Nivolumab, Cabozantinib S-Malate, and Ipilimumab in Treating Patients With Recurrent Stage IV Non-small Cell Lung Cancer

A Randomized Phase II Trial of Nivolumab, Cabozantinib Plus Nivolumab, and Cabozantinib Plus Nivolumab Plus Ipilimumab in Patients With Previously Treated Non-Squamous NSCLC

This partially randomized phase II trial studies how well nivolumab, cabozantinib s-malate, and ipilimumab work in treating patients with stage IV non-small cell lung cancer that has come back. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving nivolumab, cabozantinib s-malate, and ipilimumab may work better than cabozantinib s-malate alone in treating patients with stage IV non-small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Metastatic Lung Non-Squamous Non-Small Cell Carcinoma; Recurrent Lung Non-Squamous Non-Small Cell Carcinoma; Stage IV Lung Non-Small Cell Cancer AJCC v7
• Intervention / Treatment: Biological: Nivolumab; Biological: Ipilimumab; Drug: Cabozantinib

Detailed Description

PRIMARY OBJECTIVES:

I. To demonstrate whether combination therapy of nivolumab and cabozantinib s-malate (cabozantinib), or of nivolumab and cabozantinib, and ipilimumab as compared to nivolumab alone, extends progression-free survival (PFS) for this patient population with non-squamous non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. To estimate the overall survival for each arm of the trial. II. To estimate the best overall response rate for each arm of the trial. III. To estimate the progression free survival of the targeted therapy arm of the trial.

IV. To describe the toxicity profile of monotherapy with nivolumab, and the combination of nivolumab and cabozantinib, and the combination of nivolumab and cabozantinib and ipilimumab, in this patient population with non-squamous NSCLC.

CORRELATIVE OBJECTIVES:

I. To adjust progression free survival for each arm based on PD-L1 tumor status.

IMAGING OBJECTIVES:

I. To describe time point tumor response assessment, overall best response and progression-free survival using the conventional Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and the exploratory uni-dimensional immune response criteria (iRRC) and the imaging (i)RECIST criteria with all measurements performed by the central review.

II. To compare RECIST 1.1 imaging response assessment measurements (time point response assessment and overall best response) assess by site study personnel to those performed by central review.

EXPLORATORY TOBACCO USE OBJECTIVES:

I. To determine the effects of tobacco, operationalized as combustible tobacco (1a), other forms of tobacco (1b), and environmental tobacco exposure (ETS) (1c) on provider-reported cancer-treatment toxicity (adverse events (both clinical and hematologic) and dose modifications).

II. To determine the effects of tobacco on patient-reported physical symptoms and psychological symptoms.

III. To examine quitting behaviors and behavioral counseling/support and cessation medication utilization.

IV. To explore the effect of tobacco use and exposure on treatment duration, relative dose intensity, and therapeutic benefit.

OUTLINE: Patients are randomized to 1 of 3 arms. Patients with ROS1 gene rearrangement, MET exon 14 splice mutations, MET high amplification, or RET gene rearrangement are assigned to Arm T.

ARM A: Patients receive nivolumab at 480 mg intravenously (IV) over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive nivolumab at 480 mg IV over 60 minutes on day 1 and cabozantinib s-malate at 40 mg orally (PO) daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM C: Patients receive nivolumab at 480 mg IV over 60 minutes on day 1, cabozantinib s-malate at 40 mg PO daily on days 1-28, and ipilimumab at 1 mg/kg IV over 90 minutes every 8 weeks. Cycles for nivolumab and cabozantinib s-malate repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM T: Patients with ROS1 gene rearrangement, MET exon 14 splice mutations, MET high amplification, or RET gene rearrangement receive nivolumab at 480 mg IV over 60 minutes on day 1 and cabozantinib s-malate at 40 mg PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 5 years.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alaska
    • Anchorage, Alaska, United States, 98508
      • Anchorage Associates in Radiation Medicine
    • Anchorage, Alaska, United States, 99508
      • Alaska Breast Care and Surgery LLC
    • Anchorage, Alaska, United States, 99508
      • Alaska Oncology and Hematology LLC
    • Anchorage, Alaska, United States, 99508
      • Alaska Women's Cancer Care
    • Anchorage, Alaska, United States, 99508
      • Anchorage Oncology Centre
    • Anchorage, Alaska, United States, 99508
      • Katmai Oncology Group
    • Anchorage, Alaska, United States, 99508
      • Providence Alaska Medical Center
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • CHI Saint Vincent Cancer Center Hot Springs
    • Jonesboro, Arkansas, United States, 72401
      • NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
  • California
    • Arroyo Grande, California, United States, 93420
      • PCR Oncology
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family Cancer Center
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Colorado Springs, Colorado, United States, 80907
      • Rocky Mountain Cancer Centers-Penrose
    • Denver, Colorado, United States, 80210
      • Porter Adventist Hospital
    • Durango, Colorado, United States, 81301
      • Mercy Medical Center
    • Durango, Colorado, United States, 81301
      • Southwest Oncology PC
    • Golden, Colorado, United States, 80401
      • Mountain Blue Cancer Care Center
    • Lakewood, Colorado, United States, 80228
      • Saint Anthony Hospital
    • Lakewood, Colorado, United States, 80228
      • Rocky Mountain Cancer Centers-Lakewood
    • Littleton, Colorado, United States, 80122
      • Littleton Adventist Hospital
    • Longmont, Colorado, United States, 80501
      • Longmont United Hospital
    • Longmont, Colorado, United States, 80501
      • Rocky Mountain Cancer Centers-Longmont
    • Parker, Colorado, United States, 80138
      • Parker Adventist Hospital
    • Parker, Colorado, United States, 80138
      • Rocky Mountain Cancer Centers-Parker
    • Pueblo, Colorado, United States, 81004
      • Saint Mary Corwin Medical Center
    • Pueblo, Colorado, United States, 81008
      • Rocky Mountain Cancer Centers - Pueblo
    • Thornton, Colorado, United States, 80260
      • Rocky Mountain Cancer Centers-Thornton
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Broward Health Medical Center
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer and Blood Center LLC
    • Decatur, Georgia, United States, 30033
      • Dekalb Medical Center
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
    • Boise, Idaho, United States, 83712
      • Saint Luke's Cancer Institute - Boise
    • Caldwell, Idaho, United States, 83605
      • Saint Alphonsus Cancer Care Center-Caldwell
    • Coeur d'Alene, Idaho, United States, 83814
      • Kootenai Health - Coeur d'Alene
    • Emmett, Idaho, United States, 83617
      • Walter Knox Memorial Hospital
    • Fruitland, Idaho, United States, 83619
      • Saint Luke's Cancer Institute - Fruitland
    • Meridian, Idaho, United States, 83642
      • Idaho Urologic Institute-Meridian
    • Meridian, Idaho, United States, 83642
      • Saint Luke's Cancer Institute - Meridian
    • Nampa, Idaho, United States, 83686
      • Saint Alphonsus Medical Center-Nampa
    • Nampa, Idaho, United States, 83686
      • Saint Luke's Cancer Institute - Nampa
    • Post Falls, Idaho, United States, 83854
      • Kootenai Clinic Cancer Services - Post Falls
    • Sandpoint, Idaho, United States, 83864
      • Kootenai Cancer Clinic
    • Twin Falls, Idaho, United States, 83301
      • Saint Luke's Cancer Institute - Twin Falls
  • Illinois
    • Aurora, Illinois, United States, 60504
      • Rush - Copley Medical Center
    • Bloomington, Illinois, United States, 61704
      • Illinois CancerCare-Bloomington
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare-Canton
    • Carbondale, Illinois, United States, 62902
      • Memorial Hospital of Carbondale
    • Carterville, Illinois, United States, 62918
      • SIH Cancer Institute
    • Carthage, Illinois, United States, 62321
      • Illinois CancerCare-Carthage
    • Centralia, Illinois, United States, 62801
      • Centralia Oncology Clinic
    • Danville, Illinois, United States, 61832
      • Carle on Vermilion
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Cancer Care Specialists of Illinois - Decatur
    • Effingham, Illinois, United States, 62401
      • Crossroads Cancer Center
    • Effingham, Illinois, United States, 62401
      • Carle Physician Group-Effingham
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare-Eureka
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
    • Galesburg, Illinois, United States, 61401
      • Western Illinois Cancer Treatment Center
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Glenview, Illinois, United States, 60026
      • NorthShore University HealthSystem-Glenbrook Hospital
    • Highland Park, Illinois, United States, 60035
      • NorthShore University HealthSystem-Highland Park Hospital
    • Hines, Illinois, United States, 60141
      • Edward Hines Jr VA Hospital
    • Kewanee, Illinois, United States, 61443
      • Illinois CancerCare-Kewanee Clinic
    • Macomb, Illinois, United States, 61455
      • Illinois CancerCare-Macomb
    • Mattoon, Illinois, United States, 61938
      • Carle Physician Group-Mattoon/Charleston
    • Moline, Illinois, United States, 61265
      • Trinity Medical Center
    • O'Fallon, Illinois, United States, 62269
      • Cancer Care Center of O'Fallon
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Pekin, Illinois, United States, 61554
      • Illinois CancerCare-Pekin
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare-Peru
    • Peru, Illinois, United States, 61354
      • Valley Radiation Oncology
    • Princeton, Illinois, United States, 61356
      • Illinois CancerCare-Princeton
    • Rockford, Illinois, United States, 61114
      • SwedishAmerican Regional Cancer Center/ACT
    • Skokie, Illinois, United States, 60076
      • North Shore Medical Center
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University School of Medicine
    • Springfield, Illinois, United States, 62702
      • Springfield Clinic
    • Swansea, Illinois, United States, 62226
      • Southwest Illinois Health Services LLP
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
    • Urbana, Illinois, United States, 61801
      • The Carle Foundation Hospital
    • Yorkville, Illinois, United States, 60560
      • Rush-Copley Healthcare Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46805
      • Parkview Hospital Randallia
    • Fort Wayne, Indiana, United States, 46845
      • Parkview Regional Medical Center
    • Richmond, Indiana, United States, 47374
      • Reid Health
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic PC - Ames
    • Ames, Iowa, United States, 50010
      • Mary Greeley Medical Center
    • Boone, Iowa, United States, 50036
      • McFarland Clinic PC-Boone
    • Clive, Iowa, United States, 50325
      • Mercy Cancer Center-West Lakes
    • Clive, Iowa, United States, 50325
      • Medical Oncology and Hematology Associates-West Des Moines
    • Council Bluffs, Iowa, United States, 51503
      • Alegent Health Mercy Hospital
    • Creston, Iowa, United States, 50801
      • Greater Regional Medical Center
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates-Des Moines
    • Des Moines, Iowa, United States, 50314
      • Broadlawns Medical Center
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates-Laurel
    • Fort Dodge, Iowa, United States, 50501
      • McFarland Clinic PC-Trinity Cancer Center
    • Fort Dodge, Iowa, United States, 50501
      • Trinity Regional Medical Center
    • Jefferson, Iowa, United States, 50129
      • McFarland Clinic PC-Jefferson
    • Marshalltown, Iowa, United States, 50158
      • McFarland Clinic PC-Marshalltown
    • West Des Moines, Iowa, United States, 50266-7700
      • Methodist West Hospital
    • West Des Moines, Iowa, United States, 50266
      • Mercy Medical Center-West Lakes
  • Kansas
    • Garden City, Kansas, United States, 67846
      • Central Care Cancer Center - Garden City
    • Great Bend, Kansas, United States, 67530
      • Central Care Cancer Center - Great Bend
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Lenexa, Kansas, United States, 66219
      • Kansas Institute of Medicine Cancer and Blood Center
    • Lenexa, Kansas, United States, 66219
      • Minimally Invasive Surgery Hospital
    • Overland Park, Kansas, United States, 66209
      • Menorah Medical Center
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Wichita
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Flaget Memorial Hospital
    • Corbin, Kentucky, United States, 40701
      • Baptist Health Corbin
    • Corbin, Kentucky, United States, 40701
      • Commonwealth Cancer Center-Corbin
    • Lexington, Kentucky, United States, 40504
      • Saint Joseph Radiation Oncology Resource Center
    • Lexington, Kentucky, United States, 40509
      • Saint Joseph Hospital East
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
    • London, Kentucky, United States, 40741
      • Saint Joseph London
    • Louisville, Kentucky, United States, 40202
      • Jewish Hospital
    • Louisville, Kentucky, United States, 40245
      • UofL Health Medical Center Northeast
    • Louisville, Kentucky, United States, 40207
      • Baptist Health Louisville
    • Louisville, Kentucky, United States, 40215
      • Saints Mary and Elizabeth Hospital
    • Madisonville, Kentucky, United States, 42431
      • Baptist Health Madisonville/Merle Mahr Cancer Center
    • Paducah, Kentucky, United States, 42003
      • Baptist Health Paducah
    • Shepherdsville, Kentucky, United States, 40165
      • Jewish Hospital Medical Center South
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Ochsner Health Center-Summa
    • Baton Rouge, Louisiana, United States, 70816
      • Medical Center of Baton Rouge
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center Jefferson
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
    • Cumberland, Maryland, United States, 21502
      • UPMC Western Maryland
    • Salisbury, Maryland, United States, 21801
      • TidalHealth Peninsula Regional
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • Saint Joseph Mercy Hospital
    • Brighton, Michigan, United States, 48114
      • Saint Joseph Mercy Brighton
    • Brighton, Michigan, United States, 48114
      • Trinity Health IHA Medical Group Hematology Oncology - Brighton
    • Canton, Michigan, United States, 48188
      • Saint Joseph Mercy Canton
    • Canton, Michigan, United States, 48188
      • Trinity Health IHA Medical Group Hematology Oncology - Canton
    • Caro, Michigan, United States, 48723
      • Caro Cancer Center
    • Chelsea, Michigan, United States, 48118
      • Saint Joseph Mercy Chelsea
    • Chelsea, Michigan, United States, 48118
      • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
    • Clarkston, Michigan, United States, 48346
      • Hematology Oncology Consultants-Clarkston
    • Clarkston, Michigan, United States, 48346
      • Newland Medical Associates-Clarkston
    • Detroit, Michigan, United States, 48236
      • Ascension Saint John Hospital
    • East China Township, Michigan, United States, 48054
      • Great Lakes Cancer Management Specialists-Doctors Park
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesee Cancer and Blood Disease Treatment Center
    • Flint, Michigan, United States, 48503
      • Genesee Hematology Oncology PC
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Academic Hematology Oncology Specialists
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Michigan Breast Specialists-Grosse Pointe Woods
    • Lansing, Michigan, United States, 48912
      • Sparrow Hospital
    • Livonia, Michigan, United States, 48154
      • Trinity Health Saint Mary Mercy Livonia Hospital
    • Livonia, Michigan, United States, 48154
      • Hope Cancer Clinic
    • Macomb, Michigan, United States, 48044
      • Great Lakes Cancer Management Specialists-Macomb Medical Campus
    • Macomb, Michigan, United States, 48044
      • Michigan Breast Specialists-Macomb Township
    • Marlette, Michigan, United States, 48453
      • Saint Mary's Oncology/Hematology Associates of Marlette
    • Monroe, Michigan, United States, 48162
      • Toledo Clinic Cancer Centers-Monroe
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Pontiac, Michigan, United States, 48341
      • 21st Century Oncology-Pontiac
    • Pontiac, Michigan, United States, 48341
      • Hope Cancer Center
    • Pontiac, Michigan, United States, 48341
      • Newland Medical Associates-Pontiac
    • Port Huron, Michigan, United States, 48060
      • Lake Huron Medical Center
    • Port Huron, Michigan, United States, 48060
      • Huron Medical Center PC
    • Rochester Hills, Michigan, United States, 48309
      • Great Lakes Cancer Management Specialists-Rochester Hills
    • Saginaw, Michigan, United States, 48601
      • Ascension Saint Mary's Hospital
    • Saginaw, Michigan, United States, 48604
      • Oncology Hematology Associates of Saginaw Valley PC
    • Sterling Heights, Michigan, United States, 48312
      • Bhadresh Nayak MD PC-Sterling Heights
    • Tawas City, Michigan, United States, 48764
      • Ascension Saint Joseph Hospital
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
    • Warren, Michigan, United States, 48088
      • Advanced Breast Care Center PLLC
    • Warren, Michigan, United States, 48093
      • Great Lakes Cancer Management Specialists-Macomb Professional Building
    • Warren, Michigan, United States, 48093
      • Macomb Hematology Oncology PC
    • Warren, Michigan, United States, 48093
      • Michigan Breast Specialists-Warren
    • West Branch, Michigan, United States, 48661
      • Saint Mary's Oncology/Hematology Associates of West Branch
    • Ypsilanti, Michigan, United States, 48197
      • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
    • Ypsilanti, Michigan, United States, 48106
      • Huron Gastroenterology PC
  • Minnesota
    • Bemidji, Minnesota, United States, 56601
      • Sanford Joe Lueken Cancer Center
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Maple Grove, Minnesota, United States, 55369
      • Fairview Clinics and Surgery Center Maple Grove
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA-Maplewood
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55454
      • Health Partners Inc
    • New Ulm, Minnesota, United States, 56073
      • New Ulm Medical Center
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
    • Stillwater, Minnesota, United States, 55082
      • Lakeview Hospital
    • Thief River Falls, Minnesota, United States, 56701
      • Sanford Thief River Falls Medical Center
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Rice Memorial Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology PA-Woodbury
    • Worthington, Minnesota, United States, 56187
      • Sanford Cancer Center Worthington
    • Wyoming, Minnesota, United States, 55092
      • Fairview Lakes Medical Center
  • Mississippi
    • Pascagoula, Mississippi, United States, 39581
      • Singing River Hospital
  • Missouri
    • Bolivar, Missouri, United States, 65613
      • Central Care Cancer Center - Bolivar
    • Bonne Terre, Missouri, United States, 63628
      • Parkland Health Center-Bonne Terre
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Cape Girardeau, Missouri, United States, 63703
      • Southeast Cancer Center
    • Independence, Missouri, United States, 64057
      • Centerpoint Medical Center LLC
    • Jefferson City, Missouri, United States, 65109
      • Capital Region Southwest Campus
    • Kansas City, Missouri, United States, 64132
      • Research Medical Center
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Sainte Genevieve, Missouri, United States, 63670
      • Sainte Genevieve County Memorial Hospital
    • Sullivan, Missouri, United States, 63080
      • Missouri Baptist Sullivan Hospital
    • Sunset Hills, Missouri, United States, 63127
      • Missouri Baptist Outpatient Center-Sunset Hills
  • Montana
    • Anaconda, Montana, United States, 59711
      • Community Hospital of Anaconda
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Benefis Healthcare- Sletten Cancer Institute
    • Helena, Montana, United States, 59601
      • Saint Peter's Community Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Missoula, Montana, United States, 59804
      • Community Medical Hospital
    • Missoula, Montana, United States, 59802
      • Saint Patrick Hospital - Community Hospital
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • CHI Health Saint Francis
    • Kearney, Nebraska, United States, 68847
      • CHI Health Good Samaritan
    • Kearney, Nebraska, United States, 68845
      • Heartland Hematology and Oncology
    • Lincoln, Nebraska, United States, 68510
      • Saint Elizabeth Regional Medical Center
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
    • Omaha, Nebraska, United States, 68124
      • Alegent Health Bergan Mercy Medical Center
    • Omaha, Nebraska, United States, 68122
      • Alegent Health Immanuel Medical Center
    • Omaha, Nebraska, United States, 68130
      • Alegent Health Lakeside Hospital
    • Omaha, Nebraska, United States, 68131
      • Creighton University Medical Center
    • Omaha, Nebraska, United States, 68122
      • Hematology and Oncology Consultants PC
    • Papillion, Nebraska, United States, 68046
      • Midlands Community Hospital
  • Nevada
    • Carson City, Nevada, United States, 89703
      • Carson Tahoe Regional Medical Center
    • Henderson, Nevada, United States, 89052
      • Comprehensive Cancer Centers of Nevada - Henderson
    • Henderson, Nevada, United States, 89052
      • OptumCare Cancer Care at Seven Hills
    • Henderson, Nevada, United States, 89052
      • Cancer and Blood Specialists-Henderson
    • Henderson, Nevada, United States, 89052
      • Las Vegas Cancer Center-Henderson
    • Henderson, Nevada, United States, 89074
      • Comprehensive Cancer Centers of Nevada-Southeast Henderson
    • Henderson, Nevada, United States, 89074
      • GenesisCare USA - Henderson
    • Henderson, Nevada, United States, 89052
      • Comprehensive Cancer Centers of Nevada-Horizon Ridge
    • Las Vegas, Nevada, United States, 89144
      • Summerlin Hospital Medical Center
    • Las Vegas, Nevada, United States, 89102
      • OptumCare Cancer Care at Charleston
    • Las Vegas, Nevada, United States, 89106
      • Radiation Oncology Centers of Nevada Central
    • Las Vegas, Nevada, United States, 89109
      • GenesisCare USA - Las Vegas
    • Las Vegas, Nevada, United States, 89119
      • Radiation Oncology Centers of Nevada Southeast
    • Las Vegas, Nevada, United States, 89128
      • Comprehensive Cancer Centers of Nevada - Northwest
    • Las Vegas, Nevada, United States, 89128
      • OptumCare Cancer Care at MountainView
    • Las Vegas, Nevada, United States, 89144
      • Comprehensive Cancer Centers of Nevada-Summerlin
    • Las Vegas, Nevada, United States, 89148
      • Comprehensive Cancer Centers of Nevada
    • Las Vegas, Nevada, United States, 89148
      • OptumCare Cancer Care at Fort Apache
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada - Central Valley
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cancer and Blood Specialists-Shadow
    • Las Vegas, Nevada, United States, 89109
      • HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
    • Las Vegas, Nevada, United States, 89113
      • HealthCare Partners Medical Group Oncology/Hematology-San Martin
    • Las Vegas, Nevada, United States, 89121
      • Cancer Therapy and Integrative Medicine
    • Las Vegas, Nevada, United States, 89128
      • Cancer and Blood Specialists-Tenaya
    • Las Vegas, Nevada, United States, 89128
      • GenesisCare USA - Vegas Tenaya
    • Las Vegas, Nevada, United States, 89128
      • HealthCare Partners Medical Group Oncology/Hematology-Tenaya
    • Las Vegas, Nevada, United States, 89148-2405
      • Las Vegas Cancer Center-Medical Center
    • Las Vegas, Nevada, United States, 89148
      • GenesisCare USA - Fort Apache
    • Las Vegas, Nevada, United States, 89149
      • HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
    • Las Vegas, Nevada, United States, 89128
      • Ann M Wierman MD LTD
    • Las Vegas, Nevada, United States, 89102
      • Desert West Surgery
    • Las Vegas, Nevada, United States, 89103
      • Hope Cancer Care of Nevada
    • Las Vegas, Nevada, United States, 89169
      • University Cancer Center
    • Pahrump, Nevada, United States, 89048
      • Hope Cancer Care of Nevada-Pahrump
    • Reno, Nevada, United States, 89502
      • Renown Regional Medical Center
    • Reno, Nevada, United States, 89503
      • Saint Mary's Regional Medical Center
    • Reno, Nevada, United States, 89509
      • Radiation Oncology Associates
  • New Hampshire
    • Concord, New Hampshire, United States, 03301
      • New Hampshire Oncology Hematology PA-Concord
    • Manchester, New Hampshire, United States, 03103
      • Solinsky Center for Cancer Care
  • New Jersey
    • Mount Holly, New Jersey, United States, 08060
      • Virtua Memorial
    • Voorhees, New Jersey, United States, 08043
      • Virtua Voorhees
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center-Einstein Campus
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center - Moses Campus
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center-Weiler Hospital
  • North Carolina
    • Asheboro, North Carolina, United States, 27203
      • Randolph Hospital
    • Burlington, North Carolina, United States, 27215
      • Cone Health Cancer Center at Alamance Regional
    • Clinton, North Carolina, United States, 28328
      • Southeastern Medical Oncology Center-Clinton
    • Goldsboro, North Carolina, United States, 27534
      • Southeastern Medical Oncology Center-Goldsboro
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
    • Greensboro, North Carolina, United States, 27403
      • Cone Health Cancer Center
    • Hendersonville, North Carolina, United States, 28791
      • Margaret R Pardee Memorial Hospital
    • Jacksonville, North Carolina, United States, 28546
      • Southeastern Medical Oncology Center-Jacksonville
    • Jacksonville, North Carolina, United States, 28546
      • Onslow Memorial Hospital
    • Kinston, North Carolina, United States, 28501
      • Vidant Oncology-Kinston
    • Mebane, North Carolina, United States, 27302
      • Cone Heath Cancer Center at Mebane
    • Reidsville, North Carolina, United States, 27320
      • Annie Penn Memorial Hospital
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanford Bismarck Medical Center
    • Fargo, North Dakota, United States, 58122
      • Sanford Roger Maris Cancer Center
    • Fargo, North Dakota, United States, 58122
      • Sanford Broadway Medical Center
    • Fargo, North Dakota, United States, 58103
      • Sanford South University Medical Center
    • Minot, North Dakota, United States, 58701
      • Trinity Cancer Care Center
  • Ohio
    • Beavercreek, Ohio, United States, 45431
      • Indu and Raj Soin Medical Center
    • Belpre, Ohio, United States, 45714
      • Strecker Cancer Center-Belpre
    • Canton, Ohio, United States, 44710
      • Aultman Health Foundation
    • Centerville, Ohio, United States, 45459
      • Miami Valley Hospital South
    • Centerville, Ohio, United States, 45459
      • Dayton Physicians LLC-Miami Valley South
    • Chardon, Ohio, United States, 44024
      • Geauga Hospital
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Cancer Center-UC Medical Center
    • Cincinnati, Ohio, United States, 45220
      • Good Samaritan Hospital - Cincinnati
    • Cincinnati, Ohio, United States, 45242
      • Bethesda North Hospital
    • Cincinnati, Ohio, United States, 45236
      • Oncology Hematology Care Inc-Kenwood
    • Cincinnati, Ohio, United States, 45247
      • TriHealth Cancer Institute-Westside
    • Cincinnati, Ohio, United States, 45255
      • TriHealth Cancer Institute-Anderson
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43219
      • The Mark H Zangmeister Center
    • Columbus, Ohio, United States, 43214
      • Columbus Oncology and Hematology Associates Inc
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital
    • Columbus, Ohio, United States, 43213
      • Mount Carmel East Hospital
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health Center West
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Dayton Physician LLC-Miami Valley Hospital North
    • Dayton, Ohio, United States, 45415
      • Miami Valley Hospital North
    • Delaware, Ohio, United States, 43015
      • Delaware Health Center-Grady Cancer Center
    • Delaware, Ohio, United States, 43015
      • Delaware Radiation Oncology
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Elyria, Ohio, United States, 44035
      • Mercy Cancer Center-Elyria
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Hospital
    • Findlay, Ohio, United States, 45840
      • Armes Family Cancer Center
    • Findlay, Ohio, United States, 45840
      • Orion Cancer Care
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Franklin, Ohio, United States, 45005
      • Dayton Physicians LLC-Atrium
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Greenville, Ohio, United States, 45331
      • Dayton Physicians LLC-Wayne
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Kettering, Ohio, United States, 45409
      • Greater Dayton Cancer Center
    • Kettering, Ohio, United States, 45420
      • First Dayton Cancer Care
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Mansfield, Ohio, United States, 44903
      • OhioHealth Mansfield Hospital
    • Marietta, Ohio, United States, 45750
      • Marietta Memorial Hospital
    • Marion, Ohio, United States, 43302
      • OhioHealth Marion General Hospital
    • Maumee, Ohio, United States, 43537
      • Toledo Clinic Cancer Centers-Maumee
    • Maumee, Ohio, United States, 43537
      • Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
    • Mentor, Ohio, United States, 44060
      • UH Seidman Cancer Center at Lake Health Mentor Campus
    • Middleburg Heights, Ohio, United States, 44130
      • UH Seidman Cancer Center at Southwest General Hospital
    • Mount Vernon, Ohio, United States, 43050
      • Knox Community Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Hospital
    • Newark, Ohio, United States, 43055
      • Newark Radiation Oncology
    • Parma, Ohio, United States, 44129
      • University Hospitals Parma Medical Center
    • Perrysburg, Ohio, United States, 43551
      • Mercy Health Perrysburg Cancer Center
    • Portsmouth, Ohio, United States, 45662
      • Southern Ohio Medical Center
    • Sandusky, Ohio, United States, 44870
      • UH Seidman Cancer Center at Firelands Regional Medical Center
    • Springfield, Ohio, United States, 45505
      • Springfield Regional Medical Center
    • Springfield, Ohio, United States, 45504
      • Springfield Regional Cancer Center
    • Toledo, Ohio, United States, 43623
      • Mercy Health - Saint Anne Hospital
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic Cancer Centers-Toledo
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
    • Troy, Ohio, United States, 45373
      • Dayton Physicians LLC-Upper Valley
    • West Chester, Ohio, United States, 45069
      • University of Cincinnati Cancer Center-West Chester
    • Westerville, Ohio, United States, 43081
      • Saint Ann's Hospital
    • Westlake, Ohio, United States, 44145
      • UH Seidman Cancer Center at Saint John Medical Center
    • Zanesville, Ohio, United States, 43701
      • Genesis Healthcare System Cancer Care Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Oklahoma City, Oklahoma, United States, 73109
      • Integris Southwest Medical Center
    • Oklahoma City, Oklahoma, United States, 73142
      • Integris Cancer Institute of Oklahoma
    • Tulsa, Oklahoma, United States, 74146
      • Oklahoma Cancer Specialists and Research Institute-Tulsa
  • Oregon
    • Baker City, Oregon, United States, 97814
      • Saint Alphonsus Medical Center-Baker City
    • Bend, Oregon, United States, 97701
      • Saint Charles Health System
    • Clackamas, Oregon, United States, 97015
      • Clackamas Radiation Oncology Center
    • Clackamas, Oregon, United States, 97015
      • Providence Cancer Institute Clackamas Clinic
    • Coos Bay, Oregon, United States, 97420
      • Bay Area Hospital
    • Newberg, Oregon, United States, 97132
      • Providence Newberg Medical Center
    • Ontario, Oregon, United States, 97914
      • Saint Alphonsus Medical Center-Ontario
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
    • Redmond, Oregon, United States, 97756
      • Saint Charles Health System-Redmond
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital-Cedar Crest
    • Bethlehem, Pennsylvania, United States, 18017
      • Lehigh Valley Hospital - Muhlenberg
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • East Stroudsburg, Pennsylvania, United States, 18301
      • Pocono Medical Center
    • Hazleton, Pennsylvania, United States, 18201
      • Geisinger Medical Center-Cancer Center Hazleton
    • Hazleton, Pennsylvania, United States, 18201
      • Lehigh Valley Hospital-Hazleton
    • Lewisburg, Pennsylvania, United States, 17837
      • Geisinger Medical Oncology-Lewisburg
    • Lewistown, Pennsylvania, United States, 17044
      • Lewistown Hospital
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Pottstown, Pennsylvania, United States, 19464
      • Pottstown Hospital
    • Pottsville, Pennsylvania, United States, 17901
      • Geisinger Cancer Services-Pottsville
    • Scranton, Pennsylvania, United States, 18510
      • Community Medical Center
    • State College, Pennsylvania, United States, 16801
      • Geisinger Medical Group
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley/Henry Cancer Center
  • South Carolina
    • Boiling Springs, South Carolina, United States, 29316
      • Prisma Health Cancer Institute - Spartanburg
    • Clinton, South Carolina, United States, 29325
      • Prisma Health Cancer Institute - Laurens
    • Easley, South Carolina, United States, 29640
      • Prisma Health Cancer Institute - Easley
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Faris
    • Greenville, South Carolina, United States, 29615
      • Prisma Health Cancer Institute - Eastside
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Butternut
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Greenville Memorial Hospital
    • Greer, South Carolina, United States, 29650
      • Prisma Health Cancer Institute - Greer
    • Seneca, South Carolina, United States, 29672
      • Prisma Health Cancer Institute - Seneca
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117-5134
      • Sanford USD Medical Center - Sioux Falls
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Center Oncology Clinic
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Bristol Regional Medical Center
    • Chattanooga, Tennessee, United States, 37404
      • Memorial Hospital
    • Hixson, Tennessee, United States, 37343
      • Pulmonary Medicine Center of Chattanooga-Hixson
    • Johnson City, Tennessee, United States, 37604
      • Wellmont Medical Associates Oncology and Hematology-Johnson City
    • Kingsport, Tennessee, United States, 37660
      • Ballad Health Cancer Care - Kingsport
    • Kingsport, Tennessee, United States, 37660
      • Wellmont Holston Valley Hospital and Medical Center
    • Ooltewah, Tennessee, United States, 37363
      • Memorial GYN Plus
  • Texas
    • Bryan, Texas, United States, 77802
      • Saint Joseph Regional Cancer Center
    • Dallas, Texas, United States, 75235
      • Parkland Memorial Hospital
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
    • Fort Worth, Texas, United States, 76104
      • UT Southwestern/Simmons Cancer Center-Fort Worth
  • Virginia
    • Bristol, Virginia, United States, 24201
      • Wellmont Medical Associates-Bristol
    • Norton, Virginia, United States, 24273
      • Southwest VA Regional Cancer Center
  • Washington
    • Aberdeen, Washington, United States, 98520
      • Providence Regional Cancer System-Aberdeen
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Bremerton, Washington, United States, 98310
      • Harrison HealthPartners Hematology and Oncology-Bremerton
    • Bremerton, Washington, United States, 98310
      • Harrison Medical Center
    • Burien, Washington, United States, 98166
      • Highline Medical Center-Main Campus
    • Centralia, Washington, United States, 98531
      • Providence Regional Cancer System-Centralia
    • Edmonds, Washington, United States, 98026
      • Swedish Cancer Institute-Edmonds
    • Enumclaw, Washington, United States, 98022
      • Saint Elizabeth Hospital
    • Everett, Washington, United States, 98201
      • Providence Regional Cancer Partnership
    • Federal Way, Washington, United States, 98003
      • Saint Francis Hospital
    • Issaquah, Washington, United States, 98029
      • Swedish Cancer Institute-Issaquah
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Lacey, Washington, United States, 98503
      • Providence Regional Cancer System-Lacey
    • Lakewood, Washington, United States, 98499
      • Saint Clare Hospital
    • Longview, Washington, United States, 98632
      • PeaceHealth Saint John Medical Center
    • Poulsbo, Washington, United States, 98370
      • Harrison HealthPartners Hematology and Oncology-Poulsbo
    • Seattle, Washington, United States, 98107
      • Swedish Medical Center-Ballard Campus
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center-First Hill
    • Seattle, Washington, United States, 98112
      • Kaiser Permanente Washington
    • Seattle, Washington, United States, 98104
      • Pacific Gynecology Specialists
    • Seattle, Washington, United States, 98122-5711
      • Swedish Medical Center-Cherry Hill
    • Sedro-Woolley, Washington, United States, 98284
      • PeaceHealth United General Medical Center
    • Shelton, Washington, United States, 98584
      • Providence Regional Cancer System-Shelton
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties PLLC
    • Tacoma, Washington, United States, 98405
      • Franciscan Research Center-Northwest Medical Plaza
    • Vancouver, Washington, United States, 98664
      • PeaceHealth Southwest Medical Center
    • Walla Walla, Washington, United States, 99362
      • Providence Saint Mary Regional Cancer Center
    • Yelm, Washington, United States, 98597
      • Providence Regional Cancer System-Yelm
  • Wisconsin
    • Antigo, Wisconsin, United States, 54409
      • Langlade Hospital and Cancer Center
    • Burlington, Wisconsin, United States, 53105
      • Aurora Cancer Care-Southern Lakes VLCC
    • Fond Du Lac, Wisconsin, United States, 54937
      • Aurora Health Center-Fond du Lac
    • Germantown, Wisconsin, United States, 53022
      • Aurora Health Care Germantown Health Center
    • Grafton, Wisconsin, United States, 53024
      • Aurora Cancer Care-Grafton
    • Green Bay, Wisconsin, United States, 54311
      • Aurora BayCare Medical Center
    • Kenosha, Wisconsin, United States, 53142
      • Aurora Cancer Care-Kenosha South
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • Marinette, Wisconsin, United States, 54143
      • Aurora Bay Area Medical Group-Marinette
    • Milwaukee, Wisconsin, United States, 53209
      • Aurora Cancer Care-Milwaukee
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Saint Luke's Medical Center
    • Milwaukee, Wisconsin, United States, 53233
      • Aurora Sinai Medical Center
    • New Richmond, Wisconsin, United States, 54017
      • Cancer Center of Western Wisconsin
    • Oshkosh, Wisconsin, United States, 54904
      • Vince Lombardi Cancer Clinic - Oshkosh
    • Racine, Wisconsin, United States, 53406
      • Aurora Cancer Care-Racine
    • Sheboygan, Wisconsin, United States, 53081
      • Vince Lombardi Cancer Clinic-Sheboygan
    • Summit, Wisconsin, United States, 53066
      • Aurora Medical Center in Summit
    • Two Rivers, Wisconsin, United States, 54241
      • Vince Lombardi Cancer Clinic-Two Rivers
    • Wausau, Wisconsin, United States, 54401
      • Aspirus Regional Cancer Center
    • Wauwatosa, Wisconsin, United States, 53226
      • Aurora Cancer Care-Milwaukee West
    • West Allis, Wisconsin, United States, 53227
      • Aurora West Allis Medical Center
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Aspirus Cancer Care - Wisconsin Rapids
  • Wyoming
    • Cody, Wyoming, United States, 82414
      • Billings Clinic-Cody
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria (Step 0):

• Patients with tumors with the following molecular alterations must submit testing results via Medidata Rave to determine eligibility to Arm T; the study chair, co-chair, biology co-chair, or a delegate must review the molecular testing and agree that the testing meets one of the molecular eligibility criteria below:

  • ROS1 gene rearrangement by fluorescence in situ hybridization (FISH) or deoxyribonucleic acid (DNA) analysis (may have progressed on prior crizotinib therapy)
  • MET exon 14 splice mutations on DNA analysis (may have progressed on prior crizotinib therapy)
  • MET high amplification by FISH or DNA analysis or other MET mutations predicted to be sensitive to MET inhibitor (no prior targeted therapy allowed)

  • RET gene rearrangement by FISH or DNA analysis (no prior targeted therapy allowed)

    • Institutions will be notified of the patient's eligibility status for Arm T within two (2) business days of submission of the molecular testing reports
    • If patients do not have tumors with the above molecular alterations noted proceed directly to step 1

Inclusion Criteria (Step 1):

• For patients with known molecular alterations, institution has been notified that patient is deemed eligible for Arm T per review of molecular testing reports
• Pathologically confirmed non-squamous non-small cell lung carcinoma (NSCLC)
• Stage IV disease (includes M1a, M1b, or recurrent disease), according to the 7th edition of the lung cancer tumor, node, and metastasis (TNM) classification system
• Predominant non-squamous histology (patients with NSCLC not otherwise specified [NOS] are eligible); mixed tumors will be categorized by the predominant cell type; if small cell elements are present the patient is ineligible
• Tumors must be tested and known negative for EGFR tyrosine kinase inhibitor (TKI) sensitizing mutations (EGFR exon 19 deletions, L858R, L861Q, G719X) and ALK gene rearrangements by routine Clinical Laboratory Improvement Act (CLIA)-certified clinical testing methods; negative circulating tumor DNA results alone are not acceptable; prior testing for tumor PD-L1 status is not required

• Patients must have progressed radiographically following first line platinum-based chemotherapy, no additional lines of therapy are permitted

  • NOTE: Prior adjuvant chemotherapy for early stage disease does not count as one line of therapy if 12 months or greater elapsed between completion of adjuvant therapy and initiation of first-line systemic therapy; if less than 12 months elapsed, adjuvant chemotherapy counts as one line of therapy
  • Exception for targeted therapy sub-study (Arm T): At least one line of prior chemotherapy or targeted therapy is required, but there is no limit on number of prior treatments
• Patients must have measurable disease as defined by RECIST v. 1.1 criteria; baseline measurements and evaluation of all sites of disease must be obtained within 4 weeks prior to registration

• Any prior chemotherapy (based on administration schedule) must have been completed in greater than or equal to the following times prior to registration:

  • Chemotherapy/ targeted oral therapy administered in a daily or weekly schedule must be completed >= 1 week prior to registration;
  • Any chemotherapy administered in an every 2 week or greater schedule must be completed >= 2 weeks prior to registration
  • Additionally, patients should be recovered to equal to or less than grade 1 toxicities related to any prior treatment, unless adverse event (AE)(s) are clinically nonsignificant and/or stable on supportive therapy

• Patients with no known brain metastasis must have baseline brain imaging within 12 weeks prior to study registration not demonstrating brain metastases OR patients with known brain metastases must have baseline brain imaging within 4 weeks prior to study registration and meet all of the following criteria:

  • Have completed treatment to all symptomatic brain metastases (with whole brain radiation or radiosurgery) >= 4 weeks prior to registration, or have undergone complete neurosurgical resection >= 3 months prior to registration
  • Be clinically stable from brain metastases at time of screening, if no treatment was administered
  • Known leptomeningeal disease is not allowed
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Patients must have anticipated life expectancy greater than 3 months
• Absolute neutrophil count >= 1,500/mm^3 (within 2 weeks prior to registration)
• Platelets >= 100,000/mm^3 (within 2 weeks prior to registration)
• Hemoglobin >= 9 g/dL (within 2 weeks prior to registration)
• Subject has prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) test =< 1.3 x the laboratory upper limit of normal (ULN) (within 2 weeks prior to registration)
• Total bilirubin =< 1.5 x ULN (within 2 weeks prior to registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x ULN (within 2 weeks prior to registration)
• Serum albumin >= 2.8 g/dL (within 2 weeks prior to registration)

• Serum calcium (absolute or albumin corrected), magnesium and potassium >= lower limit of normal (LLN) (within 2 weeks prior to registration)

  • NOTE: serum calcium, magnesium and potassium can be replaced if values are below LLN
• Creatinine =< 1.5 x ULN or calculated (Cockcroft-Gault formula) or measured creatinine clearance >= 50 mL/min/1.73 m^2 (normalized to body surface area [BSA]) for patients with creatinine levels greater than 1.5 times the institutional normal (within 2 weeks prior to registration)
• Screening urine dipstick must equal 0 or "trace"; if urine dipstick results are >= 1+, or if dipstick was not performed, calculation of urine protein creatinine (UPC) is required and patients must have a UPC ratio =< 1 to participate in the study (within 2 weeks prior to registration)
• Patients must have corrected QT interval calculated by the Fridericia formula (QTcF) =< 500 ms within 28 days before registration

• Patients must be able to swallow tablets

  • All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
  • A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• Women of childbearing potential (WOCBP) and males who are sexually active with WOCBP must use an accepted and effective method of contraception or abstain from sexual intercourse for at least one week prior to the start of treatment, and continue for 5 months after the last dose of protocol treatment for women of childbearing potential and 7 months after the last dose of protocol treatment for males who are sexually active with WOCBP

Exclusion Criteria (Step 1):

• Small cell elements are present

• Prior anti-MET therapy such as crizotinib or cabozantinib, or PD-1/PD-L1 immune checkpoint inhibitor therapy (such as nivolumab, pembrolizumab, atezolizumab) or CTLA4 inhibitor therapy (such as ipilimumab); prior allergic reaction to small molecule tyrosine kinase inhibitors or monoclonal antibodies

  • Exception for targeted therapy sub-study (Arm T): Prior crizotinib may be allowed depending on the gene alteration
• Prior radiation therapy for bone metastasis within 2 weeks; any other radiation therapy within 4 weeks prior to registration
• Known leptomeningeal disease
• Impaired decision-making capacity (IDMC)
• Clinically-significant gastrointestinal bleeding within 6 months prior to registration
• Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months prior to registration
• Drug induced pneumonitis within 3 months prior to registration
• Signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
• Radiographic evidence of cavitating pulmonary lesion(s)
• Tumor invading any major blood vessels
• Evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or mainstem endobronchial tumor within 28 days before the first dose of cabozantinib

• Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel); allowed anticoagulants are the following:

  • Low-dose aspirin for cardioprotection (per local applicable guidelines) is permitted
  • Low molecular weight heparins (LMWH) or unfractionated heparin is permitted
  • Anticoagulation with therapeutic doses of LMWH is allowed in subjects without known brain metastases who are on a stable dose of LMWH for at least 6 weeks before first dose of study treatment, and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
• Concomitant treatment of strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort)

• Cardiovascular disorders including:

  • Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening
  • Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic, or > 100 mm Hg diastolic despite optimal antihypertensive treatment within 7 days prior to registration

  • Any of the following within 6 months prior to registration:

    • Unstable angina pectoris
    • Clinically-significant cardiac arrhythmias
    • Stroke (including transient ischemic attack [TIA], or other ischemic event)
    • Myocardial infarction

• Gastrointestinal disorders associated with a high risk of perforation or fistula formation within 3 months prior to registration:

  • Active peptic ulcer disease
  • Inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis
  • Known malabsorption syndrome
  • Bowel obstruction or gastric outlet obstruction
  • Percutaneous endoscopic gastrostomy (PEG) tube placement

• Gastrointestinal disorders associated with a high risk of perforation or fistula formation within 6 months prior to registration:

  • Abdominal fistula
  • Gastrointestinal perforation
  • Intra-abdominal abscess; Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 6 months prior to registration

• Any of the following conditions:

  • Grade 3 or greater infection, or infection requiring intravenous systemic treatment within 28 days prior to registration; patients should be off antibiotics at the time of registration.
  • Serious non-healing wound/ulcer/bone fracture within 28 days prior to registration
  • History of organ transplant
  • Concurrent symptomatic untreated hypothyroidism within 7 days prior to registration

  • History of surgery as follows:

    • Major surgery (as an example, surgery requiring anesthesia and a > 24 hour hospital stay) within 3 months prior to registration, with wound healing at least 28 days prior to registration
    • Minor surgery within 28 days prior to registration with complete wound healing at least 10 days prior to registration
    • Minor procedures within 7 days prior to registration such as thoracentesis, paracentesis, or 18 g or smaller needle biopsy of tumor
    • Patients with clinically relevant ongoing complications from prior surgery are not eligible
• Currently active other malignancies which require systemic treatment
• 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; patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption); physiologic replacement doses of systemic corticosteroids are permitted, even if < 10 mg/day prednisone equivalents; a brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted
• Active autoimmune disease or known history of autoimmune disease for which recurrence may affect vital organ function or require immune suppressive treatment including systemic corticosteroids; these include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, autoimmune hepatitis; patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease; patients with vitiligo, endocrine deficiencies including type I diabetes mellitus or thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible; patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
• Ongoing major illness or psychosocial issues that would limit compliance with the protocol
• Pregnant or breast-feeding

• Patients with known human immunodeficiency virus (HIV) disease taking antiretroviral therapy are excluded because there are no safety data with the combination of antiretroviral therapy and cabozantinib or ipilimumab or nivolumab with ipilimumab

  • Patients with known chronic active hepatitis B (defined as a positive hepatitis B surface antigen and/or hepatitis B viral load in the last

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A (nivolumab); Patients receive nivolumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Biological: Nivolumab; Given IV; Other Names: BMS-936558; MDX1106
Experimental: Arm B (nivolumab, cabozantinib); Patients receive nivolumab IV over 60 minutes on day 1 and cabozantinib s-malate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Biological: Nivolumab; Given IV; Other Names: BMS-936558; MDX1106; Drug: Cabozantinib; Given PO; Other Names: XL-184; Cabometyx®; EXEL-7184; EXEL-02977184; Cabozantinib s-malate
Experimental: Arm C (nivolumab, cabozantinib, ipilimumab); Patients receive nivolumab IV over 60 minutes on day 1, cabozantinib s-malate PO daily on days 1-28, and ipilimumab IV over 90 minutes every 8 weeks. Cycles for nivolumab and cabozantinib s-malate repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Biological: Nivolumab; Given IV; Other Names: BMS-936558; MDX1106; Biological: Ipilimumab; Given IV; Other Names: MDX-010; Yervoy; Anti-CTLA-4 monoclonal antibody; Drug: Cabozantinib; Given PO; Other Names: XL-184; Cabometyx®; EXEL-7184; EXEL-02977184; Cabozantinib s-malate
Experimental: Arm T (Targeted cohort; nivolumab, cabozantinib); Patients with ROS1 gene rearrangement, MET exon 14 splice mutations, MET high amplification, or RET gene rearrangement receive nivolumab IV over 60 minutes on day 1 and cabozantinib s-malate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Biological: Nivolumab; Given IV; Other Names: BMS-936558; MDX1106; Drug: Cabozantinib; Given PO; Other Names: XL-184; Cabometyx®; EXEL-7184; EXEL-02977184; Cabozantinib s-malate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	Progression-free survival is defined as time from randomization to documented disease progression or death from any cause, whichever occurs first. Progression is defined as appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions and/or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. PFS will be estimated using the Kaplan-Meier method.	Every 3 months up to 4 years and 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival is defined as time from randomization to death or date last known alive.	Every 3 months up to 4 years and 2 months
Best Overall Response	Best overall response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Response is defined as either complete response (CR) or partial response (PR). Complete response is defined as disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. For Arm T patients, to be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no less than four weeks after the criteria for response are first met. Arm A, B, and C patients do not require confirmation scans for CR or PR.	Every 3 months up to 4 years and 2 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) by Programmed Death-ligand 1 (PD-L1) Status	Progression-free survival is defined as time from randomization to documented disease progression or death from any cause, whichever occurs first. Progression is defined as appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions and/or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. PFS will be estimated using the Kaplan-Meier method.	Every 3 months for 5 years
The Distribution of Best Overall Response by RECIST 1.1 Criteria, Uni-dimensional Immune Response Criteria (iRRC) and Immune Response Evaluation Criteria in Solid Tumors (iRECIST) Criteria	Best overall response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria: Response is defined as either complete response (CR) or partial response (PR). Complete response is defined as disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Response by iRRC is defined as per RECIST1.1. Measurements of iRECIST response will be performed as described by Seymour et al with time point and over all response assessments categorized as immune complete response (iCR), immune partial response (iPR), immune stable disease (iSD), immune unconfirmed progressive disease (iUPD) and confirmed progressive disease (iCPD).	Every 3 months for 5 years
Response Per RECIST1.1 Performed by Central Review and by Site Study Personnel	Best overall response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria: Response is defined as either complete response (CR) or partial response (PR). Complete response is defined as disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.	Every 3 months for 5 years
Effects of Tobacco on Provider-reported Cancer-treatment Toxicity and Dose Modifications	A combined analysis of the data from the selected Eastern Cooperative Oncology Group (ECOG) and the American College of Radiology Imaging Network (ACRIN) trials is planned. Data collected from the tobacco use assessment in each parent study will not be analyzed and reported in the clinical study report.	Assessed every 4 weeks until 30 days after treatment completion, up to 5 years
Effects of Tobacco on Patient-reported Physical Symptoms and Psychological Symptoms	A combined analysis of the data from the selected ECOG-ACRIN trials is planned. Data collected from the tobacco use assessment in each parent study will not be analyzed and reported in the clinical study report. Psychological Symptom Assessment: Anxiety & Depression: (The Patient Reported Outcomes Measurement Information System (PROMIS®)). The 4-item Short Form PROMIS® for anxiety and depression will be administered. Score ranges between 4 and 20. Higher scores indicate more anxiety/depression. Physical Symptom Assessment by Functional Assessment of Chronic Illness Therapy (FACIT): Six symptom items (general pain, fatigue, nausea, cough, sleep difficulties, shortness of breath) from FACIT will be used for evaluation. Score ranges between 5 and 20. Higher scores indicate higher shame.	Baseline, 3 months and 6 months
Assessment of Quitting Behaviors, Behavioral Counseling/Support and Cessation Medication Utilization	A combined analysis of the data from the selected ECOG-ACRIN trials is planned. Data collected from the tobacco use assessment in each parent study will not be analyzed and reported in the clinical study report.	Baseline, 3 months and 6 months
Effects of Tobacco Use and Exposure on Treatment Duration, Relative Dose Intensity, and Therapeutic Benefit	A combined analysis of the data from the selected ECOG-ACRIN trials is planned. Data collected from the tobacco use assessment in each parent study will not be analyzed and reported in the clinical study report.	Assessed every 3 months for 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Joel W Neal, ECOG-ACRIN Cancer Research Group

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2018
• Primary Completion (Actual): May 9, 2022
• Study Completion (Actual): December 21, 2022

Study Registration Dates

• First Submitted: March 13, 2018
• First Submitted That Met QC Criteria: March 16, 2018
• First Posted (Actual): March 19, 2018

Study Record Updates

• Last Update Posted (Actual): October 17, 2023
• Last Update Submitted That Met QC Criteria: September 22, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; Nivolumab; Ipilimumab; Cabozantinib
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID Numbers: NCI-2017-01008 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180820 (U.S. NIH Grant/Contract); EA5152 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No