S1403, Afatinib Dimaleate With or Without Cetuximab in Treating Patients With Newly Diagnosed Stage IV or Recurrent, EGFR Mutation Positive Non-small Cell Lung Cancer

February 7, 2024 updated by: SWOG Cancer Research Network

A Randomized Phase II/III Trial of Afatinib Plus Cetuximab Versus Afatinib Alone in Treatment-Naive Patients With Advanced, EGFR Mutation Positive Non-small Cell Lung Cancer (NSCLC)

This randomized phase II/III trial studies how well afatinib dimaleate with cetuximab works and compares it with afatinib dimaleate alone in treating patients with newly diagnosed stage IV or recurrent (has come back), epidermal growth factor receptor (EGFR) mutation positive non-small cell lung cancer. Afatinib dimaleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, may block tumor growth in different ways by targeting certain cells. It is not yet known whether afatinib dimaleate is more effective when given alone or with cetuximab in treating patients with non-small cell lung cancer.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate if there is sufficient evidence to continue to the phase III component by comparing progression-free survival (PFS) between patients randomized to afatinib (afatinib dimaleate) in combination with cetuximab versus afatinib alone in the first-line treatment of patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC). (Phase II) II. To determine the efficacy of the combination of afatinib and cetuximab compared to afatinib alone as measured by overall survival (OS) in the first-line treatment of patients with advanced EGFR-mutant NSCLC. (Phase III)

SECONDARY OBJECTIVES:

I. To evaluate the overall response rate (confirmed and unconfirmed, complete and partial responses) in the subset of patients with measurable disease treated with afatinib plus cetuximab compared to afatinib alone.

II. To assess the safety of each treatment arm when used in the first-line setting.

III. To compare time to treatment failure and time to treatment discontinuation between randomized to afatinib in combination with cetuximab versus afatinib alone.

TERTIARY OBJECTIVES:

I. To investigate the molecular mechanisms that confer benefit from afatinib and afatinib plus cetuximab by evaluating whether the presence of de novo EGFR T790M mutation or other molecular alterations in the pre-treatment tumor influence the clinical outcomes.

II. To quantitatively assess whether the ratio of sensitizing EGFR (EGFRs) mutation to EGFR T790M influences outcome and is altered during treatment.

III. To evaluate the frequency of known mechanisms of resistance to EGFR-directed therapies in the context of afatinib plus cetuximab and afatinib alone treatment.

IV. To identify potential novel predictors of benefit to afatinib plus cetuximab.

V. To identify potential new mechanisms of resistance to EGFR-directed therapies.

VI. To establish patient-derived xenografts (PDXs) from a subset of patients by re-biopsy at the time of progressive disease for drug testing and genomic analysis.

VII. To assess whether circulating tumor markers can be used as indicators of sensitivity and resistance to afatinib plus cetuximab and afatinib alone.

VIII. To determine whether the levels of EGFR protein by immunohistochemistry predict for benefit to afatinib plus cetuximab and afatinib alone.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive afatinib dimaleate orally (PO) once daily (QD) on days 1-28 and cetuximab intravenously (IV) over 2 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive afatinib dimaleate as in Arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 years.

Study Type

Interventional

Enrollment (Actual)

174

Phase

Phase 2
Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Arkansas
  - Fort Smith, Arkansas, United States, 72903
    - Mercy Hospital Fort Smith
  - Hot Springs, Arkansas, United States, 71913
    - CHI Saint Vincent Cancer Center Hot Springs
  - Jonesboro, Arkansas, United States, 72401
    - Fowler Family Center for Cancer Care
- California
  - Anaheim, California, United States, 92807
    - Kaiser Permanente-Anaheim
  - Arroyo Grande, California, United States, 93420
    - PCR Oncology
  - Auburn, California, United States, 95602
    - Sutter Auburn Faith Hospital
  - Auburn, California, United States, 95603
    - Sutter Cancer Centers Radiation Oncology Services-Auburn
  - Bakersfield, California, United States, 93301
    - AIS Cancer Center at San Joaquin Community Hospital
  - Baldwin Park, California, United States, 91706
    - Kaiser Permanente-Baldwin Park
  - Bellflower, California, United States, 90706
    - Kaiser Permanente-Bellflower
  - Berkeley, California, United States, 94704
    - Alta Bates Summit Medical Center-Herrick Campus
  - Burlingame, California, United States, 94010
    - Mills-Peninsula Medical Center
  - Cameron Park, California, United States, 95682
    - Sutter Cancer Centers Radiation Oncology Services-Cameron Park
  - Castro Valley, California, United States, 94546
    - Eden Hospital Medical Center
  - Davis, California, United States, 95616
    - Sutter Davis Hospital
  - Fontana, California, United States, 92335
    - Kaiser Permanente-Fontana
  - Fremont, California, United States, 94538
    - Palo Alto Medical Foundation-Fremont
  - Harbor City, California, United States, 90710
    - Kaiser Permanente - Harbor City
  - Irvine, California, United States, 92618
    - Kaiser Permanente-Irvine
  - La Jolla, California, United States, 92093
    - UC San Diego Moores Cancer Center
  - Los Angeles, California, United States, 90027
    - Kaiser Permanente Los Angeles Medical Center
  - Los Angeles, California, United States, 90034
    - Kaiser Permanente-Cadillac
  - Marysville, California, United States, 95901
    - Fremont - Rideout Cancer Center
  - Merced, California, United States, 95340
    - Mercy UC Davis Cancer Center
  - Modesto, California, United States, 95355
    - Memorial Medical Center
  - Mountain View, California, United States, 94040
    - Palo Alto Medical Foundation-Camino Division
  - Mountain View, California, United States, 94040
    - Palo Alto Medical Foundation-Gynecologic Oncology
  - Novato, California, United States, 94945
    - Sutter Cancer Research Consortium
  - Palo Alto, California, United States, 94301
    - Palo Alto Medical Foundation Health Care
  - Panorama City, California, United States, 91402
    - Kaiser Permanente - Panorama City
  - Rancho Mirage, California, United States, 92270
    - Eisenhower Medical Center
  - Riverside, California, United States, 92505
    - Kaiser Permanente-Riverside
  - Roseville, California, United States, 95661
    - Sutter Cancer Centers Radiation Oncology Services-Roseville
  - Roseville, California, United States, 95661
    - Sutter Roseville Medical Center
  - Sacramento, California, United States, 95816
    - Sutter Medical Center Sacramento
  - Sacramento, California, United States, 95817
    - University of California Davis Comprehensive Cancer Center
  - San Diego, California, United States, 92120
    - Kaiser Permanente-San Diego Zion
  - San Diego, California, United States, 92108
    - Kaiser Permanente-San Diego Mission
  - San Francisco, California, United States, 94115
    - California Pacific Medical Center-Pacific Campus
  - San Marcos, California, United States, 92069
    - Kaiser Permanente-San Marcos
  - Santa Cruz, California, United States, 95065
    - Palo Alto Medical Foundation-Santa Cruz
  - Santa Rosa, California, United States, 95403
    - Sutter Pacific Medical Foundation
  - Sunnyvale, California, United States, 94086
    - Palo Alto Medical Foundation-Sunnyvale
  - Truckee, California, United States, 96161
    - Gene Upshaw Memorial Tahoe Forest Cancer Center
  - Vacaville, California, United States, 95687
    - Northbay Cancer Center
  - Vacaville, California, United States, 95687
    - Sutter Cancer Centers Radiation Oncology Services-Vacaville
  - Vallejo, California, United States, 94589
    - Sutter Solano Medical Center/Cancer Center
  - Woodland Hills, California, United States, 91367
    - Kaiser Permanente-Woodland Hills
- Colorado
  - Colorado Springs, Colorado, United States, 80907
    - Penrose-Saint Francis Healthcare
  - Colorado Springs, Colorado, United States, 80907
    - Rocky Mountain Cancer Centers-Penrose
  - Denver, Colorado, United States, 80210
    - Porter Adventist Hospital
  - Durango, Colorado, United States, 81301
    - Mercy Medical Center
  - Durango, Colorado, United States, 81301
    - Southwest Oncology PC
  - Golden, Colorado, United States, 80401
    - Mountain Blue Cancer Care Center
  - Lakewood, Colorado, United States, 80228
    - Saint Anthony Hospital
  - Lakewood, Colorado, United States, 80228
    - Rocky Mountain Cancer Centers-Lakewood
  - Littleton, Colorado, United States, 80122
    - Littleton Adventist Hospital
  - Longmont, Colorado, United States, 80501
    - Longmont United Hospital
  - Longmont, Colorado, United States, 80501
    - Rocky Mountain Cancer Centers-Longmont
  - Parker, Colorado, United States, 80138
    - Parker Adventist Hospital
  - Parker, Colorado, United States, 80138
    - Rocky Mountain Cancer Centers-Parker
  - Pueblo, Colorado, United States, 81004
    - Saint Mary Corwin Medical Center
  - Pueblo, Colorado, United States, 81008
    - Rocky Mountain Cancer Centers - Pueblo
  - Thornton, Colorado, United States, 80260
    - Rocky Mountain Cancer Centers-Thornton
- Connecticut
  - Derby, Connecticut, United States, 06418
    - Smilow Cancer Hospital-Derby Care Center
  - Fairfield, Connecticut, United States, 06824
    - Smilow Cancer Hospital Care Center-Fairfield
  - Guilford, Connecticut, United States, 06437
    - Yale-New Haven Shoreline Medical Center
  - Hartford, Connecticut, United States, 06105
    - Smilow Cancer Hospital Care Center at Saint Francis
  - Middletown, Connecticut, United States, 06457
    - Middlesex Hospital
  - New Haven, Connecticut, United States, 06520
    - Yale University
  - North Haven, Connecticut, United States, 06473
    - Yale-New Haven Hospital North Haven Medical Center
  - Orange, Connecticut, United States, 06477
    - Smilow Cancer Hospital-Orange Care Center
  - Torrington, Connecticut, United States, 06790
    - Smilow Cancer Hospital-Torrington Care Center
  - Trumbull, Connecticut, United States, 06611
    - Smilow Cancer Hospital Care Center-Trumbull
  - Waterbury, Connecticut, United States, 06708
    - Smilow Cancer Hospital-Waterbury Care Center
- Delaware
  - Lewes, Delaware, United States, 19958
    - Beebe Medical Center
  - Newark, Delaware, United States, 19713
    - Helen F Graham Cancer Center
  - Newark, Delaware, United States, 19713
    - Delaware Clinical and Laboratory Physicians PA
  - Newark, Delaware, United States, 19713
    - Medical Oncology Hematology Consultants PA
  - Newark, Delaware, United States, 19718
    - Christiana Care Health System-Christiana Hospital
  - Newark, Delaware, United States, 19713
    - Regional Hematology and Oncology PA
  - Rehoboth Beach, Delaware, United States, 19971
    - Beebe Health Campus
  - Seaford, Delaware, United States, 19973
    - Nanticoke Memorial Hospital
  - Wilmington, Delaware, United States, 19801
    - Christiana Care Health System-Wilmington Hospital
- Florida
  - Jacksonville, Florida, United States, 32207
    - Baptist MD Anderson Cancer Center
  - Pensacola, Florida, United States, 32504
    - Sacred Heart Hospital
- Georgia
  - Macon, Georgia, United States, 31201
    - Medical Center of Central Georgia
  - Macon, Georgia, United States, 31201
    - Central Georgia Gynecologic Oncology
  - Savannah, Georgia, United States, 31405
    - Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
  - Savannah, Georgia, United States, 31404
    - Memorial University Medical Center
  - Savannah, Georgia, United States, 31404
    - Summit Cancer Care-Memorial
  - Savannah, Georgia, United States, 31405
    - Low Country Cancer Care Associates PC
  - Savannah, Georgia, United States, 31405
    - Summit Cancer Care-Candler
  - Valdosta, Georgia, United States, 31602
    - South Georgia Medical Center/Pearlman Cancer Center
- Hawaii
  - 'Aiea, Hawaii, United States, 96701
    - Pali Momi Medical Center
  - 'Aiea, Hawaii, United States, 96701
    - The Cancer Center of Hawaii-Pali Momi
  - 'Aiea, Hawaii, United States, 96701
    - Hawaii Oncology Inc-Pali Momi
  - Honolulu, Hawaii, United States, 96813
    - Queen's Medical Center
  - Honolulu, Hawaii, United States, 96817
    - The Cancer Center of Hawaii-Liliha
  - Honolulu, Hawaii, United States, 96813
    - Straub Clinic and Hospital
  - Honolulu, Hawaii, United States, 96813
    - University of Hawaii Cancer Center
  - Honolulu, Hawaii, United States, 96817
    - Hawaii Cancer Care Inc-Liliha
  - Honolulu, Hawaii, United States, 96817
    - Kuakini Medical Center
  - Honolulu, Hawaii, United States, 96826
    - Kapiolani Medical Center for Women and Children
  - Honolulu, Hawaii, United States, 96813
    - Island Urology
  - Honolulu, Hawaii, United States, 96813
    - Hawaii Cancer Care Inc-POB II
  - Honolulu, Hawaii, United States, 96813
    - Hawaii Oncology Inc-POB I
  - Honolulu, Hawaii, United States, 96817
    - Hawaii Oncology Inc-Kuakini
  - Lihue, Hawaii, United States, 96766
    - Wilcox Memorial Hospital and Kauai Medical Clinic
- Idaho
  - Boise, Idaho, United States, 83706
    - Saint Alphonsus Cancer Care Center-Boise
  - Caldwell, Idaho, United States, 83605
    - Saint Alphonsus Cancer Care Center-Caldwell
  - Coeur d'Alene, Idaho, United States, 83814
    - Kootenai Medical Center
  - Emmett, Idaho, United States, 83617
    - Walter Knox Memorial Hospital
  - Meridian, Idaho, United States, 83642
    - Idaho Urologic Institute-Meridian
  - Nampa, Idaho, United States, 83686
    - Saint Alphonsus Medical Center-Nampa
  - Post Falls, Idaho, United States, 83854
    - Kootenai Cancer Center
  - Sandpoint, Idaho, United States, 83864
    - Kootenai Cancer Clinic
- Illinois
  - Aurora, Illinois, United States, 60504
    - Rush - Copley Medical Center
  - Bloomington, Illinois, United States, 61704
    - Illinois CancerCare-Bloomington
  - Bloomington, Illinois, United States, 61701
    - Saint Joseph Medical Center
  - Canton, Illinois, United States, 61520
    - Illinois CancerCare-Canton
  - Carbondale, Illinois, United States, 62902
    - Memorial Hospital of Carbondale
  - Carterville, Illinois, United States, 62918
    - SIH Cancer Institute
  - Carthage, Illinois, United States, 62321
    - Illinois CancerCare-Carthage
  - Centralia, Illinois, United States, 62801
    - Centralia Oncology Clinic
  - Danville, Illinois, United States, 61832
    - Carle on Vermilion
  - Decatur, Illinois, United States, 62526
    - Decatur Memorial Hospital
  - Decatur, Illinois, United States, 62526
    - Cancer Care Specialists of Central Illinois
  - Effingham, Illinois, United States, 62401
    - Crossroads Cancer Center
  - Effingham, Illinois, United States, 62401
    - Carle Physician Group-Effingham
  - Elmhurst, Illinois, United States, 60126
    - Elmhurst Memorial Hospital
  - Eureka, Illinois, United States, 61530
    - Illinois CancerCare-Eureka
  - Galesburg, Illinois, United States, 61401
    - Western Illinois Cancer Treatment Center
  - Galesburg, Illinois, United States, 61401
    - Illinois CancerCare-Galesburg
  - Kewanee, Illinois, United States, 61443
    - Illinois CancerCare-Kewanee Clinic
  - Macomb, Illinois, United States, 61455
    - Illinois CancerCare-Macomb
  - Mattoon, Illinois, United States, 61938
    - Carle Physician Group-Mattoon/Charleston
  - Maywood, Illinois, United States, 60153
    - Loyola University Medical Center
  - Moline, Illinois, United States, 61265
    - Garneau, Stewart C MD (UIA Investigator)
  - Moline, Illinois, United States, 61265
    - Spector, David MD (UIA Investigator)
  - Moline, Illinois, United States, 61265
    - Trinity Medical Center
  - Mount Vernon, Illinois, United States, 62864
    - Good Samaritan Regional Health Center
  - Naperville, Illinois, United States, 60540
    - Edward Hospital/Cancer Center
  - Ottawa, Illinois, United States, 61350
    - Illinois CancerCare-Ottawa Clinic
  - Ottawa, Illinois, United States, 61350
    - Radiation Oncology of Northern Illinois
  - Pekin, Illinois, United States, 61554
    - Illinois CancerCare-Pekin
  - Pekin, Illinois, United States, 61554
    - OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
  - Peoria, Illinois, United States, 61637
    - OSF Saint Francis Medical Center
  - Peoria, Illinois, United States, 61615
    - Illinois CancerCare-Peoria
  - Peoria, Illinois, United States, 61615
    - OSF Saint Francis Radiation Oncology at Peoria Cancer Center
  - Peoria, Illinois, United States, 61603
    - Methodist Medical Center of Illinois
  - Peru, Illinois, United States, 61354
    - Illinois CancerCare-Peru
  - Peru, Illinois, United States, 61354
    - Valley Radiation Oncology
  - Plainfield, Illinois, United States, 60585
    - Edward Hospital/Cancer Center?Plainfield
  - Princeton, Illinois, United States, 61356
    - Illinois CancerCare-Princeton
  - Rockford, Illinois, United States, 61114
    - SwedishAmerican Regional Cancer Center/ACT
  - Springfield, Illinois, United States, 62781
    - Memorial Medical Center
  - Springfield, Illinois, United States, 62702
    - Southern Illinois University School of Medicine
  - Springfield, Illinois, United States, 62702
    - Springfield Clinic
  - Springfield, Illinois, United States, 62702
    - Central Illinois Hematology Oncology Center
  - Swansea, Illinois, United States, 62226
    - Cancer Care Specialists of Illinois-Swansea
  - Swansea, Illinois, United States, 62226
    - Memorial and Saint Elizabeth's Health Care Services LLP
  - Urbana, Illinois, United States, 61801
    - Carle Cancer Center
  - Urbana, Illinois, United States, 61801
    - The Carle Foundation Hospital
  - Yorkville, Illinois, United States, 60560
    - Rush-Copley Healthcare Center
- Indiana
  - Evansville, Indiana, United States, 47713
    - Deaconess Clinic Downtown
  - Fort Wayne, Indiana, United States, 46805
    - Parkview Hospital Randallia
  - Michigan City, Indiana, United States, 46360
    - Franciscan Saint Anthony Health-Michigan City
  - Michigan City, Indiana, United States, 46360
    - Woodland Cancer Care Center
  - Newburgh, Indiana, United States, 47630
    - Chancellor Center for Oncology
  - Richmond, Indiana, United States, 47374
    - Reid Health
- Iowa
  - Ames, Iowa, United States, 50010
    - Mary Greeley Medical Center
  - Ames, Iowa, United States, 50010
    - McFarland Clinic PC-William R Bliss Cancer Center
  - Bettendorf, Iowa, United States, 52722
    - Constantinou, Costas L MD (UIA Investigator)
  - Boone, Iowa, United States, 50036
    - McFarland Clinic PC-Boone
  - Clive, Iowa, United States, 50325
    - Mercy Cancer Center-West Lakes
  - Clive, Iowa, United States, 50325
    - Medical Oncology and Hematology Associates-West Des Moines
  - Council Bluffs, Iowa, United States, 51503
    - Alegent Health Mercy Hospital
  - Creston, Iowa, United States, 50801
    - Greater Regional Medical Center
  - Des Moines, Iowa, United States, 50314
    - Mercy Medical Center - Des Moines
  - Des Moines, Iowa, United States, 50314
    - Medical Oncology and Hematology Associates-Laurel
  - Fort Dodge, Iowa, United States, 50501
    - McFarland Clinic PC-Trinity Cancer Center
  - Jefferson, Iowa, United States, 50129
    - McFarland Clinic PC-Jefferson
  - Marshalltown, Iowa, United States, 50158
    - McFarland Clinic PC-Marshalltown
  - Sioux City, Iowa, United States, 51101
    - Siouxland Regional Cancer Center
  - West Des Moines, Iowa, United States, 50266
    - Mercy Medical Center-West Lakes
- Kansas
  - Chanute, Kansas, United States, 66720
    - Cancer Center of Kansas - Chanute
  - Coffeyville, Kansas, United States, 67337
    - Coffeyville Regional Medical Center
  - Dodge City, Kansas, United States, 67801
    - Cancer Center of Kansas - Dodge City
  - El Dorado, Kansas, United States, 67042
    - Cancer Center of Kansas - El Dorado
  - Fort Scott, Kansas, United States, 66701
    - Cancer Center of Kansas - Fort Scott
  - Garden City, Kansas, United States, 67846
    - Saint Catherine Hospital
  - Great Bend, Kansas, United States, 67530
    - Central Care Cancer Center - Great Bend
  - Great Bend, Kansas, United States, 67530
    - Saint Rose Ambulatory and Surgery Center
  - Hays, Kansas, United States, 67601
    - Hays Medical Center
  - Independence, Kansas, United States, 67301
    - Cancer Center of Kansas-Independence
  - Kansas City, Kansas, United States, 66160
    - University of Kansas Cancer Center
  - Kansas City, Kansas, United States, 66112
    - University of Kansas Cancer Center-West
  - Kingman, Kansas, United States, 67068
    - Cancer Center of Kansas-Kingman
  - Lawrence, Kansas, United States, 66044
    - Lawrence Memorial Hospital
  - Lenexa, Kansas, United States, 66219
    - Kansas Institute of Medicine Cancer and Blood Center
  - Lenexa, Kansas, United States, 66219
    - Minimally Invasive Surgery Hospital
  - Liberal, Kansas, United States, 67905
    - Cancer Center of Kansas-Liberal
  - Manhattan, Kansas, United States, 66502
    - Cancer Center of Kansas-Manhattan
  - McPherson, Kansas, United States, 67460
    - Cancer Center of Kansas - McPherson
  - Newton, Kansas, United States, 67114
    - Cancer Center of Kansas - Newton
  - Olathe, Kansas, United States, 66061
    - Olathe Medical Center
  - Overland Park, Kansas, United States, 66210
    - University of Kansas Cancer Center-Overland Park
  - Overland Park, Kansas, United States, 66209
    - Menorah Medical Center
  - Overland Park, Kansas, United States, 66213
    - Saint Luke's South Hospital
  - Parsons, Kansas, United States, 67357
    - Cancer Center of Kansas - Parsons
  - Pittsburg, Kansas, United States, 66762
    - Via Christi Hospital-Pittsburg
  - Prairie Village, Kansas, United States, 66208
    - Kansas City NCI Community Oncology Research Program
  - Pratt, Kansas, United States, 67124
    - Cancer Center of Kansas - Pratt
  - Salina, Kansas, United States, 67401
    - Salina Regional Health Center
  - Salina, Kansas, United States, 67401
    - Cancer Center of Kansas - Salina
  - Topeka, Kansas, United States, 66606
    - Saint Francis Hospital and Medical Center - Topeka
  - Wellington, Kansas, United States, 67152
    - Cancer Center of Kansas - Wellington
  - Westwood, Kansas, United States, 66205
    - University of Kansas Hospital-Westwood Cancer Center
  - Wichita, Kansas, United States, 67208
    - Cancer Center of Kansas-Wichita Medical Arts Tower
  - Wichita, Kansas, United States, 67214
    - Cancer Center of Kansas - Wichita
  - Wichita, Kansas, United States, 67208
    - Associates In Womens Health
  - Wichita, Kansas, United States, 67214
    - Via Christi Regional Medical Center
  - Winfield, Kansas, United States, 67156
    - Cancer Center of Kansas - Winfield
- Kentucky
  - Bardstown, Kentucky, United States, 40004
    - Flaget Memorial Hospital
  - Corbin, Kentucky, United States, 40701
    - Commonwealth Cancer Center-Corbin
  - Crestview Hills, Kentucky, United States, 41017
    - Oncology Hematology Care Inc-Crestview
  - Lexington, Kentucky, United States, 40504
    - Saint Joseph Radiation Oncology Resource Center
  - Lexington, Kentucky, United States, 40509
    - Saint Joseph Hospital East
  - Louisville, Kentucky, United States, 40202
    - Jewish Hospital
  - Louisville, Kentucky, United States, 40215
    - Saints Mary and Elizabeth Hospital
  - Louisville, Kentucky, United States, 40245
    - Jewish Hospital Medical Center Northeast
  - Shepherdsville, Kentucky, United States, 40165
    - Jewish Hospital Medical Center South
- Maine
  - Augusta, Maine, United States, 04330
    - Harold Alfond Center for Cancer Care
  - Bangor, Maine, United States, 04401
    - Eastern Maine Medical Center
  - Brewer, Maine, United States, 04412
    - Lafayette Family Cancer Center-EMMC
  - Rockport, Maine, United States, 04856
    - Penobscot Bay Medical Center
- Massachusetts
  - Beverly, Massachusetts, United States, 01915
    - Beverly Hospital
  - Burlington, Massachusetts, United States, 01805
    - Lahey Hospital and Medical Center
  - Gloucester, Massachusetts, United States, 01930
    - Addison Gilbert Hospital
  - Winchester, Massachusetts, United States, 01890
    - Winchester Hospital
- Michigan
  - Ann Arbor, Michigan, United States, 48109
    - University of Michigan Comprehensive Cancer Center
  - Ann Arbor, Michigan, United States, 48106
    - Saint Joseph Mercy Hospital
  - Battle Creek, Michigan, United States, 49017
    - Bronson Battle Creek
  - Brighton, Michigan, United States, 48114
    - Saint Joseph Mercy Brighton
  - Brighton, Michigan, United States, 48114
    - IHA Hematology Oncology Consultants-Brighton
  - Canton, Michigan, United States, 48188
    - Saint Joseph Mercy Canton
  - Canton, Michigan, United States, 48188
    - IHA Hematology Oncology Consultants-Canton
  - Caro, Michigan, United States, 48723
    - Caro Cancer Center
  - Chelsea, Michigan, United States, 48118
    - Saint Joseph Mercy Chelsea
  - Chelsea, Michigan, United States, 48118
    - IHA Hematology Oncology Consultants-Chelsea
  - Clarkston, Michigan, United States, 48346
    - Hematology Oncology Consultants-Clarkston
  - Clarkston, Michigan, United States, 48346
    - Newland Medical Associates-Clarkston
  - Dearborn, Michigan, United States, 48124
    - Beaumont Hospital-Dearborn
  - Detroit, Michigan, United States, 48236
    - Saint John Hospital and Medical Center
  - Detroit, Michigan, United States, 48201
    - Wayne State University/Karmanos Cancer Institute
  - East China Township, Michigan, United States, 48054
    - Great Lakes Cancer Management Specialists-Doctors Park
  - Farmington Hills, Michigan, United States, 48334
    - Weisberg Cancer Treatment Center
  - Flint, Michigan, United States, 48503
    - Hurley Medical Center
  - Flint, Michigan, United States, 48503
    - Genesee Cancer and Blood Disease Treatment Center
  - Flint, Michigan, United States, 48503
    - Genesee Hematology Oncology PC
  - Flint, Michigan, United States, 48503
    - Genesys Hurley Cancer Institute
  - Grand Rapids, Michigan, United States, 49503
    - Spectrum Health at Butterworth Campus
  - Grand Rapids, Michigan, United States, 49503
    - Mercy Health Saint Mary's
  - Grosse Pointe Woods, Michigan, United States, 48236
    - Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
  - Grosse Pointe Woods, Michigan, United States, 48236
    - Michigan Breast Specialists-Grosse Pointe Woods
  - Grosse Pointe Woods, Michigan, United States, 48236
    - Lymphoma Clinic of Michigan
  - Jackson, Michigan, United States, 49201
    - Allegiance Health
  - Kalamazoo, Michigan, United States, 49007
    - West Michigan Cancer Center
  - Kalamazoo, Michigan, United States, 49007
    - Bronson Methodist Hospital
  - Kalamazoo, Michigan, United States, 49001
    - Borgess Medical Center
  - Lansing, Michigan, United States, 48912
    - Sparrow Hospital
  - Livonia, Michigan, United States, 48154
    - Saint Mary Mercy Hospital
  - Livonia, Michigan, United States, 48154
    - Hope Cancer Clinic
  - Macomb, Michigan, United States, 48044
    - Great Lakes Cancer Management Specialists-Macomb Medical Campus
  - Macomb, Michigan, United States, 48044
    - Michigan Breast Specialists-Macomb Township
  - Marlette, Michigan, United States, 48453
    - Saint Mary's Oncology/Hematology Associates of Marlette
  - Marquette, Michigan, United States, 49855
    - UP Health System Marquette
  - Marquette, Michigan, United States, 49855
    - UP Health System Hematology Oncology Marquette
  - Monroe, Michigan, United States, 48162
    - Monroe Cancer Center
  - Muskegon, Michigan, United States, 49444
    - Mercy Health Mercy Campus
  - Niles, Michigan, United States, 49120
    - Lakeland Community Hospital
  - Pontiac, Michigan, United States, 48341
    - Saint Joseph Mercy Oakland
  - Pontiac, Michigan, United States, 48341
    - 21st Century Oncology-Pontiac
  - Pontiac, Michigan, United States, 48341
    - Hope Cancer Center
  - Pontiac, Michigan, United States, 48341
    - Newland Medical Associates-Pontiac
  - Port Huron, Michigan, United States, 48060
    - Lake Huron Medical Center
  - Port Huron, Michigan, United States, 48060
    - Huron Medical Center PC
  - Reed City, Michigan, United States, 49677
    - Spectrum Health Reed City Hospital
  - Rochester Hills, Michigan, United States, 48309
    - Great Lakes Cancer Management Specialists-Rochester Hills
  - Saginaw, Michigan, United States, 48601
    - Saint Mary's of Michigan
  - Saginaw, Michigan, United States, 48604
    - Oncology Hematology Associates of Saginaw Valley PC
  - Saint Joseph, Michigan, United States, 49085
    - Marie Yeager Cancer Center
  - Saint Joseph, Michigan, United States, 49085
    - Lakeland Hospital
  - Sterling Heights, Michigan, United States, 48312
    - Bhadresh Nayak MD PC-Sterling Heights
  - Tawas City, Michigan, United States, 48764
    - Saint Joseph Health System-Tawas City
  - Traverse City, Michigan, United States, 49684
    - Munson Medical Center
  - Warren, Michigan, United States, 48093
    - Saint John Macomb-Oakland Hospital
  - Warren, Michigan, United States, 48088
    - Advanced Breast Care Center PLLC
  - Warren, Michigan, United States, 48093
    - Great Lakes Cancer Management Specialists-Macomb Professional Building
  - Warren, Michigan, United States, 48093
    - Macomb Hematology Oncology PC
  - Warren, Michigan, United States, 48093
    - Michigan Breast Specialists-Warren
  - Warren, Michigan, United States, 48093
    - Bhadresh Nayak MD PC-Warren
  - West Branch, Michigan, United States, 48661
    - Saint Mary's Oncology/Hematology Associates of West Branch
  - Wyoming, Michigan, United States, 49519
    - Metro Health Hospital
  - Ypsilanti, Michigan, United States, 48106
    - Huron Gastroenterology PC
  - Ypsilanti, Michigan, United States, 48197
    - IHA Hematology Oncology Consultants-Ann Arbor
- Minnesota
  - Bemidji, Minnesota, United States, 56601
    - Sanford Clinic North-Bemidgi
  - Burnsville, Minnesota, United States, 55337
    - Fairview Ridges Hospital
  - Coon Rapids, Minnesota, United States, 55433
    - Mercy Hospital
  - Edina, Minnesota, United States, 55435
    - Fairview-Southdale Hospital
  - Fridley, Minnesota, United States, 55432
    - Unity Hospital
  - Maple Grove, Minnesota, United States, 55369
    - Fairview Maple Grove Medical Center
  - Maplewood, Minnesota, United States, 55109
    - Saint John's Hospital - Healtheast
  - Maplewood, Minnesota, United States, 55109
    - Minnesota Oncology Hematology PA-Maplewood
  - Minneapolis, Minnesota, United States, 55415
    - Hennepin County Medical Center
  - Minneapolis, Minnesota, United States, 55407
    - Abbott-Northwestern Hospital
  - Minneapolis, Minnesota, United States, 55454
    - Health Partners Inc
  - New Ulm, Minnesota, United States, 56073
    - New Ulm Medical Center
  - Robbinsdale, Minnesota, United States, 55422
    - North Memorial Medical Health Center
  - Saint Louis Park, Minnesota, United States, 55416
    - Park Nicollet Clinic - Saint Louis Park
  - Saint Paul, Minnesota, United States, 55101
    - Regions Hospital
  - Saint Paul, Minnesota, United States, 55102
    - United Hospital
  - Shakopee, Minnesota, United States, 55379
    - Saint Francis Regional Medical Center
  - Stillwater, Minnesota, United States, 55082
    - Lakeview Hospital
  - Waconia, Minnesota, United States, 55387
    - Ridgeview Medical Center
  - Willmar, Minnesota, United States, 56201
    - Rice Memorial Hospital
  - Woodbury, Minnesota, United States, 55125
    - Minnesota Oncology Hematology PA-Woodbury
  - Wyoming, Minnesota, United States, 55092
    - Fairview Lakes Medical Center
- Mississippi
  - New Albany, Mississippi, United States, 38652
    - Baptist Memorial Hospital and Cancer Center-Union County
  - Oxford, Mississippi, United States, 38655
    - Baptist Memorial Hospital and Cancer Center-Oxford
  - Pascagoula, Mississippi, United States, 39581
    - Singing River Hospital
  - Southhaven, Mississippi, United States, 38671
    - Baptist Memorial Hospital and Cancer Center-Desoto
- Missouri
  - Bolivar, Missouri, United States, 65613
    - Central Care Cancer Center - Bolivar
  - Bonne Terre, Missouri, United States, 63628
    - Parkland Health Center-Bonne Terre
  - Branson, Missouri, United States, 65616
    - Cox Cancer Center Branson
  - Cape Girardeau, Missouri, United States, 63703
    - Saint Francis Medical Center
  - Cape Girardeau, Missouri, United States, 63703
    - Southeast Cancer Center
  - Independence, Missouri, United States, 64057
    - Centerpoint Medical Center LLC
  - Jefferson City, Missouri, United States, 65109
    - Capital Region Medical Center-Goldschmidt Cancer Center
  - Joplin, Missouri, United States, 64804
    - Freeman Health System
  - Joplin, Missouri, United States, 64804
    - Mercy Hospital Joplin
  - Kansas City, Missouri, United States, 64128
    - Kansas City Veterans Affairs Medical Center
  - Kansas City, Missouri, United States, 64131
    - The University of Kansas Cancer Center-South
  - Kansas City, Missouri, United States, 64111
    - Saint Luke's Hospital of Kansas City
  - Kansas City, Missouri, United States, 64132
    - Research Medical Center
  - Kansas City, Missouri, United States, 64108
    - Truman Medical Center
  - Kansas City, Missouri, United States, 64118
    - Heartland Hematology and Oncology Associates Incorporated
  - Kansas City, Missouri, United States, 64154
    - The University of Kansas Cancer Center-North
  - Lee's Summit, Missouri, United States, 64086
    - Saint Luke's East - Lee's Summit
  - Lee's Summit, Missouri, United States, 64064
    - The University of Kansas Cancer Center-Lee's Summit
  - Liberty, Missouri, United States, 64068
    - Liberty Radiation Oncology Center
  - Rolla, Missouri, United States, 65401
    - Delbert Day Cancer Institute at PCRMC
  - Rolla, Missouri, United States, 65401
    - Mercy Clinic-Rolla-Cancer and Hematology
  - Saint Joseph, Missouri, United States, 64507
    - Heartland Regional Medical Center
  - Saint Louis, Missouri, United States, 63131
    - Missouri Baptist Medical Center
  - Saint Louis, Missouri, United States, 63141
    - Mercy Hospital Saint Louis
  - Saint Louis, Missouri, United States, 63109
    - Saint Louis Cancer and Breast Institute-South City
  - Sainte Genevieve, Missouri, United States, 63670
    - Sainte Genevieve County Memorial Hospital
  - Springfield, Missouri, United States, 65807
    - CoxHealth South Hospital
  - Springfield, Missouri, United States, 65804
    - Mercy Hospital Springfield
  - Sullivan, Missouri, United States, 63080
    - Missouri Baptist Sullivan Hospital
  - Sunset Hills, Missouri, United States, 63127
    - Missouri Baptist Outpatient Center-Sunset Hills
- Montana
  - Billings, Montana, United States, 59101
    - Billings Clinic Cancer Center
  - Billings, Montana, United States, 59101
    - Saint Vincent Healthcare
  - Bozeman, Montana, United States, 59715
    - Bozeman Deaconess Hospital
  - Butte, Montana, United States, 59701
    - Saint James Community Hospital and Cancer Treatment Center
  - Great Falls, Montana, United States, 59405
    - Benefis Healthcare- Sletten Cancer Institute
  - Helena, Montana, United States, 59601
    - Saint Peter's Community Hospital
  - Kalispell, Montana, United States, 59901
    - Kalispell Regional Medical Center
  - Missoula, Montana, United States, 59804
    - Community Medical Hospital
  - Missoula, Montana, United States, 59802
    - Saint Patrick Hospital - Community Hospital
- Nebraska
  - Grand Island, Nebraska, United States, 68803
    - CHI Health Saint Francis
  - Kearney, Nebraska, United States, 68847
    - CHI Health Good Samaritan
  - Kearney, Nebraska, United States, 68845
    - Heartland Hematology and Oncology
  - Lincoln, Nebraska, United States, 68506
    - Nebraska Hematology and Oncology
  - Lincoln, Nebraska, United States, 68510
    - Nebraska Cancer Research Center
  - Lincoln, Nebraska, United States, 68510
    - Saint Elizabeth Regional Medical Center
  - Lincoln, Nebraska, United States, 68510
    - Southeast Nebraska Cancer Center
  - Norfolk, Nebraska, United States, 68701
    - Faith Regional Health Services Carson Cancer Center
  - North Platte, Nebraska, United States, 69101
    - Great Plains Health Callahan Cancer Center
  - Omaha, Nebraska, United States, 68114
    - Nebraska Methodist Hospital
  - Omaha, Nebraska, United States, 68124
    - Alegent Health Bergan Mercy Medical Center
  - Omaha, Nebraska, United States, 68122
    - Alegent Health Immanuel Medical Center
  - Omaha, Nebraska, United States, 68130
    - Alegent Health Lakeside Hospital
  - Omaha, Nebraska, United States, 68131
    - Creighton University Medical Center
  - Omaha, Nebraska, United States, 68124
    - Nebraska Cancer Specialists - Omaha
  - Omaha, Nebraska, United States, 68130
    - Oncology Hematology West PC
  - Omaha, Nebraska, United States, 68122
    - Hematology and Oncology Consultants PC
  - Papillion, Nebraska, United States, 68046
    - Midlands Community Hospital
  - Scottsbluff, Nebraska, United States, 69361
    - Regional West Medical Center Cancer Center
- Nevada
  - Carson City, Nevada, United States, 89703
    - Carson Tahoe Regional Medical Center
  - Henderson, Nevada, United States, 89052
    - Comprehensive Cancer Centers of Nevada - Henderson
  - Henderson, Nevada, United States, 89052
    - Cancer and Blood Specialists-Henderson
  - Henderson, Nevada, United States, 89052
    - Las Vegas Cancer Center-Henderson
  - Henderson, Nevada, United States, 89074
    - Comprehensive Cancer Centers of Nevada-Southeast Henderson
  - Henderson, Nevada, United States, 89074
    - 21st Century Oncology-Henderson
  - Henderson, Nevada, United States, 89052
    - Comprehensive Cancer Centers of Nevada-Horizon Ridge
  - Las Vegas, Nevada, United States, 89144
    - Summerlin Hospital Medical Center
  - Las Vegas, Nevada, United States, 89106
    - Radiation Oncology Centers of Nevada Central
  - Las Vegas, Nevada, United States, 89119
    - Radiation Oncology Centers of Nevada Southeast
  - Las Vegas, Nevada, United States, 89128
    - Comprehensive Cancer Centers of Nevada - Northwest
  - Las Vegas, Nevada, United States, 89144
    - Comprehensive Cancer Centers of Nevada-Summerlin
  - Las Vegas, Nevada, United States, 89148
    - Comprehensive Cancer Centers of Nevada
  - Las Vegas, Nevada, United States, 89169
    - Comprehensive Cancer Centers of Nevada - Central Valley
  - Las Vegas, Nevada, United States, 89102
    - University Medical Center of Southern Nevada
  - Las Vegas, Nevada, United States, 89106
    - Cancer and Blood Specialists-Shadow
  - Las Vegas, Nevada, United States, 89109
    - HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
  - Las Vegas, Nevada, United States, 89113
    - HealthCare Partners Medical Group Oncology/Hematology-San Martin
  - Las Vegas, Nevada, United States, 89121
    - Cancer Therapy and Integrative Medicine
  - Las Vegas, Nevada, United States, 89128
    - Cancer and Blood Specialists-Tenaya
  - Las Vegas, Nevada, United States, 89128
    - HealthCare Partners Medical Group Oncology/Hematology-Tenaya
  - Las Vegas, Nevada, United States, 89148-2405
    - Las Vegas Cancer Center-Medical Center
  - Las Vegas, Nevada, United States, 89149
    - HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
  - Las Vegas, Nevada, United States, 89109
    - 21st Century Oncology
  - Las Vegas, Nevada, United States, 89128
    - 21st Century Oncology-Vegas Tenaya
  - Las Vegas, Nevada, United States, 89148
    - 21st Century Oncology-Fort Apache
  - Las Vegas, Nevada, United States, 89148
    - Nevada Cancer Specialists-Fort Apache
  - Las Vegas, Nevada, United States, 89128
    - Ann M Wierman MD LTD
  - Las Vegas, Nevada, United States, 89169
    - University Cancer Center
  - Pahrump, Nevada, United States, 89048
    - Hope Cancer Care of Nevada-Pahrump
  - Reno, Nevada, United States, 89502
    - Renown Regional Medical Center
  - Reno, Nevada, United States, 89503
    - Saint Mary's Regional Medical Center
  - Reno, Nevada, United States, 89509
    - Radiation Oncology Associates
- New Hampshire
  - Lebanon, New Hampshire, United States, 03756
    - Dartmouth Hitchcock Medical Center
  - Manchester, New Hampshire, United States, 03102
    - Norris Cotton Cancer Center-Manchester
  - Nashua, New Hampshire, United States, 03063
    - Norris Cotton Cancer Center-Nashua
- New Jersey
  - Englewood, New Jersey, United States, 07631
    - Englewood Hospital and Medical Center
  - Newark, New Jersey, United States, 07112
    - Newark Beth Israel Medical Center
  - Vineland, New Jersey, United States, 08360
    - Inspira Medical Center Vineland
  - Woodbury, New Jersey, United States, 08096
    - Inspira Medical Center Woodbury
- New Mexico
  - Albuquerque, New Mexico, United States, 87102
    - University of New Mexico Cancer Center
  - Albuquerque, New Mexico, United States, 87102
    - Lovelace Medical Center-Saint Joseph Square
  - Albuquerque, New Mexico, United States, 87109
    - New Mexico Oncology Hematology Consultants
  - Las Cruces, New Mexico, United States, 88011
    - Memorial Medical Center - Las Cruces
  - Santa Fe, New Mexico, United States, 87505
    - Christus Saint Vincent Regional Cancer Center
- New York
  - Middletown, New York, United States, 10940
    - Orange Regional Medical Center
  - Rochester, New York, United States, 14642
    - University of Rochester
  - Utica, New York, United States, 13502
    - Faxton-Saint Luke's Healthcare
- North Carolina
  - Asheville, North Carolina, United States, 28801
    - Cancer Care of Western North Carolina
  - Asheville, North Carolina, United States, 28801
    - Mission Hospital-Memorial Campus
  - Asheville, North Carolina, United States, 28803
    - Asheville Hematology-Oncology Associates
  - Clinton, North Carolina, United States, 28328
    - Southeastern Medical Oncology Center-Clinton
  - Clinton, North Carolina, United States, 28328
    - Sampson Radiation Oncology
  - Goldsboro, North Carolina, United States, 27534
    - Southeastern Medical Oncology Center-Goldsboro
  - Goldsboro, North Carolina, United States, 27534
    - Wayne Memorial Hospital
  - Goldsboro, North Carolina, United States, 27534
    - Wayne Radiation Oncology
  - Hendersonville, North Carolina, United States, 28791
    - Hendersonville Hematology and Oncology at Pardee
  - Hendersonville, North Carolina, United States, 28791
    - Margaret R Pardee Memorial Hospital
  - Hendersonville, North Carolina, United States, 28792
    - Park Ridge Hospital Breast Health Center
  - Jacksonville, North Carolina, United States, 28546
    - Southeastern Medical Oncology Center-Jacksonville
  - Jacksonville, North Carolina, United States, 28546
    - Onslow Memorial Hospital
  - Kinston, North Carolina, United States, 28501
    - Kinston Medical Specialists PA
  - Wilson, North Carolina, United States, 27893
    - Southeastern Medical Oncology Center-Wilson
- North Dakota
  - Bismarck, North Dakota, United States, 58501
    - Sanford Bismarck Medical Center
  - Fargo, North Dakota, United States, 58122
    - Sanford Broadway Medical Center
  - Fargo, North Dakota, United States, 58122
    - Sanford Clinic North-Fargo
  - Fargo, North Dakota, United States, 58122
    - Roger Maris Cancer Center
  - Grand Forks, North Dakota, United States, 58201
    - Altru Cancer Center
  - Minot, North Dakota, United States, 58701
    - Trinity Cancer Care Center
- Ohio
  - Akron, Ohio, United States, 44307
    - Akron General Medical Center
  - Beavercreek, Ohio, United States, 45431
    - Indu and Raj Soin Medical Center
  - Belpre, Ohio, United States, 45714
    - Strecker Cancer Center-Belpre
  - Canton, Ohio, United States, 44708
    - Mercy Medical Center
  - Centerville, Ohio, United States, 45459
    - Miami Valley Hospital South
  - Centerville, Ohio, United States, 45459
    - Dayton Physicians LLC-Miami Valley South
  - Chillicothe, Ohio, United States, 45601
    - Adena Regional Medical Center
  - Cincinnati, Ohio, United States, 45220
    - Good Samaritan Hospital - Cincinnati
  - Cincinnati, Ohio, United States, 45242
    - Bethesda North Hospital
  - Cincinnati, Ohio, United States, 45242
    - Oncology Hematology Care Inc-Blue Ash
  - Cincinnati, Ohio, United States, 45202
    - Oncology Hematology Care Inc-Eden Park
  - Cincinnati, Ohio, United States, 45211
    - Oncology Hematology Care Inc-Mercy West
  - Cincinnati, Ohio, United States, 45236
    - Oncology Hematology Care Inc-Kenwood
  - Cincinnati, Ohio, United States, 45230
    - Oncology Hematology Care Inc - Anderson
  - Cincinnati, Ohio, United States, 45247
    - TriHealth Cancer Institute-Westside
  - Cincinnati, Ohio, United States, 45255
    - TriHealth Cancer Institute-Anderson
  - Columbus, Ohio, United States, 43214
    - Riverside Methodist Hospital
  - Columbus, Ohio, United States, 43219
    - The Mark H Zangmeister Center
  - Columbus, Ohio, United States, 43214
    - Columbus Oncology and Hematology Associates Inc
  - Columbus, Ohio, United States, 43228
    - Doctors Hospital
  - Columbus, Ohio, United States, 43215
    - Grant Medical Center
  - Columbus, Ohio, United States, 43222
    - Mount Carmel Health Center West
  - Dayton, Ohio, United States, 45406
    - Good Samaritan Hospital - Dayton
  - Dayton, Ohio, United States, 45409
    - Miami Valley Hospital
  - Dayton, Ohio, United States, 45415
    - Dayton Physicians LLC-Samaritan North
  - Dayton, Ohio, United States, 45415
    - Samaritan North Health Center
  - Delaware, Ohio, United States, 43015
    - Delaware Health Center-Grady Cancer Center
  - Delaware, Ohio, United States, 43015
    - Delaware Radiation Oncology
  - Delaware, Ohio, United States, 43015
    - Grady Memorial Hospital
  - Fairfield, Ohio, United States, 45014
    - Oncology Hematology Care Inc-Healthplex
  - Findlay, Ohio, United States, 45840
    - Blanchard Valley Hospital
  - Findlay, Ohio, United States, 45840
    - Armes Family Cancer Center
  - Findlay, Ohio, United States, 45840
    - Orion Cancer Care
  - Franklin, Ohio, United States, 45005-1066
    - Atrium Medical Center-Middletown Regional Hospital
  - Franklin, Ohio, United States, 45005
    - Dayton Physicians LLC-Atrium
  - Greenville, Ohio, United States, 45331
    - Wayne Hospital
  - Greenville, Ohio, United States, 45331
    - Dayton Physicians LLC-Wayne
  - Kettering, Ohio, United States, 45429
    - Kettering Medical Center
  - Kettering, Ohio, United States, 45409
    - Greater Dayton Cancer Center
  - Kettering, Ohio, United States, 45420
    - First Dayton Cancer Care
  - Lancaster, Ohio, United States, 43130
    - Fairfield Medical Center
  - Marietta, Ohio, United States, 45750
    - Marietta Memorial Hospital
  - Middletown, Ohio, United States, 45042
    - Dayton Physicians LLC-Signal Point
  - Mount Vernon, Ohio, United States, 43050
    - Knox Community Hospital
  - Newark, Ohio, United States, 43055
    - Licking Memorial Hospital
  - Newark, Ohio, United States, 43055
    - Newark Radiation Oncology
  - Portsmouth, Ohio, United States, 45662
    - Southern Ohio Medical Center
  - Sidney, Ohio, United States, 45365
    - Dayton Physicians LLC-Wilson
  - Springfield, Ohio, United States, 45505
    - Springfield Regional Medical Center
  - Springfield, Ohio, United States, 45504
    - Springfield Regional Cancer Center
  - Sylvania, Ohio, United States, 43560
    - Flower Hospital
  - Toledo, Ohio, United States, 43606
    - The Toledo Hospital/Toledo Children's Hospital
  - Troy, Ohio, United States, 45373
    - Upper Valley Medical Center
  - Troy, Ohio, United States, 45373
    - Dayton Physicians LLC-Upper Valley
  - Westerville, Ohio, United States, 43081
    - Saint Ann's Hospital
  - Zanesville, Ohio, United States, 43701
    - Genesis Healthcare System Cancer Care Center
- Oklahoma
  - Oklahoma City, Oklahoma, United States, 73104
    - University of Oklahoma Health Sciences Center
  - Oklahoma City, Oklahoma, United States, 73120
    - Mercy Hospital Oklahoma City
- Oregon
  - Baker City, Oregon, United States, 97814
    - Saint Alphonsus Medical Center-Baker City
  - Grants Pass, Oregon, United States, 97527
    - Three Rivers Community Hospital
  - Medford, Oregon, United States, 97504
    - Providence Medford Medical Center
  - Medford, Oregon, United States, 97504
    - Rogue Valley Medical Center
  - Ontario, Oregon, United States, 97914
    - Saint Alphonsus Medical Center-Ontario
  - Portland, Oregon, United States, 97227
    - Kaiser Permanente Northwest
- Pennsylvania
  - Allentown, Pennsylvania, United States, 18103
    - Lehigh Valley Hospital-Cedar Crest
  - Beaver, Pennsylvania, United States, 15009
    - UPMC-Heritage Valley Health System Beaver
  - Bethlehem, Pennsylvania, United States, 18017
    - Lehigh Valley Hospital - Muhlenberg
  - Chadds Ford, Pennsylvania, United States, 19317
    - Christiana Care Health System-Concord Health Center
  - Ephrata, Pennsylvania, United States, 17522
    - Ephrata Cancer Center
  - Ephrata, Pennsylvania, United States, 17522
    - Ephrata Community Hospital
  - Gettysburg, Pennsylvania, United States, 17325
    - Adams Cancer Center
  - Greensburg, Pennsylvania, United States, 15601
    - UPMC Cancer Centers - Arnold Palmer Pavilion
  - Hanover, Pennsylvania, United States, 17331
    - Cherry Tree Cancer Center
  - Johnstown, Pennsylvania, United States, 15901
    - UPMC-Johnstown/John P. Murtha Regional Cancer Center
  - Lebanon, Pennsylvania, United States, 17042
    - Sechler Family Cancer Center
  - McKeesport, Pennsylvania, United States, 15132
    - UPMC Cancer Center at UPMC McKeesport
  - Moon, Pennsylvania, United States, 15108
    - UPMC-Coraopolis/Heritage Valley Radiation Oncology
  - Philadelphia, Pennsylvania, United States, 19140
    - Temple University Hospital
  - Pittsburgh, Pennsylvania, United States, 15213
    - UPMC-Magee Womens Hospital
  - Pittsburgh, Pennsylvania, United States, 15232
    - University of Pittsburgh Cancer Institute (UPCI)
  - Pittsburgh, Pennsylvania, United States, 15232
    - UPMC-Shadyside Hospital
  - Pittsburgh, Pennsylvania, United States, 15213
    - UPMC-Presbyterian Hospital
  - Pittsburgh, Pennsylvania, United States, 15215
    - UPMC-Saint Margaret
  - Pittsburgh, Pennsylvania, United States, 15237
    - UPMC-Passavant Hospital
  - Pittsburgh, Pennsylvania, United States, 15243
    - UPMC-Saint Clair Hospital Cancer Center
  - Reading, Pennsylvania, United States, 19605
    - Penn State Health Saint Joseph Medical Center
  - Sayre, Pennsylvania, United States, 18840
    - Guthrie Medical Group PC-Robert Packer Hospital
  - Seneca, Pennsylvania, United States, 16346
    - UPMC Cancer Center at UPMC Northwest
  - Uniontown, Pennsylvania, United States, 15401
    - UPMC Uniontown Hospital Radiation Oncology
  - Washington, Pennsylvania, United States, 15301
    - UPMC Washington Hospital Radiation Oncology
  - West Chester, Pennsylvania, United States, 19380
    - Chester County Hospital
  - Williamsport, Pennsylvania, United States, 17701
    - UPMC Susquehanna
  - York, Pennsylvania, United States, 17403
    - WellSpan Health-York Cancer Center
  - York, Pennsylvania, United States, 17403
    - WellSpan Health-York Hospital
- South Carolina
  - Easley, South Carolina, United States, 29640
    - Greenville Health System Cancer Institute-Easley
  - Florence, South Carolina, United States, 29506
    - McLeod Regional Medical Center
  - Greenville, South Carolina, United States, 29607
    - Saint Francis Cancer Center
  - Greenville, South Carolina, United States, 29601
    - Saint Francis Hospital
  - Greenville, South Carolina, United States, 29605
    - Greenville Health System Cancer Institute-Faris
  - Greenville, South Carolina, United States, 29605
    - Greenville Memorial Hospital
  - Greenville, South Carolina, United States, 29615
    - Greenville Health System Cancer Institute-Eastside
  - Greenville, South Carolina, United States, 29605
    - Greenville Health System Cancer Institute-Butternut
  - Greer, South Carolina, United States, 29650
    - Greenville Health System Cancer Institute-Greer
  - Seneca, South Carolina, United States, 29672
    - Greenville Health System Cancer Institute-Seneca
  - Spartanburg, South Carolina, United States, 29307
    - Greenville Health System Cancer Institute-Spartanburg
- South Dakota
  - Sioux Falls, South Dakota, United States, 57117-5134
    - Sanford USD Medical Center - Sioux Falls
  - Sioux Falls, South Dakota, United States, 57104
    - Sanford Cancer Center Oncology Clinic
- Tennessee
  - Bartlett, Tennessee, United States, 38133
    - Boston Baskin Cancer Center-Bartlett
  - Chattanooga, Tennessee, United States, 37404
    - Memorial Hospital
  - Collierville, Tennessee, United States, 38017
    - Integrity Oncology PLLC-Collierville
  - Franklin, Tennessee, United States, 37067
    - Vanderbilt-Ingram Cancer Center Cool Springs
  - Hixson, Tennessee, United States, 37343
    - Pulmonary Medicine Center of Chattanooga-Hixson
  - Memphis, Tennessee, United States, 38120
    - Baptist Memorial Hospital and Cancer Center-Memphis
  - Memphis, Tennessee, United States, 38120
    - Baptist Memorial Hospital for Women
  - Memphis, Tennessee, United States, 38120
    - Family Cancer Center-Memphis
  - Nashville, Tennessee, United States, 37232
    - Vanderbilt University/Ingram Cancer Center
  - Nashville, Tennessee, United States, 37204
    - Vanderbilt Breast Center at One Hundred Oaks
  - Ooltewah, Tennessee, United States, 37363
    - Memorial GYN Plus
- Texas
  - Bryan, Texas, United States, 77802
    - Saint Joseph Regional Cancer Center
  - San Antonio, Texas, United States, 78229
    - University of Texas Health Science Center at San Antonio
- Vermont
  - Saint Johnsbury, Vermont, United States, 05819
    - Norris Cotton Cancer Center-North
- Washington
  - Bremerton, Washington, United States, 98310
    - Harrison HealthPartners Hematology and Oncology-Bremerton
  - Bremerton, Washington, United States, 98310
    - Harrison Medical Center
  - Burien, Washington, United States, 98166
    - Highline Medical Center-Main Campus
  - Enumclaw, Washington, United States, 98022
    - Saint Elizabeth Hospital
  - Federal Way, Washington, United States, 98003
    - Saint Francis Hospital
  - Lakewood, Washington, United States, 98499
    - Saint Clare Hospital
  - Poulsbo, Washington, United States, 98370
    - Harrison HealthPartners Hematology and Oncology-Poulsbo
  - Tacoma, Washington, United States, 98405
    - Northwest Medical Specialties PLLC
  - Tacoma, Washington, United States, 98405
    - Franciscan Research Center-Northwest Medical Plaza
- West Virginia
  - Huntington, West Virginia, United States, 25702
    - Saint Mary's Medical Center
- Wisconsin
  - Antigo, Wisconsin, United States, 54409
    - Langlade Hospital and Cancer Center
  - Burlington, Wisconsin, United States, 53105
    - Aurora Cancer Care-Southern Lakes VLCC
  - Chippewa Falls, Wisconsin, United States, 54729
    - Marshfield Clinic-Chippewa Center
  - Eau Claire, Wisconsin, United States, 54701
    - Marshfield Clinic Cancer Center at Sacred Heart
  - Eau Claire, Wisconsin, United States, 54701
    - Sacred Heart Hospital
  - Eau Claire, Wisconsin, United States, 54701
    - Marshfield Clinic Cancer Center - Eau Claire
  - Fond Du Lac, Wisconsin, United States, 54937
    - Aurora Health Center-Fond du Lac
  - Germantown, Wisconsin, United States, 53022
    - Aurora Health Care Germantown Health Center
  - Grafton, Wisconsin, United States, 53024
    - Aurora Cancer Care-Grafton
  - Green Bay, Wisconsin, United States, 54311
    - Aurora BayCare Medical Center
  - Kenosha, Wisconsin, United States, 53142
    - Aurora Cancer Care-Kenosha South
  - La Crosse, Wisconsin, United States, 54601
    - Gundersen Lutheran Medical Center
  - Ladysmith, Wisconsin, United States, 54848
    - Marshfield Clinic - Ladysmith Center
  - Marinette, Wisconsin, United States, 54143
    - Aurora Bay Area Medical Group-Marinette
  - Marinette, Wisconsin, United States, 54143
    - Bay Area Medical Center
  - Marinette, Wisconsin, United States, 54143
    - Vince Lombardi Cancer Clinic-Marinette
  - Marshfield, Wisconsin, United States, 54449
    - Marshfield Clinic
  - Marshfield, Wisconsin, United States, 54449
    - Marshfield Medical Center
  - Mequon, Wisconsin, United States, 53097
    - Columbia Saint Mary's Hospital - Ozaukee
  - Milwaukee, Wisconsin, United States, 53209
    - Aurora Cancer Care-Milwaukee
  - Milwaukee, Wisconsin, United States, 53215
    - Aurora Saint Luke's Medical Center
  - Milwaukee, Wisconsin, United States, 53233
    - Aurora Sinai Medical Center
  - Milwaukee, Wisconsin, United States, 53211
    - Columbia Saint Mary's Water Tower Medical Commons
  - Minocqua, Wisconsin, United States, 54548
    - Marshfield Clinic-Minocqua Center
  - New Richmond, Wisconsin, United States, 54017
    - Cancer Center of Western Wisconsin
  - Oshkosh, Wisconsin, United States, 54904
    - Vince Lombardi Cancer Clinic - Oshkosh
  - Racine, Wisconsin, United States, 53406
    - Aurora Cancer Care-Racine
  - Rice Lake, Wisconsin, United States, 54868
    - Lakeview Medical Center-Marshfield Clinic
  - Rice Lake, Wisconsin, United States, 54868
    - Marshfield Clinic-Rice Lake Center
  - Sheboygan, Wisconsin, United States, 53081
    - Vince Lombardi Cancer Clinic-Sheboygan
  - Stevens Point, Wisconsin, United States, 54482
    - Marshfield Clinic Stevens Point Center
  - Stevens Point, Wisconsin, United States, 54481
    - Ascension Saint Michael's Hospital
  - Stevens Point, Wisconsin, United States, 54481
    - Saint Michael's Hospital
  - Summit, Wisconsin, United States, 53066
    - Aurora Medical Center in Summit
  - Two Rivers, Wisconsin, United States, 54241
    - Vince Lombardi Cancer Clinic-Two Rivers
  - Waukesha, Wisconsin, United States, 53188
    - Aurora Cancer Care-Waukesha
  - Wausau, Wisconsin, United States, 54401
    - Aspirus Regional Cancer Center
  - Wausau, Wisconsin, United States, 54401
    - Marshfield Clinic-Wausau Center
  - Wauwatosa, Wisconsin, United States, 53226
    - Aurora Cancer Care-Milwaukee West
  - West Allis, Wisconsin, United States, 53227
    - Aurora West Allis Medical Center
  - Weston, Wisconsin, United States, 54476
    - Diagnostic and Treatment Center
  - Weston, Wisconsin, United States, 54476
    - Marshfield Clinic - Weston Center
  - Wisconsin Rapids, Wisconsin, United States, 54494
    - Marshfield Clinic - Wisconsin Rapids Center
  - Wisconsin Rapids, Wisconsin, United States, 54494
    - Aspirus UW Cancer Center
- Wyoming
  - Cody, Wyoming, United States, 82414
    - Big Horn Basin Cancer Center
  - Cody, Wyoming, United States, 82414
    - Billings Clinic-Cody
  - Sheridan, Wyoming, United States, 82801
    - Welch Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Child
Adult
Older Adult

Accepts Healthy Volunteers

Description

Inclusion Criteria:

Patients must have histologically or cytologically confirmed stage IV (American Joint Committee on Cancer [AJCC] 7th Edition) or recurrent non-small cell lung cancer (NSCLC)
Patients must have documented presence of an EGFR exon 19 deltion or exon 21 (L858R) substitution mutation; T790M mutation or other molecular abnormality will be allowed as long as it accompanies one of the mutations listed above; EGFR testing must be performed using a Food and Drug Administration (FDA)-approved test or in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
Patients must have tissue available and must agree to submission of tissue and blood; one to two paraffin-embedded tissue blocks or 15-20 unstained slides are requested (a minimum of 12 slides is required); cytology (i.e. fine-needle aspirations, pleural effusion specimens) is acceptable if a cell block or sufficient unstained slides are available; tumor material must be reviewed by a local pathologist who must confirm that at least 100 viable tumor cells are present in the sample and sign the S1403 Pathology Review Form; patients must also be willing to submit blood samples for correlative research at baseline, during treatment and at progression
Patients enrolled at sites participating in the Repeat Biopsy Study must agree to submission of tissue obtained by a repeat biopsy performed at the time of disease progression
Patients must not have received any prior systemic anticancer therapy for advanced or metastatic disease including chemotherapy or EGFR tyrosine kinase inhibitor therapy (including gefitinib, erlotinib, afatinib, or any experimental EGFR tyrosine kinase inhibitors [TKI] agents); prior chemotherapy for non-metastatic disease (i.e. adjuvant therapy or concurrent chemo-radiotherapy) is allowed as long as > 12 months has passed since completion of therapy; adjuvant EGFR-directed therapy is not allowed; local therapy (i.e. palliative radiotherapy) is allowed as long as a period of 7 days has passed since the last dose was received and the patient has recovered from any associated toxicity at the time of registration
Patients may have measurable or non-measurable disease documented by computed tomography (CT) or magnetic resonance imaging (MRI) within 42 days prior to registration; the CT from a combined positron emission tomography (PET)/CT may be used only if it is of diagnostic quality; laboratory parameters are not acceptable as the only evidence of disease; in order to qualify as measurable, measurable disease must be outside previous radiation field; all disease must be assessed and documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
Patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to registration; patient must not have symptomatic brain metastases or evidence of leptomeningeal carcinomatosis; patients with asymptomatic brain metastases are eligible if off of steroids for at least 7 days prior to registration without development of symptoms
Patients must not have any known clinically active interstitial lung disease
Absolute neutrophil count (ANC) >= 1,500/mcL
Platelets >= 75,000/mcL
Hemoglobin >= 9 g/dL
Total bilirubin =< 1.5 x institutional upper limit of normal (IULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x IULN (or =< 5 x IULN for patients with known liver metastases)
Serum creatinine =< 1.5 x IULN OR measured or calculated creatinine clearance >= 60 mL/min
Patients must not have significant gastrointestinal disorders with diarrhea as a major symptom (e.g. Crohn's disease, malabsorption, etc)
Patients must be able to swallow medication by oral route
Patients must not have a history of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of 3, unstable angina or poorly controlled arrhythmia or myocardial infarction within 6 months prior to registration; if clinically indicated, echocardiogram or multigated acquisition (MUGA) must be performed and cardiac ejection fraction must be >= 50%
Patients must not have had major surgery within 28 days prior to registration or be scheduled for surgery during the projected course of protocol treatment; tumor biopsy is allowed
Patients must not have a known history of active hepatitis B infection (defined as presence of hepatitis B surface antigen [Hep B sAg] and/ or Hep B deoxyribonucleic acid [DNA]), active hepatitis C infection (defined as presence of hepatitis C [Hep C] ribonucleic acid [RNA]) and/or known human immunodeficiency virus (HIV) seropositive
Patients must not have any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the study drug
Patients must not be planning to receive any other investigational agents during the course of protocol treatment
Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to afatinib and/or cetuximab
Prestudy history and physical must be obtained with 28 days prior to registration
Patients must have Zubrod performance status of 0 - 2
No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years
Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: None (Open Label)

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (afatinib dimaleate, cetuximab) Patients receive afatinib dimaleate PO QD on days 1-28 and cetuximab IV over 2 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis Correlative studies Drug: Afatinib Dimaleate Given PO Other Names: (2E)-N-(4-((3-Chloro-4-fluorophenyl)amino)-7-(((3S)-tetrahydrofuran-3-yl)oxy)quinazolin- 6-yl)-4-(dimethylamino)but-2-enamide bis(hydrogen (2Z)-but-2-enedioate) BIBW 2992MA2 BIBW2992 MA2 Gilotrif Biological: Cetuximab Given IV Other Names: Erbitux IMC-C225 Chimeric Anti-EGFR Monoclonal Antibody Chimeric MoAb C225 Chimeric Monoclonal Antibody C225
Active Comparator: Arm II (afatinib dimaleate) Patients receive afatinib dimaleate as in Arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis Correlative studies Drug: Afatinib Dimaleate Given PO Other Names: (2E)-N-(4-((3-Chloro-4-fluorophenyl)amino)-7-(((3S)-tetrahydrofuran-3-yl)oxy)quinazolin- 6-yl)-4-(dimethylamino)but-2-enamide bis(hydrogen (2Z)-but-2-enedioate) BIBW 2992MA2 BIBW2992 MA2 Gilotrif

Participant Group / Arm

Intervention / Treatment

Experimental: Arm I (afatinib dimaleate, cetuximab)

Patients receive afatinib dimaleate PO QD on days 1-28 and cetuximab IV over 2 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis

Correlative studies

Drug: Afatinib Dimaleate

Given PO

Other Names:

(2E)-N-(4-((3-Chloro-4-fluorophenyl)amino)-7-(((3S)-tetrahydrofuran-3-yl)oxy)quinazolin- 6-yl)-4-(dimethylamino)but-2-enamide bis(hydrogen (2Z)-but-2-enedioate)
BIBW 2992MA2
BIBW2992 MA2
Gilotrif

Biological: Cetuximab

Given IV

Other Names:

Erbitux
IMC-C225
Chimeric Anti-EGFR Monoclonal Antibody
Chimeric MoAb C225
Chimeric Monoclonal Antibody C225

Active Comparator: Arm II (afatinib dimaleate)

Patients receive afatinib dimaleate as in Arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis

Correlative studies

Drug: Afatinib Dimaleate

Given PO

Other Names:

(2E)-N-(4-((3-Chloro-4-fluorophenyl)amino)-7-(((3S)-tetrahydrofuran-3-yl)oxy)quinazolin- 6-yl)-4-(dimethylamino)but-2-enamide bis(hydrogen (2Z)-but-2-enedioate)
BIBW 2992MA2
BIBW2992 MA2
Gilotrif

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year Overall Survival Rate Time Frame: Up to 3 years post registration	Percentage of participants still alive 2 years post registration. KM estimate at 2 years is presented, Overall Survival assessed for a total of 3 years in order to calculate value.	Up to 3 years post registration
Progression-Free Survival Time Frame: up to 3 years post registration	From date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed, as well as an absolute increase of at least 0.5 cm. Unequivocal progression of non-measurable disease in the opinion of treating physician. Appearance of any new lesion/site. Death due to disease without prior documentation of progression and without symptomatic deterioration.	up to 3 years post registration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rates Time Frame: Up to 3 years	Percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of appropriate diameters of all target measurable lesions; Overall Response (OR) = CR + PR.	Up to 3 years
Time to Treatment Discontinuation Time Frame: up to 3 years post-registration	From date of registration to date of discontinuation of treatment or death due to any cause	up to 3 years post-registration
Time to Treatment Failure Time Frame: assessed up to 3 years post registration	From date of registration to date of first documentation of progression or symptomatic deterioration, early discontinuation of treatment, or death due to any cause.	assessed up to 3 years post registration
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Time Frame: Duration of treatment and follow up until death or 3 years post registration	Routine Adverse Events are reported by CTCAE4.0. For serious adverse event reporting, we updated from CTCAE4.0 to CTCAE5.0. . Only adverse events that are possibly, probably or definitely related to study drug are reported.	Duration of treatment and follow up until death or 3 years post registration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Copy Number Alterations in MET, EGFR, and HER2, Analyzed Using Fluorescence in Situ Hybridization Time Frame: Baseline up to 3 years (after disease progression)	For each of these markers, a one-sample t-test (or Wilcoxon signed-rank test) will be used to test the null hypothesis that the absolute difference between the copy number after progression and the copy number in the pre-treatment specimen (or an appropriate transformation of the difference, determined after exploratory data analysis) is not equal to zero.	Baseline up to 3 years (after disease progression)
Change in the Ratio of Sensitizing EGFR Mutation to EGFR T790 Mutation Time Frame: Baseline up to 3 years (at progression)	To evaluate if EGFRs/EGFR T790M is lower at progression than in pre-treatment specimens among patients with results available for pre-treatment and progression, a one-sample t-test (or Wilcoxon signed-rank test) will be used to test the null hypothesis that the difference between the progression ratio and the pre-treatment ratio (or an appropriate transformation of the difference, determined after exploratory data analysis) is greater than zero in favor of the alternative that the difference is less than zero.	Baseline up to 3 years (at progression)
EGFR Immunohistochemistry H-score Time Frame: Baseline	To evaluate the hypothesis that H-score positive status at baseline is associated with absolute difference in PFS (and OS) among patients randomized to receive afatinib dimaleate monotherapy a test of interaction will be performed at the 1-sided 20% level.	Baseline
Levels of Circulating Tumor Markers Time Frame: Up to 3 years	Tumor marker levels over time will be evaluated using a linear mixed model for continuous markers and using generalized estimating equations for binary markers. A landmark analysis will be used to evaluate the correlation between post-randomization biomarker values and PFS and OS (from the landmark timepoint) using a Cox proportional hazards model.	Up to 3 years
Presence of de Novo EGFR T790M Mutation or Other Molecular Alterations Time Frame: Baseline	To evaluate if the presence of de novo T790M mutation is associated with primary resistance to afatinib dimaleate, PFS and OS will be compared between T790M mutation positive and negative patients randomized to the afatinib dimaleate monotherapy arm using a log-rank test..	Baseline
Ratio of Sensitizing EGFR Mutation to EGFR T790 Mutation Time Frame: Up to 3 years	To evaluate if the ratio of EGFR sensitizing mutation to EGFR T790M mutation (EGFRs/EGFR T790M) among patients with T790M is predictive for afatinib dimaleate monotherapy, analyses will be performed in a similar fashion to the evaluation of T790M among patients with measurable T790M (which defines T790M). Cox regression will be used to assess the predictive association of the ratio in the afatinib dimaleate monotherapy arm with both OS and PFS	Up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

SWOG Cancer Research Network

Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator: Sarah Goldberg, SWOG Cancer Research Network

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Goldberg SB, Redman MW, Lilenbaum R, Politi K, Stinchcombe TE, Horn L, Chen EH, Mashru SH, Gettinger SN, Melnick MA, Herbst RS, Baumgart MA, Miao J, Moon J, Kelly K, Gandara DR. Randomized Trial of Afatinib Plus Cetuximab Versus Afatinib Alone for First-Line Treatment of EGFR-Mutant Non-Small-Cell Lung Cancer: Final Results From SWOG S1403. J Clin Oncol. 2020 Dec 1;38(34):4076-4085. doi: 10.1200/JCO.20.01149. Epub 2020 Oct 6.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 7, 2015

Primary Completion (Actual)

September 25, 2018

Study Completion (Estimated)

December 15, 2024

Study Registration Dates

First Submitted

May 6, 2015

First Submitted That Met QC Criteria

May 6, 2015

First Posted (Estimated)

May 8, 2015

Study Record Updates

Last Update Posted (Estimated)

February 9, 2024

Last Update Submitted That Met QC Criteria

February 7, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Other Study ID Numbers

S1403 (Other Identifier: CTEP)
U10CA180888 (U.S. NIH Grant/Contract)
NCI-2014-02405 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
BI 1200.124

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Study Overview

Status

Conditions

Intervention / Treatment

Detailed Description

Study Type

Enrollment (Actual)

Phase

Contacts and Locations

Study Locations

Participation Criteria

Eligibility Criteria

Ages Eligible for Study

Accepts Healthy Volunteers

Description

Study Plan

How is the study designed?

Design Details

Number of Arms

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Secondary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Other Outcome Measures

Outcome Measure

Measure Description

Time Frame

Collaborators and Investigators

Sponsor

Collaborators

Investigators

Publications and helpful links

General Publications

Study record dates

Study Major Dates

Study Start (Actual)

Primary Completion (Actual)

Study Completion (Estimated)

Study Registration Dates

First Submitted

First Submitted That Met QC Criteria

First Posted (Estimated)

Study Record Updates

Last Update Posted (Estimated)

Last Update Submitted That Met QC Criteria

Last Verified

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Clinical Trials on Recurrent Non-Small Cell Lung Carcinoma

Clinical Trials on Laboratory Biomarker Analysis

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