Erlotinib Hydrochloride and Cabozantinib-s-Malate Alone or in Combination as Second or Third Line Therapy in Treating Patients With Stage IV Non-small Cell Lung Cancer

Recurrent Lung Non-Small Cell Carcinoma Clinical Trial

Official title:

A Randomized Phase II Trial of Erlotinib, Cabozantinib, or Erlotinib Plus Cabozantinib as 2nd or 3rd Line Therapy in Patients With EGFR Wild-Type NSCLC

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01708954
• Other study ID #: NCI-2012-01938
• Secondary ID: NCI-2012-01938EC
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 13, 2013
• Est. completion date: March 7, 2025

Study information

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

Clinical Trial Summary

This randomized phase II trial studies how well giving erlotinib hydrochloride and cabozantinib-s-malate alone or in combination works as second or third line therapy in treating patient with stage IV non-small cell lung cancer. Erlotinib hydrochloride and cabozantinib-s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving erlotinib hydrochloride together with cabozantinib-s-malate is more effective than erlotinib hydrochloride or cabozantinib-s-malate alone in treating non-small cell lung cancer.

Description:

PRIMARY OBJECTIVES: I. To compare the progression-free survival (PFS) associated with patients treated with erlotinib (erlotinib hydrochloride) versus (vs) erlotinib plus cabozantinib (cabozantinib-s-malate). II. To compare the PFS associated with patients treated with erlotinib vs cabozantinib. SECONDARY OBJECTIVES: I. To evaluate overall survival in the three treatment arms. II. To evaluate best objective response rate in the three treatment arms. III. To define the toxicity associated with each regimen. IV. To conduct correlative science studies that will help to select predictive biomarkers of response to therapy, including mesenchymal-epidermal transition (MET) expression and potentially other tissue biomarkers, plasma biomarkers, and bone scans. OUTLINE: Patients are randomized to 1 of 3 treatment arms. ARM A (erlotinib): Patients receive erlotinib orally (PO) daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM B (cabozantinib): Patients receive cabozantinib PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM C (erlotinib+cabozantinib): Patients receive erlotinib as patients in Arm A and cabozantinib as patients in Arm B. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM Z: Patients achieving disease progression in Arm A or Arm B may receive erlotinib and cabozantinib as patients in Arm C. Courses 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 2 years and then every 6 months for 3 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 125
• Est. completion date: March 7, 2025
• Est. primary completion date: August 14, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Criteria:

• Tumor with a sensitizing mutation in epidermal growth factor receptor (EGFR), defined

as follows:

• EGFR mutation testing of tumor has been performed and did not demonstrate an EGFR tyrosine kinase inhibitor sensitizing mutation; at minimum, testing for EGFR exon 19 deletion and exon 21 L858R mutations must have been included; OR
• EGFR mutation testing has been attempted and is inconclusive (for example, due to lack of sufficient deoxyribonucleic acid [DNA] yield); OR
• EGFR mutation status is unknown but tumor is positive for at least one alternative driver mutation, i.e: Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, v-raf murine sarcoma viral oncogene homolog B (BRAF) mutation, human epidermal growth factor receptor 2 (HER2) mutation, ret proto-oncogene (RET) rearrangement/fusion, or one not listed following approval by the study chair prior to registration

Inclusion Criteria:

• INCLUSION CRITERIA STEP 1:
• Cytologically or histologically confirmed non-small cell lung carcinoma (NSCLC)
• 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
• Stage IV disease (includes M1a, M1b, or recurrent disease), according to the 7th edition of the lung cancer TNM classification system
• Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria; baseline measurements and evaluation of all sites of disease must be obtained within 4 weeks prior to registration
• Prior to registration, the investigator/site must confirm that sufficient pathology material representative of patient's cancer is available for submission for MET immunohistochemical (IHC) testing
• Patients must have received one or two lines of prior chemotherapy (first line platinum-doublet based chemotherapy plus switch maintenance chemotherapy counts as one line of therapy); 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
• Any prior chemotherapy (based on administration schedule) must have been completed in greater than or equal to the time frames specified in the protocol
• Patients must have discontinued treatment with any other type of investigational agent >= 4 weeks prior to registration
• Patients must have recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 =< grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant adverse events (AEs)
• Patients with no known brain metastasis at baseline must have baseline brain imaging within 12 weeks prior to study registration not demonstrating brain metastases; patients with brain metastases at baseline must have baseline brain imagining within 4 weeks prior to study registration and meet all of the specific criteria for brain mets listed in the protocol
• Radiation related toxicities must have resolved to =< grade 1 prior to registration
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-2
• Patients must have an anticipated life expectancy greater than 3 months
• Acceptable bone marrow, renal and hepatic function within 2 weeks prior to registration as defined in the protocol
• 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
• INCLUSION CRITERIA STEP 2:
• Patients must have met all eligibility requirements for Step 1 at time of registration to Step 1 to be eligible for Step 2
• Patients must have radiographic progressive disease per RECIST v1.1 criteria after >= 2 courses of therapy on Arm A or Arm B
• Patients must be registered to Step 2 within 4 weeks of the last dose of treatment administration from Step 1
• Patients must have an ECOG performance status between 0-2
• Patients must have recovered to baseline (pre-Step 1) or CTCAE version 4.0 <= grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant AEs

Exclusion Criteria:

• EXCLUSION CRITERIA STEP 1:
• Patients without sufficient pathology material representative of the patient's cancer (tumor block or 10 unstained slides)
• Prior erlotinib, other EGFR tyrosine kinase inhibitor therapy, vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor therapy, Met tyrosine kinase inhibitor therapy, or Met monoclonal antibody (MetMAb); prior antibody therapy such as bevacizumab or cetuximab is allowed with a washout period depending on dosing interval and investigational nature
• Prior radiation therapy to the thoracic cavity, abdomen, or pelvis within 3 months prior to registration, to bone or brain metastasis within 14 days prior to registration, or to any other site within 28 days prior to registration
• History of the following: Clinically-significant gastrointestinal (GI) bleeding within 6 months prior to registration; Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months prior to registration; Any other signs indicative of pulmonary hemorrhage within 3 months prior to registration
• Radiographic or other evidence of the following within 28 days prior to registration:
• Tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor; Cavitating pulmonary lesion(s); Tumor in contact with, invading or encasing any major blood vessels
• Psychiatric illness/social situations that would limit compliance with study requirements
• History of major thrombotic events (deep vein thrombosis [DVT] or pulmonary embolism [PE]) within 6 months prior to registration
• Concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, low molecular weight heparin (LMWH), thrombin or Factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel). (low dose aspirin [=< 81 mg/day] and prophylactic LMWH are permitted)
• Concomitant treatment of strong cytochrome P450 3A4 (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; Any history of congenital long QT syndrome; 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
• GI disorders particularly those associated with a high risk of perforation or fistula formation specified in the protocol
• Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months prior to registration
• Uncontrolled, significant, intercurrent or recent illness
• Prior malignancy within 2 years prior to registration which required systemic treatment or is currently active
• Pregnant or breast-feeding
• Patients with known human immunodeficiency virus (HIV) disease taking antiretroviral therapy
• Known chronic active hepatitis B
• EXCLUSION CRITERIA (STEP 2):
• Intervening anticancer treatment or major surgical procedure(s) between Step 1 and Step 2, except palliative radiation to the bone finishing >= 2 weeks prior to registration to Step 2
• Central nervous system (CNS) progression; patients with stable CNS disease are allowed
• Intercurrent illness or disease complication that the investigator believes would limit the ability to safely tolerate the combination of erlotinib and cabozantinib

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Recurrent Lung Non-Small Cell Carcinoma
• Stage IV Lung Non-Small Cell Cancer AJCC v7

Intervention

Drug:
• Cabozantinib S-malate
Given PO
• Erlotinib Hydrochloride
Given PO

Other:
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
United States	Bixby Medical Center	Adrian	Michigan
United States	Hickman Cancer Center	Adrian	Michigan
United States	Summa Health System - Akron Campus	Akron	Ohio
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Dell Seton Medical Center at The University of Texas	Austin	Texas
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Ochsner Health Center-Summa	Baton Rouge	Louisiana
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Constantinou, Costas L MD (UIA Investigator)	Bettendorf	Iowa
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	IU Health Bloomington	Bloomington	Indiana
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	McFarland Clinic - Boone	Boone	Iowa
United States	Boulder Community Hospital	Boulder	Colorado
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Cleveland Clinic Mercy Hospital	Canton	Ohio
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	Northwestern University	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	Case Western Reserve University	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Columbus NCI Community Oncology Research Program	Columbus	Ohio
United States	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Carle at The Riverfront	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Atlanta VA Medical Center	Decatur	Georgia
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Heartland Cancer Research NCORP	Decatur	Illinois
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Delaware Radiation Oncology	Delaware	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Rose	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	Western States Cancer Research NCORP	Denver	Colorado
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Doylestown Hospital	Doylestown	Pennsylvania
United States	Mercy Medical Center	Durango	Colorado
United States	Veterans Adminstration New Jersey Health Care System	East Orange	New Jersey
United States	HSHS Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Elkhart Clinic	Elkhart	Indiana
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana
United States	Christiana Care - Union Hospital	Elkton	Maryland
United States	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado
United States	Swedish Medical Center	Englewood	Colorado
United States	UPMC Hillman Cancer Center Erie	Erie	Pennsylvania
United States	Green Bay Oncology - Escanaba	Escanaba	Michigan
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Clinic North-Fargo	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Fredericksburg Oncology Inc	Fredericksburg	Virginia
United States	Unity Hospital	Fridley	Minnesota
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	Mountain Blue Cancer Care Center	Golden	Colorado
United States	North Colorado Medical Center	Greeley	Colorado
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	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	Rocky Mountain Cancer Centers-Greenwood Village	Greenwood Village	Colorado
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Cancer and Blood Specialists-Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada
United States	GenesisCare USA - Henderson	Henderson	Nevada
United States	Las Vegas Cancer Center-Henderson	Henderson	Nevada
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Hematology Oncology Associates of Illinois-Highland Park	Highland Park	Illinois
United States	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	IU Health Central Indiana Cancer Centers-East	Indianapolis	Indiana
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	Allegiance Health	Jackson	Michigan
United States	McFarland Clinic - Jefferson	Jefferson	Iowa
United States	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Presence Saint Mary's Hospital	Kankakee	Illinois
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Community Howard Regional Health	Kokomo	Indiana
United States	IU Health La Porte Hospital	La Porte	Indiana
United States	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	University of Michigan Health - Sparrow Lansing	Lansing	Michigan
United States	Memorial Medical Center - Las Cruces	Las Cruces	New Mexico
United States	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada
United States	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada
United States	GenesisCare USA - Fort Apache	Las Vegas	Nevada
United States	GenesisCare USA - Las Vegas	Las Vegas	Nevada
United States	GenesisCare USA - Vegas Tenaya	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada
United States	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada
United States	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Beebe Medical Center	Lewes	Delaware
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	AMG Libertyville - Oncology	Libertyville	Illinois
United States	Lima Memorial Hospital	Lima	Ohio
United States	Saint Rita's Medical Center	Lima	Ohio
United States	Nebraska Cancer Research Center	Lincoln	Nebraska
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	McKee Medical Center	Loveland	Colorado
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Medical Center of Central Georgia	Macon	Georgia
United States	Dean Hematology and Oncology Clinic	Madison	Wisconsin
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Cancer Center of Kansas-Manhattan	Manhattan	Kansas
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	McFarland Clinic - Marshalltown	Marshalltown	Iowa
United States	Marshfield Medical Center	Marshfield	Wisconsin
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Cancer Center of Kansas - McPherson	McPherson	Kansas
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana
United States	Woodland Cancer Care Center	Michigan City	Indiana
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana
United States	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana
United States	Memorial Medical Center	Modesto	California
United States	Garneau, Stewart C MD (UIA Investigator)	Moline	Illinois
United States	Porubcin, Michael MD (UIA Investigator)	Moline	Illinois
United States	Spector, David MD (UIA Investigator)	Moline	Illinois
United States	Trinity Medical Center	Moline	Illinois
United States	Illinois CancerCare-Monmouth	Monmouth	Illinois
United States	Mercy Memorial Hospital	Monroe	Michigan
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	Community Hospital of Monterey Peninsula	Monterey	California
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Morristown Medical Center	Morristown	New Jersey
United States	Virtua Memorial	Mount Holly	New Jersey
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	IU Health Ball Memorial Hospital	Muncie	Indiana
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Ochsner Baptist Medical Center	New Orleans	Louisiana
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Christiana Gynecologic Oncology LLC	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Licking Memorial Hospital	Newark	Ohio
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Newark Radiation Oncology	Newark	Ohio
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Illinois Cancer Specialists-Niles	Niles	Illinois
United States	Carle Cancer Institute Normal	Normal	Illinois
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Saint Charles Hospital	Oregon	Ohio
United States	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	VA Palo Alto Health Care System	Palo Alto	California
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Parker Adventist Hospital	Parker	Colorado
United States	Rocky Mountain Cancer Centers-Parker	Parker	Colorado
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Illinois Valley Hospital	Peru	Illinois
United States	Einstein Medical Center Philadelphia	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Eisenhower Medical Center	Rancho Mirage	California
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Swedish American Hospital	Rockford	Illinois
United States	SwedishAmerican Regional Cancer Center/ACT	Rockford	Illinois
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Cancer Therapy and Research Center at The UT Health Science Center at San Antonio	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
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	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	South Bend Clinic	South Bend	Indiana
United States	Memorial Medical Center	Springfield	Illinois
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Overlook Hospital	Summit	New Jersey
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio
United States	Saint Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio
United States	University of Toledo	Toledo	Ohio
United States	University of Texas Health Science Center at Tyler	Tyler	Texas
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Inspira Medical Center Vineland	Vineland	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Ascension Saint Clare's Hospital	Weston	Wisconsin
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Michiana Hematology Oncology PC-Westville	Westville	Indiana
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Wheeling Hospital/Schiffler Cancer Center	Wheeling	West Virginia
United States	Dickstein Cancer Treatment Center	White Plains	New York
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Wichita NCI Community Oncology Research Program	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Aspirus Cancer Care - Wisconsin Rapids	Wisconsin Rapids	Wisconsin
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	Main Line Health NCORP	Wynnewood	Pennsylvania
United States	WellSpan Health-York Hospital	York	Pennsylvania
United States	York Hospital	York	Maine
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)	PFS is defined as the time from randomization to documented disease progression or death from any cause, whichever occurred first. Patients who had not experienced an event of interest by the time of analysis were censored at the date of last disease assessment.	Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry, up to 5 years
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to death from any cause or date of last known alive.	Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry, up to 5 years
Secondary	Proportion of Patients With Objective Response	Objective response is defined as complete response (CR) or partial response (PR) evaluated using RECIST v 1.1. CR is defined as disappearance of all lesions and any pathological lymph nodes must have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions and persistence of one or more non-target lesion(s).	Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry, up to 5 years
Secondary	Proportion of Patients With MET Positivity	Submission of archival tissue for central MET IHC testing was required for this study, and total MET IHC testing was conducted at the Brigham and Women's Hospital using the c-Met clone CVD13 (arabbit polyclonal). Membranous and cytoplasmic staining were individually scored, and positivity was declared if MET was expressed in either the membrane or cytoplasm.	Assessed at baseline
Secondary	Proportion of Patients With Worst Grade Toxicities of Grade 3 or Higher		Assessed every 4 weeks while on treatment and for 30 days after the end of treatment