Clinical trial NCT02135042: Individualized Treatment in Treating Patients With Stage II-IVB Nasopharyngeal Cancer Based on EBV DNA
Official title: Randomized Phase II and Phase III Studies of Individualized Treatment for Nasopharyngeal Carcinoma Based on Biomarker Epstein Barr Virus (EBV) Deoxyribonucleic Acid (DNA)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Epstein-Barr Virus Infection
Stage II Nasopharyngeal Carcinoma
Stage III Nasopharyngeal Carcinoma
Stage IVA Nasopharyngeal Carcinoma
Stage IVB Nasopharyngeal Carcinoma
Lead sponsor: NRG Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-05-09
Enrollment: 685
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: There are two study questions we are asking in this randomized phase II/III trial based on a blood biomarker, Epstein Barr virus (EBV) deoxyribonucleic acid (DNA) for locoregionally advanced non-metastatic nasopharyngeal cancer. All patients will first undergo standard concurrent chemotherapy and radiation therapy. When this standard treatment is completed, if there is no detectable EBV DNA in their plasma, then patients are randomized to either standard adjuvant cisplatin and fluorouracil chemotherapy or observation. If there is still detectable levels of plasma EBV DNA, patients will be randomized to standard cisplatin and fluorouracil chemotherapy versus gemcitabine and paclitaxel. Radiation therapy uses high energy x rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, fluorouracil, gemcitabine hydrochloride, and paclitaxel work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving cisplatin and fluorouracil is more effective than gemcitabine hydrochloride and paclitaxel after radiation therapy in treating patients with nasopharyngeal cancer.

Detailed description: PRIMARY OBJECTIVES:

I. To determine whether substituting adjuvant concurrent high dose cisplatin (CDDP) and fluorouracil (5-FU) with gemcitabine (gemcitabine hydrochloride) and paclitaxel will result in superior progression-free survival. (Detectable Plasma Epstein Barr Virus \[EBV\] Deoxyribonucleic Acid \[DNA\] Cohort randomized Phase II) II. To determine whether omitting adjuvant CDDP and 5-FU (observation alone in the adjuvant setting) will result in non-inferior overall survival as compared with those patients receiving adjuvant CDDP and 5-FU chemotherapy. (Undetectable Plasma EBV DNA Cohort Phase III)

SECONDARY OBJECTIVES:

I. Time to distant metastasis. (Randomized Phase II and Phase III) II. Time to local progression. (Randomized Phase II and Phase III) III. Time to regional progression. (Randomized Phase II and Phase III) IV. Progression-free survival (Undetectable Cohort). V. Overall survival (Detectable Cohort). VI. Acute and late toxicity profiles based on clinician-reported Common Terminology Criteria for Adverse Events (CTCAE), version (v.) 4. (Randomized Phase II and Phase III) VII. Death during or within 30 days of end of protocol treatment. (Randomized Phase II and Phase III) VIII. Quality of life (general and physical well-being). (Randomized Phase II and Phase III) IX. Quality of life (hearing). (Randomized Phase II and Phase III) X. Quality of life (peripheral neuropathy). (Randomized Phase II and Phase III) XI. Cost effectiveness. (Randomized Phase II and Phase III)

OUTLINE:

Patients undergo intensity modulated radiation therapy (IMRT) once daily (QD) 5 days a week for 6.5 weeks and receive low-dose cisplatin intravenously (IV) over 30-60 minutes once weekly during IMRT. Beginning 1 week after chemoradiation, plasma samples are collected for EBV DNA analysis.

PHASE II: Patients with detectable EBV DNA from pre-treatment analysis are randomized to 1 of 2 treatment arms.

ARM I: Patients receive PF regimen comprising cisplatin IV over 60-120 minutes and fluorouracil IV over 96 hours continuously beginning at least 4 weeks after completion of IMRT. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive GT regimen comprising paclitaxel IV over 1 hour and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 at least 4 weeks after completion of IMRT. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

PHASE III:

Patients with undetectable EBV DNA from pre-treatment analysis are randomized to 1 of 2 treatment arms.

ARM III: Patients receive PF regimen as in Arm I.

ARM IV: Patients undergo clinical observation.

After completion of study treatment, patients are followed up every 4 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Eligibility criteria: Inclusion Criteria:

* Biopsy proven (from primary lesion and/or lymph nodes) diagnosis of cancer of the nasopharynx
* Sites are required to complete Step 1 registration before submitting specimens for EBV DNA analysis.

  * Patients must have detectable pretreatment plasma EBV DNA, determined by the central lab prior to Step 2 registration (see Section 10.2 for details of specimen submission).
  * For patients who have detectable plasma EBV DNA tested at one of the credentialed central labs (listed on the EBV DNA Testing Specimen Transmittal form) within 28 days prior to Step 1 registration: that test result can be used for eligibility without the need for re-testing. To use this test result for eligibility, the central lab must enter the test result through the pathology portal, and the site must follow the instructions in Section 5.4.
* Stage II-IVB disease (AJCC, 7th ed.) with no evidence of distant metastasis, based upon the following minimum diagnostic workup:

  * History/physical examination by a Medical Oncologist or Clinical Oncologist or Radiation Oncologist or ENT, which must include an endoscopic evaluation, a complete list of current medications, and assessment of weight and weight loss in the past 6 months within 21 days prior to registration;
  * Evaluation of tumor extent required within 28 days prior to registration:
* MRI of the nasopharynx and neck; or CT of the nasopharynx and neck with ≤ 3 mm contiguous slices with contrast and bone windows (to evaluate base of skull involvement).

Note: If a treatment planning CT scan is used, it must be with ≤ 3 mm contiguous slices with contrast and be read by a radiologist.

Please refer to section 6.3.2 for MRI requirement for target delineation.

* To rule out distant metastasis, patients must undergo the following imaging within 28 days prior to registration:

  1. a CT scan with contrast of the chest and abdomen (required), and the pelvis (optional), or a total body PET/CT scan (non-contrast PET/CT is acceptable);
  2. a bone scan only when there is suspicion of bone metastases (a PET/CT scan can substitute for the bone scan).
* Zubrod performance status 0-1 within 21 days prior to registration
* Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3
* Platelets ≥ 100,000 cells/mm\^3
* Hemoglobin ≥ 8.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin \[Hgb\] ≥ 8.0 g/dl is acceptable)
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 x institutional ULN
* Alkaline phosphatase ≤ 1.5 x institutional ULN
* Serum creatinine ≤ 1.5 mg/dl or calculated creatinine clearance (CC) ≥ 50 ml/min determined by 24-hour urine collection or estimated by Cockcroft-Gault formula
* Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential
* Women of childbearing potential and male participants who are sexually active must agree to use a medically effective means of birth control throughout protocol treatment
* Patient must provide study specific informed consent prior to study entry, including the mandatory pre-treatment plasma EBV DNA assay

Exclusion Criteria:

* Prior invasive malignancy (except node negative, non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
* Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable; however, at least 6-weeks recovery is necessary if the last regimen included nitrosourea or mitomycin
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* Patients with hearing loss assessed to be primarily sensorineural in nature, requiring a hearing aid, or intervention (i.e. interfering in a clinically significant way with activities of daily living); a conductive hearing loss that is tumor-related is allowed
* ≥ Grade 2 peripheral sensory neuropathy (CTCAE, v. 4.0)
* Severe, active co-morbidity, defined as follows:

  * Major medical or psychiatric illness, which in the investigator's opinion would interfere with the completion of therapy and follow up or with full understanding of the risks and potential complications of the therapy
  * Unstable angina and/or uncontrolled congestive heart failure within the past 6 months
  * Myocardial infarction within the last 6 months
  * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; note that patients switched from IV antibiotics and currently on oral antibiotics whose infection is assessed to be adequately treated or controlled are eligible
  * Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to 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 necessary because the treatments involved in this protocol may be significantly immunosuppressive.
* Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
* Prior allergic reaction to the study drug(s) involved in this protocol
* Patients with undetectable pre-treatment plasma EBV DNA

Primary outcomes:
measure: Overall survival (OS) (Undetectable Plasma EBV DNA Cohort Phase III)
timeFrame: Up to 7 years
measure: Progression-free survival (PFS) (Detectable Plasma EBV DNA Cohort Phase II)
timeFrame: Up to 7 years
Secondary outcomes:
measure: Changes in pure tone audiometry (Phase II and III)
timeFrame: Baseline to up to 1 year
measure: Changes in QOL (hearing) as assessed by the Hearing Handicap Inventory for the Elderly-Screening version (HHIE-S) (Phase II and III)
timeFrame: Baseline to up to 24 months
measure: Changes in QOL (peripheral neuropathy) as assessed by the FACT-Taxane (Phase II and III)
timeFrame: Baseline to up to 24 months
measure: Changes in quality of life (QOL) (general and physical well-being) assessed using the Functional Assessment of Cancer Therapy (FACT)-Nasopharyngeal (NP) (Phase II and III)
timeFrame: Baseline to up to 24 months
measure: Cost effectiveness as assessed by the health-related QOL (HRQOL) from the EuroQol (EQ-5D) instrument (Phase II and III)
timeFrame: Up to 24 months
measure: Incidence of acute grade 3-5 adverse events (Phase II and III)
timeFrame: Up to 7 years
measure: Incidence of death (Phase II and III)
timeFrame: Up to 30 days of end of protocol treatment
measure: Incidence of late grade 3-5 adverse events (Phase II and III)
timeFrame: Up to 7 years
measure: OS (Detectable Plasma EBV DNA Cohort Phase II)
timeFrame: Up to 7 years
measure: PFS (Undetectable Plasma EBV DNA Cohort Phase III)
timeFrame: Up to 7 years
measure: Time to distant metastasis (DM) (Phase II and III)
timeFrame: Up to 7 years
measure: Time to local progression (Phase II and III)
timeFrame: Up to 7 years
measure: Time to regional progression (Phase II and III)
timeFrame: Up to 7 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Cancer Center
state: Alabama
city: Birmingham
country: United States
facility: The Kirklin Clinic at Acton Road
state: Alabama
city: Tucson
country: United States
facility: Banner University Medical Center - Tucson
state: Arizona
city: Auburn
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Auburn
state: California
city: Berkeley
country: United States
facility: Alta Bates Summit Medical Center-Herrick Campus
state: California
city: Burlingame
country: United States
facility: Mills-Peninsula Medical Center
state: California
city: Cameron Park
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Cameron Park
state: California
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Dublin
country: United States
facility: Kaiser Permanente Dublin
state: California
city: Fresno
country: United States
facility: Fresno Cancer Center
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores 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: 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: Palo Alto
country: United States
facility: Stanford Cancer Institute Palo Alto
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: San Francisco
country: United States
facility: UCSF Medical Center-Mount Zion
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Mission Bay
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente Medical Center - Santa Clara
state: California
city: South Pasadena
country: United States
facility: City of Hope South Pasadena
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: Vacaville
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Vacaville
state: California
city: Golden
country: United States
facility: SCL Health Cancer Centers of Colorado - Lutheran Medical Center
state: Colorado
city: Greeley
country: United States
facility: North Colorado Medical Center
state: Colorado
city: Loveland
country: United States
facility: McKee Medical Center
state: Colorado
city: Parker
country: United States
facility: Parker Adventist Hospital
state: Colorado
city: Wheat Ridge
country: United States
facility: SCL Health Lutheran Medical Center
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Newark
country: United States
facility: Helen F Graham Cancer Center
state: Delaware
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Jacksonville
country: United States
facility: Baptist MD Anderson Cancer Center
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: Atlanta
country: United States
facility: Emory Saint Joseph's Hospital
state: Georgia
city: 'Aiea
country: United States
facility: The Cancer Center of Hawaii-Pali Momi
state: Hawaii
city: Honolulu
country: United States
facility: Queen's Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: The Cancer Center of Hawaii-Liliha
state: Hawaii
city: Boise
country: United States
facility: Saint Alphonsus Cancer Care Center-Boise
state: Idaho
city: Aurora
country: United States
facility: Rush - Copley Medical Center
state: Illinois
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: Decatur
country: United States
facility: Cancer Care Specialists of Illinois - Decatur
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Effingham
country: United States
facility: Crossroads Cancer Center
state: Illinois
city: Springfield
country: United States
facility: Memorial Medical Center
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Iowa City
country: United States
facility: University of Iowa/Holden Comprehensive Cancer Center
state: Iowa
city: Wichita
country: United States
facility: Ascension Via Christi Hospitals Wichita
state: Kansas
city: Wichita
country: United States
facility: Wesley Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel 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: Ann Arbor
country: United States
facility: Saint Joseph Mercy Hospital
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: Brownstown
country: United States
facility: Henry Ford Cancer Institute-Downriver
state: Michigan
city: Canton
country: United States
facility: Saint Joseph Mercy Canton
state: Michigan
city: Clarkston
country: United States
facility: McLaren Cancer Institute-Clarkston
state: Michigan
city: Clinton Township
country: United States
facility: Henry Ford Macomb Hospital-Clinton Township
state: Michigan
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Farmington Hills
country: United States
facility: Weisberg Cancer Treatment Center
state: Michigan
city: Flint
country: United States
facility: McLaren Cancer Institute-Flint
state: Michigan
city: Flint
country: United States
facility: Singh and Arora Hematology Oncology PC
state: Michigan
city: Lansing
country: United States
facility: Karmanos Cancer Institute at McLaren Greater Lansing
state: Michigan
city: Lansing
country: United States
facility: Mid-Michigan Physicians-Lansing
state: Michigan
city: Lansing
country: United States
facility: Sparrow Hospital
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: Petoskey
country: United States
facility: McLaren Cancer Institute-Northern Michigan
state: Michigan
city: Pontiac
country: United States
facility: Saint Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: McLaren-Port Huron
state: Michigan
city: Saginaw
country: United States
facility: Ascension Saint Mary's Hospital
state: Michigan
city: West Bloomfield
country: United States
facility: Henry Ford West Bloomfield Hospital
state: Michigan
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Burnsville
country: United States
facility: Minnesota Oncology - Burnsville
state: Minnesota
city: Fridley
country: United States
facility: Unity Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology Hematology PA-Maplewood
state: Minnesota
city: Minneapolis
country: United States
facility: Abbott-Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Robbinsdale
country: United States
facility: North Memorial Medical Health Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Willmar
country: United States
facility: Rice Memorial Hospital
state: Minnesota
city: Cape Girardeau
country: United States
facility: Saint Francis Medical Center
state: Missouri
city: Creve Coeur
country: United States
facility: Siteman Cancer Center at West County Hospital
state: Missouri
city: Rolla
country: United States
facility: Delbert Day Cancer Institute at PCRMC
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center-South County
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center at Saint Peters Hospital
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Springfield
country: United States
facility: CoxHealth South Hospital
state: Missouri
city: Butte
country: United States
facility: Saint James Community Hospital and Cancer Treatment Center
state: Montana
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Las Vegas
country: United States
facility: Radiation Oncology Centers of Nevada Central
state: Nevada
city: Las Vegas
country: United States
facility: Radiation Oncology Centers of Nevada Southeast
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: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Newark
country: United States
facility: Rutgers New Jersey Medical School
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center-Einstein Campus
state: New York
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: Brooklyn
country: United States
facility: Maimonides Medical Center
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: 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: New York Proton Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Sleepy Hollow
country: United States
facility: Memorial Sloan Kettering Sleepy Hollow
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
city: Akron
country: United States
facility: Cleveland Clinic Akron General
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: Elyria
country: United States
facility: Mercy Cancer Center-Elyria
state: Ohio
city: Mansfield
country: United States
facility: Cleveland Clinic Cancer Center Mansfield
state: Ohio
city: Sandusky
country: United States
facility: North Coast Cancer Care
state: Ohio
city: Strongsville
country: United States
facility: Cleveland Clinic Cancer Center Strongsville
state: Ohio
city: Sylvania
country: United States
facility: ProMedica Flower Hospital
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: Oklahoma City
country: United States
facility: Mercy Hospital Oklahoma City
state: Oklahoma
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: Chadds Ford
country: United States
facility: Christiana Care Health System-Concord Health Center
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Lewisburg
country: United States
facility: Geisinger Medical Oncology-Lewisburg
state: Pennsylvania
city: Lewistown
country: United States
facility: Lewistown Hospital
state: Pennsylvania
city: Pottsville
country: United States
facility: Geisinger Cancer Services-Pottsville
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Geisinger Wyoming Valley/Henry Cancer Center
state: Pennsylvania
city: Boiling Springs
country: United States
facility: Prisma Health Cancer Institute - Spartanburg
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Cancer Institute - Faris
state: South Carolina
city: Greenville
country: United States
facility: Saint Francis Cancer Center
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Cancer Institute - Eastside
state: South Carolina
city: Greer
country: United States
facility: Prisma Health Cancer Institute - Greer
state: South Carolina
city: Greer
country: United States
facility: Gibbs Cancer Center-Pelham
state: South Carolina
city: Seneca
country: United States
facility: Prisma Health Cancer Institute - Seneca
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Center
state: South Carolina
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: American Fork
country: United States
facility: American Fork Hospital / Huntsman Intermountain Cancer Center
state: Utah
city: Cedar City
country: United States
facility: Sandra L Maxwell Cancer Center
state: Utah
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: Riverton
country: United States
facility: Riverton Hospital
state: Utah
city: Saint George
country: United States
facility: Saint George Regional Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists-Salt Lake City
state: Utah
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Portsmouth
country: United States
facility: Naval Medical Center - Portsmouth
state: Virginia
city: Vancouver
country: United States
facility: Legacy Salmon Creek Hospital
state: Washington
city: Antigo
country: United States
facility: Langlade Hospital and Cancer Center
state: Wisconsin
city: Eau Claire
country: United States
facility: HSHS Sacred Heart Hospital
state: Wisconsin
city: Eau Claire
country: United States
facility: Marshfield Medical Center-EC 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
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Medical Center-Marshfield
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Minocqua
country: United States
facility: Marshfield Clinic-Minocqua Center
state: Wisconsin
city: Rice Lake
country: United States
facility: Marshfield Medical Center-Rice Lake
state: Wisconsin
city: Stevens Point
country: United States
facility: Ascension Saint Michael's Hospital
state: Wisconsin
city: Stevens Point
country: United States
facility: Marshfield Medical Center-River Region at Stevens Point
state: Wisconsin
city: Wausau
country: United States
facility: Aspirus Regional Cancer Center
state: Wisconsin
city: Weston
country: United States
facility: Diagnostic and Treatment Center
state: Wisconsin
city: Weston
country: United States
facility: Marshfield Medical Center - Weston
state: Wisconsin
city: Wisconsin Rapids
country: United States
facility: Aspirus Cancer Care - Wisconsin Rapids
state: Wisconsin
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Toronto
country: Canada
facility: University Health Network-Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University Department of Oncology
state: Quebec
city: Montreal
country: Canada
facility: The Research Institute of the McGill University Health Centre (MUHC)
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Shatin
country: China
facility: Chinese University of Hong Kong-Prince of Wales Hospital
state: Hong Kong
city: Guangdong Province
country: China
facility: Zhongshan Hospital Fudan University
state: Shanghai
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
city: Chai Wan
country: Hong Kong
facility: Pamela Youde Nethersole Eastern Hospital
city: San Juan
country: Puerto Rico
facility: Centro Comprensivo de Cancer de UPR
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Hospital-Lin Kou Medical Center
Study officials:
affiliation: NRG Oncology
name: Nancy Lee
role: PRINCIPAL_INVESTIGATOR
References: