Temozolomide and Radiation Therapy With or Without Bevacizumab in Treating Patients With Newly Diagnosed Glioblastoma
Glioblastoma, Gliosarcoma, Supratentorial Glioblastoma
About this trial
This is an interventional treatment trial for Glioblastoma
Eligibility Criteria
Inclusion Criteria:
- Histologically proven diagnosis of glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV) confirmed by central review prior to step 2 registration
Tumor tissue that is determined by central pathology review prior to step 2 registration to be of sufficient size for analysis of O-6-methylguanine-DNA methyltransferase (MGMT) and determination of molecular profile
- Patients must have at least 1 block of tumor tissue; submission of 2 blocks is strongly encouraged to maximize the chances of eligibility; at least 1 cubic centimeter of tissue composed primarily of tumor must be present
- CUSA (Cavitron ultrasonic aspirator)-derived material is not allowed; fresh frozen tumor tissue acquisition is encouraged
- Diagnosis must be made by surgical excision, either partial or complete; stereotactic biopsy is not allowed because it will not provide sufficient tissue for MGMT analysis
- The tumor tissue should be sent as soon as possible to maximize the likelihood of eligibility; tumor tissue should be submitted by 4 weeks after the surgical procedure so that the study registration and treatment can commence by the mandatory 5 week post-surgery outer limit
- Sites must submit tissue fir central review in order to obtain the MGMT analysis; patients from sites not following protocol-specified process for obtaining MGMT results will be made ineligible
- The tumor must have a supratentorial component
- History/physical examination within 14 days prior to step 2 registration
- The patient must have recovered from the effects of surgery, postoperative infection, and other complications before step 2 registration
A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively and postoperatively prior to the initiation of radiotherapy; the postoperative scan must be performed within 28 days prior to step 1 registration
- An MRI or computed tomography (CT) scan (potentially in addition to the postoperative scan) must be obtained within 10 days prior to the start of radiation therapy and must not demonstrate significant postoperative hemorrhage defined as > 1 cm diameter of blood; if > 1 cm of acute blood is detected, the patient will be ineligible for this trial; the radiation planning MRI or CT scan may be used to determine presence of hemorrhage
- Patients unable to undergo MR imaging because of non-compatible devices can be enrolled, provided pre- and postoperative contrast-enhanced CT scans are obtained and are of sufficient quality; preoperative and postoperative scans must be the same type; such patients cannot be enrolled into the advanced imaging component
- Documentation of steroid doses within 14 days prior to step 2 registration
- Karnofsky performance status >= 70
- Absolute neutrophil count (ANC) >= 1,800 cells/mm^3
- Platelets >= 100,000 cells/mm^3
- Hemoglobin >= 10.0 g/dL (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 10.0 g/dl is acceptable)
- Blood urea nitrogen (BUN) =< 30 mg/dL within 14 days prior to step 2 registration
- Creatinine =< 1.7 mg/dl within 14 days prior to step 2 registration
- Urine protein screened by urine analysis for urine protein creatinine (UPC) ratio; for UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg
- Bilirubin =< 2.0 mg/dl within 14 days prior to step 2 registration
- Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 3 x normal range within 14 days prior to step 2 registration
- Systolic blood pressure =< 160 mg Hg or diastolic pressure =< 90 mm Hg within 14 days prior to step 2 registration
- Electrocardiogram without evidence of acute cardiac ischemia within 14 days prior to step 2 registration
- Prothrombin time/international normalized ratio (PT INR) < 1.4 for patients not on warfarin confirmed by testing within 14 days prior to step 2 registration
Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight [LMW] heparin) must meet both of the following criteria:
- No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
- In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of LMW heparin
- Patient must provide study specific informed consent prior to study entry
- Women of childbearing potential and male participants must practice adequate contraception
- For females of child-bearing potential, negative serum pregnancy test within 14 days prior to step 2 registration
Exclusion Criteria:
- Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for >= 3 years; (for example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible)
- Recurrent or multifocal malignant gliomas
- Metastases detected below the tentorium or beyond the cranial vault
- Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable, except prior temozolomide or bevacizumab; prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted
- Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields
Severe, active co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure within the last 6 months
- Transmural myocardial infarction within the last 6 months
- Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of >= 2 mm using the analysis of an electrocardiogram (EKG) performed within 14 days of step 2 registration
- New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to step 2 registration
- History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months
- Serious and inadequately controlled cardiac arrhythmia
- Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease
- Evidence of bleeding diathesis or coagulopathy
- Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to step 2 registration, with the exception of the craniotomy for tumor resection
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol
- Acquired immune deficiency syndrome (AIDS) based upon current Center for Disease Control (CDC) definition; note, however, that HIV testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive
- Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity
- Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy
- Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
- Pregnant or lactating women
- Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study
- For American College of Radiology Imaging Network (ACRIN) 6686 Advanced Imaging: inability to undergo MRI (e.g., due to safety reasons, such as presence of a pacemaker)
Sites / Locations
- Providence Hospital
- Providence Alaska Medical Center
- Mayo Clinic in Arizona
- Arizona Oncology Services Foundation
- Arizona Oncology Associates-West Orange Grove
- Sutter Cancer Centers Radiation Oncology Services-Auburn
- Alta Bates Summit Medical Center-Herrick Campus
- Sutter Cancer Centers Radiation Oncology Services-Cameron Park
- Mercy San Juan Medical Center
- John Muir Medical Center-Concord Campus
- City of Hope Comprehensive Cancer Center
- California Cancer Center - North Fresno
- Cancer Care Associates of Fresno Medical Group Inc
- Saint Jude Medical Center
- UC San Diego Moores Cancer Center
- USC / Norris Comprehensive Cancer Center
- Memorial Medical Center
- Bay Area Tumor Institute
- Kaiser Permanente Oakland-Broadway
- Saint Joseph Hospital - Orange
- Pomona Valley Hospital Medical Center
- Kaiser Permanente-Rancho Cordova Cancer Center
- Rohnert Park Cancer Center
- Sutter Cancer Centers Radiation Oncology Services-Roseville
- The Permanente Medical Group-Roseville Radiation Oncology
- Sutter Medical Center Sacramento
- Mercy General Hospital Radiation Oncology Center
- South Sacramento Cancer Center
- University of California San Diego
- California Pacific Medical Center-Pacific Campus
- Kaiser Permanente Medical Center - Santa Clara
- Kaiser Permanente Cancer Treatment Center
- Sutter Cancer Centers Radiation Oncology Services-Vacaville
- John Muir Medical Center-Walnut Creek
- Rocky Mountain Cancer Centers-Aurora
- Boulder Community Hospital
- Penrose-Saint Francis Healthcare
- Porter Adventist Hospital
- Swedish Medical Center
- Poudre Valley Hospital
- Rocky Mountain Cancer Centers-Littleton
- North Suburban Medical Center
- SCL Health Lutheran Medical Center
- Saint Vincent's Medical Center
- Hartford Hospital
- The Hospital of Central Connecticut
- Yale University
- William Backus Hospital
- Broward Health Medical Center
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital
- Integrated Community Oncology Network-Florida Cancer Center Beaches
- Baptist MD Anderson Cancer Center
- Integrated Community Oncology Network-Southside Cancer Center
- Mayo Clinic in Florida
- Baptist Medical Center South
- Mount Sinai Medical Center
- Baptist Hospital of Miami
- 21st Century Oncology-Orange Park
- Florida Hospital Orlando
- UF Cancer Center at Orlando Health
- 21st Century Oncology-Palatka
- Sacred Heart Hospital
- Integrated Community Oncology Network-Flager Cancer Center
- Robert and Carol Weissman Cancer Center at Martin Health
- Piedmont Hospital
- Emory University Hospital/Winship Cancer Institute
- John B Amos Cancer Center
- Dekalb Medical Center
- Northeast Georgia Medical Center-Gainesville
- Southern Regional Medical Center
- Memorial University Medical Center
- University of Hawaii Cancer Center
- Saint Alphonsus Cancer Care Center-Boise
- Northwest Community Hospital
- Northwestern University
- John H Stroger Jr Hospital of Cook County
- University of Chicago Comprehensive Cancer Center
- Decatur Memorial Hospital
- Ingalls Memorial Hospital
- Loyola University Medical Center
- Trinity Medical Center
- Edward Hospital/Cancer Center
- Advocate Lutheran General Hospital
- Methodist Medical Center of Illinois
- Memorial Medical Center
- IU Health Bloomington
- Radiation Oncology Associates PC
- Parkview Hospital Randallia
- IU Health Methodist Hospital
- Community Cancer Center East
- IU Health Central Indiana Cancer Centers-East
- Community Cancer Center North
- Saint Vincent Hospital and Health Care Center
- IU Health Ball Memorial Hospital
- Northern Indiana Cancer Research Consortium
- McFarland Clinic PC-William R Bliss Cancer Center
- Physicians' Clinic of Iowa PC
- Iowa Methodist Medical Center
- Mercy Medical Center - Des Moines
- University of Iowa/Holden Comprehensive Cancer Center
- Mercy Medical Center - North Iowa
- University of Kansas Cancer Center
- University of Kansas Cancer Center-Overland Park
- Kansas City NCI Community Oncology Research Program
- Via Christi Regional Medical Center
- Wesley Medical Center
- The James Graham Brown Cancer Center at University of Louisville
- Mary Bird Perkins Cancer Center
- Ochsner Medical Center Jefferson
- Louisiana State University Health Sciences Center Shreveport
- Central Maine Medical Center
- Maine Medical Center- Scarborough Campus
- Anne Arundel Medical Center
- University of Maryland/Greenebaum Cancer Center
- Saint Agnes Hospital
- Massachusetts General Hospital Cancer Center
- Saint Anne's Hospital
- Cape Cod Hospital
- Lowell General Hospital
- D'Amour Center for Cancer Care
- Saint Joseph Mercy Hospital
- Beaumont Hospital-Dearborn
- Saint John Hospital and Medical Center
- Genesys Regional Medical Center-West Flint Campus
- West Michigan Cancer Center
- Sparrow Hospital
- William Beaumont Hospital-Royal Oak
- Saint Mary's of Michigan
- Saint John Macomb-Oakland Hospital
- Sanford Clinic North-Bemidgi
- Fairview Ridges Hospital
- Mercy Hospital
- Saint Luke's Hospital of Duluth
- Minnesota Oncology Hematology PA-Maplewood
- Abbott-Northwestern Hospital
- North Memorial Medical Health Center
- Mayo Clinic
- Coborn Cancer Center at Saint Cloud Hospital
- Park Nicollet Clinic - Saint Louis Park
- Regions Hospital
- United Hospital
- Ridgeview Medical Center
- Singing River Hospital
- Cape Radiation Oncology
- Siteman Cancer Center at West County Hospital
- Truman Medical Center
- The University of Kansas Cancer Center-South
- The University of Kansas Cancer Center-North
- Washington University School of Medicine
- Siteman Cancer Center at Saint Peters Hospital
- Billings Clinic Cancer Center
- CHI Health Good Samaritan
- Saint Elizabeth Regional Medical Center
- Nebraska Methodist Hospital
- Alegent Health Immanuel Medical Center
- Alegent Health Bergan Mercy Medical Center
- University of Nebraska Medical Center
- Nevada Cancer Research Foundation CCOP
- Renown Regional Medical Center
- Concord Hospital
- Dartmouth Hitchcock Medical Center
- Elliot Hospital
- Saint Barnabas Medical Center
- Monmouth Medical Center
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
- Riverview Medical Center/Booker Cancer Center
- Sparta Cancer Treatment Center
- Lovelace Medical Center-Downtown
- University of New Mexico Cancer Center
- New Mexico Oncology Hematology Consultants
- New York Oncology Hematology PC - Albany
- Montefiore Medical Center - Moses Campus
- Maimonides Medical Center
- Sands Cancer Center
- Memorial Sloan-Kettering Cancer Center
- South Nassau Communities
- Hudson Valley Oncology Associates
- Highland Hospital
- University Radiation Oncology
- University of Rochester
- Stony Brook University Medical Center
- State University of New York Upstate Medical University
- Mission Hospital-Memorial Campus
- Carolinas Medical Center/Levine Cancer Institute
- Novant Health Presbyterian Medical Center
- Margaret R Pardee Memorial Hospital
- FirstHealth of the Carolinas-Moore Regional Hosiptal
- Duke Women's Cancer Care Raleigh
- Novant Health Forsyth Medical Center
- Southeast Clinical Oncology Research (SCOR) Consortium NCORP
- Sanford Broadway Medical Center
- Summa Akron City Hospital/Cooper Cancer Center
- Akron General Medical Center
- Summa Barberton Hospital
- UHHS-Chagrin Highlands Medical Center
- Mercy Medical Center
- Aultman Health Foundation
- University of Cincinnati/Barrett Cancer Center
- Case Western Reserve University
- MetroHealth Medical Center
- Cleveland Clinic Cancer Center/Fairview Hospital
- Cleveland Clinic Foundation
- Ohio State University Comprehensive Cancer Center
- Riverside Methodist Hospital
- Grant Medical Center
- The Mark H Zangmeister Center
- Toledo Clinic Cancer Centers-Maumee
- Hillcrest Hospital Cancer Center
- Lake University Ireland Cancer Center
- Southwest General Health Center Ireland Cancer Center
- Saint Charles Hospital
- Cancer Care Center, Incorporated
- North Coast Cancer Care
- Trinity's Tony Teramana Cancer Center
- Flower Hospital
- Mercy Saint Anne Hospital
- University Pointe
- UHHS-Westlake Medical Center
- University of Oklahoma Health Sciences Center
- Natalie Warren Bryant Cancer Center at Saint Francis
- Willamette Valley Cancer Center
- Legacy Good Samaritan Hospital and Medical Center
- Providence Portland Medical Center
- Providence Saint Vincent Medical Center
- Salem Hospital
- Abington Memorial Hospital
- Lehigh Valley Hospital-Cedar Crest
- UPMC-Heritage Valley Health System Beaver
- Saint Luke's University Hospital-Bethlehem Campus
- Bryn Mawr Hospital
- Geisinger Medical Center
- Northeast Radiation Oncology Center
- Pocono Medical Center
- The Regional Cancer Center
- Fox Chase Cancer Center Buckingham
- Adams Cancer Center
- UPMC Cancer Centers - Arnold Palmer Pavilion
- Cherry Tree Cancer Center
- Penn State Milton S Hershey Medical Center
- UPMC-Johnstown/John P. Murtha Regional Cancer Center
- Armstrong Center for Medicine and Health
- Lancaster General Hospital
- UPMC Cancer Center at UPMC McKeesport
- Intercommunity Cancer Center
- Allegheny Valley Hospital
- UPMC Jameson
- Paoli Memorial Hospital
- Thomas Jefferson University Hospital
- Fox Chase Cancer Center
- Aria Health-Torresdale Campus
- Allegheny General Hospital
- UPMC-Shadyside Hospital
- UPMC Jefferson Regional Radiation Oncology
- UPMC-Passavant Hospital
- UPMC Cancer Center at UPMC Northwest
- UPMC Washington Hospital Radiation Oncology
- Reading Hospital
- Lankenau Medical Center
- WellSpan Health-York Hospital
- Rhode Island Hospital
- Spartanburg Medical Center
- Rapid City Regional Hospital
- Sanford Cancer Center-Oncology Clinic
- Erlanger Medical Center
- Jackson-Madison County General Hospital
- Thompson Cancer Survival Center
- Texas Oncology-Arlington South
- Texas Oncology Bedford
- Saint Joseph Regional Cancer Center
- Texas Oncology Methodist Charlton Cancer Center
- UT Southwestern/Simmons Cancer Center-Dallas
- Texas Oncology-Denton South
- The Klabzuba Cancer Center
- University of Texas Medical Branch
- M D Anderson Cancer Center
- Texas Oncology-Longview Cancer Center
- Covenant Medical Center-Lakeside
- West Texas Cancer Center
- University of Texas Health Science Center at San Antonio
- Texas Cancer Center-Sherman
- Texas Oncology Cancer Center Sugar Land
- Tyler Cancer Center
- Intermountain Medical Center
- McKay-Dee Hospital Center
- Utah Valley Regional Medical Center
- Dixie Medical Center Regional Cancer Center
- Utah Cancer Specialists-Salt Lake City
- Huntsman Cancer Institute/University of Utah
- LDS Hospital
- University of Vermont Medical Center
- Inova Alexandria Hospital
- Sentara Norfolk General Hospital
- Naval Medical Center - Portsmouth
- PeaceHealth Saint Joseph Medical Center
- Harrison Medical Center
- Virginia Mason Medical Center
- Swedish Medical Center-First Hill
- Cancer Care Northwest - Spokane South
- PeaceHealth Southwest Medical Center
- Compass Oncology Vancouver
- North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
- Wheeling Hospital/Schiffler Cancer Center
- Langlade Hospital and Cancer Center
- Radiology Associates of Appleton/ThedaCare Regional Medical Center
- Marshfield Clinic Cancer Center at Sacred Heart
- Sacred Heart Hospital
- Bellin Memorial Hospital
- Saint Vincent Hospital Cancer Center Green Bay
- Saint Vincent Hospital Cancer Center at Saint Mary's
- UW Cancer Center Johnson Creek
- Gundersen Lutheran Medical Center
- Dean Hematology and Oncology Clinic
- University of Wisconsin Hospital and Clinics
- Bay Area Medical Center
- Marshfield Clinic
- Marshfield Medical Center
- Froedtert and the Medical College of Wisconsin
- Marshfield Clinic-Minocqua Center
- Saint Michael's Hospital
- ProHealth Waukesha Memorial Hospital
- Aspirus Regional Cancer Center
- Diagnostic and Treatment Center
- Marshfield Clinic - Weston Center
- Aspirus UW Cancer Center
- Doctor H. Bliss Murphy Cancer Centre
- Health Sciences North
- CHUM - Hopital Notre-Dame
- McGill University Department of Oncology
- Allan Blair Cancer Centre
- Tel Aviv Sourasky Medical Center
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Arm I (radiation therapy, temozolomide, placebo)
Arm II (radiation therapy, temozolomide, bevacizumab)
Patients undergo intensity-modulated radiation therapy or 3-dimensional conformal radiation therapy 5 days a week for 6 weeks and receive temozolomide PO QD for up to 7 weeks. Beginning 4 weeks after completion of chemotherapy and radiation therapy, patients receive temozolomide PO QD on days 1-5. Treatment with temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive placebo IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemotherapy and radiation therapy and continuing until the completion of temozolomide.
Patients undergo radiation therapy and receive temozolomide as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemoradiotherapy and continuing until the completion of adjuvant temozolomide.