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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT02438722
Other study ID # S1403
Secondary ID NCI-2014-02405BI
Status Active, not recruiting
Phase Phase 2/Phase 3
First received
Last updated
Start date May 7, 2015
Est. completion date December 15, 2024

Study information

Verified date February 2024
Source SWOG Cancer Research Network
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 174
Est. completion date December 15, 2024
Est. primary completion date September 25, 2018
Accepts healthy volunteers No
Gender All
Age group N/A and older
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

Drug:
Afatinib Dimaleate
Given PO
Biological:
Cetuximab
Given IV
Other:
Laboratory Biomarker Analysis
Correlative studies

Locations

Country Name City State
United States Hawaii Oncology Inc-Pali Momi 'Aiea Hawaii
United States Pali Momi Medical Center 'Aiea Hawaii
United States The Cancer Center of Hawaii-Pali Momi 'Aiea Hawaii
United States Akron General Medical Center Akron Ohio
United States Lovelace Medical Center-Saint Joseph Square Albuquerque New Mexico
United States New Mexico Oncology Hematology Consultants Albuquerque New Mexico
United States University of New Mexico Cancer Center Albuquerque New Mexico
United States Lehigh Valley Hospital-Cedar Crest Allentown Pennsylvania
United States Mary Greeley Medical Center Ames Iowa
United States McFarland Clinic PC-William R Bliss Cancer Center Ames Iowa
United States Kaiser Permanente-Anaheim Anaheim California
United States Saint Joseph Mercy Hospital Ann Arbor Michigan
United States University of Michigan Comprehensive Cancer Center Ann Arbor Michigan
United States Langlade Hospital and Cancer Center Antigo Wisconsin
United States PCR Oncology Arroyo Grande California
United States Asheville Hematology-Oncology Associates Asheville North Carolina
United States Cancer Care of Western North Carolina Asheville North Carolina
United States Mission Hospital-Memorial Campus Asheville North Carolina
United States Sutter Auburn Faith Hospital Auburn California
United States Sutter Cancer Centers Radiation Oncology Services-Auburn Auburn California
United States Harold Alfond Center for Cancer Care Augusta Maine
United States Rush - Copley Medical Center Aurora Illinois
United States Saint Alphonsus Medical Center-Baker City Baker City Oregon
United States AIS Cancer Center at San Joaquin Community Hospital Bakersfield California
United States Kaiser Permanente-Baldwin Park Baldwin Park California
United States Eastern Maine Medical Center Bangor Maine
United States Flaget Memorial Hospital Bardstown Kentucky
United States Boston Baskin Cancer Center-Bartlett Bartlett Tennessee
United States Bronson Battle Creek Battle Creek Michigan
United States UPMC-Heritage Valley Health System Beaver Beaver Pennsylvania
United States Indu and Raj Soin Medical Center Beavercreek Ohio
United States Kaiser Permanente-Bellflower Bellflower California
United States Strecker Cancer Center-Belpre Belpre Ohio
United States Sanford Clinic North-Bemidgi Bemidji Minnesota
United States Alta Bates Summit Medical Center-Herrick Campus Berkeley California
United States Lehigh Valley Hospital - Muhlenberg Bethlehem Pennsylvania
United States Constantinou, Costas L MD (UIA Investigator) Bettendorf Iowa
United States Beverly Hospital Beverly Massachusetts
United States Billings Clinic Cancer Center Billings Montana
United States Saint Vincent Healthcare Billings Montana
United States Sanford Bismarck Medical Center Bismarck North Dakota
United States Illinois CancerCare-Bloomington Bloomington Illinois
United States Saint Joseph Medical Center Bloomington Illinois
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 PC-Boone Boone Iowa
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 Lafayette Family Cancer Center-EMMC Brewer Maine
United States IHA Hematology Oncology Consultants-Brighton Brighton Michigan
United States Saint Joseph Mercy Brighton Brighton Michigan
United States Saint Joseph Regional Cancer Center Bryan Texas
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 Saint Alphonsus Cancer Care Center-Caldwell Caldwell Idaho
United States Sutter Cancer Centers Radiation Oncology Services-Cameron Park Cameron Park California
United States IHA Hematology Oncology Consultants-Canton Canton Michigan
United States Illinois CancerCare-Canton Canton Illinois
United States Mercy Medical Center Canton Ohio
United States Saint Joseph Mercy Canton Canton Michigan
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 Caro Cancer Center Caro Michigan
United States Carson Tahoe Regional Medical Center Carson City Nevada
United States SIH Cancer Institute Carterville Illinois
United States Illinois CancerCare-Carthage Carthage Illinois
United States Eden Hospital Medical Center Castro Valley California
United States Dayton Physicians LLC-Miami Valley South Centerville Ohio
United States Miami Valley Hospital South Centerville Ohio
United States Centralia Oncology Clinic Centralia Illinois
United States Christiana Care Health System-Concord Health Center Chadds Ford Pennsylvania
United States Cancer Center of Kansas - Chanute Chanute Kansas
United States Memorial Hospital Chattanooga Tennessee
United States IHA Hematology Oncology Consultants-Chelsea Chelsea Michigan
United States Saint Joseph Mercy Chelsea Chelsea Michigan
United States Adena Regional Medical Center Chillicothe Ohio
United States Marshfield Clinic-Chippewa Center Chippewa Falls Wisconsin
United States Bethesda North Hospital Cincinnati Ohio
United States Good Samaritan Hospital - Cincinnati Cincinnati 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 TriHealth Cancer Institute-Anderson Cincinnati Ohio
United States TriHealth Cancer Institute-Westside Cincinnati Ohio
United States Hematology Oncology Consultants-Clarkston Clarkston Michigan
United States Newland Medical Associates-Clarkston Clarkston Michigan
United States Sampson Radiation Oncology Clinton North Carolina
United States Southeastern Medical Oncology Center-Clinton Clinton North Carolina
United States Medical Oncology and Hematology Associates-West Des Moines Clive Iowa
United States Mercy Cancer Center-West Lakes Clive Iowa
United States Big Horn Basin Cancer Center Cody Wyoming
United States Billings Clinic-Cody Cody Wyoming
United States Kootenai Medical Center Coeur d'Alene Idaho
United States Coffeyville Regional Medical Center Coffeyville Kansas
United States Integrity Oncology PLLC-Collierville Collierville Tennessee
United States Penrose-Saint Francis Healthcare Colorado Springs Colorado
United States Rocky Mountain Cancer Centers-Penrose Colorado Springs Colorado
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 Riverside Methodist Hospital Columbus Ohio
United States The Mark H Zangmeister Center Columbus Ohio
United States Mercy Hospital Coon Rapids Minnesota
United States Commonwealth Cancer Center-Corbin Corbin Kentucky
United States Alegent Health Mercy Hospital Council Bluffs Iowa
United States Greater Regional Medical Center Creston Iowa
United States Oncology Hematology Care Inc-Crestview Crestview Hills Kentucky
United States Carle on Vermilion Danville Illinois
United States Sutter Davis Hospital Davis California
United States Dayton Physicians LLC-Samaritan North Dayton Ohio
United States Good Samaritan Hospital - Dayton Dayton Ohio
United States Miami Valley Hospital Dayton Ohio
United States Samaritan North Health Center Dayton Ohio
United States Beaumont Hospital-Dearborn Dearborn Michigan
United States Cancer Care Specialists of Central Illinois 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 Porter Adventist Hospital Denver Colorado
United States Smilow Cancer Hospital-Derby Care Center Derby Connecticut
United States Medical Oncology and Hematology Associates-Laurel Des Moines Iowa
United States Mercy Medical Center - Des Moines Des Moines Iowa
United States Saint John Hospital and Medical Center Detroit Michigan
United States Wayne State University/Karmanos Cancer Institute Detroit Michigan
United States Cancer Center of Kansas - Dodge City Dodge City Kansas
United States Mercy Medical Center Durango Colorado
United States Southwest Oncology PC Durango Colorado
United States Greenville Health System Cancer Institute-Easley Easley South Carolina
United States Great Lakes Cancer Management Specialists-Doctors Park East China Township Michigan
United States Marshfield Clinic Cancer Center - Eau Claire Eau Claire Wisconsin
United States Marshfield Clinic Cancer Center at Sacred Heart Eau Claire Wisconsin
United States Sacred Heart Hospital Eau Claire Wisconsin
United States Fairview-Southdale Hospital Edina Minnesota
United States Carle Physician Group-Effingham Effingham Illinois
United States Crossroads Cancer Center Effingham Illinois
United States Cancer Center of Kansas - El Dorado El Dorado Kansas
United States Elmhurst Memorial Hospital Elmhurst Illinois
United States Walter Knox Memorial Hospital Emmett Idaho
United States Englewood Hospital and Medical Center Englewood New Jersey
United States Saint Elizabeth Hospital Enumclaw Washington
United States Ephrata Cancer Center Ephrata Pennsylvania
United States Ephrata Community Hospital Ephrata Pennsylvania
United States Illinois CancerCare-Eureka Eureka Illinois
United States Deaconess Clinic Downtown Evansville Indiana
United States Oncology Hematology Care Inc-Healthplex Fairfield Ohio
United States Smilow Cancer Hospital Care Center-Fairfield Fairfield Connecticut
United States Roger Maris Cancer Center Fargo North Dakota
United States Sanford Broadway Medical Center Fargo North Dakota
United States Sanford Clinic North-Fargo Fargo North Dakota
United States Weisberg Cancer Treatment Center Farmington Hills Michigan
United States Saint Francis Hospital Federal Way Washington
United States Armes Family Cancer Center Findlay Ohio
United States Blanchard Valley Hospital Findlay Ohio
United States Orion Cancer Care Findlay Ohio
United States Genesee Cancer and Blood Disease Treatment Center Flint Michigan
United States Genesee Hematology Oncology PC Flint Michigan
United States Genesys Hurley Cancer Institute Flint Michigan
United States Hurley Medical Center Flint Michigan
United States McLeod Regional Medical Center Florence South Carolina
United States Aurora Health Center-Fond du Lac Fond Du Lac Wisconsin
United States Kaiser Permanente-Fontana Fontana California
United States McFarland Clinic PC-Trinity Cancer Center Fort Dodge Iowa
United States Cancer Center of Kansas - Fort Scott Fort Scott Kansas
United States Mercy Hospital Fort Smith Fort Smith Arkansas
United States Parkview Hospital Randallia Fort Wayne Indiana
United States Atrium Medical Center-Middletown Regional Hospital Franklin Ohio
United States Dayton Physicians LLC-Atrium Franklin Ohio
United States Vanderbilt-Ingram Cancer Center Cool Springs Franklin Tennessee
United States Palo Alto Medical Foundation-Fremont Fremont California
United States Unity Hospital Fridley Minnesota
United States Illinois CancerCare-Galesburg Galesburg Illinois
United States Western Illinois Cancer Treatment Center Galesburg Illinois
United States Saint Catherine Hospital Garden City Kansas
United States Aurora Health Care Germantown Health Center Germantown Wisconsin
United States Adams Cancer Center Gettysburg Pennsylvania
United States Addison Gilbert Hospital Gloucester Massachusetts
United States Mountain Blue Cancer Care Center Golden Colorado
United States Southeastern Medical Oncology Center-Goldsboro Goldsboro North Carolina
United States Wayne Memorial Hospital Goldsboro North Carolina
United States Wayne Radiation Oncology Goldsboro North Carolina
United States Aurora Cancer Care-Grafton Grafton Wisconsin
United States Altru Cancer Center Grand Forks North Dakota
United States CHI Health Saint Francis Grand Island Nebraska
United States Mercy Health Saint Mary's Grand Rapids Michigan
United States Spectrum Health at Butterworth Campus Grand Rapids Michigan
United States Three Rivers Community Hospital Grants Pass Oregon
United States Central Care Cancer Center - Great Bend Great Bend Kansas
United States Saint Rose Ambulatory and Surgery Center Great Bend Kansas
United States Benefis Healthcare- Sletten Cancer Institute Great Falls Montana
United States Aurora BayCare Medical Center Green Bay Wisconsin
United States UPMC Cancer Centers - Arnold Palmer Pavilion Greensburg Pennsylvania
United States Dayton Physicians LLC-Wayne Greenville Ohio
United States Greenville Health System Cancer Institute-Butternut Greenville South Carolina
United States Greenville Health System Cancer Institute-Eastside Greenville South Carolina
United States Greenville Health System Cancer Institute-Faris Greenville South Carolina
United States Greenville Memorial Hospital Greenville South Carolina
United States Saint Francis Cancer Center Greenville South Carolina
United States Saint Francis Hospital Greenville South Carolina
United States Wayne Hospital Greenville Ohio
United States Greenville Health System Cancer Institute-Greer Greer South Carolina
United States Great Lakes Cancer Management Specialists-Van Elslander Cancer Center Grosse Pointe Woods Michigan
United States Lymphoma Clinic of Michigan Grosse Pointe Woods Michigan
United States Michigan Breast Specialists-Grosse Pointe Woods Grosse Pointe Woods Michigan
United States Yale-New Haven Shoreline Medical Center Guilford Connecticut
United States Cherry Tree Cancer Center Hanover Pennsylvania
United States Kaiser Permanente - Harbor City Harbor City California
United States Smilow Cancer Hospital Care Center at Saint Francis Hartford Connecticut
United States Hays Medical Center Hays Kansas
United States Saint Peter's Community Hospital Helena Montana
United States 21st Century Oncology-Henderson Henderson Nevada
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-Horizon Ridge Henderson Nevada
United States Comprehensive Cancer Centers of Nevada-Southeast Henderson Henderson Nevada
United States Las Vegas Cancer Center-Henderson Henderson Nevada
United States Hendersonville Hematology and Oncology at Pardee Hendersonville North Carolina
United States Margaret R Pardee Memorial Hospital Hendersonville North Carolina
United States Park Ridge Hospital Breast Health Center Hendersonville North Carolina
United States Pulmonary Medicine Center of Chattanooga-Hixson Hixson Tennessee
United States Hawaii Cancer Care Inc-Liliha Honolulu Hawaii
United States Hawaii Cancer Care Inc-POB II Honolulu Hawaii
United States Hawaii Oncology Inc-Kuakini Honolulu Hawaii
United States Hawaii Oncology Inc-POB I Honolulu Hawaii
United States Island Urology Honolulu Hawaii
United States Kapiolani Medical Center for Women and Children Honolulu Hawaii
United States Kuakini Medical Center Honolulu Hawaii
United States Queen's Medical Center Honolulu Hawaii
United States Straub Clinic and Hospital Honolulu Hawaii
United States The Cancer Center of Hawaii-Liliha Honolulu Hawaii
United States University of Hawaii Cancer Center Honolulu Hawaii
United States CHI Saint Vincent Cancer Center Hot Springs Hot Springs Arkansas
United States Saint Mary's Medical Center Huntington West Virginia
United States Cancer Center of Kansas-Independence Independence Kansas
United States Centerpoint Medical Center LLC Independence Missouri
United States Kaiser Permanente-Irvine Irvine California
United States Allegiance Health Jackson Michigan
United States Baptist MD Anderson Cancer Center Jacksonville Florida
United States Onslow Memorial Hospital Jacksonville North Carolina
United States Southeastern Medical Oncology Center-Jacksonville Jacksonville North Carolina
United States McFarland Clinic PC-Jefferson Jefferson Iowa
United States Capital Region Medical Center-Goldschmidt Cancer Center Jefferson City Missouri
United States UPMC-Johnstown/John P. Murtha Regional Cancer Center Johnstown Pennsylvania
United States Fowler Family Center for Cancer Care Jonesboro Arkansas
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 Heartland Hematology and Oncology Associates Incorporated Kansas City Missouri
United States Kansas City Veterans Affairs Medical Center 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-North Kansas City Missouri
United States The University of Kansas Cancer Center-South Kansas City Missouri
United States Truman Medical Center Kansas City Missouri
United States University of Kansas Cancer Center Kansas City Kansas
United States University of Kansas Cancer Center-West Kansas City Kansas
United States CHI Health Good Samaritan Kearney Nebraska
United States Heartland Hematology and Oncology Kearney Nebraska
United States Aurora Cancer Care-Kenosha South Kenosha Wisconsin
United States First Dayton Cancer Care Kettering Ohio
United States Greater Dayton Cancer Center Kettering Ohio
United States Kettering Medical Center Kettering Ohio
United States Illinois CancerCare-Kewanee Clinic Kewanee Illinois
United States Cancer Center of Kansas-Kingman Kingman Kansas
United States Kinston Medical Specialists PA Kinston North Carolina
United States Gundersen Lutheran Medical Center La Crosse Wisconsin
United States UC San Diego Moores Cancer Center La Jolla California
United States Marshfield Clinic - Ladysmith Center Ladysmith Wisconsin
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 Sparrow Hospital Lansing Michigan
United States Memorial Medical Center - Las Cruces Las Cruces New Mexico
United States 21st Century Oncology Las Vegas Nevada
United States 21st Century Oncology-Fort Apache Las Vegas Nevada
United States 21st Century Oncology-Vegas Tenaya Las Vegas Nevada
United States Ann M Wierman MD LTD Las Vegas Nevada
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 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 Specialists-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 Cancer Center Las Vegas Nevada
United States University Medical Center of Southern Nevada Las Vegas Nevada
United States Lawrence Memorial Hospital Lawrence Kansas
United States Dartmouth Hitchcock Medical Center Lebanon New Hampshire
United States Sechler Family Cancer Center Lebanon Pennsylvania
United States Saint Luke's East - Lee's Summit Lee's Summit Missouri
United States The University of Kansas Cancer Center-Lee's Summit Lee's Summit Missouri
United States Kansas Institute of Medicine Cancer and Blood Center Lenexa Kansas
United States Minimally Invasive Surgery Hospital Lenexa Kansas
United States Beebe Medical Center Lewes Delaware
United States Saint Joseph Hospital East Lexington Kentucky
United States Saint Joseph Radiation Oncology Resource Center Lexington Kentucky
United States Cancer Center of Kansas-Liberal Liberal Kansas
United States Liberty Radiation Oncology Center Liberty Missouri
United States Wilcox Memorial Hospital and Kauai Medical Clinic Lihue Hawaii
United States Nebraska Cancer Research Center Lincoln Nebraska
United States Nebraska Hematology and Oncology Lincoln Nebraska
United States Saint Elizabeth Regional Medical Center Lincoln Nebraska
United States Southeast Nebraska Cancer Center Lincoln Nebraska
United States Littleton Adventist Hospital Littleton Colorado
United States Hope Cancer Clinic Livonia Michigan
United States Saint Mary Mercy Hospital Livonia Michigan
United States Longmont United Hospital Longmont Colorado
United States Rocky Mountain Cancer Centers-Longmont Longmont Colorado
United States Kaiser Permanente Los Angeles Medical Center Los Angeles California
United States Kaiser Permanente-Cadillac Los Angeles California
United States Jewish Hospital Louisville Kentucky
United States Jewish Hospital Medical Center Northeast Louisville Kentucky
United States Saints Mary and Elizabeth Hospital Louisville Kentucky
United States Great Lakes Cancer Management Specialists-Macomb Medical Campus Macomb Michigan
United States Illinois CancerCare-Macomb Macomb Illinois
United States Michigan Breast Specialists-Macomb Township Macomb Michigan
United States Central Georgia Gynecologic Oncology Macon Georgia
United States Medical Center of Central Georgia Macon Georgia
United States Norris Cotton Cancer Center-Manchester Manchester New Hampshire
United States Cancer Center of Kansas-Manhattan Manhattan Kansas
United States Fairview Maple Grove Medical Center Maple Grove Minnesota
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 Vince Lombardi Cancer Clinic-Marinette Marinette Wisconsin
United States Saint Mary's Oncology/Hematology Associates of Marlette Marlette Michigan
United States UP Health System Hematology Oncology Marquette Marquette Michigan
United States UP Health System Marquette Marquette Michigan
United States McFarland Clinic PC-Marshalltown Marshalltown Iowa
United States Marshfield Clinic Marshfield Wisconsin
United States Marshfield Medical Center Marshfield Wisconsin
United States Fremont - Rideout Cancer Center Marysville California
United States Carle Physician Group-Mattoon/Charleston Mattoon Illinois
United States Loyola University Medical Center Maywood Illinois
United States UPMC Cancer Center at UPMC McKeesport McKeesport Pennsylvania
United States Cancer Center of Kansas - McPherson McPherson Kansas
United States Providence Medford Medical Center Medford Oregon
United States Rogue Valley Medical Center Medford Oregon
United States Baptist Memorial Hospital and Cancer Center-Memphis Memphis Tennessee
United States Baptist Memorial Hospital for Women Memphis Tennessee
United States Family Cancer Center-Memphis Memphis Tennessee
United States Columbia Saint Mary's Hospital - Ozaukee Mequon Wisconsin
United States Mercy UC Davis Cancer Center Merced California
United States Idaho Urologic Institute-Meridian Meridian Idaho
United States Franciscan Saint Anthony Health-Michigan City Michigan City Indiana
United States Woodland Cancer Care Center Michigan City Indiana
United States Dayton Physicians LLC-Signal Point Middletown Ohio
United States Middlesex Hospital Middletown Connecticut
United States Orange Regional Medical Center Middletown New York
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 Columbia Saint Mary's Water Tower Medical Commons Milwaukee Wisconsin
United States Abbott-Northwestern Hospital Minneapolis Minnesota
United States Health Partners Inc 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 Community Medical Hospital Missoula Montana
United States Saint Patrick Hospital - Community Hospital Missoula Montana
United States Memorial Medical Center Modesto California
United States Garneau, Stewart C MD (UIA Investigator) Moline Illinois
United States Spector, David MD (UIA Investigator) Moline Illinois
United States Trinity Medical Center Moline Illinois
United States Monroe Cancer Center Monroe Michigan
United States UPMC-Coraopolis/Heritage Valley Radiation Oncology Moon Pennsylvania
United States Good Samaritan Regional Health Center Mount Vernon Illinois
United States Knox Community Hospital Mount Vernon Ohio
United States Palo Alto Medical Foundation-Camino Division Mountain View California
United States Palo Alto Medical Foundation-Gynecologic Oncology Mountain View California
United States Mercy Health Mercy Campus Muskegon Michigan
United States Saint Alphonsus Medical Center-Nampa Nampa Idaho
United States Edward Hospital/Cancer Center Naperville Illinois
United States Norris Cotton Cancer Center-Nashua Nashua New Hampshire
United States Vanderbilt Breast Center at One Hundred Oaks Nashville Tennessee
United States Vanderbilt University/Ingram Cancer Center Nashville Tennessee
United States Baptist Memorial Hospital and Cancer Center-Union County New Albany Mississippi
United States Yale University New Haven Connecticut
United States Cancer Center of Western Wisconsin New Richmond Wisconsin
United States New Ulm Medical Center New Ulm Minnesota
United States Christiana Care Health System-Christiana Hospital 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 Regional Hematology and Oncology PA Newark Delaware
United States Chancellor Center for Oncology Newburgh Indiana
United States Cancer Center of Kansas - Newton Newton Kansas
United States Lakeland Community Hospital Niles Michigan
United States Faith Regional Health Services Carson Cancer Center Norfolk Nebraska
United States Yale-New Haven Hospital North Haven Medical Center North Haven Connecticut
United States Great Plains Health Callahan Cancer Center North Platte Nebraska
United States Sutter Cancer Research Consortium Novato California
United States Mercy Hospital Oklahoma City Oklahoma City Oklahoma
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Olathe Medical Center Olathe Kansas
United States Alegent Health Bergan Mercy Medical Center Omaha Nebraska
United States Alegent Health Immanuel Medical Center Omaha Nebraska
United States Alegent Health Lakeside Hospital Omaha Nebraska
United States Creighton University Medical Center Omaha Nebraska
United States Hematology and Oncology Consultants PC Omaha Nebraska
United States Nebraska Cancer Specialists - Omaha Omaha Nebraska
United States Nebraska Methodist Hospital Omaha Nebraska
United States Oncology Hematology West PC Omaha Nebraska
United States Saint Alphonsus Medical Center-Ontario Ontario Oregon
United States Memorial GYN Plus Ooltewah Tennessee
United States Smilow Cancer Hospital-Orange Care Center Orange Connecticut
United States Vince Lombardi Cancer Clinic - Oshkosh Oshkosh Wisconsin
United States Illinois CancerCare-Ottawa Clinic Ottawa Illinois
United States Radiation Oncology of Northern Illinois Ottawa Illinois
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 Baptist Memorial Hospital and Cancer Center-Oxford Oxford Mississippi
United States Hope Cancer Care of Nevada-Pahrump Pahrump Nevada
United States Palo Alto Medical Foundation Health Care Palo Alto California
United States Kaiser Permanente - Panorama City Panorama City California
United States Midlands Community Hospital Papillion Nebraska
United States Parker Adventist Hospital Parker Colorado
United States Rocky Mountain Cancer Centers-Parker Parker Colorado
United States Cancer Center of Kansas - Parsons Parsons Kansas
United States Singing River Hospital Pascagoula Mississippi
United States Illinois CancerCare-Pekin Pekin Illinois
United States OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center Pekin Illinois
United States Sacred Heart Hospital Pensacola Florida
United States Illinois CancerCare-Peoria Peoria Illinois
United States Methodist Medical Center of Illinois Peoria Illinois
United States OSF Saint Francis Medical Center Peoria Illinois
United States OSF Saint Francis Radiation Oncology at Peoria Cancer Center Peoria Illinois
United States Illinois CancerCare-Peru Peru Illinois
United States Valley Radiation Oncology Peru Illinois
United States Temple University Hospital Philadelphia Pennsylvania
United States Via Christi Hospital-Pittsburg Pittsburg Kansas
United States University of Pittsburgh Cancer Institute (UPCI) Pittsburgh Pennsylvania
United States UPMC-Magee Womens Hospital 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 Edward Hospital/Cancer Center?Plainfield Plainfield Illinois
United States 21st Century Oncology-Pontiac Pontiac Michigan
United States Hope Cancer Center Pontiac Michigan
United States Newland Medical Associates-Pontiac Pontiac Michigan
United States Saint Joseph Mercy Oakland Pontiac Michigan
United States Huron Medical Center PC Port Huron Michigan
United States Lake Huron Medical Center Port Huron Michigan
United States Kaiser Permanente Northwest Portland Oregon
United States Southern Ohio Medical Center Portsmouth Ohio
United States Kootenai Cancer Center 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 Cancer Center of Kansas - Pratt Pratt Kansas
United States Illinois CancerCare-Princeton Princeton Illinois
United States Rocky Mountain Cancer Centers - Pueblo Pueblo Colorado
United States Saint Mary Corwin Medical Center Pueblo Colorado
United States Aurora Cancer Care-Racine Racine Wisconsin
United States Eisenhower Medical Center Rancho Mirage California
United States Penn State Health Saint Joseph Medical Center Reading Pennsylvania
United States Spectrum Health Reed City Hospital Reed City Michigan
United States Beebe Health Campus Rehoboth Beach Delaware
United States Radiation Oncology Associates Reno Nevada
United States Renown Regional Medical Center Reno Nevada
United States Saint Mary's Regional Medical Center Reno Nevada
United States Lakeview Medical Center-Marshfield Clinic Rice Lake Wisconsin
United States Marshfield Clinic-Rice Lake Center Rice Lake Wisconsin
United States Reid Health Richmond Indiana
United States Kaiser Permanente-Riverside Riverside California
United States North Memorial Medical Health Center Robbinsdale Minnesota
United States University of Rochester Rochester New York
United States Great Lakes Cancer Management Specialists-Rochester Hills Rochester Hills Michigan
United States SwedishAmerican Regional Cancer Center/ACT Rockford Illinois
United States Penobscot Bay Medical Center Rockport Maine
United States Delbert Day Cancer Institute at PCRMC Rolla Missouri
United States Mercy Clinic-Rolla-Cancer and Hematology Rolla Missouri
United States Sutter Cancer Centers Radiation Oncology Services-Roseville Roseville California
United States Sutter Roseville Medical Center Roseville California
United States Sutter Medical Center Sacramento Sacramento California
United States University of California Davis Comprehensive Cancer Center Sacramento California
United States Oncology Hematology Associates of Saginaw Valley PC Saginaw Michigan
United States Saint Mary's of Michigan Saginaw Michigan
United States Norris Cotton Cancer Center-North Saint Johnsbury Vermont
United States Heartland Regional Medical Center Saint Joseph Missouri
United States Lakeland Hospital Saint Joseph Michigan
United States Marie Yeager Cancer Center Saint Joseph Michigan
United States Mercy Hospital Saint Louis 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 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 Sainte Genevieve County Memorial Hospital Sainte Genevieve Missouri
United States Cancer Center of Kansas - Salina Salina Kansas
United States Salina Regional Health Center Salina Kansas
United States University of Texas Health Science Center at San Antonio San Antonio Texas
United States Kaiser Permanente-San Diego Mission San Diego California
United States Kaiser Permanente-San Diego Zion San Diego California
United States California Pacific Medical Center-Pacific Campus San Francisco California
United States Kaiser Permanente-San Marcos San Marcos California
United States Kootenai Cancer Clinic Sandpoint Idaho
United States Palo Alto Medical Foundation-Santa Cruz Santa Cruz California
United States Christus Saint Vincent Regional Cancer Center Santa Fe New Mexico
United States Sutter Pacific Medical Foundation Santa Rosa California
United States Lewis Cancer and Research Pavilion at Saint Joseph's/Candler Savannah Georgia
United States Low Country Cancer Care Associates PC Savannah Georgia
United States Memorial University Medical Center Savannah Georgia
United States Summit Cancer Care-Candler Savannah Georgia
United States Summit Cancer Care-Memorial Savannah Georgia
United States Guthrie Medical Group PC-Robert Packer Hospital Sayre Pennsylvania
United States Regional West Medical Center Cancer Center Scottsbluff Nebraska
United States Nanticoke Memorial Hospital Seaford Delaware
United States Greenville Health System Cancer Institute-Seneca Seneca South Carolina
United States UPMC Cancer Center at UPMC Northwest Seneca Pennsylvania
United States Saint Francis Regional Medical Center Shakopee Minnesota
United States Vince Lombardi Cancer Clinic-Sheboygan Sheboygan Wisconsin
United States Jewish Hospital Medical Center South Shepherdsville Kentucky
United States Welch Cancer Center Sheridan Wyoming
United States Dayton Physicians LLC-Wilson Sidney Ohio
United States Siouxland Regional Cancer Center Sioux City Iowa
United States Sanford Cancer Center Oncology Clinic Sioux Falls South Dakota
United States Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota
United States Baptist Memorial Hospital and Cancer Center-Desoto Southhaven Mississippi
United States Greenville Health System Cancer Institute-Spartanburg Spartanburg South Carolina
United States Central Illinois Hematology Oncology Center Springfield Illinois
United States CoxHealth South Hospital Springfield Missouri
United States Memorial Medical Center Springfield Illinois
United States Mercy Hospital Springfield Springfield Missouri
United States Southern Illinois University School of Medicine Springfield Illinois
United States Springfield Clinic Springfield Illinois
United States Springfield Regional Cancer Center Springfield Ohio
United States Springfield Regional Medical Center Springfield Ohio
United States Bhadresh Nayak MD PC-Sterling Heights Sterling Heights Michigan
United States Ascension Saint Michael's Hospital Stevens Point Wisconsin
United States Marshfield Clinic Stevens Point Center Stevens Point Wisconsin
United States Saint Michael's Hospital Stevens Point Wisconsin
United States Lakeview Hospital Stillwater Minnesota
United States Missouri Baptist Sullivan Hospital Sullivan Missouri
United States Aurora Medical Center in Summit Summit Wisconsin
United States Palo Alto Medical Foundation-Sunnyvale Sunnyvale California
United States Missouri Baptist Outpatient Center-Sunset Hills Sunset Hills Missouri
United States Cancer Care Specialists of Illinois-Swansea Swansea Illinois
United States Memorial and Saint Elizabeth's Health Care Services LLP Swansea Illinois
United States Flower Hospital Sylvania Ohio
United States Franciscan Research Center-Northwest Medical Plaza Tacoma Washington
United States Northwest Medical Specialties PLLC Tacoma Washington
United States Saint Joseph Health System-Tawas City Tawas City Michigan
United States Rocky Mountain Cancer Centers-Thornton Thornton Colorado
United States The Toledo Hospital/Toledo Children's Hospital Toledo Ohio
United States Saint Francis Hospital and Medical Center - Topeka Topeka Kansas
United States Smilow Cancer Hospital-Torrington Care Center Torrington Connecticut
United States Munson Medical Center Traverse City Michigan
United States Dayton Physicians LLC-Upper Valley Troy Ohio
United States Upper Valley Medical Center Troy Ohio
United States Gene Upshaw Memorial Tahoe Forest Cancer Center Truckee California
United States Smilow Cancer Hospital Care Center-Trumbull Trumbull Connecticut
United States Vince Lombardi Cancer Clinic-Two Rivers Two Rivers Wisconsin
United States UPMC Uniontown Hospital Radiation Oncology Uniontown Pennsylvania
United States Carle Cancer Center Urbana Illinois
United States The Carle Foundation Hospital Urbana Illinois
United States Faxton-Saint Luke's Healthcare Utica New York
United States Northbay Cancer Center Vacaville California
United States Sutter Cancer Centers Radiation Oncology Services-Vacaville Vacaville California
United States South Georgia Medical Center/Pearlman Cancer Center Valdosta Georgia
United States Sutter Solano Medical Center/Cancer Center Vallejo California
United States Inspira Medical Center Vineland Vineland New Jersey
United States Ridgeview Medical Center Waconia Minnesota
United States Advanced Breast Care Center PLLC Warren Michigan
United States Bhadresh Nayak MD PC-Warren Warren Michigan
United States Great Lakes Cancer Management Specialists-Macomb Professional Building Warren Michigan
United States Macomb Hematology Oncology PC Warren Michigan
United States Michigan Breast Specialists-Warren Warren Michigan
United States Saint John Macomb-Oakland Hospital Warren Michigan
United States UPMC Washington Hospital Radiation Oncology Washington Pennsylvania
United States Smilow Cancer Hospital-Waterbury Care Center Waterbury Connecticut
United States Aurora Cancer Care-Waukesha Waukesha Wisconsin
United States Aspirus Regional Cancer Center Wausau Wisconsin
United States Marshfield Clinic-Wausau Center Wausau Wisconsin
United States Aurora Cancer Care-Milwaukee West Wauwatosa Wisconsin
United States Cancer Center of Kansas - Wellington Wellington Kansas
United States Aurora West Allis Medical Center West Allis Wisconsin
United States Saint Mary's Oncology/Hematology Associates of West Branch West Branch Michigan
United States Chester County Hospital West Chester Pennsylvania
United States Mercy Medical Center-West Lakes West Des Moines Iowa
United States Saint Ann's Hospital Westerville Ohio
United States Diagnostic and Treatment Center Weston Wisconsin
United States Marshfield Clinic - Weston Center Weston Wisconsin
United States University of Kansas Hospital-Westwood Cancer Center Westwood Kansas
United States Associates In Womens Health Wichita Kansas
United States Cancer Center of Kansas - Wichita Wichita Kansas
United States Cancer Center of Kansas-Wichita Medical Arts Tower Wichita Kansas
United States Via Christi Regional Medical Center Wichita Kansas
United States UPMC Susquehanna Williamsport Pennsylvania
United States Rice Memorial Hospital Willmar Minnesota
United States Christiana Care Health System-Wilmington Hospital Wilmington Delaware
United States Southeastern Medical Oncology Center-Wilson Wilson North Carolina
United States Winchester Hospital Winchester Massachusetts
United States Cancer Center of Kansas - Winfield Winfield Kansas
United States Aspirus UW Cancer Center Wisconsin Rapids Wisconsin
United States Marshfield Clinic - Wisconsin Rapids Center Wisconsin Rapids Wisconsin
United States Inspira Medical Center Woodbury Woodbury New Jersey
United States Minnesota Oncology Hematology PA-Woodbury Woodbury Minnesota
United States Kaiser Permanente-Woodland Hills Woodland Hills California
United States Fairview Lakes Medical Center Wyoming Minnesota
United States Metro Health Hospital Wyoming Michigan
United States WellSpan Health-York Cancer Center York Pennsylvania
United States WellSpan Health-York Hospital York Pennsylvania
United States Rush-Copley Healthcare Center Yorkville Illinois
United States Huron Gastroenterology PC Ypsilanti Michigan
United States IHA Hematology Oncology Consultants-Ann Arbor Ypsilanti Michigan
United States Genesis Healthcare System Cancer Care Center Zanesville Ohio

Sponsors (2)

Lead Sponsor Collaborator
SWOG Cancer Research Network National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Change in Copy Number Alterations in MET, EGFR, and HER2, Analyzed Using Fluorescence in Situ Hybridization 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)
Other Change in the Ratio of Sensitizing EGFR Mutation to EGFR T790 Mutation 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)
Other EGFR Immunohistochemistry H-score 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
Other Levels of Circulating Tumor Markers 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
Other Presence of de Novo EGFR T790M Mutation or Other Molecular Alterations 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
Other Ratio of Sensitizing EGFR Mutation to EGFR T790 Mutation 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
Primary 2-year Overall Survival Rate 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
Primary Progression-Free Survival 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 Response Rates 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
Secondary Time to Treatment Discontinuation From date of registration to date of discontinuation of treatment or death due to any cause up to 3 years post-registration
Secondary Time to Treatment Failure 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
Secondary Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs 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
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