AzTrials
AzTrials

GlioblastomaPhase 2NCT02179086

Dose-Escalated Photon IMRT or Proton Beam Radiation Therapy Versus Standard-Dose Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma

A Phase 2 study testing Photon Beam Radiation Therapy, Proton Beam Radiation Therapy and Temozolomide in people with Glioblastoma, run by NRG Oncology at 237 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This randomized phase II trial studies how well dose-escalated photon intensity-modulated radiation therapy (IMRT) or proton beam radiation therapy works compared with standard-dose radiation therapy when given with temozolomide in patients with newly diagnosed glioblastoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma
What is being tested?
Photon Beam Radiation Therapy, Proton Beam Radiation Therapy and Temozolomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
624 participants
Where
237 sitesin 2 countries
Study dates
4 Dec 2014to 7 Jul 2030
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • PRIOR TO STEP 1 REGISTRATION
  • A diagnostic contrast-enhanced MRI (no other scan type allowed) of the brain must be performed postoperatively; the residual enhancing tumor and/or resection cavity must have a maximal diameter of 5 cm or less; 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
  • The postoperative brain MRI should be obtained within 72 hours of resection; if it is not obtained within 72 hours post-resection, then an MRI obtained 2 weeks or longer after surgery is required and can be utilized to ensure maximal diameter of residual tumor and/or resection cavity is 5 cm or less
  • For cases where a gross total resection of enhancing tumor is performed, but postoperative surgical cavity is NOT identifiable, the patient will be excluded from the trial
  • Tumor tissue must be available for submission for central pathology review
  • Timing requirements:
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  • If MGMT has been assessed locally by LabCorps or MD Anderson Cancer Center Molecular Diagnostics Lab (MDACC-MDL):
  • Tissue for central pathology review and central MGMT assessment and the official LabCorps or MDACC-MDL MGMT result must be received by the NRG Oncology Biospecimen Bank on or before postoperative calendar day 40
  • The site's local MGMT report from LabCorp or MDACC-MDL will then be used to stratify the patient; a post-stratification MGMT central review will be performed, but step 2 registration and protocol treatment can proceed without central review of MGMT
  • Patients whose tissue for central pathology review and official LabCorps or MDACC-MDL MGMT result cannot be received by NRG Oncology Biospecimen Bank on or before 40 calendar days after surgery may NOT enroll on this trial, as central pathology review and stratification will not be complete in time for the patient to start treatment within 49 calendar days following surgery
  • If MGMT has not been assessed locally by LabCorps or MDACC-MDL:
  • Tissue for central pathology review and central MGMT assessment must be received by the NRG Oncology Biospecimen Bank on or before postoperative calendar day 30
  • Central MGMT analysis will be performed at MDACC-MDL and used for patient stratification; results will be conveyed to NRG Oncology within 10 business days of receipt of the tissue
  • Patients who have not had local MGMT assessment by LabCorps or MDACC-MDL and whose tissue for central pathology review cannot be received by NRG Oncology Biospecimen Bank on or before 30 calendar days after surgery may NOT enroll on this trial, as central pathology review and stratification will not be complete in time for the patient to start treatment within 49 calendar days following surgery
  • Tissue Requirements:
  • Patients must have at least 1 block of tumor tissue; submission of 2 blocks is strongly encouraged to maximize the chances of eligibility; in total, at least 1 cubic centimeter of tissue composed primarily of tumor must be present
  • Submission of an accompanying hematoxylin and eosin H\&E slide(s) is MANDATORY
  • Diagnosis must be made by surgical excision, either partial or complete; stereotactic biopsy and cavitronic ultrasonic surgical (CUSA) techniques are not allowed
  • The 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 central analysis of MGMT status
  • 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
  • Complete blood count (CBC)/differential obtained within 28 days prior to step 2 registration
  • Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (obtained within 28 days prior to step 2 registration)
  • Platelets >= 100,000 cells/mm^3 (obtained within 28 days prior to step 2 registration)
  • Hemoglobin >= 10.0 g/dl (obtained within 28 days prior to step 2 registration) (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) (within 28 days prior to step 2 registration)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN (within 28 days prior to step 2 registration)
  • Negative serum pregnancy test obtained for females of child-bearing potential within 28 days prior to step 2 registration
  • As of Amendment 2, if the registering site is a photon center (registering patients to group I), the patient must agree to participate in the advanced imaging sub-study

Who cannot join

  • 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
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  • 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 (Note: EKG to be performed only if clinical suspicion of cardiac issue)
  • 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; the need to exclude patients with AIDS from this protocol is because the treatments involved in this protocol may be significantly immunosuppressive with potentially fatal outcomes in patients already immunosuppressed
  • 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; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
  • Patients 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

Trial locations and contacts

237 sites in 2 countries.

237 sites in 2 countries

United States230 sites

  • Cleveland Clinic Akron General

    Akron, Ohio, 44307

  • Trinity Health Saint Joseph Mercy Hospital Ann Arbor

    Ann Arbor, Michigan, 48106

  • University of Michigan Rogel Cancer Center

    Ann Arbor, Michigan, 48109

  • Langlade Hospital and Cancer Center

    Antigo, Wisconsin, 54409

  • Mission Hospital

    Asheville, North Carolina, 28801

  • Emory Proton Therapy Center

    Atlanta, Georgia, 30308

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Sutter Cancer Centers Radiation Oncology Services-Auburn

    Auburn, California, 95603

  • Dell Seton Medical Center at The University of Texas

    Austin, Texas, 78701

  • Austin Cancer Centers-Central Austin

    Austin, Texas, 78702

  • Texas Oncology-Austin Midtown

    Austin, Texas, 78705

  • Texas Oncology - Central Austin Cancer Center

    Austin, Texas, 78731

  • Texas Oncology - South Austin Cancer Center

    Austin, Texas, 78745

  • Austin Cancer Centers-North

    Austin, Texas, 78758

  • AIS Cancer Center at San Joaquin Community Hospital

    Bakersfield, California, 93301

  • Maryland Proton Treatment Center

    Baltimore, Maryland, 21201

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey, 07920

  • McLaren Cancer Institute-Bay City

    Bay City, Michigan, 48706

  • UHHS-Chagrin Highlands Medical Center

    Beachwood, Ohio, 44122

  • UM Upper Chesapeake Medical Center

    Bel Air, Maryland, 21014

  • Sanford Joe Lueken Cancer Center

    Bemidji, Minnesota, 56601

  • Alta Bates Summit Medical Center-Herrick Campus

    Berkeley, California, 94704

  • Central Vermont Medical Center/National Life Cancer Treatment

    Berlin Corners, Vermont, 05602

  • Saint Luke's University Hospital-Bethlehem Campus

    Bethlehem, Pennsylvania, 18015

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Sanford Bismarck Medical Center

    Bismarck, North Dakota, 58501

  • Boca Raton Regional Hospital

    Boca Raton, Florida, 33486

  • Prisma Health Cancer Institute - Spartanburg

    Boiling Springs, South Carolina, 29316

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Boston Medical Center

    Boston, Massachusetts, 02118

  • New York-Presbyterian/Brooklyn Methodist Hospital

    Brooklyn, New York, 11215

  • University of Vermont Medical Center

    Burlington, Vermont, 05401

  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park

    Cameron Park, California, 95682

  • Eden Hospital Medical Center

    Castro Valley, California, 94546

  • Mercy Hospital

    Cedar Rapids, Iowa, 52403

  • Geauga Hospital

    Chardon, Ohio, 44024

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Northwestern University

    Chicago, Illinois, 60611

  • John H Stroger Jr Hospital of Cook County

    Chicago, Illinois, 60612

  • Rush MD Anderson Cancer Center

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • University of Cincinnati Cancer Center-UC Medical Center

    Cincinnati, Ohio, 45219

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Cleveland Clinic Cancer Center/Fairview Hospital

    Cleveland, Ohio, 44111

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • UCHealth Memorial Hospital Central

    Colorado Springs, Colorado, 80909

  • Central Maryland Radiation Oncology in Howard County

    Columbia, Maryland, 21044

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Mass General/North Shore Cancer Center

    Danvers, Massachusetts, 01923

  • Corewell Health Dearborn Hospital

    Dearborn, Michigan, 48124

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Northwestern Medicine Cancer Center Kishwaukee

    DeKalb, Illinois, 60115

  • Texas Oncology - Denison Cancer Center

    Denison, Texas, 75020

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Saint Luke's Hospital of Duluth

    Duluth, Minnesota, 55805

  • Northeast Radiation Oncology Center

    Dunmore, Pennsylvania, 18512

  • Mercy Cancer Center-Elyria

    Elyria, Ohio, 44035

  • Ephrata Cancer Center

    Ephrata, Pennsylvania, 17522

  • Willamette Valley Cancer Center

    Eugene, Oregon, 97401

  • Sanford Roger Maris Cancer Center

    Fargo, North Dakota, 58122

  • McLaren Cancer Institute-Flint

    Flint, Michigan, 48532

  • Texas Oncology-Flower Mound

    Flower Mound, Texas, 75028

  • Poudre Valley Hospital

    Fort Collins, Colorado, 80524

  • Radiation Oncology Associates PC

    Fort Wayne, Indiana, 46804

  • Parkview Hospital Randallia

    Fort Wayne, Indiana, 46805

  • Parkview Regional Medical Center

    Fort Wayne, Indiana, 46845

  • Texas Oncology - Fort Worth Cancer Center

    Fort Worth, Texas, 76104

  • Fresno Cancer Center

    Fresno, California, 93720

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • University of Texas Medical Branch

    Galveston, Texas, 77555-0565

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • Adams Cancer Center

    Gettysburg, Pennsylvania, 17325

  • UM Baltimore Washington Medical Center/Tate Cancer Center

    Glen Burnie, Maryland, 21061

  • Corewell Health Grand Rapids Hospitals - Butterworth Hospital

    Grand Rapids, Michigan, 49503

  • Trinity Health Grand Rapids Hospital

    Grand Rapids, Michigan, 49503

  • Marin General Hospital

    Greenbrae, California, 94904

  • Prisma Health Cancer Institute - Faris

    Greenville, South Carolina, 29605

  • Prisma Health Cancer Institute - Eastside

    Greenville, South Carolina, 29615

  • Self Regional Healthcare

    Greenwood, South Carolina, 29646

  • Prisma Health Cancer Institute - Greer

    Greer, South Carolina, 29650

  • Legacy Mount Hood Medical Center

    Gresham, Oregon, 97030

  • UPMC Pinnacle Cancer Center/Community Osteopathic Campus

    Harrisburg, Pennsylvania, 17109

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

  • Hartford Hospital

    Hartford, Connecticut, 06102

  • Memorial Hermann Memorial City Medical Center

    Houston, Texas, 77024

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Cleveland Clinic Cancer Center Independence

    Independence, Ohio, 44131

  • IU Health Methodist Hospital

    Indianapolis, Indiana, 46202

  • Community Cancer Center East

    Indianapolis, Indiana, 46219

  • Community Cancer Center South

    Indianapolis, Indiana, 46227

  • Community Cancer Center North

    Indianapolis, Indiana, 46256

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Baptist MD Anderson Cancer Center

    Jacksonville, Florida, 32207

  • University of Florida Health Science Center - Jacksonville

    Jacksonville, Florida, 32209

  • Baptist Medical Center South

    Jacksonville, Florida, 32258

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • North Kansas City Hospital

    Kansas City, Missouri, 64116

  • University of Kansas Cancer Center - North

    Kansas City, Missouri, 64154

  • Tennessee Cancer Specialists-Dowell Springs

    Knoxville, Tennessee, 37909

  • Gundersen Lutheran Medical Center

    La Crosse, Wisconsin, 54601

  • Northwell Health/Center for Advanced Medicine

    Lake Success, New York, 11042

  • McLaren Cancer Institute-Lapeer Region

    Lapeer, Michigan, 48446

  • Comprehensive Cancer Centers of Nevada

    Las Vegas, Nevada, 89148

  • UTMB Cancer Center at Victory Lakes

    League City, Texas, 77573

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

  • Sechler Family Cancer Center

    Lebanon, Pennsylvania, 17042

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Trinity Health Saint Mary Mercy Livonia Hospital

    Livonia, Michigan, 48154

  • Logan Regional Hospital

    Logan, Utah, 84321

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • Norton Hospital Pavilion and Medical Campus

    Louisville, Kentucky, 40202

  • Lowell General Hospital

    Lowell, Massachusetts, 01854

  • Covenant Medical Center-Lakeside

    Lubbock, Texas, 79410

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • Fremont - Rideout Cancer Center

    Marysville, California, 95901

  • Hillcrest Hospital Cancer Center

    Mayfield Heights, Ohio, 44124

  • Froedtert Menomonee Falls Hospital

    Menomonee Falls, Wisconsin, 53051

  • UH Seidman Cancer Center at Lake Health Mentor Campus

    Mentor, Ohio, 44060

  • Miami Cancer Institute

    Miami, Florida, 33176

  • UH Seidman Cancer Center at Southwest General Hospital

    Middleburg Heights, Ohio, 44130

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Memorial Medical Center

    Modesto, California, 95355

  • McLaren Cancer Institute-Macomb

    Mount Clemens, Michigan, 48043

  • McLaren Cancer Institute-Central Michigan

    Mount Pleasant, Michigan, 48858

  • IU Health Ball Memorial Hospital

    Muncie, Indiana, 47303

  • Intermountain Medical Center

    Murray, Utah, 84107

  • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

    New Brunswick, New Jersey, 08903

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • UC Comprehensive Cancer Center at Silver Cross

    New Lenox, Illinois, 60451

  • Ochsner Medical Center Jefferson

    New Orleans, Louisiana, 70121

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Kaiser Permanente Oakland-Broadway

    Oakland, California, 94611

  • McKay-Dee Hospital Center

    Ogden, Utah, 84403

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Saint Joseph Hospital - Orange

    Orange, California, 92868

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • University of Kansas Cancer Center-Overland Park

    Overland Park, Kansas, 66210

  • McLaren Cancer Institute-Owosso

    Owosso, Michigan, 48867

  • Palo Alto Medical Foundation Health Care

    Palo Alto, California, 94301

  • Advocate Lutheran General Hospital

    Park Ridge, Illinois, 60068

  • University Hospitals Parma Medical Center

    Parma, Ohio, 44129

  • Capital Health Medical Center-Hopewell

    Pennington, New Jersey, 08534

  • OSF Saint Francis Medical Center

    Peoria, Illinois, 61637

  • McLaren Cancer Institute-Northern Michigan

    Petoskey, Michigan, 49770

  • University of Pennsylvania/Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Jefferson Torresdale Hospital

    Philadelphia, Pennsylvania, 19114

  • Saint Joseph's Hospital and Medical Center

    Phoenix, Arizona, 85013

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • Pomona Valley Hospital Medical Center

    Pomona, California, 91767

  • Trinity Health Saint Joseph Mercy Oakland Hospital

    Pontiac, Michigan, 48341

  • Legacy Good Samaritan Hospital and Medical Center

    Portland, Oregon, 97210

  • Utah Valley Regional Medical Center

    Provo, Utah, 84604

  • Kaiser Permanente-Rancho Cordova Cancer Center

    Rancho Cordova, California, 95670

  • Renown Regional Medical Center

    Reno, Nevada, 89502

  • Saint Mary's Regional Medical Center

    Reno, Nevada, 89503

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Rohnert Park Cancer Center

    Rohnert Park, California, 94928

  • Sutter Cancer Centers Radiation Oncology Services-Roseville

    Roseville, California, 95661

  • The Permanente Medical Group-Roseville Radiation Oncology

    Roseville, California, 95678

  • Texas Oncology-Seton Williamson

    Round Rock, Texas, 78665

  • Texas Oncology - Round Rock Cancer Center

    Round Rock, Texas, 78681

  • Corewell Health William Beaumont University Hospital

    Royal Oak, Michigan, 48073

  • Sutter Medical Center Sacramento

    Sacramento, California, 95816

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • South Sacramento Cancer Center

    Sacramento, California, 95823

  • Coborn Cancer Center at Saint Cloud Hospital

    Saint Cloud, Minnesota, 56303

  • Dartmouth Cancer Center - North

    Saint Johnsbury, Vermont, 05819

  • Corewell Health Lakeland Hospitals - Saint Joseph Hospital

    Saint Joseph, Michigan, 49085

  • Regions Hospital

    Saint Paul, Minnesota, 55101

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • California Pacific Medical Center-Pacific Campus

    San Francisco, California, 94115

  • North Coast Cancer Care

    Sandusky, Ohio, 44870

  • UH Seidman Cancer Center at Firelands Regional Medical Center

    Sandusky, Ohio, 44870

  • Palo Alto Medical Foundation-Santa Cruz

    Santa Cruz, California, 95065

  • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler

    Savannah, Georgia, 31405

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • FHCC at Northwest Hospital

    Seattle, Washington, 98133

  • FHCC Proton Therapy Center

    Seattle, Washington, 98133

  • University of Washington Medical Center - Montlake

    Seattle, Washington, 98195

  • Prisma Health Cancer Institute - Seneca

    Seneca, South Carolina, 29672

  • Willis-Knighton Medical and Cancer Center

    Shreveport, Louisiana, 71103

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota, 57117-5134

  • ProCure Proton Therapy Center-Somerset

    Somerset, New Jersey, 08873

  • Kaiser Permanente Cancer Treatment Center

    South San Francisco, California, 94080

  • Springfield Memorial Hospital

    Springfield, Illinois, 62781

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Saint George Regional Medical Center

    St. George, Utah, 84770

  • Cleveland Clinic Cancer Center Strongsville

    Strongsville, Ohio, 44136

  • Texas Oncology Cancer Center Sugar Land

    Sugar Land, Texas, 77479

  • Palo Alto Medical Foundation-Sunnyvale

    Sunnyvale, California, 94086

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

  • University of Toledo

    Toledo, Ohio, 43614

  • Corewell Health Beaumont Troy Hospital

    Troy, Michigan, 48085

  • Arizona Oncology Associates-West Orange Grove

    Tucson, Arizona, 85704

  • Banner University Medical Center - Tucson

    Tucson, Arizona, 85719

  • Texas Oncology - Tyler

    Tyler, Texas, 75702

  • Compass Oncology Vancouver

    Vancouver, Washington, 98684

  • Legacy Salmon Creek Hospital

    Vancouver, Washington, 98686

  • Virtua Voorhees

    Voorhees Township, New Jersey, 08043

  • John Muir Medical Center-Walnut Creek

    Walnut Creek, California, 94598

  • Northwestern Medicine Cancer Center Warrenville

    Warrenville, Illinois, 60555

  • UW Cancer Center at ProHealth Care

    Waukesha, Wisconsin, 53188

  • Aspirus Regional Cancer Center

    Wausau, Wisconsin, 54401

  • University of Cincinnati Cancer Center-West Chester

    West Chester, Ohio, 45069

  • Reading Hospital

    West Reading, Pennsylvania, 19611

  • UHHS-Westlake Medical Center

    Westlake, Ohio, 44145

  • Wheeling Hospital/Schiffler Cancer Center

    Wheeling, West Virginia, 26003

  • Novant Health Forsyth Medical Center

    Winston-Salem, North Carolina, 27103

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

  • Cleveland Clinic Wooster Family Health and Surgery Center

    Wooster, Ohio, 44691

  • WellSpan Health-York Cancer Center

    York, Pennsylvania, 17403

Other trials in United States

Canada7 sites

  • CHUM - Centre Hospitalier de l'Universite de Montreal

    Montreal, Quebec, H2X 3E4

  • The Research Institute of the McGill University Health Centre (MUHC)

    Montreal, Quebec, H3H 2R9

  • Ottawa Hospital and Cancer Center-General Campus

    Ottawa, Ontario, K1H 8L6

  • CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)

    Québec, Quebec, G1R 2J6

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan, S7N 4H4

  • BCCA-Vancouver Island Cancer Centre

    Victoria, British Columbia, V8R 6V5

  • Windsor Regional Cancer Centre

    Windsor, Ontario, N8W 2X3

Other trials in Canada

About this study

Official title: Randomized Phase II Trial of Hypofractionated Dose-Escalated Photon IMRT or Proton Beam Therapy Versus Conventional Photon Irradiation With Concomitant and Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma

This randomized phase II trial studies how well dose-escalated photon intensity-modulated radiation therapy (IMRT) or proton beam radiation therapy works compared with standard-dose radiation therapy when given with temozolomide in patients with newly diagnosed glioblastoma. Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells and shrink tumors. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs, such as temozolomide, may make tumor cells more sensitive to radiation therapy. It is not yet known whether dose-escalated photon IMRT or proton beam radiation therapy is more effective than standard-dose radiation therapy with temozolomide in treating glioblastoma.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine if dose-escalated and -intensified photon IMRT or proton beam therapy (using a dose-per-fraction escalation with simultaneous integrated boost) with concomitant and adjuvant temozolomide improves overall survival, as compared to standard-dose photon irradiation with concomitant and adjuvant temozolomide.

SECONDARY OBJECTIVES:

  1. To indirectly compare dose-escalated and -intensified photon IMRT to dose-escalated and -intensified proton beam therapy in terms of overall survival.

II. To indirectly compare and record toxicities of dose-escalated and -intensified photon IMRT versus dose-escalated and -intensified proton beam therapy and directly compare the toxicities of these approaches versus standard-dose photon irradiation on the backbone of concomitant and adjuvant temozolomide.

III. To determine if dose-escalated and -intensified IMRT or proton beam therapy (using a dose-per-fraction escalation with simultaneous integrated boost) with concomitant and adjuvant temozolomide improves perceived cognitive symptom severity, as compared to standard-dose photon irradiation with concomitant and adjuvant temozolomide.

IV. To determine if dose-escalated and -intensified photon IMRT or proton beam therapy (using a dose-per-fraction escalation with simultaneous integrated boost) with concomitant and adjuvant temozolomide improves neurocognitive function, as compared to standard-dose photon irradiation with concomitant and adjuvant temozolomide.

  1. To indirectly determine if dose-escalated and -intensified proton beam therapy with concomitant and adjuvant temozolomide improves perceived cognitive symptom severity, as compared to dose-escalated and -intensified photon IMRT, and to directly compare symptom burden with these approaches versus standard-dose photon irradiation on the backbone of concomitant and adjuvant temozolomide.

VI. To indirectly determine if dose-escalated and -intensified proton beam therapy with concomitant and adjuvant temozolomide improves neurocognitive function, as compared to dose-escalated and -intensified photon IMRT, and to directly compare neurocognitive function with these approaches versus standard-dose photon irradiation on the backbone of concomitant and adjuvant temozolomide.

EXPLORATORY OBJECTIVES:

  1. Tissue banking for future translational science projects that will be determined based on the state of the science at the time the primary endpoint is reported and will be submitted to National Cancer Institute (NCI) for review and approval.

II. To prospectively compare CD4 lymphopenia between dose-escalated and intensified proton beam therapy, dose-escalated and -intensified photon IMRT, and standard-dose photon irradiation and determine whether CD4 lymphopenia impacts overall survival.

III. To explore the most appropriate and clinically relevant technological parameters to ensure quality and effectiveness throughout radiation therapy processes, including imaging, simulation, patient immobilization, target and critical structure definition, treatment planning, image guidance and delivery.

IIIa. To establish feasibility and clinical relevancy of quality assurance guidelines.

IIIb. To evaluate efficacy of quality assurance tools. IV. To explore the most appropriate and clinically relevant advanced and standard magnetic resonance imaging (MRI) imaging parameters.

IVa. To evaluate the feasibility of differentiating pseudo-progression and true progression in a multi institutional setting using magnetic resonance (MR) diffusion and perfusion imaging.

IVb. To evaluate for early, imaging biomarkers of response and overall survival.

OUTLINE: Patients are assigned to 1 of 2 groups depending on enrolling institution. Within each group, patients will be randomized 1:2 in favor of the experimental arms.

GROUP 1 = PHOTON IMRT CENTERS. GROUP 2 = PROTON CENTERS.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter.

Conditions
Glioblastoma
Being tested
Photon Beam Radiation Therapy, Proton Beam Radiation Therapy, Temozolomide
Medical subject headings
Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Photon Beam Radiation TherapyRadiation

    Also called External beam radiation therapy using photons (procedure), Photon, Photon EBRT, Photon External Beam Radiotherapy

    daily fractions

  • Proton Beam Radiation TherapyRadiation

    Also called External beam radiation therapy protons (procedure), External Beam Radiotherapy (protons), PBRT, Proton

    Undergo dose-escalated and -intensified proton beam radiation therapy

  • TemozolomideDrug

    Also called CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831

    tablet

Study groups in NCT02179086
Study groupRoleWhat they receive
Group 1 - Standard RT (Photon) (Arm A1)Active comparatorGroup 1 = Photon IMRT centers. Participants undergo standard-dose postoperative photon radiotherapy using 3-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) administered once daily, 5 days per week. Treatment consists of 46 Gy in 23 fractions followed by a sequential boost to a total dose of 60 Gy in 30 fractions. Participants receive concurrent temozolomide orally once daily during radiotherapy for up to 49 days and adjuvant temozolomide orally once daily on days 1-5 of each 28-day cycle for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Radiation: Photon Beam Radiation Therapy; Drug: Temozolomide
Group 2 - Standard RT (Proton) (Arm A2)Active comparatorGroup 2 = Proton centers. Participants undergo the same standard-dose postoperative radiotherapy regimen described for Arm A1 but delivered using proton beam therapy. Participants receive concurrent and adjuvant temozolomide as described for Arm A1.
Receives: Radiation: Photon Beam Radiation Therapy; Drug: Temozolomide
Group 1 - Intensified RT (Photon) (Arm B)ExperimentalGroup 1 = Photon IMRT centers. 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 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Radiation: Photon Beam Radiation Therapy; Drug: Temozolomide
Group 2 - Intensified RT (Proton) (Arm C)ExperimentalGroup 2 = Proton centers. Participants undergo the same radiotherapy regimen described for Arm B but delivered using proton beam therapy. The elective target volume receives 50 Gy(RBE) in 30 fractions, and the boost target volume receives 75 Gy(RBE) in 30 fractions. Participants receive concurrent and adjuvant temozolomide as described for Arm A1.
Receives: Radiation: Proton Beam Radiation Therapy; Drug: Temozolomide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Median Survival Time (Within Center Group)

    Comparisons occur between standard vs. intensified RT arms within group (Group 1: photon IMRT centers; Group 2: proton centers). Median survival times were estimated using the Kaplan-Meier method, censoring participants alive at the time of analysis. Comparisons occur between standard vs. intensified RT arms within group (Group 1: photon IMRT centers; Group 2: proton centers)

    Measured: Randomization to death or last follow-up. Median follow-up at time of analysis was 16.2 months for Group 1 and 18.3 months for Group 2.

Secondary outcomes (7)

  1. Median Survival Time (Between Experimental Arms)

    Per the protocol, this outcome measure would be addressed only if both experimental (intensified RT) arms were statistically significantly different from their respective control (standard RT) arms, as defined in the primary outcome measure. If that condition were satisfied, the experimental (intensified RT) arms from each group would be compared with each other. Median survival times would be estimated using the Kaplan-Meier method, censoring participants alive at the time of analysis.

    Measured: Randomization to death or last follow-up. Median follow-up at time of analysis was 16.2 months for Group 1 and 18.3 months for Group 2.

  2. Median Progression-free Survival Time

    Progression is defined as any of the following: ≥25% increase in sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration, with the treating institution encouraged to differentiate progression from pseudoprogression and radionecrosis using surgical resection, biopsy, and alternative imaging accordingly. Median progression-free survival times were estimated using the Kaplan-Meier method, censoring participants alive at the time of analysis. Comparisons occur between standard vs. intensified RT arms within group (Group 1: photon IMRT centers; Group 2: proton centers).

    Measured: Randomization to progression, death, or last follow-up, whichever occurs first. Median follow-up at time of analysis was 16.2 months for Group 1 and 18.3 months for Group 2.

  3. Proportion of Participants With a Grade 3 or Higher Adverse Event

    Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Proportions were estimated using an exact binomial distribution. Comparisons occur between standard vs. intensified RT arms within group (Group 1: photon IMRT centers; Group 2: proton centers)

    Measured: Randomization to death or last follow-up. Median follow-up at time of analysis was 16.2 months for Group 1 and 18.3 months for Group 2.

  4. Change From Baseline in the M.D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Factor Score After Cycle 3

    The MD Anderson Symptom Inventory for brain tumor (MDASI-BT) is a 28-item multi-symptom patient-reported outcome measure assessing the severity of symptoms experienced by cancer patients and the interference with daily living caused by these symptoms, with 9 items specific to brain tumors. Each item ranges from 0 (best condition) to 10 (worst condition). A subscale score (Cognitive Factor) is the average of the subscale items, given that a specified minimum numbers of items were completed. A score worse than baseline by at least one is considered deterioration. Change is calculated as time point - baseline such that a positive change value indicates worse symptoms compared to baseline. Comparisons occur between standard vs. intensified RT arms within group (Group 1: photon IMRT centers; Group 2: proton centers).

    Measured: Baseline and end of cycle 3 of adjuvant temozolomide (approximately 24 weeks after start of chemoradiation)

  5. Change From Baseline in the M.D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Factor Score After Cycle 12

    The MD Anderson Symptom Inventory for brain tumor (MDASI-BT) is a 28-item multi-symptom patient-reported outcome measure assessing the severity of symptoms experienced by cancer patients and the interference with daily living caused by these symptoms, with 9 items specific to brain tumors. Each item ranges from 0 (best condition) to 10 (worst condition). A subscale score (Cognitive Factor) is the average of the subscale items, given that a specified minimum numbers of items were completed. A score worse than baseline by at least one is considered deterioration. Change is calculated as time point - baseline such that a positive change value indicates worse symptoms compared to baseline. Comparisons occur between standard vs. intensified RT arms within group (Group 1: photon IMRT centers; Group 2: proton centers).

    Measured: Baseline and end of cycle 12 of adjuvant temozolomide (approximately 60 weeks after start of chemoradiation)

  6. Change From Baseline in the Clinical Trial Battery Composite Standardized Score at End of Cycle 3

    The Clinical Trial Battery Composite Standardized Score is calculated as the arithmetic mean of multiple standardized neurocognitive test scores assessing memory, processing speed, executive function, and verbal fluency. Scores are standardized (z-scores) adjusted for age, education, and gender, with a mean of 0 and standard deviation of 1. A participant must have the majority of component scores available to calculate the composite. Possible scores are standardized z-scores that typically range from approximately -3 to +3, with higher scores indicating a better outcome. Change is calculated as time point minus baseline such that a positive change value indicates improvement and a negative change value indicates decline. Comparisons are made between standard-dose and intensified radiation therapy arms within group (Group 1: photon IMRT centers; Group 2: proton centers).

    Measured: Baseline and end of cycle 3 of adjuvant temozolomide (approximately 24 weeks after start of chemoradiation)

  7. Change From Baseline in the Clinical Trial Battery Composite Standardized Score at End of Cycle 12

    The Clinical Trial Battery Composite Standardized Score is calculated as the arithmetic mean of multiple standardized neurocognitive test scores assessing memory, processing speed, executive function, and verbal fluency. Scores are standardized (z-scores) adjusted for age, education, and gender, with a mean of 0 and standard deviation of 1. A participant must have the majority of component scores available to calculate the composite. Possible scores are standardized z-scores that typically range from approximately -3 to +3, with higher scores indicating a better outcome. Change is calculated as time point minus baseline such that a positive change value indicates improvement and a negative change value indicates decline. Comparisons are made between standard-dose and intensified radiation therapy arms within group (Group 1: photon IMRT centers; Group 2: proton centers).

    Measured: Baseline and end of cycle 3 of adjuvant temozolomide (approximately 24 weeks after start of chemoradiation)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jul 2014 (estimated)
  2. Study start4 Dec 2014
  3. Primary completion7 Jul 2025
  4. Study completion7 Jul 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Participants were randomized within each group in a 1:2 ratio to standard-dose and intensified radiation therapy arms.
Masking
None (open label)
Enrolment
624 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02179086
Sponsor's protocol ID
NRG-BN001
Other IDs
NCI-2014-01072, NRG-BN001, NRG-BN001, P50CA127001, U10CA180868
Status last verified
Sep 2026
First submitted
27 Jun 2014
Last updated
1 Oct 2026
Data monitoring committee
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Photon Beam Radiation Therapy, Proton Beam Radiation Therapy and Temozolomide in people with Glioblastoma, run by NRG Oncology at 237 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 36 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 237 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Median Survival Time (Within Center Group) (time frame: Randomization to death or last follow-up. Median follow-up at time of analysis was 16.2 months for Group 1 and 18.3 months for Group 2.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02179086.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2026.

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