Radiation Therapy, Paclitaxel, and Carboplatin With or Without Trastuzumab in Treating Patients With Esophageal Cancer

Gastroesophageal Junction Adenocarcinoma Clinical Trial

Official title:

A Phase III Trial Evaluating the Addition of Trastuzumab to Trimodality Treatment of HER2-Overexpressing Esophageal Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01196390
• Other study ID #: NCI-2011-02601
• Secondary ID: NCI-2011-02601CD
• Status: Completed
• Phase: Phase 3
• Start date: February 14, 2011
• Est. completion date: August 15, 2023

Study information

• Verified date: August 2023
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase III trial studies how well radiation therapy, paclitaxel, and carboplatin with or without trastuzumab work in treating patients with esophageal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, 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. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving radiation therapy and combination chemotherapy together with or without trastuzumab is more effective in treating esophageal cancer.

Description:

PRIMARY OBJECTIVES: l. To determine if trastuzumab increases disease-free survival when combined with trimodality treatment (radiation plus chemotherapy followed by surgery) for patients with human epidermal growth factor receptor 2 (HER2)-overexpressing esophageal adenocarcinoma. SECONDARY OBJECTIVES: I. To evaluate if the addition of trastuzumab to trimodality treatment increases the pathologic complete response rate and overall survival for patients with HER2-overexpressing esophageal adenocarcinoma. II. To develop a tissue bank of tumor tissue from patients with non-metastatic esophageal adenocarcinoma. III. To determine molecular correlates of complete pathologic response, disease-free survival, and overall survival for patients with HER2-overexpressing esophageal adenocarcinoma treated with neoadjuvant and maintenance trastuzumab. IV. To evaluate predictors of cardiotoxicity in patients with esophageal cancer treated with trastuzumab and chemoradiation. V. To evaluate adverse events associated with the addition of trastuzumab to trimodality treatment for patients with non-metastatic esophageal adenocarcinoma. PATIENT-REPORTED QUALITY OF LIFE OBJECTIVES: I. To determine if the addition of trastuzumab to trimodality treatment improves the patient-reported Functional Assessment of Cancer Therapy for Esophageal Cancer (FACT-E) Esophageal Cancer Subscale (ECS) score. II. To determine if an improvement in the FACT-E ECS score at 6-8 weeks post completion of neoadjuvant chemoradiation correlates with pathologic complete response. III. To determine if pathologic complete response correlates with the FACT-E ECS score at 1 year and/or 2 years from the start of chemoradiation. IV. To determine if the addition of trastuzumab to trimodality treatment improves the Swallow Index and Eating Index Subscale scores of the FACT-E. V. To determine if the addition of trastuzumab to paclitaxel, carboplatin, and radiation impacts quality-adjusted survival. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive trastuzumab intravenously (IV) over 30-90 minutes on days 1, 8, 15, 22, 29, 36, and 57 and paclitaxel IV over 60 minutes and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Beginning 21-56 days after surgery, patients receive trastuzumab IV over 30-90 minutes. Treatment repeats every 21 days for 13 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive paclitaxel IV over 60 minutes and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Within 5-8 weeks after completion of radiotherapy, all patients undergo surgery. After completion of study therapy, patients are followed up every 4 months for 2 years and then yearly thereafter.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 203
• Est. completion date: August 15, 2023
• Est. primary completion date: December 23, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pathologically confirmed primary adenocarcinoma of the esophagus that involves the mid (up to 25 cm), distal, or esophagogastric junction; the cancer may involve the stomach up to 5 cm
• Endoscopy with biopsy
• PRIOR TO STEP 1 REGISTRATION BUT WITHIN 56 DAYS PRIOR TO STEP 2 REGISTRATION
• Intent to submit tissue for central HER2 testing
• Stage T1N1-2, T2-3N0-2, according to the American Joint Committee on Cancer (AJCC) 7th

edition staging, based on the following minimum diagnostic work-up:

• Chest/abdominal/pelvic computed tomography (CT) or whole-body positron emission tomography (PET)/CT (NOTE: if CT is performed at this time point, whole-body PET/CT will be required prior to step 2 registration; PET/CT of skull base to mid-thigh is acceptable) (NOTE: if adenopathy is noted on CT or whole-body PET/CT scan, an endoscopic ultrasound is not required prior to STEP 2 registration as long as adequate tissue has been obtained for central HER2 testing)
• Patients may have regional adenopathy including para-esophageal, gastric, gastrohepatic and celiac nodes; if celiac adenopathy is present, it must be =< 2 cm
• Patients with tumors at the level of the carina or above must undergo bronchoscopy to exclude fistula
• Zubrod performance status 0-2
• 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)
• Creatinine =< 2 times upper limit of normal
• Bilirubin =< 1.5 times upper limit of normal
• Aspartate aminotransferase (AST) =< 3.0 times upper limit of normal
• For women of childbearing potential, a negative serum or urine pregnancy test
• Patients must sign a study-specific informed consent prior to study entry
• CONDITIONS FOR PATIENT ELIGIBILITY PRIOR TO STEP 2 REGISTRATION (HER2-POSITIVE PATIENTS ONLY)
• HER2 expressing adenocarcinoma of the esophagus centrally
• Surgical consultation to confirm that patient will be able to undergo curative resection after completion of chemoradiation within 56 days prior to step 2 registration
• Radiation oncology consultation to confirm that disease can be encompassed in a radiotherapy field within 56 days prior to step 2 registration
• Consultation with a medical oncologist within 56 days prior to step 2 registration
• Stage T1N1-2, T2-3N0-2, according to the AJCC 7th edition staging, based upon the

following minimum diagnostic work-up:

• History/physical examination, with documentation of the patient's weight, within 14 days prior to step 2 registration
• Whole-body PET/CT scan within 56 days prior to step 2 registration (if only CT performed prior to step 1 registration)
• Endoscopic ultrasound within 56 days prior to step 2 registration, unless the patient is found to have adenopathy per CT or whole-body PET/CT scan
• Electrocardiogram (EKG) within 56 days prior to step 2 registration
• Serum creatinine =< 2 x the upper limit or normal within 14 days prior to step 2 registration
• Zubrod performance status 0-2 within 14 days prior to step 2 registration
• For women of childbearing potential, a negative serum pregnancy test within 14 days prior to step 2 registration
• Left ventricular ejection fraction (LVEF) >= institutional lower limit of normal by cardiac echocardiogram (echo) or multi gated acquisition (MUGA) scan within 56 days prior to step 2 registration
• Women of childbearing potential and sexually active male participants must agree to practice adequate contraception while on study and for at least 60 days following the last dose of chemotherapy or trastuzumab

Exclusion Criteria:

• Patients with cervical esophageal carcinoma
• Patients with T1N0 disease, T4 disease, and proximal esophageal cancers (15-24 cm)
• Prior systemic chemotherapy for esophageal cancer; note that prior chemotherapy for a different cancer is allowable
• Prior radiation therapy for esophageal cancer or prior chest radiotherapy
• Prior anthracycline or taxane
• Evidence of tracheoesophageal fistula or invasion into the trachea or major bronchi
• Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 2 years (e.g., carcinoma in situ of the breast, oral cavity, or cervix are permissible)
• Medical contraindications to esophagectomy
• Prior therapy with any agent targeting the HER2 pathway or human epidermal growth factor receptor 1 (HER1) (epidermal growth factor receptor [EGFR]) pathway
• Prior therapy with trastuzumab
• Prior allergic reaction to the study drugs involved in this protocol or to a monoclonal antibody
• Previous history of congestive heart failure
• Severe, active comorbidity, defined as follows:
• Unstable angina in the last 6 months
• Transmural myocardial infarction within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of 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; protocol-specific requirements may also exclude immunocompromised patients
• Pregnant or nursing women or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception

Related Conditions & MeSH terms

• Adenocarcinoma
• Esophageal Adenocarcinoma
• Esophageal Neoplasms
• Gastroesophageal Junction Adenocarcinoma
• Stage IB Esophageal Cancer AJCC v7
• Stage IIA Esophageal Cancer AJCC v7
• Stage IIB Esophageal Cancer AJCC v7
• Stage IIIA Esophageal Cancer AJCC v7
• Stage IIIB Esophageal Cancer AJCC v7

Intervention

Drug:
• Carboplatin
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Paclitaxel
Given IV

Other:
• Quality-of-Life Assessment
Ancillary studies

Radiation:
• Radiation Therapy
Undergo radiation therapy

Procedure:
• Therapeutic Conventional Surgery
Undergo surgery

Biological:
• Trastuzumab
Given IV

Locations

Country	Name	City	State
United States	Bixby Medical Center	Adrian	Michigan
United States	Hickman Cancer Center	Adrian	Michigan
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	Summa Health System - Akron Campus	Akron	Ohio
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	AdventHealth Altamonte	Altamonte Springs	Florida
United States	American Fork Hospital / Huntsman Intermountain Cancer Center	American Fork	Utah
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Cancer Care Center at Island Hospital	Anacortes	Washington
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	Northwest Community Hospital	Arlington Heights	Illinois
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Grady Health System	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	MultiCare Auburn Medical Center	Auburn	Washington
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Summa Health System - Barberton Campus	Barberton	Ohio
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	UPMC-Heritage Valley Health System Beaver	Beaver	Pennsylvania
United States	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana
United States	UM Upper Chesapeake Medical Center	Bel Air	Maryland
United States	Overlake Medical Center	Bellevue	Washington
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Mac Neal Hospital	Berwyn	Illinois
United States	Constantinou, Costas L MD (UIA Investigator)	Bettendorf	Iowa
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	The Kirklin Clinic at Acton Road	Birmingham	Alabama
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	McFarland Clinic - Boone	Boone	Iowa
United States	Boston Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Boulder Community Hospital	Boulder	Colorado
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Cox Cancer Center Branson	Branson	Missouri
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Harrison Medical Center	Bremerton	Washington
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Mills-Peninsula Medical Center	Burlingame	California
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Sands Cancer Center	Canandaigua	New York
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Mercy San Juan Medical Center	Carmichael	California
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	East Bay Radiation Oncology Center	Castro Valley	California
United States	Sandra L Maxwell Cancer Center	Cedar City	Utah
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Geauga Hospital	Chardon	Ohio
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	Atrium Health Pineville/LCI-Pineville	Charlotte	North Carolina
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	Saint Luke's Hospital	Chesterfield	Missouri
United States	Northwestern University	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Weiss Memorial Hospital	Chicago	Illinois
United States	Enloe Medical Center	Chico	California
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Oncology Hematology Care Inc-Anderson	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Blue Ash	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Eden Park	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Mercy West	Cincinnati	Ohio
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Case Western Reserve University	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Columbus NCI Community Oncology Research Program	Columbus	Ohio
United States	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Atrium Health Cabarrus/LCI-Concord	Concord	North Carolina
United States	Concord Hospital	Concord	New Hampshire
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Oncology Hematology Care Inc-Crestview	Crestview Hills	Kentucky
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Danville Regional Medical Center	Danville	Virginia
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton NCI Community Oncology Research Program	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Delaware Radiation Oncology	Delaware	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Rose	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	Western States Cancer Research NCORP	Denver	Colorado
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wentworth-Douglass Hospital	Dover	New Hampshire
United States	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Epic Care-Dublin	Dublin	California
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Northeast Radiation Oncology Center	Dunmore	Pennsylvania
United States	Mercy Medical Center	Durango	Colorado
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	HSHS Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Elkhart Clinic	Elkhart	Indiana
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana
United States	Mercy Cancer Center-Elyria	Elyria	Ohio
United States	Bay Area Breast Surgeons Inc	Emeryville	California
United States	Epic Care Partners in Cancer Care	Emeryville	California
United States	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado
United States	Swedish Medical Center	Englewood	Colorado
United States	Green Bay Oncology - Escanaba	Escanaba	Michigan
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Oncology Hematology Care Inc-Healthplex	Fairfield	Ohio
United States	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota
United States	Piedmont Fayette Hospital	Fayetteville	Georgia
United States	Saint Francis Hospital	Federal Way	Washington
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Parkview Hospital Randallia	Fort Wayne	Indiana
United States	Radiation Oncology Associates PC	Fort Wayne	Indiana
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Fredericksburg Oncology Inc	Fredericksburg	Virginia
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Fresno Cancer Center	Fresno	California
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Unity Hospital	Fridley	Minnesota
United States	Northeast Georgia Medical Center-Gainesville	Gainesville	Georgia
United States	University of Texas Medical Branch	Galveston	Texas
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	Glens Falls Hospital	Glens Falls	New York
United States	Mountain Blue Cancer Care Center	Golden	Colorado
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Marin General Hospital	Greenbrae	California
United States	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Rocky Mountain Cancer Centers-Greenwood Village	Greenwood Village	Colorado
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Hartford Hospital	Hartford	Connecticut
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Cancer and Blood Specialists-Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada
United States	GenesisCare USA - Henderson	Henderson	Nevada
United States	Las Vegas Cancer Center-Henderson	Henderson	Nevada
United States	Houston Methodist Hospital	Houston	Texas
United States	Centerpoint Medical Center LLC	Independence	Missouri
United States	Franciscan Health Indianapolis	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	McFarland Clinic - Jefferson	Jefferson	Iowa
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	UPMC-Johnstown/John P. Murtha Regional Cancer Center	Johnstown	Pennsylvania
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Presence Saint Mary's Hospital	Kankakee	Illinois
United States	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	The University of Kansas Cancer Center-South	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	University of Kansas Cancer Center-West	Kansas City	Kansas
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Kettering Medical Center	Kettering	Ohio
United States	Ballad Health Cancer Care - Kingsport	Kingsport	Tennessee
United States	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee
United States	Vidant Oncology-Kinston	Kinston	North Carolina
United States	AdventHealth Kissimmee	Kissimmee	Florida
United States	Community Howard Regional Health	Kokomo	Indiana
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	IU Health La Porte Hospital	La Porte	Indiana
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Lancaster Radiation Oncology	Lancaster	Ohio
United States	Sparrow Hospital	Lansing	Michigan
United States	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada
United States	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada
United States	GenesisCare USA - Fort Apache	Las Vegas	Nevada
United States	GenesisCare USA - Las Vegas	Las Vegas	Nevada
United States	GenesisCare USA - Vegas Tenaya	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada
United States	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada
United States	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	Summerlin Hospital Medical Center	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	UTMB Cancer Center at Victory Lakes	League City	Texas
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	Central Maine Medical Center	Lewiston	Maine
United States	Saint Joseph Regional Medical Center	Lewiston	Idaho
United States	Baptist Health Lexington	Lexington	Kentucky
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Liberty Radiation Oncology Center	Liberty	Missouri
United States	Lima Memorial Hospital	Lima	Ohio
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Logan Regional Hospital	Logan	Utah
United States	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Los Angeles County-USC Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	McKee Medical Center	Loveland	Colorado
United States	Covenant Medical Center-Lakeside	Lubbock	Texas
United States	Medical Center of Central Georgia	Macon	Georgia
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	McFarland Clinic - Marshalltown	Marshalltown	Iowa
United States	Marshfield Medical Center	Marshfield	Wisconsin
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Contra Costa Regional Medical Center	Martinez	California
United States	Matthews Radiation Oncology Center	Matthews	North Carolina
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	UPMC Cancer Center at UPMC McKeesport	McKeesport	Pennsylvania
United States	Summa Health Medina Medical Center	Medina	Ohio
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	Midstate Medical Center	Meriden	Connecticut
United States	Miami Cancer Institute	Miami	Florida
United States	UH Seidman Cancer Center at Southwest General Hospital	Middleburg Heights	Ohio
United States	Middlesex Hospital	Middletown	Connecticut
United States	Dana-Farber/Brigham and Women's Cancer Center at Milford Regional	Milford	Massachusetts
United States	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Zablocki Veterans Administration Medical Center	Milwaukee	Wisconsin
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Trinity Cancer Care Center	Minot	North Dakota
United States	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana
United States	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Providence Hospital	Mobile	Alabama
United States	Kaiser Permanente-Modesto	Modesto	California
United States	Memorial Medical Center	Modesto	California
United States	Garneau, Stewart C MD (UIA Investigator)	Moline	Illinois
United States	Porubcin, Michael MD (UIA Investigator)	Moline	Illinois
United States	Spector, David MD (UIA Investigator)	Moline	Illinois
United States	Trinity Medical Center	Moline	Illinois
United States	Atrium Health Union/LCI-Union	Monroe	North Carolina
United States	Mercy Memorial Hospital	Monroe	Michigan
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	UPMC Hillman Cancer Center in Coraopolis	Moon	Pennsylvania
United States	Morristown Medical Center	Morristown	New Jersey
United States	Virtua Memorial	Mount Holly	New Jersey
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Skagit Valley Hospital	Mount Vernon	Washington
United States	El Camino Hospital	Mountain View	California
United States	IU Health Ball Memorial Hospital	Muncie	Indiana
United States	Intermountain Medical Center	Murray	Utah
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Allegheny Valley Hospital	Natrona Heights	Pennsylvania
United States	UPMC Cancer Center-Natrona Heights	Natrona Heights	Pennsylvania
United States	UPMC Jameson	New Castle	Pennsylvania
United States	Yale University	New Haven	Connecticut
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai Union Square	New York	New York
United States	Mount Sinai West	New York	New York
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Christiana Gynecologic Oncology LLC	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Licking Memorial Hospital	Newark	Ohio
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Newark Radiation Oncology	Newark	Ohio
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Lakeland Hospital Niles	Niles	Michigan
United States	Southwest VA Regional Cancer Center	Norton	Virginia
United States	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut
United States	William Backus Hospital	Norwich	Connecticut
United States	Sutter Cancer Research Consortium	Novato	California
United States	Ascension Providence Hospitals - Novi	Novi	Michigan
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Tumor Institute	Oakland	California
United States	Hematology and Oncology Associates-Oakland	Oakland	California
United States	Highland General Hospital	Oakland	California
United States	Kaiser Permanente Oakland-Broadway	Oakland	California
United States	Kaiser Permanente-Oakland	Oakland	California
United States	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Capital Medical Center	Olympia	Washington
United States	Providence - Saint Peter Hospital	Olympia	Washington
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Saint Charles Hospital	Oregon	Ohio
United States	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	AdventHealth East Orlando	Orlando	Florida
United States	AdventHealth Orlando	Orlando	Florida
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Parker Adventist Hospital	Parker	Colorado
United States	Rocky Mountain Cancer Centers-Parker	Parker	Colorado
United States	University Hospitals Parma Medical Center	Parma	Ohio
United States	Singing River Hospital	Pascagoula	Mississippi
United States	Capital Health Medical Center-Hopewell	Pennington	New Jersey
United States	American College of Radiology Imaging Network	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Jefferson Torresdale Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Mayo Clinic Hospital in Arizona	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	UPMC Jefferson Regional Radiation Oncology	Pittsburgh	Pennsylvania
United States	UPMC-Passavant Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Presbyterian Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Saint Clair Hospital Cancer Center	Pittsburgh	Pennsylvania
United States	UPMC-Saint Margaret	Pittsburgh	Pennsylvania
United States	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania
United States	Berkshire Medical Center - Cancer Center	Pittsfield	Massachusetts
United States	Valley Medical Oncology Consultants	Pleasanton	California
United States	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Maine Medical Center-Bramhall Campus	Portland	Maine
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas
United States	Miriam Hospital	Providence	Rhode Island
United States	Radiation Oncology Associates Incorporated	Providence	Rhode Island
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	UNC Rex Healthcare	Raleigh	North Carolina
United States	Kaiser Permanente-Rancho Cordova Cancer Center	Rancho Cordova	California
United States	University Hospitals Portage Medical Center	Ravenna	Ohio
United States	Kaiser Permanente-Redwood City	Redwood City	California
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Renown Regional Medical Center	Reno	Nevada
United States	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Kaiser Permanente-Richmond	Richmond	California
United States	Reid Health	Richmond	Indiana
United States	West Suburban Medical Center	River Forest	Illinois
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Highland Hospital	Rochester	New York
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Wilmot Cancer Institute Radiation Oncology at Greece	Rochester	New York
United States	Rock Hill Radiation Therapy Center	Rock Hill	South Carolina
United States	SwedishAmerican Regional Cancer Center/ACT	Rockford	Illinois
United States	Rohnert Park Cancer Center	Rohnert Park	California
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Kaiser Permanente-Roseville	Roseville	California
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Kaiser Permanente - Sacramento	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	South Sacramento Cancer Center	Sacramento	California
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Saint George Regional Medical Center	Saint George	Utah
United States	Saint Helena Hospital	Saint Helena	California
United States	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Salem Hospital	Salem	Oregon
United States	UH Seidman Cancer Center at Salem Regional Medical Center	Salem	Ohio
United States	Salina Regional Health Center	Salina	Kansas
United States	TidalHealth Peninsula Regional	Salisbury	Maryland
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California
United States	Kaiser Permanente-San Rafael	San Rafael	California
United States	North Coast Cancer Care	Sandusky	Ohio
United States	UH Seidman Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Maine Medical Center- Scarborough Campus	Scarborough	Maine
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	FHCC South Lake Union	Seattle	Washington
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Kaiser Permanente Washington	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	University of Washington Medical Center - Montlake	Seattle	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania
United States	Olympic Medical Cancer Care Center	Sequim	Washington
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Memorial Sloan Kettering Sleepy Hollow	Sleepy Hollow	New York
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	South Bend Clinic	South Bend	Indiana
United States	Kaiser Permanente Cancer Treatment Center	South San Francisco	California
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Dana-Farber/Brigham and Women's Cancer Center at South Shore	South Weymouth	Massachusetts
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	Sparta Cancer Treatment Center	Sparta	New Jersey
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Evergreen Hematology and Oncology PS	Spokane	Washington
United States	Baystate Medical Center	Springfield	Massachusetts
United States	CoxHealth South Hospital	Springfield	Missouri
United States	D'Amour Center for Cancer Care	Springfield	Massachusetts
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Robert and Carol Weissman Cancer Center at Martin Health	Stuart	Florida
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	Overlook Hospital	Summit	New Jersey
United States	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	MultiCare Allenmore Hospital	Tacoma	Washington
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Northwest NCI Community Oncology Research Program	Tacoma	Washington
United States	Saint Joseph Medical Center	Tacoma	Washington
United States	North Suburban Medical Center	Thornton	Colorado
United States	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	Saint Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio
United States	University of Toledo	Toledo	Ohio
United States	Upper Valley Medical Center	Troy	Ohio
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	Memorial Sloan Kettering Nassau	Uniondale	New York
United States	UPMC Uniontown Hospital Radiation Oncology	Uniontown	Pennsylvania
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	Compass Oncology Vancouver	Vancouver	Washington
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	MD Anderson Cancer Center at Cooper-Voorhees	Voorhees	New Jersey
United States	Virtua Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	UPMC Washington Hospital Radiation Oncology	Washington	Pennsylvania
United States	Aurora Cancer Care-Waukesha	Waukesha	Wisconsin
United States	Fulton County Health Center	Wauseon	Ohio
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Froedtert West Bend Hospital/Kraemer Cancer Center	West Bend	Wisconsin
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Reading Hospital	West Reading	Pennsylvania
United States	Saint Ann's Hospital	Westerville	Ohio
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Michiana Hematology Oncology PC-Westville	Westville	Indiana
United States	Wexford Health and Wellness Pavilion	Wexford	Pennsylvania
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Wheeling Hospital/Schiffler Cancer Center	Wheeling	West Virginia
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	AdventHealth Winter Park	Winter Park	Florida
United States	Cancer Treatment Center	Wooster	Ohio
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	Main Line Health NCORP	Wynnewood	Pennsylvania
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free Survival (DFS)	A disease event is defined as local/regional persistence or recurrence of the cancer under study, distant metastases, a new second primary cancer, or death due to any cause. Participants undergoing surgery who had an R2 resection and participants not undergoing surgery who had a positive endoscopic biopsy or no biopsy at all were considered to have local persistence of disease. Disease-free survival time is defined as time from randomization to the date of first disease event or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis was to occur after 162 events were reported.	From randomization to last follow-up. Maximum follow-up at time of analysis was 8.0 years.
Secondary	Percentage of Participants With Pathologic Complete Response at Surgery	Pathologic Complete Response (pCR) is evaluated after surgery and is based on the pathology review of the submitted surgical specimen. Pathologic Complete Response occurs if the pathologist determines that the resected esophageal specimen, accompanying lymph nodes, and surgical margins are all free of tumor.	At the time of surgery, 5-8 weeks after completion of radiation therapy.
Secondary	Overall Survival	Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis occurred after 109 deaths were reported.	From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.
Secondary	Frequency of Highest Grade Adverse Event Per Participant	Common Terminology Criteria for Adverse Events (version 4.0 before 4-1-2018; then version 5.0) grades adverse event severity from 1=mild to 5=death. Summary data provided is in this outcome measure; see Adverse Events Module for specific adverse event data.	From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.
Secondary	Percentage of Patients With Improvement in the Functional Assessment of Cancer Therapy - Esophagus (FACT-E) Esophageal Cancer Subscale (ECS) Subscale After Treatment	The ECS is a 17-item self-report instrument designed to measure multidimensional quality of life in patients with esophagus cancer with a total score ranging from 0-68. It is to be administered with the Functional Assessment of Cancer Therapy - General (FACT-G). A higher score indicates better QOL. Improvement is defined as an increase from the baseline score of at least 5 points.	Baseline, 6-8 weeks after end of radiation therapy (approximately 11.5-13.5 weeks from treatment start), 1 and 2 years from treatment start
Secondary	Quality-adjusted Survival		From randomization to last follow-up. Maximum follow-up at time of primary outcome measure analysis was 8 years.
Secondary	Molecular Correlates of Efficacy		From randomization to last follow-up. Maximum follow-up at time of primary outcome measure analysis was 8 years.
Secondary	Number of Participants With Any Cardiac Adverse Events Regardless of Attribution	Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event (AE) severity from 1=mild to 5=death. Logistic regression was used to evaluate treatment arm, clinical tumor stage (T stage), Zubrod Performance Status, gender, presence of adenopathy, and age as possible predictors of cardiac adverse events. Results of the final model are reported in the statistical analysis section. Summary adverse event data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.	From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.

External Links

•   Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.