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

• ClinicalTrials.gov Identifier: NCT02179086
• Recruitment Status: Active, not recruiting
• First Posted: July 1, 2014
• Last Update Posted: May 19, 2022
• Sponsor: NRG Oncology
• Collaborators: National Cancer Institute (NCI); Radiation Therapy Oncology Group
• Information provided by (Responsible Party): NRG Oncology

Study Description

Brief 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. 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.

Condition or disease	Intervention/treatment	Phase
Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma	Radiation: 3-dimensional conformal radiation therapy; Radiation: intensity-modulated radiation therapy; Radiation: photon beam radiation therapy; Radiation: proton beam radiation therapy; Drug: temozolomide; Other: laboratory biomarker analysis	Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. 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:

I. 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 photon 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.

V. 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.

TERTIARY OBJECTIVES:

I. 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.

• To establish feasibility and clinical relevancy of quality assurance guidelines.
• To evaluate efficacy of quality assurance tools.

IV. To explore the most appropriate and clinically relevant advanced and standard MRI imaging parameters.

• To evaluate the feasibility of differentiating pseudo-progression and true progression in a multi institutional setting using MR diffusion and perfusion imaging.
• 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 I (PHOTON IMRT CENTERS): Patients are randomized to 1 of 2 treatment arms.

ARM A1: Patients undergo standard-dose photon irradiation using 3-dimensional conformal radiation therapy (3D-CRT) or IMRT once daily (QD), 5 days a week for 23 fractions plus a boost of 7 additional fractions.

ARM B: Patients undergo dose-escalated and -intensified photon IMRT QD, 5 days a week for a total of 30 fractions.

GROUP II (PROTON CENTERS): Patients are randomized to 1 of 2 treatment arms.

ARM A2: Patients undergo standard-dose photon irradiation using 3D-CRT or IMRT as in Arm A1.

ARM C: Patients undergo dose-escalated and -intensified proton beam radiation therapy QD, 5 days a week for a total of 30 fractions.

In all treatment arms, patients receive temozolomide orally (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.

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 624 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 27, 2014
• Estimated Primary Completion Date: May 2024
• Estimated Study Completion Date: May 2026

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Arm A1 (control); 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.	Radiation: 3-dimensional conformal radiation therapy; Undergo standard-dose 3D-CRT; Other Names: 3D conformal radiation therapy; 3D-CRT; Radiation: intensity-modulated radiation therapy; Undergo standard-dose IMRT; Other Name: IMRT; Drug: temozolomide; Given PO; Other Names: SCH 52365; Temodal; Temodar; TMZ; Other: laboratory biomarker analysis; Correlative studies
Experimental: Arm B (photon IMRT); 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.	Radiation: photon beam radiation therapy; Undergo dose-escalated and -intensified photon IMRT; Radiation: intensity-modulated radiation therapy; Undergo dose-escalated and -intensified photon IMRT; Other Name: IMRT; Drug: temozolomide; Given PO; Other Names: SCH 52365; Temodal; Temodar; TMZ; Other: laboratory biomarker analysis; Correlative studies
Active Comparator: Arm A2 (control); 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.	Radiation: 3-dimensional conformal radiation therapy; Undergo standard-dose 3D-CRT; Other Names: 3D conformal radiation therapy; 3D-CRT; Radiation: intensity-modulated radiation therapy; Undergo standard-dose IMRT; Other Name: IMRT; Drug: temozolomide; Given PO; Other Names: SCH 52365; Temodal; Temodar; TMZ; Other: laboratory biomarker analysis; Correlative studies
Experimental: Arm C (proton beam radiation therapy); 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.	Radiation: proton beam radiation therapy; Undergo dose-escalated and -intensified proton beam radiation therapy; Drug: temozolomide; Given PO; Other Names: SCH 52365; Temodal; Temodar; TMZ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures :

1. Overall survival (OS) compared between dose-escalated and -intensified photon IMRT or proton beam therapy with concomitant and adjuvant temozolomide and the standard-dose photon irradiation with concomitant and adjuvant temozolomide [ Time Frame: Date of randomization to the date of death due to any cause, assessed up to 5 years ]
   OS rate will be estimated using the Kaplan-Meier method, and differences between treatment arms will be tested in a stratified log-rank test, consistent with the stratified randomization. The OS rates by MGMT, recursive partitioning analysis (RPA) class and other prognostic factors will be estimated by Kaplan-Meier methods and compared using the log-rank test. Multivariate analyses with the Cox proportional hazard model for OS will be performed to assess the treatment effect adjusting for patient-specific risk factors.

Secondary Outcome Measures :

1. OS when compared between dose-escalated and -intensified photon IMRT to dose-escalated and -intensified proton beam therapy [ Time Frame: Date of randomization to the date of death, assessed up to 5 years ]
   If the instrumental variable assumptions hold, OS rate will be estimated using the Kaplan-Meier method, and differences between treatment arms will be tested in the log-rank test.
2. Progression-free survival (PFS) [ Time Frame: Date of randomization to the date of progression or death, assessed up to 5 years ]
   PFS rates will be estimated using the Kaplan-Meier method and comparisons between treatment arms will be made in the same manner as for OS.
3. Incidence of treatment-related toxicity, as measured by the Common Terminology Criteria for Adverse Events version 4 [ Time Frame: Up to 5 years ]
   Differences in observed severities of toxicities (grade 3+) between groups will be estimated using an exact binomial distribution together with 95% confidence interval. The difference between the 2 groups will be tested using a chi square test. If the instrumental variable assumptions hold the experimental arms will also be compared.
4. Change in perceived cognitive function, as measured by M.D. Anderson Symptom Inventory Brain Tumor [ Time Frame: Baseline to up to 60 weeks ]
   The change from baseline to each follow-up time point for the perceived cognitive symptom severity score will each be compared using a t-test with alpha=0.05, or Wilcoxon test if the data is not normally distributed, between treatment arms within each group. If the instrumental variable assumptions hold and the perceived cognitive function is significantly different within both groups, a test will be performed to compare between the 2 experimental arms.
5. Change in neurocognitive function, as measured by Hopkins' Verbal Learning Test-Revised, Trail Making Test Parts A and B, and Controlled Oral Word Association Test [ Time Frame: Baseline to up to 60 weeks ]
   The change from baseline to each follow-up time point for the perceived Clinical Trial Battery (CTB) composite score will each be compared using a t-test with alpha=0.05, or Wilcoxon test if the data is not normally distributed, between treatment arms within each group. If the instrumental variable assumptions hold and the CTB composite score is significantly different within both groups, a test will be performed to compare between the 2 experimental arms.
6. Change in CD4 lymphopenia count [ Time Frame: Baseline to up to 5 years ]
   The change from baseline to the completion of radiation will be compared between the control and experimental arms in each group using a t-test. If the instrumental variable assumptions hold, then it will be compared between the experimental arms. A repeated measures analysis, using a mixed effects model, will be used to assess the change of CD4 lymphopenia across time. CD4 count at 2 months after beginning therapy (dichotomized at 200) was shown to be prognostic of OS. This will be assessed here based on the CD4 count at the completion of chemoradiation which matches best to 2-months.
7. Use of magnetic resonance diffusion and perfusion imaging to differentiate between tumor progression and pseudo-progression [ Time Frame: Up to 5 years ]
   Retrospective analysis will be performed to evaluate and refine the method and the threshold cut-off point determined from our previous single institute data set to determine progression using the first one-third of the patient data collected in this trial. If the initial analysis supports our preliminary results with sufficient high sensitivity and specificity, e.g., 80% specificity and 90% sensitivity or higher, results will be validated using the remaining two-thirds of the imaging data.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States, 35233

United States, Arizona

Saint Joseph's Hospital and Medical Center

Phoenix, Arizona, United States, 85013

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, United States, 85054

Mayo Clinic in Arizona

Scottsdale, Arizona, United States, 85259

Arizona Oncology Associates-West Orange Grove

Tucson, Arizona, United States, 85704

Banner University Medical Center - Tucson

Tucson, Arizona, United States, 85719

United States, Arkansas

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States, 72205

United States, California

Sutter Cancer Centers Radiation Oncology Services-Auburn

Auburn, California, United States, 95603

AIS Cancer Center at San Joaquin Community Hospital

Bakersfield, California, United States, 93301

Alta Bates Summit Medical Center-Herrick Campus

Berkeley, California, United States, 94704

Sutter Cancer Centers Radiation Oncology Services-Cameron Park

Cameron Park, California, United States, 95682

Eden Hospital Medical Center

Castro Valley, California, United States, 94546

Fresno Cancer Center

Fresno, California, United States, 93720

Marin General Hospital

Greenbrae, California, United States, 94904

Loma Linda University Medical Center

Loma Linda, California, United States, 92354

Los Angeles County-USC Medical Center

Los Angeles, California, United States, 90033

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States, 90033

Cedars Sinai Medical Center

Los Angeles, California, United States, 90048

Fremont - Rideout Cancer Center

Marysville, California, United States, 95901

Memorial Medical Center

Modesto, California, United States, 95355

Kaiser Permanente Oakland-Broadway

Oakland, California, United States, 94611

Saint Joseph Hospital - Orange

Orange, California, United States, 92868

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, United States, 92868

Palo Alto Medical Foundation Health Care

Palo Alto, California, United States, 94301

Pomona Valley Hospital Medical Center

Pomona, California, United States, 91767

Kaiser Permanente-Rancho Cordova Cancer Center

Rancho Cordova, California, United States, 95670

Rohnert Park Cancer Center

Rohnert Park, California, United States, 94928

Sutter Cancer Centers Radiation Oncology Services-Roseville

Roseville, California, United States, 95661

The Permanente Medical Group-Roseville Radiation Oncology

Roseville, California, United States, 95678

Sutter Medical Center Sacramento

Sacramento, California, United States, 95816

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States, 95817

South Sacramento Cancer Center

Sacramento, California, United States, 95823

California Pacific Medical Center-Pacific Campus

San Francisco, California, United States, 94115

Palo Alto Medical Foundation-Santa Cruz

Santa Cruz, California, United States, 95065

Kaiser Permanente Cancer Treatment Center

South San Francisco, California, United States, 94080

Palo Alto Medical Foundation-Sunnyvale

Sunnyvale, California, United States, 94086

Sutter Cancer Centers Radiation Oncology Services-Vacaville

Vacaville, California, United States, 95687

John Muir Medical Center-Walnut Creek

Walnut Creek, California, United States, 94598

United States, Colorado

UCHealth Memorial Hospital Central

Colorado Springs, Colorado, United States, 80909

Poudre Valley Hospital

Fort Collins, Colorado, United States, 80524

United States, Connecticut

Hartford Hospital

Hartford, Connecticut, United States, 06102

United States, Florida

Boca Raton Regional Hospital

Boca Raton, Florida, United States, 33486

University of Florida Health Science Center - Gainesville

Gainesville, Florida, United States, 32610

Baptist MD Anderson Cancer Center

Jacksonville, Florida, United States, 32207

University of Florida Health Science Center - Jacksonville

Jacksonville, Florida, United States, 32209

Baptist Medical Center South

Jacksonville, Florida, United States, 32258

Miami Cancer Institute

Miami, Florida, United States, 33176

Moffitt Cancer Center

Tampa, Florida, United States, 33612

United States, Georgia

Emory Proton Therapy Center

Atlanta, Georgia, United States, 30308

Emory University Hospital Midtown

Atlanta, Georgia, United States, 30308

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States, 30322

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

Savannah, Georgia, United States, 31405

United States, Idaho

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, United States, 83706

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

John H Stroger Jr Hospital of Cook County

Chicago, Illinois, United States, 60612

Rush University Medical Center

Chicago, Illinois, United States, 60612

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States, 60637

Decatur Memorial Hospital

Decatur, Illinois, United States, 62526

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois, United States, 60115

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois, United States, 60134

UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, United States, 60451

Advocate Lutheran General Hospital

Park Ridge, Illinois, United States, 60068

OSF Saint Francis Medical Center

Peoria, Illinois, United States, 61637

Memorial Medical Center

Springfield, Illinois, United States, 62781

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, United States, 60555

United States, Indiana

Radiation Oncology Associates PC

Fort Wayne, Indiana, United States, 46804

Parkview Hospital Randallia

Fort Wayne, Indiana, United States, 46805

Parkview Regional Medical Center

Fort Wayne, Indiana, United States, 46845

IU Health Methodist Hospital

Indianapolis, Indiana, United States, 46202

Community Cancer Center East

Indianapolis, Indiana, United States, 46219

Community Cancer Center South

Indianapolis, Indiana, United States, 46227

Community Cancer Center North

Indianapolis, Indiana, United States, 46256

IU Health Ball Memorial Hospital

Muncie, Indiana, United States, 47303

United States, Iowa

Mercy Hospital

Cedar Rapids, Iowa, United States, 52403

Iowa Methodist Medical Center

Des Moines, Iowa, United States, 50309

United States, Kansas

University of Kansas Cancer Center

Kansas City, Kansas, United States, 66160

University of Kansas Cancer Center-Overland Park

Overland Park, Kansas, United States, 66210

United States, Kentucky

Norton Hospital Pavilion and Medical Campus

Louisville, Kentucky, United States, 40202

United States, Louisiana

Ochsner Medical Center Jefferson

New Orleans, Louisiana, United States, 70121

Willis-Knighton Medical and Cancer Center

Shreveport, Louisiana, United States, 71103

United States, Maryland

Maryland Proton Treatment Center

Baltimore, Maryland, United States, 21201

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States, 21201

UM Upper Chesapeake Medical Center

Bel Air, Maryland, United States, 21014

Central Maryland Radiation Oncology in Howard County

Columbia, Maryland, United States, 21044

UM Baltimore Washington Medical Center/Tate Cancer Center

Glen Burnie, Maryland, United States, 21061

United States, Massachusetts

Tufts Medical Center

Boston, Massachusetts, United States, 02111

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States, 02114

Boston Medical Center

Boston, Massachusetts, United States, 02118

Mass General/North Shore Cancer Center

Danvers, Massachusetts, United States, 01923

Lowell General Hospital

Lowell, Massachusetts, United States, 01854

United States, Michigan

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, United States, 48106

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States, 48109

McLaren Cancer Institute-Bay City

Bay City, Michigan, United States, 48706

Beaumont Hospital - Dearborn

Dearborn, Michigan, United States, 48124

Henry Ford Hospital

Detroit, Michigan, United States, 48202

McLaren Cancer Institute-Flint

Flint, Michigan, United States, 48532

Mercy Health Saint Mary's

Grand Rapids, Michigan, United States, 49503

Spectrum Health at Butterworth Campus

Grand Rapids, Michigan, United States, 49503

West Michigan Cancer Center

Kalamazoo, Michigan, United States, 49007

McLaren Cancer Institute-Lapeer Region

Lapeer, Michigan, United States, 48446

Saint Mary Mercy Hospital

Livonia, Michigan, United States, 48154

McLaren Cancer Institute-Macomb

Mount Clemens, Michigan, United States, 48043

McLaren Cancer Institute-Central Michigan

Mount Pleasant, Michigan, United States, 48858

McLaren Cancer Institute-Owosso

Owosso, Michigan, United States, 48867

McLaren Cancer Institute-Northern Michigan

Petoskey, Michigan, United States, 49770

Saint Joseph Mercy Oakland

Pontiac, Michigan, United States, 48341

William Beaumont Hospital-Royal Oak

Royal Oak, Michigan, United States, 48073

Lakeland Medical Center Saint Joseph

Saint Joseph, Michigan, United States, 49085

William Beaumont Hospital - Troy

Troy, Michigan, United States, 48085

United States, Minnesota

Sanford Joe Lueken Cancer Center

Bemidji, Minnesota, United States, 56601

Saint Luke's Hospital of Duluth

Duluth, Minnesota, United States, 55805

Mayo Clinic in Rochester

Rochester, Minnesota, United States, 55905

Coborn Cancer Center at Saint Cloud Hospital

Saint Cloud, Minnesota, United States, 56303

Regions Hospital

Saint Paul, Minnesota, United States, 55101

United States, Mississippi

University of Mississippi Medical Center

Jackson, Mississippi, United States, 39216

United States, Missouri

North Kansas City Hospital

Kansas City, Missouri, United States, 64116

University of Kansas Cancer Center - North

Kansas City, Missouri, United States, 64154

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

United States, Montana

Billings Clinic Cancer Center

Billings, Montana, United States, 59101

United States, Nevada

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States, 89148

Renown Regional Medical Center

Reno, Nevada, United States, 89502

Saint Mary's Regional Medical Center

Reno, Nevada, United States, 89503

United States, New Hampshire

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States, 03756

United States, New Jersey

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States, 07920

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

New Brunswick, New Jersey, United States, 08903

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States, 08903

Capital Health Medical Center-Hopewell

Pennington, New Jersey, United States, 08534

ProCure Proton Therapy Center-Somerset

Somerset, New Jersey, United States, 08873

Virtua Voorhees

Voorhees, New Jersey, United States, 08043

United States, New York

Montefiore Medical Center - Moses Campus

Bronx, New York, United States, 10467

New York-Presbyterian/Brooklyn Methodist Hospital

Brooklyn, New York, United States, 11215

Memorial Sloan Kettering Commack

Commack, New York, United States, 11725

Memorial Sloan Kettering Westchester

Harrison, New York, United States, 10604

Northwell Health/Center for Advanced Medicine

Lake Success, New York, United States, 11042

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States, 10016

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

New York, New York, United States, 10032

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

United States, North Carolina

Mission Hospital

Asheville, North Carolina, United States, 28801

Novant Health Forsyth Medical Center

Winston-Salem, North Carolina, United States, 27103

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States, 27157

United States, North Dakota

Sanford Bismarck Medical Center

Bismarck, North Dakota, United States, 58501

Sanford Roger Maris Cancer Center

Fargo, North Dakota, United States, 58122

United States, Ohio

Cleveland Clinic Akron General

Akron, Ohio, United States, 44307

UHHS-Chagrin Highlands Medical Center

Beachwood, Ohio, United States, 44122

Geauga Hospital

Chardon, Ohio, United States, 44024

University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio, United States, 45219

Case Western Reserve University

Cleveland, Ohio, United States, 44106

Cleveland Clinic Cancer Center/Fairview Hospital

Cleveland, Ohio, United States, 44111

Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States, 43210

Riverside Methodist Hospital

Columbus, Ohio, United States, 43214

Mercy Cancer Center-Elyria

Elyria, Ohio, United States, 44035

Cleveland Clinic Cancer Center Independence

Independence, Ohio, United States, 44131

Hillcrest Hospital Cancer Center

Mayfield Heights, Ohio, United States, 44124

UH Seidman Cancer Center at Lake Health Mentor Campus

Mentor, Ohio, United States, 44060

UH Seidman Cancer Center at Southwest General Hospital

Middleburg Heights, Ohio, United States, 44130

University Hospitals Parma Medical Center

Parma, Ohio, United States, 44129

North Coast Cancer Care

Sandusky, Ohio, United States, 44870

UH Seidman Cancer Center at Firelands Regional Medical Center

Sandusky, Ohio, United States, 44870

Cleveland Clinic Cancer Center Strongsville

Strongsville, Ohio, United States, 44136

University of Toledo

Toledo, Ohio, United States, 43614

University of Cincinnati Cancer Center-West Chester

West Chester, Ohio, United States, 45069

UHHS-Westlake Medical Center

Westlake, Ohio, United States, 44145

Cleveland Clinic Wooster Family Health and Surgery Center

Wooster, Ohio, United States, 44691

United States, Oklahoma

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States, 73104

United States, Oregon

Willamette Valley Cancer Center

Eugene, Oregon, United States, 97401

Legacy Mount Hood Medical Center

Gresham, Oregon, United States, 97030

Legacy Good Samaritan Hospital and Medical Center

Portland, Oregon, United States, 97210

United States, Pennsylvania

Saint Luke's University Hospital-Bethlehem Campus

Bethlehem, Pennsylvania, United States, 18015

Northeast Radiation Oncology Center

Dunmore, Pennsylvania, United States, 18512

Ephrata Cancer Center

Ephrata, Pennsylvania, United States, 17522

Adams Cancer Center

Gettysburg, Pennsylvania, United States, 17325

UPMC Pinnacle Cancer Center/Community Osteopathic Campus

Harrisburg, Pennsylvania, United States, 17109

Sechler Family Cancer Center

Lebanon, Pennsylvania, United States, 17042

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, United States, 19104

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States, 19107

Jefferson Torresdale Hospital

Philadelphia, Pennsylvania, United States, 19114

Reading Hospital

West Reading, Pennsylvania, United States, 19611

WellSpan Health-York Cancer Center

York, Pennsylvania, United States, 17403

United States, South Carolina

Prisma Health Cancer Institute - Spartanburg

Boiling Springs, South Carolina, United States, 29316

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

Prisma Health Cancer Institute - Faris

Greenville, South Carolina, United States, 29605

Prisma Health Cancer Institute - Eastside

Greenville, South Carolina, United States, 29615

Self Regional Healthcare

Greenwood, South Carolina, United States, 29646

Prisma Health Cancer Institute - Greer

Greer, South Carolina, United States, 29650

Prisma Health Cancer Institute - Seneca

Seneca, South Carolina, United States, 29672

United States, South Dakota

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States, 57117-5134

United States, Tennessee

Tennessee Cancer Specialists-Dowell Springs

Knoxville, Tennessee, United States, 37909

United States, Texas

Dell Seton Medical Center at The University of Texas

Austin, Texas, United States, 78701

Austin Cancer Centers-Central Austin

Austin, Texas, United States, 78702

Texas Oncology-Austin Midtown

Austin, Texas, United States, 78705

Texas Oncology - Central Austin Cancer Center

Austin, Texas, United States, 78731

Texas Oncology - South Austin Cancer Center

Austin, Texas, United States, 78745

Austin Cancer Centers-North

Austin, Texas, United States, 78758

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States, 75390

Texas Oncology - Denison Cancer Center

Denison, Texas, United States, 75020

Texas Oncology-Flower Mound

Flower Mound, Texas, United States, 75028

Texas Oncology - Fort Worth Cancer Center

Fort Worth, Texas, United States, 76104

University of Texas Medical Branch

Galveston, Texas, United States, 77555-0565

Memorial Hermann Memorial City Medical Center

Houston, Texas, United States, 77024

M D Anderson Cancer Center

Houston, Texas, United States, 77030

UTMB Cancer Center at Victory Lakes

League City, Texas, United States, 77573

Covenant Medical Center-Lakeside

Lubbock, Texas, United States, 79410

Texas Oncology-Seton Williamson

Round Rock, Texas, United States, 78665

Texas Oncology - Round Rock Cancer Center

Round Rock, Texas, United States, 78681

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States, 78229

Texas Oncology Cancer Center Sugar Land

Sugar Land, Texas, United States, 77479

Tyler Cancer Center

Tyler, Texas, United States, 75702

United States, Utah

Logan Regional Hospital

Logan, Utah, United States, 84321

Intermountain Medical Center

Murray, Utah, United States, 84107

McKay-Dee Hospital Center

Ogden, Utah, United States, 84403

Utah Valley Regional Medical Center

Provo, Utah, United States, 84604

Dixie Medical Center Regional Cancer Center

Saint George, Utah, United States, 84770

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States, 84112

United States, Vermont

Central Vermont Medical Center/National Life Cancer Treatment

Berlin, Vermont, United States, 05602

University of Vermont Medical Center

Burlington, Vermont, United States, 05401

Norris Cotton Cancer Center-North

Saint Johnsbury, Vermont, United States, 05819

United States, Virginia

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States, 23298

United States, Washington

SCCA Proton Therapy Center

Seattle, Washington, United States, 98133

Seattle Cancer Care Alliance at Northwest Hospital

Seattle, Washington, United States, 98133

University of Washington Medical Center - Montlake

Seattle, Washington, United States, 98195

Compass Oncology Vancouver

Vancouver, Washington, United States, 98684

Legacy Salmon Creek Hospital

Vancouver, Washington, United States, 98686

United States, West Virginia

Wheeling Hospital/Schiffler Cancer Center

Wheeling, West Virginia, United States, 26003

United States, Wisconsin

Langlade Hospital and Cancer Center

Antigo, Wisconsin, United States, 54409

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, United States, 54601

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States, 53792

Froedtert Menomonee Falls Hospital

Menomonee Falls, Wisconsin, United States, 53051

Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

UW Cancer Center at ProHealth Care

Waukesha, Wisconsin, United States, 53188

Aspirus Regional Cancer Center

Wausau, Wisconsin, United States, 54401

Canada, British Columbia

BCCA-Vancouver Island Cancer Centre

Victoria, British Columbia, Canada, V8R 6V5

Canada, Ontario

Ottawa Hospital and Cancer Center-General Campus

Ottawa, Ontario, Canada, K1H 8L6

Windsor Regional Cancer Centre

Windsor, Ontario, Canada, N8W 2X3

Canada, Quebec

CHUM - Hopital Notre-Dame

Montreal, Quebec, Canada, H2L 4M1

McGill University Department of Oncology

Montreal, Quebec, Canada, H2W 1S6

CHUM - Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, Canada, H2X 3E4

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

Montreal, Quebec, Canada, H3H 2R9

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

Quebec City, Quebec, Canada, G1R 2J6

Canada, Saskatchewan

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada, S7N 4H4

Sponsors and Collaborators

NRG Oncology

National Cancer Institute (NCI)

Radiation Therapy Oncology Group

Investigators

• Principal Investigator: Minesh Mehta, MD; NRG Oncology
• Principal Investigator: Vinai Gondi, MD; NRG Oncology

More Information

• Responsible Party: NRG Oncology
• ClinicalTrials.gov Identifier: NCT02179086
• Obsolete Identifiers: NCT02163135
• Other Study ID Numbers: NRG-BN001; NCI-2014-01072 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); NRG-BN001 ( Other Identifier: NRG Oncology ); NRG-BN001 ( Other Identifier: CTEP ); U10CA180868 ( U.S. NIH Grant/Contract )
• First Posted: July 1, 2014
• Last Update Posted: May 19, 2022
• Last Verified: May 2022

Additional relevant MeSH terms:

Glioblastoma; Gliosarcoma; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Temozolomide; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents