Maintenance Chemotherapy With or Without Local Consolidative Therapy in Treating Patients With Stage IV Non-small Cell Lung Cancer

Stage IV Non-Small Cell Lung Cancer Clinical Trial

Official title:

Maintenance Systemic Therapy Versus Local Consolidative Therapy (LCT) Plus Maintenance Systemic Therapy for Limited Metastatic Non-Small Cell Lung Cancer (NSCLC): A Randomized Phase II/III Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03137771
• Other study ID #: NRG-LU002
• Secondary ID: NCI-2016-00849NR
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 7, 2017
• Est. completion date: December 2028

Study information

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

Clinical Trial Summary

This randomized phase II/III trial studies how well giving maintenance chemotherapy with or without local consolidation therapy works in treating patients with stage IV non-small cell lung cancer. Drugs used in maintenance chemotherapy, such as docetaxel, pemetrexed disodium, erlotinib hydrochloride, and gemcitabine 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. Local consolidation therapy such as radiation/stereotactic body radiation or surgery may kill cancer cells left after initial treatment. Giving maintenance chemotherapy and local consolidation therapy together may work better than maintenance chemotherapy alone in treating patients with stage IV non-small cell lung cancer.

Description:

PRIMARY OBJECTIVES:

Phase II

To evaluate the impact of adding local consolidative therapy (LCT) to maintenance systemic therapy versus maintenance systemic therapy alone on progression-free survival for patients with metastatic non-small cell lung cancer (NSCLC) with no evidence of progression and limited metastatic sites after first-line systemic therapy.

Phase III

To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance systemic therapy alone on overall survival for patients with metastatic NSCLC with no evidence of progression and limited metastatic sites after first-line systemic therapy.

SECONDARY OBJECTIVES:

I. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance systemic therapy alone on in-field local failure.

II. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance systemic therapy alone on the time to development of new lesions.

III. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance systemic therapy alone on toxicity.

IV. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance systemic therapy alone on duration of maintenance systemic therapy usage.

V. To evaluate the effect of adding LCT to systemic therapy in limited stage IV NSCLC on Quality of Life (QOL) VI. To collect biospecimens and evaluate the correlation between clinical outcomes and circulating tumor DNA (ctDNA).

OUTLINE: Patients are randomized into 1 of 2 arms.

ARM 1 (CHEMOTHERAPY ALONE): ): Patients may receive docetaxel intravenously (IV) over 60 minutes on Day 1, erlotinib hydrochloride orally (PO) once daily (QD), or gemcitabine IV over 30 minutes on Days 1 and 8. Patients with non-squamous non-small cell lung cancer may receive pemetrexed disodium IV over 10 minutes on Day 1 alone or in combination with pembrolizumab IV over 30 minutes. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM 2 (SBRT AND CHEMOTHERAPY): Patients undergo LCT over 2-4 weeks. If LCT cannot be used to treat primary disease sites, patients also undergo intensity-modulated radiation therapy (IMRT) or 3-dimensional conformal radiation therapy (3DCRT) over 3-5 weeks. Within 2 weeks after completion of radiation therapy, patients receive chemotherapy as in Arm 1. Patients may possibly undergo surgery.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, then annually thereafter.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 218
• Est. completion date: December 2028
• Est. primary completion date: December 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have the psychological ability and general health that permits completion of the study requirements and required follow up

• Women of childbearing potential and men who are sexually active should be willing and able to use medically acceptable forms of contraception during the trial and for up to 180 days after completion of all treatment to prevent pregnancy or fathering a child.

• Pathologically proven diagnosis of NSCLC, with metastases (stage IV disease) present prior to registration; this includes patients newly diagnosed with metastatic disease or those initially diagnosed and treated for stage I-III NSCLC who ultimately develop metastases

• Appropriate stage for study entry based on the following diagnostic workup:

• History/physical examination within 30 days prior to registration

• Imaging proof of limited metastatic disease and response to therapy/stable disease, by at least CT chest through the adrenals or PET/CT within 30 days prior to registration

• Zubrod performance status 0, 1, or 2 within 30 days prior to registration

• Aspartate transaminase (AST) and alanine transaminase (ALT) = 2.5 × upper limit of normal (ULN) or = 5 × ULN with metastatic liver disease

• Total bilirubin = 1.5 × ULN

• Absolute neutrophil count (ANC) = 500 cells/mm^3

• Creatinine clearance = 45 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

• Platelets = 50,000 cells/mm^3

• Negative serum pregnancy test within one week prior to registration for females of childbearing potential

• Patients must have received first-line/induction chemotherapy (4 cycles) and achieved stable disease or a partial response

• Prior systemic chemotherapy as part of concurrent treatment approach for previously diagnosed stage III NSCLC, as adjuvant therapy for previously resected NSCLC, or for other previous cancers is permitted

• Prior radiotherapy for patients with brain metastases prior to enrollment is acceptable

• Patients must have measurable disease at baseline and 3 or fewer discrete, extracranial metastatic disease sites that are technically amenable to SBRT

• For de novo stage IV NSCLC patients (patients with metastatic disease at first presentation), primary disease must be treatable with local therapy in the form of SBRT or hypofractionated radiation; if the primary disease is found in the peripheral or central lung parenchyma without nodal disease for instance, SBRT may be employed; if primary disease is more advanced with involvement of the mediastinum (T4 tumor, N1-N3 disease, etc.), these volumes should be technically treatable with hypofractionated radiation

• If primary disease in the thoracic cavity was previously treated with local therapy in the form of surgery, any local/regional disease recurrence should be technically treatable with SBRT or hypofractionated radiation after induction systemic therapy

• Patients must be registered within 35 days of administration of the last dose of first-line/induction systemic therapy

• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

• Patients with brain metastases are eligible if these lesions have been previously treated and the patients have no clinical or radiographic evidence of progression prior to enrollment

Exclusion Criteria:

• Clinical or radiologic evidence of untreated and/or progressive brain metastases

• Cutaneous metastasis of NSCLC

• Metastatic disease invading the esophagus, stomach, intestines, or mesenteric lymph nodes if not a candidate for surgery for these lesions

• Prior invasive malignancy (except non-melanomatous skin cancer, low or intermediate risk prostate cancer, or in situ carcinoma of breast, oral cavity, skin, or cervix) unless disease free for a minimum of one year

• Metastases located within 3 cm of previously irradiated (< 3Gy per fraction) structures if if not a candidate for surgery for these lesions and if:

• Spinal cord previously irradiated to > 40 Gy

• Brachial plexus previously irradiated to > 50 Gy

• Small intestine, large intestine, or stomach previously irradiated to > 45 Gy

• Brainstem previously irradiated to > 50 Gy

• Lung previously irradiated with prior V20 Gy > 35%

• Patients receiving targeted therapy (non-cytotoxic systemic therapy) for NSCLC in the first-line setting

• If a patient has progressed in previous areas of primary disease that received definitive doses of radiation, these patients would require re-irradiation in previous high dose anatomic areas and are not eligible for this study

• Patients with malignant pleural effusions that do not resolve after first-line systemic therapy; patients with pleural effusions that have become too small for thoracentesis at the time of registration would be permitted on study, indicating a significant response to first-line chemotherapy

• Patients with more than 3 discrete locations of extra-cranial metastatic disease after first-line systemic therapy requiring more than 3 SBRT plans to cover these distinct metastatic disease entities

• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration

• Patients who are pregnant or nursing

• Participation in any investigational drug study (excluding non-oncology and/or symptom management studies) within 4 weeks prior to registration

• Known human immunodeficiency virus (HIV) positive with cluster of differentiation 4 (CD4) 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

• For patients who received immunotherapy during induction, patients on chronic steroids or who have active autoimmune disease for which they received systemic treatment in the previous 2 years with corticosteroids, disease modifying agents, or immunosuppressive drugs are not eligible. Replacement therapy (thyroxine, insulin or physiological corticosteroid replacement for adrenal or pituitary insufficiency) is allowed. Patients with active interstitial lung disease or who have a history of pneumonitis for which they had received glucocorticoids are not eligible

• Prior bevacizumab therapy or other antiangiogenic therapy in first-line or planned maintenance therapy (due to potential for increased complications from local therapy)

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Recurrent Non-Small Cell Lung Carcinoma
• Stage IV Non-Small Cell Lung Cancer

Intervention

Radiation:
• 3-Dimensional Conformal Radiation Therapy (3D-CRT)
Undergo 3DCRT

Drug:
• Docetaxel
Given IV
• Gemcitabine
Given IV

Radiation:
• Intensity-Modulated Radiation Therapy (IMRT)
Undergo IMRT

Drug:
• Pemetrexed Disodium
Given IV

Radiation:
• Stereotactic Body Radiation Therapy (SBRT)
Undergo SBRT

Drug:
• Erlotinib Hydrochloride
Given PO
• Pembrolizumab
Given IV

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	London Regional Cancer Program	London	Ontario
Canada	Ottawa Hospital and Cancer Center-General Campus	Ottawa	Ontario
Israel	Chaim Sheba Medical Center	Tel Hashomer
Saudi Arabia	King Faisal Specialist Hospital and Research Centre	Riyadh
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	Lovelace Medical Center-Saint Joseph Square	Albuquerque	New Mexico
United States	Lovelace Radiation Oncology	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Langlade Hospital and Cancer Center	Antigo	Wisconsin
United States	Ascension Saint Elizabeth Hospital	Appleton	Wisconsin
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	Augusta University Medical Center	Augusta	Georgia
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
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	McLaren Cancer Institute-Bay City	Bay City	Michigan
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Boston Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	New York-Presbyterian/Brooklyn Methodist Hospital	Brooklyn	New York
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Geauga Hospital	Chardon	Ohio
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	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	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	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
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	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Atrium Health Cabarrus/LCI-Concord	Concord	North Carolina
United States	UM Sylvester Comprehensive Cancer Center at Coral Gables	Coral Gables	Florida
United States	Good Samaritan Hospital	Corvallis	Oregon
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
United States	Porter Adventist Hospital	Denver	Colorado
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Wentworth-Douglass Hospital	Dover	New Hampshire
United States	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Saint Luke's Hospital of Duluth	Duluth	Minnesota
United States	Northeast Radiation Oncology Center	Dunmore	Pennsylvania
United States	Duke University Medical Center	Durham	North Carolina
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Saint Elizabeth Healthcare Edgewood	Edgewood	Kentucky
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Saint Vincent Hospital	Erie	Pennsylvania
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	McLaren Cancer Institute-Flint	Flint	Michigan
United States	Singh and Arora Hematology Oncology PC	Flint	Michigan
United States	Aurora Health Center-Fond du Lac	Fond Du Lac	Wisconsin
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Parkview Hospital Randallia	Fort Wayne	Indiana
United States	Parkview Regional Medical Center	Fort Wayne	Indiana
United States	UT Southwestern/Simmons Cancer Center-Fort Worth	Fort Worth	Texas
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	University of Texas Medical Branch	Galveston	Texas
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	Arizona Breast Cancer Specialists-Gilbert	Gilbert	Arizona
United States	UM Baltimore Washington Medical Center/Tate Cancer Center	Glen Burnie	Maryland
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	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	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	Self Regional Healthcare	Greenwood	South Carolina
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	UPMC Pinnacle Cancer Center/Community Osteopathic Campus	Harrisburg	Pennsylvania
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	The Radiation Oncology Center-Hilton Head/Bluffton	Hilton Head Island	South Carolina
United States	Edward Hines Jr VA Hospital	Hines	Illinois
United States	Queen's Medical Center	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	M D Anderson Cancer Center	Houston	Texas
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	Allegiance Health	Jackson	Michigan
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Kansas City Veterans Affairs Medical Center	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	UC San Diego Moores Cancer Center	La Jolla	California
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	Sparrow Hospital	Lansing	Michigan
United States	McLaren Cancer Institute-Lapeer Region	Lapeer	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Condell Memorial Hospital	Libertyville	Illinois
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Los Angeles County-USC Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
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	Covenant Medical Center-Lakeside	Lubbock	Texas
United States	Cleveland Clinic Cancer Center Mansfield	Mansfield	Ohio
United States	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Baptist Memorial Hospital and Cancer Center-Memphis	Memphis	Tennessee
United States	Froedtert Menomonee Falls Hospital	Menomonee Falls	Wisconsin
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	Miami Cancer Institute	Miami	Florida
United States	UM Sylvester Comprehensive Cancer Center at Kendall	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	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Memorial Medical Center	Modesto	California
United States	Atrium Health Union/LCI-Union	Monroe	North Carolina
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Virtua Samson Cancer Center	Moorestown	New Jersey
United States	Franciscan Health Mooresville	Mooresville	Indiana
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	McLaren Cancer Institute-Macomb	Mount Clemens	Michigan
United States	Virtua Memorial	Mount Holly	New Jersey
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	CarolinaEast Medical Center	New Bern	North Carolina
United States	Yale University	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	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	TidalHealth Richard A Henson Cancer Institute	Ocean Pines	Maryland
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Saint Joseph Hospital - Orange	Orange	California
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Ascension Mercy Hospital	Oshkosh	Wisconsin
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	University Hospitals Parma Medical Center	Parma	Ohio
United States	Arizona Center for Cancer Care-Peoria	Peoria	Arizona
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	McLaren Cancer Institute-Northern Michigan	Petoskey	Michigan
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Jefferson Torresdale Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Mayo Clinic Hospital in Arizona	Phoenix	Arizona
United States	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	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	University Hospitals Portage Medical Center	Ravenna	Ohio
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Renown Regional Medical Center	Reno	Nevada
United States	VCU Massey Cancer Center at Stony Point	Richmond	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	University of Rochester	Rochester	New York
United States	SwedishAmerican Regional Cancer Center/ACT	Rockford	Illinois
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	The Permanente Medical Group-Roseville Radiation Oncology	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	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Saint Helena Hospital	Saint Helena	California
United States	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Regions Hospital	Saint Paul	Minnesota
United States	Salinas Valley Memorial	Salinas	California
United States	TidalHealth Peninsula Regional	Salisbury	Maryland
United States	George E Wahlen Department of Veterans Affairs Medical Center	Salt Lake City	Utah
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	North Coast Cancer Care	Sandusky	Ohio
United States	UH Seidman Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio
United States	Christus Saint Vincent Regional Cancer Center	Santa Fe	New Mexico
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	Arizona Breast Cancer Specialists-Scottsdale	Scottsdale	Arizona
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	City of Hope South Pasadena	South Pasadena	California
United States	Kaiser Permanente Cancer Treatment Center	South San Francisco	California
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	Novant Cancer Institute Radiation Oncology - Supply	Supply	North Carolina
United States	Southwest Illinois Health Services LLP	Swansea	Illinois
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Tallahassee Memorial HealthCare	Tallahassee	Florida
United States	Moffitt Cancer Center	Tampa	Florida
United States	Community Medical Center	Toms River	New Jersey
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	University of Arizona Cancer Center-Orange Grove Campus	Tucson	Arizona
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	Memorial Sloan Kettering Nassau	Uniondale	New York
United States	Carle Cancer Center	Urbana	Illinois
United States	Legacy Salmon Creek Hospital	Vancouver	Washington
United States	Virtua Voorhees	Voorhees	New Jersey
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
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	Froedtert West Bend Hospital/Kraemer Cancer Center	West Bend	Wisconsin
United States	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Reading Hospital	West Reading	Pennsylvania
United States	UH Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Cleveland Clinic-Weston	Weston	Florida
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Dickstein Cancer Treatment Center	White Plains	New York
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Asplundh Cancer Pavilion	Willow Grove	Pennsylvania
United States	Novant Health Cancer Institute Radiation Oncology - Wilmington	Wilmington	North Carolina
United States	Novant Health New Hanover Regional Medical Center	Wilmington	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	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	University of Michigan Health - West	Wyoming	Michigan
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,  Saudi Arabia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase II - Progression-Free Survival (PFS)	Progression-Free Survival	From the time of randomization to date any documented progression or death due to any cause, whichever occurs first. Assessed for up to 3 years.
Primary	Phase III - Overall Survival (OS)	Overall Survival	From the time of randomization to date of death due to any cause. Assessed up to 3 years.
Secondary	Time to In-Field Failure	The time it takes for disease progression to occur within the radiation treatment field of disease will be measured.	Time from randomization to progression within the irradiated field at any time, assessed for up to 3 years
Secondary	Incidence of adverse events graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5	Will be reported with the frequency and severity (e.g., type, grade, and attribution) by arm.	Up to 3 years
Secondary	Duration of Maintenance Chemotherapy Usage	Will be performed on an intent to treat basis.	Up to 3 years
Secondary	Time to Development of New Lesions	Will be performed on an intent to treat basis.	Time from randomization to the first occurrence of any new lesions that have not been treated with local consolidative therapy, assessed for up to 3 years