Clinical trial NCT02179086: Dose-Escalated Photon IMRT or Proton Beam Radiation Therapy Versus Standard-Dose Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Glioblastoma
Lead sponsor: NRG Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-07-01
Enrollment: 606
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: PRIMARY OBJECTIVE:

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 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.

EXPLORATORY 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.

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 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.

Eligibility criteria: Inclusion Criteria:

* 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:

    * 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

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 (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

Primary outcomes:
measure: Overall survival
timeFrame: Date of randomization to the date of death due to any cause, assessed up to 5 years
Secondary outcomes:
measure: Overall survival
timeFrame: Date of randomization to the date of death, assessed up to 5 years
measure: Progression-free survival
timeFrame: Date of randomization to the date of progression or death, assessed up to 5 years
measure: Incidence of treatment-related toxicity, as measured by the Common Terminology Criteria for Adverse Events version 4
timeFrame: Up to 5 years
measure: Change in perceived cognitive function, as measured by M.D. Anderson Symptom Inventory Brain Tumor
timeFrame: Baseline to up to 60 weeks
measure: 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
timeFrame: Baseline to up to 60 weeks
measure: Change in CD4 lymphopenia count
timeFrame: Baseline to up to 5 years
measure: Use of magnetic resonance diffusion and perfusion imaging to differentiate between tumor progression and pseudo-progression
timeFrame: Baseline up to prior to cycle 4
measure: Use of magnetic resonance diffusion and perfusion imaging as early predictors of overall survival
timeFrame: Baseline up to 12 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Cancer Center
state: Alabama
city: Phoenix
country: United States
facility: Saint Joseph's Hospital and Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Hospital in Arizona
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates-West Orange Grove
state: Arizona
city: Tucson
country: United States
facility: Banner University Medical Center - Tucson
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Auburn
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Auburn
state: California
city: Bakersfield
country: United States
facility: AIS Cancer Center at San Joaquin Community Hospital
state: California
city: Berkeley
country: United States
facility: Alta Bates Summit Medical Center-Herrick Campus
state: California
city: Cameron Park
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Cameron Park
state: California
city: Castro Valley
country: United States
facility: Eden Hospital Medical Center
state: California
city: Fresno
country: United States
facility: Fresno Cancer Center
state: California
city: Greenbrae
country: United States
facility: Marin General Hospital
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Los Angeles
country: United States
facility: Los Angeles General Medical Center
state: California
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Marysville
country: United States
facility: Fremont - Rideout Cancer Center
state: California
city: Modesto
country: United States
facility: Memorial Medical Center
state: California
city: Oakland
country: United States
facility: Kaiser Permanente Oakland-Broadway
state: California
city: Orange
country: United States
facility: Saint Joseph Hospital - Orange
state: California
city: Orange
country: United States
facility: UC Irvine Health/Chao Family Comprehensive Cancer Center
state: California
city: Palo Alto
country: United States
facility: Palo Alto Medical Foundation Health Care
state: California
city: Pomona
country: United States
facility: Pomona Valley Hospital Medical Center
state: California
city: Rancho Cordova
country: United States
facility: Kaiser Permanente-Rancho Cordova Cancer Center
state: California
city: Rohnert Park
country: United States
facility: Rohnert Park Cancer Center
state: California
city: Roseville
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Roseville
state: California
city: Roseville
country: United States
facility: The Permanente Medical Group-Roseville Radiation Oncology
state: California
city: Sacramento
country: United States
facility: Sutter Medical Center Sacramento
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: South Sacramento Cancer Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center-Pacific Campus
state: California
city: Santa Cruz
country: United States
facility: Palo Alto Medical Foundation-Santa Cruz
state: California
city: South San Francisco
country: United States
facility: Kaiser Permanente Cancer Treatment Center
state: California
city: Sunnyvale
country: United States
facility: Palo Alto Medical Foundation-Sunnyvale
state: California
city: Walnut Creek
country: United States
facility: John Muir Medical Center-Walnut Creek
state: California
city: Colorado Springs
country: United States
facility: UCHealth Memorial Hospital Central
state: Colorado
city: Fort Collins
country: United States
facility: Poudre Valley Hospital
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Boca Raton
country: United States
facility: Boca Raton Regional Hospital
state: Florida
city: Gainesville
country: United States
facility: University of Florida Health Science Center - Gainesville
state: Florida
city: Jacksonville
country: United States
facility: Baptist MD Anderson Cancer Center
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Health Science Center - Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Baptist Medical Center South
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory Proton Therapy Center
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Savannah
country: United States
facility: Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
state: Georgia
city: Boise
country: United States
facility: Saint Alphonsus Cancer Care Center-Boise
state: Idaho
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: John H Stroger Jr Hospital of Cook County
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: DeKalb
country: United States
facility: Northwestern Medicine Cancer Center Kishwaukee
state: Illinois
city: Geneva
country: United States
facility: Northwestern Medicine Cancer Center Delnor
state: Illinois
city: New Lenox
country: United States
facility: UC Comprehensive Cancer Center at Silver Cross
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Springfield
country: United States
facility: Springfield Memorial Hospital
state: Illinois
city: Warrenville
country: United States
facility: Northwestern Medicine Cancer Center Warrenville
state: Illinois
city: Fort Wayne
country: United States
facility: Radiation Oncology Associates PC
state: Indiana
city: Fort Wayne
country: United States
facility: Parkview Hospital Randallia
state: Indiana
city: Fort Wayne
country: United States
facility: Parkview Regional Medical Center
state: Indiana
city: Indianapolis
country: United States
facility: IU Health Methodist Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Community Cancer Center East
state: Indiana
city: Indianapolis
country: United States
facility: Community Cancer Center South
state: Indiana
city: Indianapolis
country: United States
facility: Community Cancer Center North
state: Indiana
city: Muncie
country: United States
facility: IU Health Ball Memorial Hospital
state: Indiana
city: Cedar Rapids
country: United States
facility: Mercy Hospital
state: Iowa
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Overland Park
country: United States
facility: University of Kansas Cancer Center-Overland Park
state: Kansas
city: Louisville
country: United States
facility: Norton Hospital Pavilion and Medical Campus
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Medical Center Jefferson
state: Louisiana
city: Shreveport
country: United States
facility: Willis-Knighton Medical and Cancer Center
state: Louisiana
city: Baltimore
country: United States
facility: Maryland Proton Treatment Center
state: Maryland
city: Baltimore
country: United States
facility: University of Maryland/Greenebaum Cancer Center
state: Maryland
city: Bel Air
country: United States
facility: UM Upper Chesapeake Medical Center
state: Maryland
city: Columbia
country: United States
facility: Central Maryland Radiation Oncology in Howard County
state: Maryland
city: Glen Burnie
country: United States
facility: UM Baltimore Washington Medical Center/Tate Cancer Center
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Danvers
country: United States
facility: Mass General/North Shore Cancer Center
state: Massachusetts
city: Lowell
country: United States
facility: Lowell General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: Trinity Health Saint Joseph Mercy Hospital Ann Arbor
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Bay City
country: United States
facility: McLaren Cancer Institute-Bay City
state: Michigan
city: Dearborn
country: United States
facility: Corewell Health Dearborn Hospital
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Flint
country: United States
facility: McLaren Cancer Institute-Flint
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health Grand Rapids Hospitals - Butterworth Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Trinity Health Grand Rapids Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Lapeer
country: United States
facility: McLaren Cancer Institute-Lapeer Region
state: Michigan
city: Livonia
country: United States
facility: Trinity Health Saint Mary Mercy Livonia Hospital
state: Michigan
city: Mount Clemens
country: United States
facility: McLaren Cancer Institute-Macomb
state: Michigan
city: Mount Pleasant
country: United States
facility: McLaren Cancer Institute-Central Michigan
state: Michigan
city: Owosso
country: United States
facility: McLaren Cancer Institute-Owosso
state: Michigan
city: Petoskey
country: United States
facility: McLaren Cancer Institute-Northern Michigan
state: Michigan
city: Pontiac
country: United States
facility: Trinity Health Saint Joseph Mercy Oakland Hospital
state: Michigan
city: Royal Oak
country: United States
facility: Corewell Health William Beaumont University Hospital
state: Michigan
city: Saint Joseph
country: United States
facility: Corewell Health Lakeland Hospitals - Saint Joseph Hospital
state: Michigan
city: Troy
country: United States
facility: Corewell Health Beaumont Troy Hospital
state: Michigan
city: Bemidji
country: United States
facility: Sanford Joe Lueken Cancer Center
state: Minnesota
city: Duluth
country: United States
facility: Saint Luke's Hospital of Duluth
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Saint Cloud
country: United States
facility: Coborn Cancer Center at Saint Cloud Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: North Kansas City Hospital
state: Missouri
city: Kansas City
country: United States
facility: University of Kansas Cancer Center - North
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Reno
country: United States
facility: Renown Regional Medical Center
state: Nevada
city: Reno
country: United States
facility: Saint Mary's Regional Medical Center
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
state: New Hampshire
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Pennington
country: United States
facility: Capital Health Medical Center-Hopewell
state: New Jersey
city: Somerset
country: United States
facility: ProCure Proton Therapy Center-Somerset
state: New Jersey
city: Voorhees
country: United States
facility: Virtua Voorhees
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Campus
state: New York
city: Brooklyn
country: United States
facility: New York-Presbyterian/Brooklyn Methodist Hospital
state: New York
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester
state: New York
city: Lake Success
country: United States
facility: Northwell Health/Center for Advanced Medicine
state: New York
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at NYU Langone
state: New York
city: New York
country: United States
facility: NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Asheville
country: United States
facility: Mission Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Forsyth Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Bismarck
country: United States
facility: Sanford Bismarck Medical Center
state: North Dakota
city: Fargo
country: United States
facility: Sanford Roger Maris Cancer Center
state: North Dakota
city: Akron
country: United States
facility: Cleveland Clinic Akron General
state: Ohio
city: Beachwood
country: United States
facility: UHHS-Chagrin Highlands Medical Center
state: Ohio
city: Chardon
country: United States
facility: Geauga Hospital
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Center-UC Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Cancer Center/Fairview Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Elyria
country: United States
facility: Mercy Cancer Center-Elyria
state: Ohio
city: Independence
country: United States
facility: Cleveland Clinic Cancer Center Independence
state: Ohio
city: Mayfield Heights
country: United States
facility: Hillcrest Hospital Cancer Center
state: Ohio
city: Mentor
country: United States
facility: UH Seidman Cancer Center at Lake Health Mentor Campus
state: Ohio
city: Middleburg Heights
country: United States
facility: UH Seidman Cancer Center at Southwest General Hospital
state: Ohio
city: Parma
country: United States
facility: University Hospitals Parma Medical Center
state: Ohio
city: Sandusky
country: United States
facility: North Coast Cancer Care
state: Ohio
city: Sandusky
country: United States
facility: UH Seidman Cancer Center at Firelands Regional Medical Center
state: Ohio
city: Strongsville
country: United States
facility: Cleveland Clinic Cancer Center Strongsville
state: Ohio
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: West Chester
country: United States
facility: University of Cincinnati Cancer Center-West Chester
state: Ohio
city: Westlake
country: United States
facility: UHHS-Westlake Medical Center
state: Ohio
city: Wooster
country: United States
facility: Cleveland Clinic Wooster Family Health and Surgery Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Eugene
country: United States
facility: Willamette Valley Cancer Center
state: Oregon
city: Gresham
country: United States
facility: Legacy Mount Hood Medical Center
state: Oregon
city: Portland
country: United States
facility: Legacy Good Samaritan Hospital and Medical Center
state: Oregon
city: Bethlehem
country: United States
facility: Saint Luke's University Hospital-Bethlehem Campus
state: Pennsylvania
city: Dunmore
country: United States
facility: Northeast Radiation Oncology Center
state: Pennsylvania
city: Ephrata
country: United States
facility: Ephrata Cancer Center
state: Pennsylvania
city: Gettysburg
country: United States
facility: Adams Cancer Center
state: Pennsylvania
city: Harrisburg
country: United States
facility: UPMC Pinnacle Cancer Center/Community Osteopathic Campus
state: Pennsylvania
city: Lebanon
country: United States
facility: Sechler Family Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania/Abramson Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jefferson Torresdale Hospital
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital
state: Pennsylvania
city: York
country: United States
facility: WellSpan Health-York Cancer Center
state: Pennsylvania
city: Boiling Springs
country: United States
facility: Prisma Health Cancer Institute - Spartanburg
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Cancer Institute - Faris
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Cancer Institute - Eastside
state: South Carolina
city: Greenwood
country: United States
facility: Self Regional Healthcare
state: South Carolina
city: Greer
country: United States
facility: Prisma Health Cancer Institute - Greer
state: South Carolina
city: Seneca
country: United States
facility: Prisma Health Cancer Institute - Seneca
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center - Sioux Falls
state: South Dakota
city: Knoxville
country: United States
facility: Tennessee Cancer Specialists-Dowell Springs
state: Tennessee
city: Austin
country: United States
facility: Dell Seton Medical Center at The University of Texas
state: Texas
city: Austin
country: United States
facility: Austin Cancer Centers-Central Austin
state: Texas
city: Austin
country: United States
facility: Texas Oncology-Austin Midtown
state: Texas
city: Austin
country: United States
facility: Texas Oncology - Central Austin Cancer Center
state: Texas
city: Austin
country: United States
facility: Texas Oncology - South Austin Cancer Center
state: Texas
city: Austin
country: United States
facility: Austin Cancer Centers-North
state: Texas
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Denison
country: United States
facility: Texas Oncology - Denison Cancer Center
state: Texas
city: Flower Mound
country: United States
facility: Texas Oncology-Flower Mound
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology - Fort Worth Cancer Center
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Memorial City Medical Center
state: Texas
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: League City
country: United States
facility: UTMB Cancer Center at Victory Lakes
state: Texas
city: Lubbock
country: United States
facility: Covenant Medical Center-Lakeside
state: Texas
city: Round Rock
country: United States
facility: Texas Oncology-Seton Williamson
state: Texas
city: Round Rock
country: United States
facility: Texas Oncology - Round Rock Cancer Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Sugar Land
country: United States
facility: Texas Oncology Cancer Center Sugar Land
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Logan
country: United States
facility: Logan Regional Hospital
state: Utah
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Ogden
country: United States
facility: McKay-Dee Hospital Center
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center
state: Utah
city: Saint George
country: United States
facility: Saint George Regional Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Berlin
country: United States
facility: Central Vermont Medical Center/National Life Cancer Treatment
state: Vermont
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Saint Johnsbury
country: United States
facility: Dartmouth Cancer Center - North
state: Vermont
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
city: Seattle
country: United States
facility: FHCC at Northwest Hospital
state: Washington
city: Seattle
country: United States
facility: FHCC Proton Therapy Center
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center - Montlake
state: Washington
city: Vancouver
country: United States
facility: Compass Oncology Vancouver
state: Washington
city: Vancouver
country: United States
facility: Legacy Salmon Creek Hospital
state: Washington
city: Wheeling
country: United States
facility: Wheeling Hospital/Schiffler Cancer Center
state: West Virginia
city: Antigo
country: United States
facility: Langlade Hospital and Cancer Center
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Lutheran Medical Center
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center - University Hospital
state: Wisconsin
city: Menomonee Falls
country: United States
facility: Froedtert Menomonee Falls Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Waukesha
country: United States
facility: UW Cancer Center at ProHealth Care
state: Wisconsin
city: Wausau
country: United States
facility: Aspirus Regional Cancer Center
state: Wisconsin
city: Victoria
country: Canada
facility: BCCA-Vancouver Island Cancer Centre
state: British Columbia
city: Ottawa
country: Canada
facility: Ottawa Hospital and Cancer Center-General Campus
state: Ontario
city: Windsor
country: Canada
facility: Windsor Regional Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: CHUM - Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Montreal
country: Canada
facility: The Research Institute of the McGill University Health Centre (MUHC)
state: Quebec
city: Quebec City
country: Canada
facility: CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
Study officials:
affiliation: NRG Oncology
name: Minesh P Mehta
role: PRINCIPAL_INVESTIGATOR
References: