Chemotherapy and Radiation Therapy With or Without Metformin Hydrochloride in Treating Patients With Stage III Non-small Cell Lung Cancer

Stage IIIB Non-Small Cell Lung Cancer Clinical Trial

Official title:

Randomized Phase II Trial of Concurrent Chemoradiotherapy +/- Metformin HCL in Locally Advanced NSCLC

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02186847
• Other study ID #: NRG-LU001
• Secondary ID: NCI-2014-01071PN
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 2014
• Est. completion date: April 16, 2025

Study information

• Verified date: June 2023
• Source: NRG Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase II trial studies how well chemotherapy and radiation therapy given with or without metformin hydrochloride works in treating patients with stage III non-small cell lung cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Metformin hydrochloride may shrink tumors and keep them from coming back. It is not yet known whether chemotherapy and radiation therapy is more effective when given with or without metformin hydrochloride in treating stage III non-small cell lung cancer.

Description:

PRIMARY OBJECTIVES: I. To determine whether metformin hydrochloride (MET) added to chemoradiotherapy can improve progression-free survival (PFS) in patients with locally advanced non-small cell lung cancer (NSCLC). SECONDARY OBJECTIVES: I. Determine the effects of MET on overall survival (OS), time to local-regional progression (LRP), and time to distant metastasis (DM). II. Evaluate the effect of MET on chemoradiotherapy toxicity (Common Terminology Criteria for Adverse Events, version 4 [CTCAE, v. 4]) within 1 year of completion of all treatment. III. Collect biospecimens to develop biomarkers of MET activity. OUTLINE: Patients are randomized to 1 of 2 treatment arms. After completion of study treatment, patients are followed up at 4-6 weeks, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 170
• Est. completion date: April 16, 2025
• Est. primary completion date: April 16, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pathologically (histologically or cytologically) proven diagnosis of stage IIIA or IIIB non-small cell lung cancer within 84 days of registration; eligible histologies include adenocarcinoma, adenosquamous, large cell carcinoma, squamous carcinoma, non-lobar and non-diffuse bronchoalveolar cell carcinoma or non-small cell lung cancer not otherwise specified)
• Patients must have measurable disease
• Patients must have unresectable disease, be medically inoperable, or unwilling to undergo surgical management
• Appropriate stage for protocol entry, including no distant metastases, based upon the

following minimum diagnostic workup:

• History/physical examination, including documentation of height, weight, body surface area, and vital signs, within 30 days prior to registration
• Computed tomography (CT) with IV contrast or magnetic resonance imaging (MRI) imaging (if CT scan with contrast is medically contraindicated) of the lung and upper abdomen through the adrenal glands, required within 45 days prior to registration (recommended within 30 days prior to registration
• MRI of the brain with contrast (or CT with contrast if MRI is medically contraindicated) within 45 days prior to registration; note: the use of intravenous contrast is required for the MRI or CT; an MRI without contrast is only permitted if the patient has a contrast allergy
• Whole-body fludeoxyglucose (FDG)-positron emission tomography (PET)/CT required within 45 days prior to registration (recommended within 30 days prior to registration; note: patients do not need to have a separate CT of the chest and upper abdomen with contrast if PET/CT imaging includes a high quality CT with contrast
• Zubrod performance status 0-1
• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
• Complete blood count(CBC)/differential obtained within 14 days prior to registration

on study, with adequate bone marrow function defined as follows:

• Absolute neutrophil count (ANC) = 1,500 cells/mm3
• Platelets >= 100,000 cells/mm^3
• Hemoglobin >= 8.0 g/dl (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
• Adequate renal function within 14 days prior to registration, defined as serum creatinine within normal institutional limits or creatinine clearance must be at least 60 ml/min;
• Adequate hepatic function within 14 days prior to registration, defined as total bilirubin = 1.5 x upper limit of normal (ULN) for the institution and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase = 2.5 x ULN for the institution;
• Fasting blood glucose = 125 mg/dL within 14 days prior to registration;
• Serum albumin > 3.0 g/dl within 14 days prior to registration;
• For women of childbearing potential, a serum pregnancy test within 72 hours prior to registration;
• Patients with post-obstructive pneumonia are eligible provided they no longer require intravenous antibiotics at registration;
• Patients must be at least 3 weeks from prior thoracotomy (if performed);
• If a pleural effusion is present, the following criteria must be met at registration

to exclude malignant involvement (incurable M1a disease):

• When pleural fluid is visible on both the CT scan and on a chest x-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative;
• Effusions that are minimal (i.e. not visible under ultrasound guidance) and that are too small to safely tap are eligible.
• Women of childbearing potential and male participants must practice adequate contraception throughout the study;

Exclusion Criteria:

• Patients with mixed small cell and non-small cell histologies
• Patients with distant metastasis
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Patients currently using metformin (metformin hydrochloride), other oral hypoglycemic agents or insulin
• Patients with any history of allergic reaction to paclitaxel or other taxanes or carboplatin
• Patients with a history of chronic kidney disease or lactic acidosis
• Patients with >= 10% weight loss within the past month
• Severe, active co-morbidity, defined as follows:
• Diagnosis of type I or type II diabetes mellitus
• Uncontrolled neuropathy >= grade 2 regardless of cause
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
• Transmural myocardial infarction within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration
• Severe hepatic disease, defined as a diagnosis of Child-Pugh class B or C hepatic disease
• Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4 count < 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol
• End-stage renal disease (ie, on dialysis or dialysis has been recommended)
• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception

Related Conditions & MeSH terms

• Adenocarcinoma of Lung
• Adenocarcinoma, Bronchiolo-Alveolar
• Adenosquamous Lung Carcinoma
• Bronchioloalveolar Carcinoma
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Large Cell Lung Carcinoma
• Lung Adenocarcinoma
• Lung Neoplasms
• Non-Small Cell Lung Carcinoma
• Recurrent Non-Small Cell Lung Carcinoma
• Squamous Cell Lung Carcinoma
• Stage IIIA Non-Small Cell Lung Cancer
• Stage IIIB Non-Small Cell Lung Cancer

Intervention

Radiation:
• Radiation Therapy
Radiation therapy (RT) is given in 2 Gy fractions once daily 5 days per week to a total of 30 fractions and 60 Gy. Photons required; 3-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) permitted. Starts within 14 days of randomization (Chemoradiation arm) or 14 days after metformin starts (Chemoradiation + Metformin arm).

Drug:
• Carboplatin
2 AUC (area under the curve) via IV weekly on days 1, 8, 15, 22, 29, and 36 from start of radiation therapy. Two 21 day cycles of 6 AUC via IV starting 28-42 days after the end of radiation therapy.
• Metformin
Metformin is taken orally. Dose escalation begins 2 weeks prior to the initiation of chemoradiation. 500 mg twice daily days 1-7 of metformin. 500 mg three times daily days 8-14 of metformin. Three times a day with the following dosage: 500mg in the morning, 1000mg at noon, and 500mg in the evening concurrent with chemoradiation and through consolidation chemotherapy (days 15-126 of metformin),
• Paclitaxel
50 mg/m2 via IV weekly on days 1, 8, 15, 22, 29, and 36 from start of radiation therapy. Two 21 day cycles of 200 mg/m2 via IV 28-42 days after the end of radiation therapy.

Locations

Country	Name	City	State
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Israel	Chaim Sheba Medical Center	Tel Hashomer
United States	The Cancer Center of Hawaii-Pali Momi	'Aiea	Hawaii
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	New Mexico Oncology Hematology Consultants	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	Northwest Community Hospital	Arlington Heights	Illinois
United States	Piedmont Hospital	Atlanta	Georgia
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	University of Colorado Hospital	Aurora	Colorado
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
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	Our Lady of the Lake Physicians Group - Medical Oncology	Baton Rouge	Louisiana
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	UM Upper Chesapeake Medical Center	Bel Air	Maryland
United States	Gaston Hematology and Oncology Associates-Belmont	Belmont	North Carolina
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	IU Health Bloomington	Bloomington	Indiana
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Boston Medical Center	Boston	Massachusetts
United States	Harrison Medical Center	Bremerton	Washington
United States	New York-Presbyterian/Brooklyn Methodist Hospital	Brooklyn	New York
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Aultman Health Foundation	Canton	Ohio
United States	Mercy Medical Center	Canton	Ohio
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Eden Hospital Medical Center	Castro Valley	California
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Geauga Hospital	Chardon	Ohio
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	University of Cincinnati/Barrett Cancer Center	Cincinnati	Ohio
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	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
United States	John B Amos Cancer Center	Columbus	Georgia
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	Mercy Hospital	Coon Rapids	Minnesota
United States	Mary Bird Perkins Cancer Center - Covington	Covington	Louisiana
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Dekalb Medical Center	Decatur	Georgia
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wentworth-Douglass Hospital	Dover	New Hampshire
United States	Saint Luke's Hospital of Duluth	Duluth	Minnesota
United States	Northeast Radiation Oncology Center	Dunmore	Pennsylvania
United States	Fairview-Southdale Hospital	Edina	Minnesota
United States	Hardin Memorial Hospital	Elizabethtown	Kentucky
United States	Mercy Cancer Center-Elyria	Elyria	Ohio
United States	Swedish Medical Center	Englewood	Colorado
United States	The Regional Cancer Center	Erie	Pennsylvania
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Augusta Health Center for Cancer and Blood Disorders	Fishersville	Virginia
United States	McLaren Cancer Institute-Flint	Flint	Michigan
United States	Parkview Hospital Randallia	Fort Wayne	Indiana
United States	Radiation Oncology Associates PC	Fort Wayne	Indiana
United States	University of Texas Medical Branch	Galveston	Texas
United States	CaroMont Regional Medical Center	Gastonia	North Carolina
United States	Gaston Hematology and Oncology Associates	Gastonia	North Carolina
United States	UM Baltimore Washington Medical Center/Tate Cancer Center	Glen Burnie	Maryland
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
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	North Colorado Medical Center	Greeley	Colorado
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Greenville Health System Cancer Institute-Eastside	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Self Regional Healthcare	Greenwood	South Carolina
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Greenville Health System Cancer Institute-Greer	Greer	South Carolina
United States	Queen's Medical Center	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	Mary Bird Perkins Cancer Center - Houma	Houma	Louisiana
United States	M D Anderson Cancer Center	Houston	Texas
United States	MD Anderson in Katy	Houston	Texas
United States	The Methodist Hospital System	Houston	Texas
United States	Cleveland Clinic Cancer Center Independence	Independence	Ohio
United States	Franciscan Health Indianapolis	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	North Kansas City Hospital	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	University of Kansas Cancer Center	Kansas City	Kansas
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Kettering Medical Center	Kettering	Ohio
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	McLaren Cancer Institute-Lapeer Region	Lapeer	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	UTMB Cancer Center at Victory Lakes	League City	Texas
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	The University of Kansas Cancer Center-Lee's Summit	Lee's Summit	Missouri
United States	Baptist Health Lexington	Lexington	Kentucky
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	McKee Medical Center	Loveland	Colorado
United States	Lowell General Hospital	Lowell	Massachusetts
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Community Memorial Hospital	Menomonee Falls	Wisconsin
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	Ascension Columbia Saint Mary's Hospital Ozaukee	Mequon	Wisconsin
United States	UH Seidman Cancer Center at Southwest General Hospital	Middleburg Heights	Ohio
United States	Ascension Columbia Saint Mary's Water Tower Medical Commons	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	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	Community Medical Hospital	Missoula	Montana
United States	Memorial Medical Center	Modesto	California
United States	McLaren Cancer Institute-Macomb	Mount Clemens	Michigan
United States	Virtua Memorial	Mount Holly	New Jersey
United States	McLaren Cancer Institute-Central Michigan	Mount Pleasant	Michigan
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Intermountain Medical Center	Murray	Utah
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	MD Anderson League City	Nassau Bay	Texas
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Newark Radiation Oncology	Newark	Ohio
United States	Kaiser Permanente Oakland-Broadway	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	UF Cancer Center at Orlando Health	Orlando	Florida
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	McLaren Cancer Institute-Owosso	Owosso	Michigan
United States	21st Century Oncology-Palatka	Palatka	Florida
United States	University Hospitals Parma Medical Center	Parma	Ohio
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	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	McLaren Cancer Institute-Northern Michigan	Petoskey	Michigan
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina
United States	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kootenai Cancer Center	Post Falls	Idaho
United States	Kaiser Permanente-Rancho Cordova Cancer Center	Rancho Cordova	California
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	University of Rochester	Rochester	New York
United States	Rohnert Park Cancer Center	Rohnert Park	California
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	South Sacramento Cancer Center	Sacramento	California
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont
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	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Peninsula Regional Medical Center	Salisbury	Maryland
United States	UCSF Medical Center-Mount Zion	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	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Maine Medical Center- Scarborough Campus	Scarborough	Maine
United States	Greenville Health System Cancer Institute-Seneca	Seneca	South Carolina
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Kaiser Permanente Cancer Treatment Center	South San Francisco	California
United States	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio
United States	MD Anderson in Sugar Land	Sugar Land	Texas
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	MD Anderson in The Woodlands	The Woodlands	Texas
United States	Community Medical Center	Toms River	New Jersey
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	Lewis and Faye Manderson Cancer Center	Tuscaloosa	Alabama
United States	Saint Luke's Mountain States Tumor 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	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Virtua Voorhees	Voorhees	New Jersey
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	The Alyce and Elmore Kraemer Cancer Care Center	West Bend	Wisconsin
United States	University Pointe	West Chester	Ohio
United States	Reading Hospital	West Reading	Pennsylvania
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Wheeling Hospital/Schiffler Cancer Center	Wheeling	West Virginia
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Aspirus UW Cancer Center	Wisconsin Rapids	Wisconsin
United States	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
NRG Oncology	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Alive Without Progression (Progression-free Survival)	Progression is defined per RECIST v1.1 as change in a known lesion(s) meeting one of the following criteria: [1] At least a 20% increase in the sum of the longest diameter of target lesions such that the absolute increase must be > 5 mm. [2] Appearance of =1 new lesions. Progression-free survival time is defined as time from randomization to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.	From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.
Secondary	Percentage of Participants Alive (Overall Survival)	Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.	From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.
Secondary	Percentage of Participants With Local-regional Progression	Local-regional progression (LRP) is defined as progression within the planned treatment volume (PTV) or outside the PTV but within the same lobe(s) of the lung as the primary tumor or in regional lymph nodes. Progression is defined as change in a known lesion(s) meeting one of the following criteria: [1] = 20% increase in the sum of the longest diameter of target lesions such that the absolute increase must be > 5 mm. [2] Appearance of =1 new lesions. LRP time is defined as time from randomization to the date of first LRP, death without LRP (competing risk), or last known follow-up (censored). LRP rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 LRP events were reported.	From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.
Secondary	Percentage of Participants With Distant Metastases	Distant metastasis (DM) is defined as the appearance of = 1 new lesions at any site (including pleural or pericardial effusion) outside of the following: the planned treatment volume, the same lobe(s) of the lung as the primary tumor, or regional lymph nodes. Time to DM is defined as time from randomization to the date of first DM, death without DM (competing risk), or last known follow-up (censored). DM rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.	From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.
Secondary	Percentage of Participants With Treatment-related Grade 3 or Higher Adverse Events	Adverse events (AE) were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to adverse event. "Treatment-related" is defined definitely, probably, or possibly related to treatment.	From start of treatment to last follow-up. Maximum follow-up at time of analysis was 47.2 months.