Dose-Escalated Photon IMRT or Proton Beam Radiation Therapy Versus Standard-Dose Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma
Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma
About this trial
This is an interventional treatment trial for Adult Giant Cell Glioblastoma
Eligibility Criteria
Inclusion Criteria:
- PRIOR TO STEP 1 REGISTRATION
- A diagnostic contrast-enhanced magnetic resonance imaging (MRI) (no other scan type allowed) of the brain must be performed postoperatively within 72 hours of resection; the enhancing tumor must have a maximal diameter of 5 cm; the tumor diameter will be the greatest diameter as measured on the contrast-enhanced postoperative MRI and will include residual disease and/or the postoperative surgical cavity as appropriate; for cases where residual disease or postoperative surgical cavity is NOT identifiable (e.g., polar glioblastomas [GBMs] where a polar lobectomy is performed), the patient will be excluded from the trial
- The GBM tumor must be located in the supratentorial compartment only (any component involving the brain stem or cerebellum is not allowed)
- Patients must provide study-specific informed consent prior to step 1 registration
- PRIOR TO STEP 2 REGISTRATION
- Histologically proven diagnosis of glioblastoma (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 quantity for analysis of O6-methylguanin-DNA-methyltransferase (MGMT) status
- 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
- Diagnosis must be made by surgical excision, either partial or complete; stereotactic biopsy or cavitron ultrasonic suction aspirator (CUSA) technique are not allowed
- History/physical examination within 28 days prior to step 2 registration
- The patient must have recovered from effects of surgery, postoperative infection, and other complications within 28 days prior to step 2 registration
- Documentation of steroid doses within 28 days prior to step 2 registration
- Karnofsky performance status >= 70 within 28 days prior to step 2 registration
- Age >= 18
- 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)
- Bilirubin =< 1.5 upper limit of normal (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN
- Negative serum pregnancy test obtained for females of child-bearing potential within 28 days prior to step 2 registration
Exclusion Criteria:
- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease-free for a minimum of 3 years; (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
- Recurrent or multifocal malignant gliomas
- Any site of distant disease (for example, drop metastases from the GBM tumor site)
- Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable (except temozolomide)
- 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 at step 2 registration
- Transmural myocardial infarction within the last 6 months prior to step 2 registration
- 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 28 days prior to step 2 registration
- New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to step 2 registration
- Serious and inadequately controlled arrhythmia at step 2 registration
- Serious or non-healing wound, ulcer or bone fracture or history of abdominal fistula, intra-abdominal abscess requiring major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to step 2 registration, with the exception of the craniotomy for surgical resection
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 2 registration
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration
- Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol
- Any other severe immunocompromised condition
- 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
- End-stage renal disease (ie, on dialysis or dialysis has been recommended)
- Any other major medical illnesses or psychiatric treatments 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
- Patents treated on any other therapeutic clinical protocols within 30 days prior to step 2 registration
- Inability to undergo MRI (e.g., due to safety reasons, such as presence of a pacemaker, or severe claustrophobia)
- Postoperative tumor plus surgical bed size exceeds 5 cm in maximum diameter.
Sites / Locations
- University of Alabama at Birmingham Cancer Center
- Saint Joseph's Hospital and Medical Center
- Mayo Clinic Hospital in Arizona
- Mayo Clinic in Arizona
- Arizona Oncology Associates-West Orange Grove
- Banner University Medical Center - Tucson
- University of Arkansas for Medical Sciences
- Sutter Cancer Centers Radiation Oncology Services-Auburn
- AIS Cancer Center at San Joaquin Community Hospital
- Alta Bates Summit Medical Center-Herrick Campus
- Sutter Cancer Centers Radiation Oncology Services-Cameron Park
- Eden Hospital Medical Center
- Fresno Cancer Center
- Marin General Hospital
- Loma Linda University Medical Center
- Los Angeles County-USC Medical Center
- USC / Norris Comprehensive Cancer Center
- Cedars Sinai Medical Center
- Fremont - Rideout Cancer Center
- Memorial Medical Center
- Kaiser Permanente Oakland-Broadway
- Saint Joseph Hospital - Orange
- UC Irvine Health/Chao Family Comprehensive Cancer Center
- Palo Alto Medical Foundation Health Care
- 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
- University of California Davis Comprehensive Cancer Center
- South Sacramento Cancer Center
- California Pacific Medical Center-Pacific Campus
- Palo Alto Medical Foundation-Santa Cruz
- Kaiser Permanente Cancer Treatment Center
- Palo Alto Medical Foundation-Sunnyvale
- Sutter Cancer Centers Radiation Oncology Services-Vacaville
- John Muir Medical Center-Walnut Creek
- UCHealth Memorial Hospital Central
- Poudre Valley Hospital
- Hartford Hospital
- Boca Raton Regional Hospital
- University of Florida Health Science Center - Gainesville
- Baptist MD Anderson Cancer Center
- University of Florida Health Science Center - Jacksonville
- Baptist Medical Center South
- Miami Cancer Institute
- Moffitt Cancer Center
- Emory Proton Therapy Center
- Emory University Hospital Midtown
- Emory University Hospital/Winship Cancer Institute
- Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
- Saint Alphonsus Cancer Care Center-Boise
- Northwestern University
- John H Stroger Jr Hospital of Cook County
- Rush University Medical Center
- University of Chicago Comprehensive Cancer Center
- Decatur Memorial Hospital
- Northwestern Medicine Cancer Center Kishwaukee
- Northwestern Medicine Cancer Center Delnor
- UC Comprehensive Cancer Center at Silver Cross
- Advocate Lutheran General Hospital
- OSF Saint Francis Medical Center
- Memorial Medical Center
- Northwestern Medicine Cancer Center Warrenville
- Radiation Oncology Associates PC
- Parkview Hospital Randallia
- Parkview Regional Medical Center
- IU Health Methodist Hospital
- Community Cancer Center East
- Community Cancer Center South
- Community Cancer Center North
- IU Health Ball Memorial Hospital
- Mercy Hospital
- Iowa Methodist Medical Center
- University of Kansas Cancer Center
- University of Kansas Cancer Center-Overland Park
- Norton Hospital Pavilion and Medical Campus
- Ochsner Medical Center Jefferson
- Willis-Knighton Medical and Cancer Center
- Maryland Proton Treatment Center
- University of Maryland/Greenebaum Cancer Center
- UM Upper Chesapeake Medical Center
- Central Maryland Radiation Oncology in Howard County
- UM Baltimore Washington Medical Center/Tate Cancer Center
- Tufts Medical Center
- Massachusetts General Hospital Cancer Center
- Boston Medical Center
- Mass General/North Shore Cancer Center
- Lowell General Hospital
- Saint Joseph Mercy Hospital
- University of Michigan Comprehensive Cancer Center
- McLaren Cancer Institute-Bay City
- Beaumont Hospital - Dearborn
- Henry Ford Hospital
- McLaren Cancer Institute-Flint
- Spectrum Health at Butterworth Campus
- Trinity Health Grand Rapids Hospital
- West Michigan Cancer Center
- McLaren Cancer Institute-Lapeer Region
- Trinity Health Saint Mary Mercy Livonia Hospital
- McLaren Cancer Institute-Macomb
- McLaren Cancer Institute-Central Michigan
- McLaren Cancer Institute-Owosso
- McLaren Cancer Institute-Northern Michigan
- Saint Joseph Mercy Oakland
- William Beaumont Hospital-Royal Oak
- Lakeland Medical Center Saint Joseph
- William Beaumont Hospital - Troy
- Sanford Joe Lueken Cancer Center
- Saint Luke's Hospital of Duluth
- Mayo Clinic in Rochester
- Coborn Cancer Center at Saint Cloud Hospital
- Regions Hospital
- University of Mississippi Medical Center
- North Kansas City Hospital
- University of Kansas Cancer Center - North
- Washington University School of Medicine
- Billings Clinic Cancer Center
- Comprehensive Cancer Centers of Nevada
- Renown Regional Medical Center
- Saint Mary's Regional Medical Center
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
- Memorial Sloan Kettering Basking Ridge
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
- Rutgers Cancer Institute of New Jersey
- Capital Health Medical Center-Hopewell
- ProCure Proton Therapy Center-Somerset
- Virtua Voorhees
- Montefiore Medical Center - Moses Campus
- New York-Presbyterian/Brooklyn Methodist Hospital
- Memorial Sloan Kettering Commack
- Memorial Sloan Kettering Westchester
- Northwell Health/Center for Advanced Medicine
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
- Memorial Sloan Kettering Cancer Center
- Mission Hospital
- Novant Health Forsyth Medical Center
- Wake Forest University Health Sciences
- Sanford Bismarck Medical Center
- Sanford Roger Maris Cancer Center
- Cleveland Clinic Akron General
- UHHS-Chagrin Highlands Medical Center
- Geauga Hospital
- University of Cincinnati Cancer Center-UC Medical Center
- Case Western Reserve University
- Cleveland Clinic Cancer Center/Fairview Hospital
- Cleveland Clinic Foundation
- Ohio State University Comprehensive Cancer Center
- Riverside Methodist Hospital
- Mercy Cancer Center-Elyria
- Cleveland Clinic Cancer Center Independence
- Hillcrest Hospital Cancer Center
- UH Seidman Cancer Center at Lake Health Mentor Campus
- UH Seidman Cancer Center at Southwest General Hospital
- University Hospitals Parma Medical Center
- North Coast Cancer Care
- UH Seidman Cancer Center at Firelands Regional Medical Center
- Cleveland Clinic Cancer Center Strongsville
- University of Toledo
- University of Cincinnati Cancer Center-West Chester
- UHHS-Westlake Medical Center
- Cleveland Clinic Wooster Family Health and Surgery Center
- University of Oklahoma Health Sciences Center
- Willamette Valley Cancer Center
- Legacy Mount Hood Medical Center
- Legacy Good Samaritan Hospital and Medical Center
- Saint Luke's University Hospital-Bethlehem Campus
- Northeast Radiation Oncology Center
- Ephrata Cancer Center
- Adams Cancer Center
- UPMC Pinnacle Cancer Center/Community Osteopathic Campus
- Sechler Family Cancer Center
- University of Pennsylvania/Abramson Cancer Center
- Thomas Jefferson University Hospital
- Jefferson Torresdale Hospital
- Reading Hospital
- WellSpan Health-York Cancer Center
- Prisma Health Cancer Institute - Spartanburg
- Medical University of South Carolina
- Prisma Health Cancer Institute - Faris
- Prisma Health Cancer Institute - Eastside
- Self Regional Healthcare
- Prisma Health Cancer Institute - Greer
- Prisma Health Cancer Institute - Seneca
- Sanford USD Medical Center - Sioux Falls
- Tennessee Cancer Specialists-Dowell Springs
- Dell Seton Medical Center at The University of Texas
- Austin Cancer Centers-Central Austin
- Texas Oncology-Austin Midtown
- Texas Oncology - Central Austin Cancer Center
- Texas Oncology - South Austin Cancer Center
- Austin Cancer Centers-North
- UT Southwestern/Simmons Cancer Center-Dallas
- Texas Oncology - Denison Cancer Center
- Texas Oncology-Flower Mound
- Texas Oncology - Fort Worth Cancer Center
- University of Texas Medical Branch
- Memorial Hermann Memorial City Medical Center
- M D Anderson Cancer Center
- UTMB Cancer Center at Victory Lakes
- Covenant Medical Center-Lakeside
- Texas Oncology-Seton Williamson
- Texas Oncology - Round Rock Cancer Center
- University of Texas Health Science Center at San Antonio
- Texas Oncology Cancer Center Sugar Land
- Tyler Cancer Center
- Logan Regional Hospital
- Intermountain Medical Center
- McKay-Dee Hospital Center
- Utah Valley Regional Medical Center
- Saint George Regional Medical Center
- Huntsman Cancer Institute/University of Utah
- Central Vermont Medical Center/National Life Cancer Treatment
- University of Vermont Medical Center
- Norris Cotton Cancer Center-North
- Virginia Commonwealth University/Massey Cancer Center
- FHCC at Northwest Hospital
- SCCA Proton Therapy Center
- University of Washington Medical Center - Montlake
- Compass Oncology Vancouver
- Legacy Salmon Creek Hospital
- Wheeling Hospital/Schiffler Cancer Center
- Langlade Hospital and Cancer Center
- Gundersen Lutheran Medical Center
- University of Wisconsin Carbone Cancer Center
- Froedtert Menomonee Falls Hospital
- Medical College of Wisconsin
- UW Cancer Center at ProHealth Care
- Aspirus Regional Cancer Center
- BCCA-Vancouver Island Cancer Centre
- Ottawa Hospital and Cancer Center-General Campus
- Windsor Regional Cancer Centre
- CHUM - Hopital Notre-Dame
- McGill University Department of Oncology
- CHUM - Centre Hospitalier de l'Universite de Montreal
- The Research Institute of the McGill University Health Centre (MUHC)
- CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
- Saskatoon Cancer Centre
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Active Comparator
Experimental
Active Comparator
Experimental
Arm A1 (control)
Arm B (photon IMRT)
Arm A2 (control)
Arm C (proton beam radiation therapy)
Patients undergo standard-dose photon irradiation using 3D-CRT or IMRT QD, 5 days a week for 23 fractions plus a boost of 7 additional fractions. In all treatment arms, patients receive temozolomide PO QD on days 1-49 of radiation therapy. Beginning 4 weeks later, patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo dose-escalated and -intensified photon IMRT QD, 5 days a week for a total of 30 fractions. In all treatment arms, patients receive temozolomide PO QD on days 1-49 of radiation therapy. Beginning 4 weeks later, patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo standard-dose photon irradiation using 3D-CRT or IMRT as in Arm A1. In all treatment arms, patients receive temozolomide PO QD on days 1-49 of radiation therapy. Beginning 4 weeks later, patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo dose-escalated and -intensified proton beam therapy QD, 5 days a week for a total of 30 fractions. In all treatment arms, patients receive temozolomide PO QD on days 1-49 of radiation therapy. Beginning 4 weeks later, patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.