Testing the Addition of a New Immunotherapy Drug, Atezolizumab (MPDL3280A), to the Usual Chemoradiation (CRT) Therapy Treatment for Limited Stage Small Cell Lung Cancer (LS-SCLC)

Stage III Lung Cancer AJCC v8 Clinical Trial

Official title:

Limited Stage Small Cell Lung Cancer (LS-SCLC): A Phase III Randomized Study of Chemoradiation Versus Chemoradiation Plus Atezolizumab

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03811002
• Other study ID #: NCI-2019-00178
• Secondary ID: NCI-2019-00178NR
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 26, 2019
• Est. completion date: December 28, 2026

Study information

• Verified date: January 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II/III trial studies how well chemotherapy and radiation therapy (chemoradiation) with or without atezolizumab works in treating patients with limited stage small cell lung cancer. Drugs used in chemotherapy, such as etoposide, cisplatin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving chemoradiation with or without atezolizumab may work better in treating patients with limited stage small cell lung cancer.

Description:

PRIMARY OBJECTIVE: I. To compare overall survival (OS) for patients with LS-SCLC treated with chemoradiation +/- atezolizumab. SECONDARY OBJECTIVES: I. To compare progression free survival (PFS) for patients with limited stage small cell lung cancer (LS-SCLC) treated with chemoradiation +/- atezolizumab. II. To determine overall response rate (ORR), rates of local control, and distant metastases free survival with chemoradiation +/- atezolizumab. III. To characterize immune mediated and non-immune mediated toxicity from chemoradiotherapy plus atezolizumab. IV. To compare quality of life, as measured by the Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI), for patients undergoing chemoradiation +/- atezolizumab. V. To evaluate the quality-adjusted survival, using scores from the 5-level EuroQol 5-dimensional questionnaire (EQ-5D-5L), of chemoradiation +/- atezolizumab for patients with LS-SCLC. VI. To characterize fatigue, as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS), following chemoradiation +/- atezolizumab. VII. To determine the association of blood based tumor mutational burden (bTMB) and tissue-based tumor mutational burden (tTMB) with clinical outcome. EXPLORATORY OBJECTIVES: I. To collect biospecimens at baseline, day 1 and 3 months after the end of chemoradiotherapy, to allow for future analyses. II. To characterize patient-reported symptomatic toxicities measured by the Patient-Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive etoposide intravenously (IV) on days 1-3 and cisplatin IV or carboplatin IV on day 1. Cycles repeat every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) twice daily (BID) for approximately 3 weeks or once daily (QD) for approximately 6-7 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood specimen collection throughout the trial. ARM II: Patients receive treatment as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 or 2 of each chemotherapy cycle. Cycles repeat every 3 weeks for 17 cycles (1 year) in the absence of disease progression or unacceptable toxicity. Patients undergo blood specimen collection throughout the trial. After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years, then annually thereafter.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 545
• Est. completion date: December 28, 2026
• Est. primary completion date: December 28, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pathologically (histologically or cytologically) proven diagnosis of limited stage small cell lung cancer (Stage Tx, T1-T4, N0-3, M0, American Joint Committee on Cancer [AJCC] staging, 8th edition [Ed.]), within 60 days prior to registration
• Patients must have received one cycle of platinum/etoposide chemotherapy pre-registration (prior to study entry). Study registration must be within 21 days from day 1 of the pre-registration cycle of chemotherapy.
• Patients must have had measurable disease (per Response Evaluation Criteria in Solid Tumors [RECIST], version 1.1) prior to the required pre-registration cycle of platinum/etoposide chemotherapy
• Minimal staging requirements include:
• History/physical examination within 30 days prior to registration
• Positron emission tomography (PET)/computed tomography (CT) scan for staging within 60 days prior to registration
• CT chest and CT abdomen with IV contrast (unless contraindicated based on kidney function) within 60 days prior to registration; magnetic resonance imaging (MRI) abdomen with IV contrast allowed in place of CT abdomen
• Note: If contrast allergy exists, premedication per institutional guidelines should be performed prior to obtaining CT with contrast. The only exception to this is a documented life-threatening allergy
• MRI scan of the brain with contrast (preferred) or CT scan of the brain with contrast (allowable if there is a contraindication with MRI with contrast) within 30 days prior to registration
• Age >= 18
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 30 days prior to registration
• Absolute neutrophil count (ANC) >= 1,500/cells/mm^3 (prior to pre-registration cycle)
• Platelet count >= 100,000 cells/mm^3 (prior to pre-registration cycle)
• Hemoglobin >= 9 g/dL (prior to pre-registration cycle)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (prior to pre-registration cycle)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 x ULN (prior to pre-registration cycle)
• Adequate renal function within 30 days prior to registration defined as follows:

Creatinine clearance >= 30 mL/min by the Cockcroft-Gault (C-G) equation

• Patients presenting with a pleural effusion will be eligible if thoracentesis is cytologically negative and non-bloody or if pleural fluid is too small a volume to effectively sample by thoracentesis and does not show increased metabolic activity on CT/PET imaging
• Negative serum pregnancy test within 14 days of registration for pre-menopausal women of childbearing potential
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
• Hepatitis B/C testing prior to enrollment for patients that have not been tested before. Note: This is required even if the patient has never shown or had symptoms of hepatitis
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

Exclusion Criteria:

• Definitive clinical or radiologic evidence of metastatic disease
• Definitive surgical resection of small cell lung cancer
• Prior invasive malignancy (except non-melanomatous skin cancer, localized prostate cancer, or any early stage cancer treated with curative intent resection) unless disease free for a minimum of 2 years (carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
• More than 1 cycle of prior platinum-based chemotherapy for SCLC prior to enrollment; note that prior chemotherapy for a different cancer is allowable
• Any prior atezolizumab or other immunotherapy agent
• Prior radiotherapy to the lungs or mediastinum that would result in clinically significant overlap of radiation therapy fields; prior tangent fields for breast cancer with minimal overlap with target volumes are allowed per approval of study principal investigators (PIs)
• Patients with cytologically positive pleural or pericardial fluid are not eligible
• An active, known or suspected autoimmune disease. Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
• History of allogeneic organ transplant
• History of primary immunodeficiency
• Severe, active co-morbidity defined as follows:
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
• Active tuberculosis
• Active hepatitis B (chronic or acute) or hepatitis C infection. Note that if hepatitis status is unknown, hepatitis B/C testing is required
• Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg]) test, a positive anti-HBc (antibody to hepatitis B core antigen), and a negative viral deoxyribonucleic acid (DNA) test (only obtained if HBsAg is found positive) are eligible
• Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). (The HCV RNA test must be performed for patients who have a positive HCV antibody test.)
• Known immunosuppressive disease, for example history of bone marrow transplant or chronic lymphocytic leukemia (CLL)
• Chronic obstructive pulmonary disease (COPD) requiring chronic oral steroid therapy of > 10 mg prednisone daily or equivalent at the time of registration. Inhaled corticosteroids are not exclusionary
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 3 months
• Transmural myocardial infarction within the last 3 months
• Clinically significant interstitial lung disease
• A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception for the duration of study treatment and for 150 days after the last dose of study drug (Arm 2); this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.

Related Conditions & MeSH terms

• Carcinoma, Small Cell
• Limited Stage Lung Small Cell Carcinoma
• Lung Neoplasms
• Small Cell Lung Carcinoma
• Stage I Lung Cancer AJCC v8
• Stage II Lung Cancer AJCC v8
• Stage III Lung Cancer AJCC v8

Intervention

Radiation:
• 3-Dimensional Conformal Radiation Therapy
Undergo 3D-CRT

Drug:
• Atezolizumab
Given IV

Procedure:
• Biospecimen Collection
Correlative studies

Drug:
• Carboplatin
Given IV
• Cisplatin
Given IV
• Etoposide
Given IV

Radiation:
• Intensity-Modulated Radiation Therapy
Undergo IMRT

Other:
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
Japan	Gunma University Hospital	Gunma	Maebashi
Japan	Hiroshima University Hospital	Hiroshima City
Japan	Kagoshima City Hospital	Kagoshima City	Kagoshima
Japan	Shikoku Cancer Center	Matsuyama
Japan	Kyorin University Hospital	Mitaka-shi	Tokyo
Japan	Niigata University Medical and Dental Hospital	Niigata City	Niigata
Japan	Saitama Medical University International Medical Center	Saitama
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Tohoku University School of Medicine	Sendai	Aoba-ku
Japan	Ehime University Hospital	Toon	Ehime
United States	Hawaii Cancer Care - Westridge	'Aiea	Hawaii
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	The Cancer Center of Hawaii-Pali Momi	'Aiea	Hawaii
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Summa Health System - Akron Campus	Akron	Ohio
United States	Atrium Health Stanly/LCI-Albemarle	Albemarle	North Carolina
United States	Mayo Clinic Health System in Albert Lea	Albert Lea	Minnesota
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	Alton Memorial Hospital	Alton	Illinois
United States	McFarland Clinic - Ames	Ames	Iowa
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Langlade Hospital and Cancer Center	Antigo	Wisconsin
United States	ThedaCare Regional Cancer Center	Appleton	Wisconsin
United States	Randolph Hospital	Asheboro	North Carolina
United States	Messino Cancer Centers	Asheville	North Carolina
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Grady Health System	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Sutter Auburn Faith Hospital	Auburn	California
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	GenesisCare USA - Aventura	Aventura	Florida
United States	GenesisCare USA - Aventura FP	Aventura	Florida
United States	Saint Agnes Hospital	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Summa Health System - Barberton Campus	Barberton	Ohio
United States	MaineHealth Coastal Cancer Treatment Center	Bath	Maine
United States	Louisiana Hematology Oncology Associates LLC	Baton Rouge	Louisiana
United States	LSU Health Baton Rouge-North Clinic	Baton Rouge	Louisiana
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Medical Center of Baton Rouge	Baton Rouge	Louisiana
United States	Our Lady of the Lake Physicians Group - Medical Oncology	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	McLaren Cancer Institute-Bay City	Bay City	Michigan
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	UM Upper Chesapeake Medical Center	Bel Air	Maryland
United States	Waldo County General Hospital	Belfast	Maine
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford	Biddeford	Maine
United States	Billings Clinic Cancer Center	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph's/Candler - Bluffton Campus	Bluffton	South Carolina
United States	Boca Raton Regional Hospital	Boca Raton	Florida
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Harrison Medical Center	Bremerton	Washington
United States	Ocean University Medical Center	Brick	New Jersey
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Steward Saint Elizabeth's Medical Center	Brighton	Massachusetts
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	Crozer-Keystone Regional Cancer Center at Broomall	Broomall	Pennsylvania
United States	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Minnesota Oncology - Burnsville	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	Aultman Health Foundation	Canton	Ohio
United States	Cleveland Clinic Mercy Hospital	Canton	Ohio
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Carlisle Regional Cancer Center	Carlisle	Pennsylvania
United States	IU Health North Hospital	Carmel	Indiana
United States	Caro Cancer Center	Caro	Michigan
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Physicians' Clinic of Iowa PC	Cedar Rapids	Iowa
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	Geauga Hospital	Chardon	Ohio
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Atrium Health Pineville/LCI-Pineville	Charlotte	North Carolina
United States	Atrium Health University City/LCI-University	Charlotte	North Carolina
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Levine Cancer Institute-Ballantyne	Charlotte	North Carolina
United States	Levine Cancer Institute-SouthPark	Charlotte	North Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Saint Luke's Hospital	Chesterfield	Missouri
United States	Advocate Illinois Masonic Medical Center	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	McLaren Cancer Institute-Clarkston	Clarkston	Michigan
United States	Michigan Healthcare Professionals Clarkston	Clarkston	Michigan
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Baptist Memorial Hospital and Cancer Center-Collierville	Collierville	Tennessee
United States	Memorial Hospital North	Colorado Springs	Colorado
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
United States	Central Maryland Radiation Oncology in Howard County	Columbia	Maryland
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Atrium Health Cabarrus/LCI-Concord	Concord	North Carolina
United States	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire
United States	MD Anderson in The Woodlands	Conroe	Texas
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	UM Sylvester Comprehensive Cancer Center at Coral Gables	Coral Gables	Florida
United States	Mary Bird Perkins Cancer Center - Covington	Covington	Louisiana
United States	Greater Regional Medical Center	Creston	Iowa
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	AMG Crystal Lake - Oncology	Crystal Lake	Illinois
United States	Carle at The Riverfront	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Porter Adventist Hospital	Denver	Colorado
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Advocate Good Samaritan Hospital	Downers Grove	Illinois
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Dublin Methodist Hospital	Dublin	Ohio
United States	Saint Luke's Hospital of Duluth	Duluth	Minnesota
United States	Northeast Radiation Oncology Center	Dunmore	Pennsylvania
United States	Cancer Institute at Saint Francis Hospital	East Hills	New York
United States	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Mayo Clinic Health System-Eau Claire Clinic	Eau Claire	Wisconsin
United States	Saint Elizabeth Healthcare Edgewood	Edgewood	Kentucky
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Baptist Health Hardin	Elizabethtown	Kentucky
United States	Elmhurst Memorial Hospital	Elmhurst	Illinois
United States	Arnot Ogden Medical Center/Falck Cancer Center	Elmira	New York
United States	Ephrata Cancer Center	Ephrata	Pennsylvania
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	Beaumont Hospital - Farmington Hills	Farmington Hills	Michigan
United States	Michigan Healthcare Professionals Farmington	Farmington Hills	Michigan
United States	UPMC Cancer Center at UPMC Horizon	Farrell	Pennsylvania
United States	Piedmont Fayette Hospital	Fayetteville	Georgia
United States	Augusta Health Center for Cancer and Blood Disorders	Fishersville	Virginia
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	McLaren Cancer Institute-Flint	Flint	Michigan
United States	Singh and Arora Hematology Oncology PC	Flint	Michigan
United States	Cancer Care and Hematology-Fort Collins	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Lee Memorial Health System	Fort Myers	Florida
United States	Regional Cancer Center-Lee Memorial Health System	Fort Myers	Florida
United States	Parkview Regional Medical Center	Fort Wayne	Indiana
United States	Beebe South Coastal Health Campus	Frankford	Delaware
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	UM Baltimore Washington Medical Center/Tate Cancer Center	Glen Burnie	Maryland
United States	Crozer Regional Cancer Center at Brinton Lake	Glen Mills	Pennsylvania
United States	Glens Falls Hospital	Glens Falls	New York
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	CTCA at Western Regional Medical Center	Goodyear	Arizona
United States	Goshen Center for Cancer Care	Goshen	Indiana
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	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	UCHealth Greeley Hospital	Greeley	Colorado
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Bellin Memorial Hospital	Green Bay	Wisconsin
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Baptist Cancer Center-Grenada	Grenada	Mississippi
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Mount Carmel Grove City Hospital	Grove City	Ohio
United States	The Cancer Institute of New Jersey Hamilton	Hamilton	New Jersey
United States	Cherry Tree Cancer Center	Hanover	Pennsylvania
United States	UPMC Pinnacle Cancer Center/Community Osteopathic Campus	Harrisburg	Pennsylvania
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Advocate South Suburban Hospital	Hazel Crest	Illinois
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois
United States	South Carolina Cancer Specialists PC	Hilton Head Island	South Carolina
United States	The Radiation Oncology Center-Hilton Head/Bluffton	Hilton Head Island	South Carolina
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Kuakini Medical Center	Honolulu	Hawaii
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	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	Mary Bird Perkins Cancer Center - Houma	Houma	Louisiana
United States	Terrebonne General Medical Center	Houma	Louisiana
United States	Houston Methodist Hospital	Houston	Texas
United States	Houston Methodist West Hospital	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	MD Anderson West Houston	Houston	Texas
United States	Edwards Comprehensive Cancer Center	Huntington	West Virginia
United States	Cleveland Clinic Cancer Center Independence	Independence	Ohio
United States	Community Cancer Center East	Indianapolis	Indiana
United States	Community Cancer Center North	Indianapolis	Indiana
United States	Community Cancer Center South	Indianapolis	Indiana
United States	Franciscan Health Indianapolis	Indianapolis	Indiana
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Allegiance Health	Jackson	Michigan
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin
United States	NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro	Jonesboro	Arkansas
United States	Freeman Health System	Joplin	Missouri
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Novant Health Cancer Institute - Kernersville	Kernersville	North Carolina
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Community Howard Regional Health	Kokomo	Indiana
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Mayo Clinic Health System-Franciscan Healthcare	La Crosse	Wisconsin
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	The Watson Clinic	Lakeland	Florida
United States	Monmouth Medical Center Southern Campus	Lakewood	New Jersey
United States	Lancaster General Ann B Barshinger Cancer Institute	Lancaster	Pennsylvania
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	Karmanos Cancer Institute at McLaren Greater Lansing	Lansing	Michigan
United States	Mid-Michigan Physicians-Lansing	Lansing	Michigan
United States	University of Michigan Health - Sparrow Lansing	Lansing	Michigan
United States	McLaren Cancer Institute-Lapeer Region	Lapeer	Michigan
United States	OptumCare Cancer Care at Charleston	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma
United States	MD Anderson League City	League City	Texas
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Sechler Family Cancer Center	Lebanon	Pennsylvania
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	Baptist Health Lexington	Lexington	Kentucky
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	AMG Libertyville - Oncology	Libertyville	Illinois
United States	Saint Rita's Medical Center	Lima	Ohio
United States	Cancer Partners of Nebraska - Pine Lake	Lincoln	Nebraska
United States	Southeast Nebraska Cancer Center - 68th Street Place	Lincoln	Nebraska
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Los Angeles General Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Baptist Health Louisville	Louisville	Kentucky
United States	Norton Audubon Hospital and Medical Campus	Louisville	Kentucky
United States	Norton Brownsboro Hospital and Medical Campus	Louisville	Kentucky
United States	Norton Hospital Pavilion and Medical Campus	Louisville	Kentucky
United States	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	Medical Center of the Rockies	Loveland	Colorado
United States	Covenant Medical Center-Lakeside	Lubbock	Texas
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Michigan Healthcare Professionals Macomb	Macomb	Michigan
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Michigan Healthcare Professionals Madison Heights	Madison Heights	Michigan
United States	Southern Ocean County Medical Center	Manahawkin	New Jersey
United States	Solinsky Center for Cancer Care	Manchester	New Hampshire
United States	Mayo Clinic Health Systems-Mankato	Mankato	Minnesota
United States	Cleveland Clinic Cancer Center Mansfield	Mansfield	Ohio
United States	OhioHealth Mansfield Hospital	Mansfield	Ohio
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion	Mechanicsburg	Pennsylvania
United States	Riddle Memorial Hospital	Media	Pennsylvania
United States	Summa Health Medina Medical Center	Medina	Ohio
United States	Baptist Memorial Hospital and Cancer Center-Memphis	Memphis	Tennessee
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	Miami Cancer Institute	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	UH Seidman Cancer Center at Southwest General Hospital	Middleburg Heights	Ohio
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	Zablocki Veterans Administration Medical Center	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Trinity Cancer Care Center	Minot	North Dakota
United States	Memorial Medical Center	Modesto	California
United States	Atrium Health Union/LCI-Union	Monroe	North Carolina
United States	Franciscan Health Mooresville	Mooresville	Indiana
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Novant Health Cancer Institute - Mount Airy	Mount Airy	North Carolina
United States	McLaren Cancer Institute-Macomb	Mount Clemens	Michigan
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	Trinity Health Muskegon Hospital	Muskegon	Michigan
United States	Carolina Regional Cancer Center	Myrtle Beach	South Carolina
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Edward Hospital/Cancer Center	Naperville	Illinois
United States	Houston Methodist Saint John Hospital	Nassau Bay	Texas
United States	Jersey Shore Medical Center	Neptune	New Jersey
United States	Baptist Health Floyd	New Albany	Indiana
United States	Baptist Memorial Hospital and Cancer Center-Union County	New Albany	Mississippi
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	Mount Sinai Chelsea	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	Mount Sinai West	New York	New York
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	Providence Newberg Medical Center	Newberg	Oregon
United States	CTCA at Southeastern Regional Medical Center	Newnan	Georgia
United States	Piedmont Newnan Hospital	Newnan	Georgia
United States	Bryn Mawr Health Center	Newtown Square	Pennsylvania
United States	University of Kansas Cancer Center at North Kansas City Hospital	North Kansas City	Missouri
United States	Cancer and Hematology Centers of Western Michigan - Norton Shores	Norton Shores	Michigan
United States	Stephens Memorial Hospital	Norway	Maine
United States	Ascension Providence Hospitals - Novi	Novi	Michigan
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Olathe Health Cancer Center	Olathe	Kansas
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
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	Baptist Health Paducah	Paducah	Kentucky
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	Parker Adventist Hospital	Parker	Colorado
United States	University Hospitals Parma Medical Center	Parma	Ohio
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Capital Health Medical Center-Hopewell	Pennington	New Jersey
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	Mercy Health Perrysburg Cancer Center	Perrysburg	Ohio
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	McLaren Cancer Institute-Northern Michigan	Petoskey	Michigan
United States	Eastern Regional Medical Center	Philadelphia	Pennsylvania
United States	Jefferson Torresdale Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania
United States	Edward Hospital/Cancer Center?Plainfield	Plainfield	Illinois
United States	UM Sylvester Comprehensive Cancer Center at Plantation	Plantation	Florida
United States	21st Century Oncology-Pontiac	Pontiac	Michigan
United States	McLaren-Port Huron	Port Huron	Michigan
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Maine Medical Center-Bramhall Campus	Portland	Maine
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	University Hospitals Portage Medical Center	Ravenna	Ohio
United States	Riverview Medical Center/Booker Cancer Center	Red Bank	New Jersey
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Renown Regional Medical Center	Reno	Nevada
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	VCU Massey Cancer Center at Stony Point	Richmond	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Levine Cancer Institute-Rock Hill	Rock Hill	South Carolina
United States	Rock Hill Radiation Therapy Center	Rock Hill	South Carolina
United States	Penobscot Bay Medical Center	Rockport	Maine
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Sutter Roseville Medical Center	Roseville	California
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont
United States	Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Salina Regional Health Center	Salina	Kansas
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	North Coast Cancer Care	Sandusky	Ohio
United States	UH Seidman Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio
United States	MaineHealth Cancer Care Center of York County	Sanford	Maine
United States	MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford	Sanford	Maine
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	Maine Medical Center- Scarborough Campus	Scarborough	Maine
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Henry Ford Macomb Health Center - Shelby Township	Shelby	Michigan
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	Robert Wood Johnson University Hospital Somerset	Somerville	New Jersey
United States	Maine Medical Partners - South Portland	South Portland	Maine
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	Baptist Memorial Hospital and Cancer Center-Desoto	Southhaven	Mississippi
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Novant Health Cancer Institute - Statesville	Statesville	North Carolina
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio
United States	Houston Methodist Sugar Land Hospital	Sugar Land	Texas
United States	MD Anderson in Sugar Land	Sugar Land	Texas
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	BJC Outpatient Center at Sunset Hills	Sunset Hills	Missouri
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Moffitt Cancer Center	Tampa	Florida
United States	Ascension Saint Joseph Hospital	Tawas City	Michigan
United States	Houston Methodist The Woodlands Hospital	The Woodlands	Texas
United States	Novant Health Cancer Institute - Thomasville	Thomasville	North Carolina
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	Saint Vincent Mercy Medical Center	Toledo	Ohio
United States	Community Medical Center	Toms River	New Jersey
United States	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	GenesisCare USA - Troy	Troy	Michigan
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	Cancer Treatment Centers of America	Tulsa	Oklahoma
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	Carle Cancer Center	Urbana	Illinois
United States	Legacy Salmon Creek Hospital	Vancouver	Washington
United States	University Hospitals Sharon Health Center	Wadsworth	Ohio
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
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	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Good Samaritan University Hospital	West Islip	New York
United States	Reading Hospital	West Reading	Pennsylvania
United States	Saint Ann's Hospital	Westerville	Ohio
United States	UH Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Wheeling Hospital/Schiffler Cancer Center	Wheeling	West Virginia
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Novant Health Cancer Institute - Wilkesboro	Wilkesboro	North Carolina
United States	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Aspirus Cancer Care - Wisconsin Rapids	Wisconsin Rapids	Wisconsin
United States	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio
United States	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	University of Michigan Health - West	Wyoming	Michigan
United States	UPMC Memorial	York	Pennsylvania
United States	WellSpan Health-York Cancer Center	York	Pennsylvania
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio
United States	Midwestern Regional Medical Center	Zion	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Countries where clinical trial is conducted

United States,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Patient-reported symptomatic toxicities	Will be measured by Patient Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE). For each symptom and each domain (i.e., frequency, severity, and interference), counts and frequencies will be summarized for the worst score experienced by the patient by treatment arm.	Up to 15 months after completion of chemoradiation therapy
Primary	Overall survival (OS)	Hazard ratios will be estimated using a stratified Cox regression model. Event rates over time will be estimated within each treatment group using the Kaplan-Meier method.	From randomization to date of death due to any cause, assessed up to 5 years
Secondary	Progression free survival (PFS)	The rates at various timepoints (e.g., every 6 months after randomization) and medians of PFS for each arm will be estimated using the Kaplan-Meier method. The associated 95% confidence interval (CI) will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Stratified log-rank test will be used to compare PFS between the treatment arms. Cox proportional hazards model, stratified by the protocol-defined stratification factors, will be used to estimate the HR between the two treatment arms and its 95% confidence interval (CI).	Time from randomization to any documented progression or death due to any cause, whichever occurs first, assessed up to 5 years
Secondary	Incidence of adverse events	For each patient, the maximum severity reported for both immune mediated and non-immune mediated adverse events will be used in the summaries. Adverse events will be summarized regardless of relationship to protocol treatment as assessed by the investigator. All adverse events, adverse events leading to withdrawal, interruption or modification of protocol treatment, Grade >= 3 adverse events, and serious adverse events will be summarized. Deaths and cause of death will be summarized. The rate of treatment-related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE, v.5.0) will be reported with the frequency and severity (e.g., type, grade, and attribution) by arm; the analysis will be performed at the time of the primary endpoint analyses. All adverse events will be classified as either immune or non-immune mediated.	Up to 5 years
Secondary	Objective response rate (ORR)	The 95% CI for the difference in confirmed ORRs between the two treatment arms will be computed using the normal approximation to the binomial distribution . The 95% CI of the confirmed ORR will be calculated for each treatment arm using the Clopper-Pearson method.	Up to 5 years
Secondary	Time to progression	Will be defined as freedom from local progression, in which a failure is defined as intrathoracic tumor progression by RECIST 1.1 criteria. Local control will be analyzed as competing risks data based on cause-specific hazards approaches, where deaths without local failure will be considered as a competing event and analyzed as "censoring" of local failure. The rates at various timepoints (e.g., every 6 months after randomization) and medians of PFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95% CI will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Results from an unstratified analysis will also be provided.	Up to 5 years
Secondary	Distant metastases-free survival (DMFS)	The rates at various timepoints (e.g., every 6 months after randomization) and medians of DMFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95% confidence interval (CI) will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Stratified log-rank test will be used to compare DMFS between the treatment arms. Cox proportional hazards model, stratified by the protocol-defined stratification factors, will be used to estimate the HR between the two treatment arms and its 95% confidence interval (CI).	Time between the date of randomization and the first date of documented distant metastases or death due to any cause, whichever occurs first, assessed up to 5 years
Secondary	Quality of life (QoL)	Will be measured by the Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI). Fisher's exact test will be used to compare the proportions of patients experiencing clinically meaningful deterioration (CMD) between the two arms. FACT-TOI deterioration rates and associated 95% confidence interval will be calculated for each treatment group, based on all randomized subjects. Clopper-Pearson method will be used for calculating 95% CI. The deterioration rates of each arm will also be compared using the CMH test, stratified by histology. FACT-TOI at baseline and at each subsequent assessment, as well as their change from baseline will be summarized using descriptive statistics by treatment group as randomized. The scores at baseline and subsequent time points, as well the changes from baseline at each time point for each treatment group will be compared using the two-sample t-test.	Up to 15 months after the end of the 4th cycle of chemotherapy
Secondary	Quality-adjusted survival	Assessed using score from the 5-level EuroQol 5-dimensional questionnaire (EQ-5D-5L). Defined as the weighted sum of different time episodes added up to a total quality-adjusted life-year. Subjects' overall health state on a visual analog scale (VAS) at each assessment time point will be summarized using descriptive statistics by treatment group, as randomized. Proportion of subjects reporting problems for the five EQ-5D-5L dimensions at each assessment time point will be summarized by level of problem and by treatment group, as randomized. Percentages will be based on number subjects assessed at assessment time point. Subjects' overall health state on a visual analog scale (EQ-VAS) at each assessment time point will be summarized using descriptive statistics by treatment group, as randomized. Proportion of subjects reporting problems for the five EQ-5D dimensions at each assessment time point will be summarized by level of problem and by treatment group, as randomized.	Up to 2 years
Secondary	Level of fatigue	Will be measured by the Patient-Reported Outcomes Measurement Information System (PROMIS). Baseline and PROMIS at each subsequent assessment, as well as their change from baseline will be summarized using descriptive statistics by treatment group as randomized. The change from baseline to subsequent timepoints may be compared between treatment arms using a t-test, or Wilcoxon test if the data is non-normal.	Up to 2 years
Secondary	Blood based tumor mutational burden (bTMB) and tissue-based tumor mutational burden (tTMB)	Correlation with clinical outcomes will be done by summarizing the statistical power to detect interaction effects (ratio of hazard ratios) of 0.33 when the marker positive prevalence is 20%, at 2-sided significance level of 0.05.	Up to 5 years