Valley Radiation Oncology
- Illinois CancerCare-Princeton
- Hematology Oncology Associates of Illinois - Skokie
- Central Illinois Hematology Oncology Center
- Southern Illinois University School of Medicine
- Springfield Clinic
- Memorial Medical Center
- Cancer Care Specialists of Illinois-Swansea
- Northwestern Medicine Cancer Center Warrenville
- Michiana Hematology Oncology PC-Crown Point
- Elkhart Clinic
- Michiana Hematology Oncology PC-Elkhart
- Elkhart General Hospital
- Indiana University/Melvin and Bren Simon Cancer Center
- Community Howard Regional Health
- IU Health La Porte Hospital
- Memorial Regional Cancer Center Day Road
- Michiana Hematology Oncology PC-Mishawaka
- Saint Joseph Regional Medical Center-Mishawaka
- Michiana Hematology Oncology PC-Plymouth
- Reid Health
- Memorial Hospital of South Bend
- Michiana Hematology Oncology PC-South Bend
- South Bend Clinic
- Northern Indiana Cancer Research Consortium
- Michiana Hematology Oncology PC-Westville
- Mary Greeley Medical Center
- McFarland Clinic PC-William R Bliss Cancer Center
- Constantinou, Costas L MD (UIA Investigator)
- McFarland Clinic PC-Boone
- Mercy Hospital
- Oncology Associates at Mercy Medical Center
- McFarland Clinic PC-Trinity Cancer Center
- University of Iowa/Holden Comprehensive Cancer Center
- McFarland Clinic PC-Jefferson
- McFarland Clinic PC-Marshalltown
- Siouxland Regional Cancer Center
- Mercy Medical Center-Sioux City
- Saint Luke's Regional Medical Center
- Cancer Center of Kansas - Chanute
- Cancer Center of Kansas - Dodge City
- Cancer Center of Kansas - El Dorado
- Cancer Center of Kansas - Fort Scott
- Cancer Center of Kansas-Independence
- Cancer Center of Kansas-Kingman
- Lawrence Memorial Hospital
- Cancer Center of Kansas-Liberal
- Cancer Center of Kansas-Manhattan
- Cancer Center of Kansas - McPherson
- Cancer Center of Kansas - Newton
- Cancer Center of Kansas - Parsons
- Cancer Center of Kansas - Pratt
- Cancer Center of Kansas - Salina
- Cancer Center of Kansas - Wellington
- Associates In Womens Health
- Cancer Center of Kansas-Wichita Medical Arts Tower
- Cancer Center of Kansas - Wichita
- Via Christi Regional Medical Center
- Wichita NCI Community Oncology Research Program
- Cancer Center of Kansas - Winfield
- Baptist Health Corbin
- Oncology Hematology Care Inc-Crestview
- Hardin Memorial Hospital
- Baptist Health Lexington
- Baptist Health Madisonville/Merle Mahr Cancer Center
- Baptist Health Paducah
- Eastern Maine Medical Center
- Lafayette Family Cancer Center-EMMC
- Maine Center for Cancer Medicine-Scarborough
- Massachusetts General Hospital Cancer Center
- Dana-Farber Cancer Institute
- Massachusetts General Hospital
- Bixby Medical Center
- Hickman Cancer Center
- Saint Joseph Mercy Hospital
- Bronson Battle Creek
- Beaumont Hospital-Dearborn
- Saint John Hospital and Medical Center
- Hurley Medical Center
- Genesys Hurley Cancer Institute
- Mercy Health Saint Mary's
- Spectrum Health at Butterworth Campus
- Allegiance Health
- Borgess Medical Center
- Bronson Methodist Hospital
- West Michigan Cancer Center
- Sparrow Hospital
- Saint Mary Mercy Hospital
- Mercy Memorial Hospital
- Toledo Clinic Cancer Centers-Monroe
- Mercy Health Mercy Campus
- Lakeland Community Hospital
- Saint Joseph Mercy Oakland
- Lake Huron Medical Center
- Spectrum Health Reed City Hospital
- Saint Mary's of Michigan
- Lakeland Hospital
- Marie Yeager Cancer Center
- Munson Medical Center
- Saint John Macomb-Oakland Hospital
- Ann Arbor Hematology -Oncology Associates
- Fairview Ridges Hospital
- Mercy Hospital
- Essentia Health Cancer Center
- Essentia Health Saint Mary's Medical Center
- Miller-Dwan Hospital
- Saint Luke's Hospital of Duluth
- Fairview-Southdale Hospital
- Unity Hospital
- Hutchinson Area Health Care
- Minnesota Oncology Hematology PA-Maplewood
- Saint John's Hospital - Healtheast
- Abbott-Northwestern Hospital
- Hennepin County Medical Center
- Health Partners Inc
- New Ulm Medical Center
- North Memorial Medical Health Center
- Mayo Clinic
- Coborn Cancer Center at Saint Cloud Hospital
- Saint Cloud Hospital
- Metro Minnesota Community Oncology Research Consortium
- Park Nicollet Clinic - Saint Louis Park
- Regions Hospital
- United Hospital
- Saint Francis Regional Medical Center
- Lakeview Hospital
- Ridgeview Medical Center
- Rice Memorial Hospital
- Minnesota Oncology Hematology PA-Woodbury
- Parkland Health Center-Bonne Terre
- Saint Francis Medical Center
- Southeast Cancer Center
- Capital Region Medical Center-Goldschmidt Cancer Center
- Washington University School of Medicine
- Missouri Baptist Medical Center
- Sainte Genevieve County Memorial Hospital
- Missouri Baptist Sullivan Hospital
- Missouri Baptist Outpatient Center-Sunset Hills
- Billings Clinic Cancer Center
- Montana Cancer Consortium NCORP
- Saint Vincent Healthcare
- Bozeman Deaconess Hospital
- Saint James Community Hospital and Cancer Treatment Center
- Benefis Healthcare- Sletten Cancer Institute
- Saint Peter's Community Hospital
- Kalispell Regional Medical Center
- Saint Patrick Hospital - Community Hospital
- Community Medical Hospital
- University of Nebraska Medical Center
- New Hampshire Oncology Hematology PA-Concord
- New Hampshire Oncology Hematology PA-Hooksett
- LRGHealthcare-Lakes Region General Hospital
- Dartmouth Hitchcock Medical Center
- Cooper Hospital University Medical Center
- MD Anderson Cancer Center at Cooper-Voorhees
- Hematology Oncology Associates of Central New York-Auburn
- Hematology Oncology Associates of Central New York-East Syracuse
- Mount Sinai Hospital
- Memorial Sloan-Kettering Cancer Center
- State University of New York Upstate Medical University
- Hematology Oncology Associates of Central New York-Onondaga Hill
- Wayne Memorial Hospital
- Kinston Medical Specialists PA
- Wake Forest University Health Sciences
- Altru Cancer Center
- Strecker Cancer Center-Belpre
- Toledo Clinic Cancer Centers-Bowling Green
- Adena Regional Medical Center
- Oncology Hematology Care Inc-Eden Park
- Oncology Hematology Care Inc-Mercy West
- Oncology Hematology Care Inc - Anderson
- Oncology Hematology Care Inc-Kenwood
- Oncology Hematology Care Inc-Blue Ash
- Columbus Oncology and Hematology Associates Inc
- Riverside Methodist Hospital
- Columbus NCI Community Oncology Research Program
- Grant Medical Center
- The Mark H Zangmeister Center
- Mount Carmel Health Center West
- Doctors Hospital
- Good Samaritan Hospital - Dayton
- Miami Valley Hospital
- Samaritan North Health Center
- Delaware Health Center-Grady Cancer Center
- Delaware Radiation Oncology
- Grady Memorial Hospital
- Oncology Hematology Care Inc-Healthplex
- Blanchard Valley Hospital
- Atrium Medical Center-Middletown Regional Hospital
- Wayne Hospital
- Kettering Medical Center
- Fairfield Medical Center
- Lima Memorial Hospital
- Marietta Memorial Hospital
- OneHealth Marion General Hospital
- Toledo Clinic Cancer Centers-Maumee
- Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
- Knox Community Hospital
- Licking Memorial Hospital
- Newark Radiation Oncology
- Saint Charles Hospital
- Toledo Clinic Cancer Centers-Oregon
- Southern Ohio Medical Center
- Springfield Regional Medical Center
- Flower Hospital
- Mercy Hospital of Tiffin
- Saint Vincent Mercy Medical Center
- University of Toledo
- Toledo Community Hospital Oncology Program CCOP
- Mercy Saint Anne Hospital
- Toledo Clinic Cancer Centers-Toledo
- Upper Valley Medical Center
- Fulton County Health Center
- Saint Ann's Hospital
- Genesis Healthcare System Cancer Care Center
- University of Oklahoma Health Sciences Center
- Oklahoma Cancer Specialists and Research Institute-Tulsa
- Lehigh Valley Hospital-Cedar Crest
- Lehigh Valley Hospital - Muhlenberg
- PinnacleHealth Cancer Center-Community Campus
- Reading Hospital
- Greenville Health System Cancer Institute-Easley
- Greenville Health System Cancer Institute-Andrews
- Greenville Health System Cancer Institute-Butternut
- Greenville Health System Cancer Institute-Faris
- Greenville Memorial Hospital
- Greenville Health System Cancer Institute-Eastside
- Greenville Health System Cancer Institute-Greer
- Greenville Health System Cancer Institute-Seneca
- Greenville Health System Cancer Institute-Spartanburg
- Rapid City Regional Hospital
- University Medical Center Brackenridge
- UT Southwestern/Simmons Cancer Center-Dallas
- Huntsman Cancer Institute/University of Utah
- University of Virginia Cancer Center
- Fredericksburg Oncology Inc
- Gundersen Lutheran Medical Center
- University of Wisconsin Hospital and Clinics
- Community Memorial Hospital
- Froedtert and the Medical College of Wisconsin
- ProHealth D N Greenwald Center
- Cancer Center of Western Wisconsin
- ProHealth Oconomowoc Memorial Hospital
- ProHealth Waukesha Memorial Hospital
- Rocky Mountain Oncology
- Big Horn Basin Cancer Center
- Billings Clinic-Cody
- Welch Cancer Center
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Arm I (bevacizumab and TRC105)
Arm II (bevacizumab)
Patients receive bevacizumab IV over 30-90 minutes on day 1 and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 8 and 11 of course 1 and days 1 and 8 of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Patients receive bevacizumab as in arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.