Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy

Clear Cell Renal Cell Carcinoma Clinical Trial

Official title:

Randomized Phase III Trial Comparing Everolimus Versus Everolimus Plus Bevacizumab for Advanced Renal Cell Carcinoma Progressing After Treatment With Tyrosine Kinase Inhibitors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01198158
• Other study ID #: NCI-2011-02603
• Secondary ID: NCI-2011-02603CD
• Status: Terminated
• Phase: Phase 3
• Start date: September 15, 2010
• Est. completion date: December 16, 2017

Study information

• Verified date: March 2019
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase III trial studies giving everolimus together with bevacizumab to see how well it works compared to everolimus alone in treating patients with advanced kidney cancer that progressed after first-line therapy. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can interfere with tumor growth by blocking the ability of tumor cells to grow and spread. Everolimus and bevacizumab may also stop the growth of kidney cancer by blocking blood flow to the tumor. It is not yet known whether giving everolimus together with bevacizumab is better than everolimus alone in treating patients with advanced kidney cancer that has progressed after first-line therapy.

Description:

PRIMARY OBJECTIVES:

l. To compare the overall survival of patients receiving bevacizumab plus everolimus and everolimus alone among patients with advanced renal cell carcinoma progressing after first line vascular epidermal growth factor receptor (VEGFR)-tyrosine kinase inhibitor (TKI) treatment.

SECONDARY OBJECTIVES:

I. To compare the progression-free survival and proportion who experience an objective response (defined as complete clinical response [cCR] + partial response [PR]) in patients with advanced renal cell carcinoma receiving bevacizumab plus everolimus and everolimus alone.

II. To compare grade 3 or higher toxicity in patients receiving each treatment regimen.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive everolimus orally (PO) once daily (QD) on days 1-28.

ARM II: Patients receive everolimus PO QD on days 1-28 and bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 8 weeks until disease progression and then every 6 months for up to 5.5 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 77
• Est. completion date: December 16, 2017
• Est. primary completion date: December 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Renal cell carcinoma with some component of clear cell histology

• Metastatic or unresectable disease

• Must have been treated with at least 1 prior VEGFR tyrosine kinase inhibitor treatment and have progressed or have been intolerant to treatment

• No prior systemic therapy with a vascular endothelial growth factor (VEGF) binding agent (e.g., bevacizumab)

• No prior systemic therapy with any mechanistic target of rapamycin (mTOR) inhibitor (e.g., sirolimus, temsirolimus, everolimus)

• Prior cytokine therapy is allowed

• Any systemic therapy must be completed at least 4 weeks prior to registration

• >= 2 weeks since any prior radiation (including palliative)

• Patients must not have had a major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks prior to study registration, and must have fully recovered from any such procedure

• The following are not considered to be major procedures: thoracentesis, paracentesis, port placement, laparoscopy, thoracoscopy, bronchoscopy, endoscopic ultrasonographic procedures, mediastinoscopy, skin biopsies, incisional biopsies and routine dental procedures

• Patients must have measurable disease by RECIST criteria; lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 2 cm with conventional techniques or as >= 1 cm with spiral computed tomography (CT) scan

• No active brain metastases: patients with treated, stable brain metastases for at least three months are eligible as long as they meet the following criteria:

• Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 3 months, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or CT) (stable dose of anticonvulsants are allowed); treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, linear accelerator [LINAC], or equivalent) or a combination as deemed appropriate by the treating physician; patients with central nervous system (CNS) metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to day 1 are not eligible

• Baseline brain imaging (MRI/CT) is required

• No serious non-healing wound, ulcer, or bone fracture

• No arterial thrombotic events within 6 months of registration:

• Including transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus, unstable angina or angina requiring surgical or medical intervention in the past 6 months, or myocardial infarction (MI); patients with clinically significant peripheral artery disease (i.e., claudication on less than one block), significant vascular disease (i.e., aortic aneurysm, history of aortic dissection), or any other arterial thrombotic event are ineligible

• Patients who have experienced a deep venous thrombosis or pulmonary embolus within the past 6 months must be on stable therapeutic anticoagulation to be enrolled to this study

• Patients receiving anti-platelet agents and prophylactic anticoagulation are eligible

• No inadequately controlled hypertension: (defined as a blood pressure of >= 160 mmHg systolic and/or >= 90 mmHg diastolic on medication), or any prior history of hypertensive crisis or hypertensive encephalopathy

• No known severe impairment of lung function, defined as >= grade 2 dyspnea or cough, or either:

• Requirement of supplemental oxygen, or

• In cases where pulmonary function or pulse oximetry tests have been obtained, forced expiratory volume of the lung in one second (FEV1) or forced vital capacity (FVC) are < 50% of predicted, or single breath diffusing capacity of the lung for carbon monoxide (DLCO) is < 35% of predicted or resting room oxygen saturation is less than 90%

• No active or severe liver disease (e.g. acute or chronic hepatitis, cirrhosis)

• No positive serology for anti-hemoglobin C (HBC) or anti-hepatitis C virus (HCV) antibodies; hepatitis B virus (HBV) seropositive patients (hepatitis B surface antigen [HBsAg] positive) are eligible if they are closely monitored for evidence of active HBV infection by HBV deoxryribonucleic acid (DNA) testing and agree to receive suppressive therapy with lamivudine or other HBV-suppressive therapy until at least 4 weeks after the last dose of everolimus

• No New York Heart Association (NYHA) class >= 2 congestive heart failure

• No active bleeding or chronic hemorrhagic diathesis or increased risk for bleeding:

Including but not limited to history of major bleeding within 6 months (e.g. gastrointestinal, lung, CNS sites; or required transfusion support)

• No history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to the initiation of treatment

• No ongoing immunosuppressive therapy: including chronic systemic treatment with corticosteroids (>= 10 mg/day prednisone equivalent)

• Archival tissue must be available for submission: though it is optional patients to choose to participate in the correlative substudies or not

• Patients who are pregnant or nursing are not eligible

• Women of child bearing potential must have a negative serum or urine pregnancy test within 16 days prior to registration

• Women of child-bearing potential include:

• Any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea >= 12 consecutive months)

• Women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35m IU/mL

• Women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy)

• Performance status Eastern Cooperative Oncology Group (ECOG) 0-2 or Karnofsky score >= 60%

• Granulocytes >= 1,500/µL

• Platelet count >= 100,000/µL

• Calculated creatinine clearance >= 30 mL/minute (modified Cockroft and Gault formula)

• Bilirubin =< 1.5 x upper limits of normal

• Aspartate aminotransferase (AST) =< 2.5 x upper limits of normal (ULN)

• Fasting serum triglycerides =< 200 mg/dL

• Serum cholesterol =< 300 mg/dL

• Fasting serum glucose =< 1.5 x ULN

• Urine protein to creatinine ratio < 1.0 or urine protein =< 1+

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Clear Cell Renal Cell Carcinoma
• Recurrent Renal Cell Carcinoma
• Stage III Renal Cell Cancer AJCC v7
• Stage IV Renal Cell Cancer AJCC v7

Intervention

Biological:
• Bevacizumab
Given IV

Drug:
• Everolimus
Given PO

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Pharmacological Study
Correlative studies

Locations

Country	Name	City	State
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Bixby Medical Center	Adrian	Michigan
United States	Hickman Cancer Center	Adrian	Michigan
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio
United States	Phoebe Putney Memorial Hospital	Albany	Georgia
United States	Medini, Eitan MD (UIA Investigator)	Alexandria	Minnesota
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	Kaiser Permanente-Anaheim	Anaheim	California
United States	Langlade Hospital and Cancer Center	Antigo	Wisconsin
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	Fox Valley Hematology and Oncology SC-Appleton	Appleton	Wisconsin
United States	PCR Oncology	Arroyo Grande	California
United States	Mission Hospital Inc-Memorial Campus	Asheville	North Carolina
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Kaiser Permanente-Baldwin Park	Baldwin Park	California
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Summa Barberton Hospital	Barberton	Ohio
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	McLaren Cancer Institute-Bay City	Bay City	Michigan
United States	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana
United States	Kaiser Permanente-Bellflower	Bellflower	California
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	University of Iowa Healthcare Cancer Services Quad Cities	Bettendorf	Iowa
United States	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	Saint Vincent Frontier Cancer Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Mid Dakota Clinic	Bismarck	North Dakota
United States	Saint Alexius Medical Center	Bismarck	North Dakota
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Saint Luke's Mountain States Tumor Institute	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Boulder Community Hospital	Boulder	Colorado
United States	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Cox Cancer Center Branson	Branson	Missouri
United States	Steward Saint Elizabeth's Medical Center	Brighton	Massachusetts
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Veterans Affairs Western New York Health Care System-Buffalo	Buffalo	New York
United States	Mills-Peninsula Medical Center	Burlingame	California
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	University of Vermont College of Medicine	Burlington	Vermont
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Butler Memorial Hospital	Butler	Pennsylvania
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Graham Hospital Association	Canton	Illinois
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Mercy Medical Center	Canton	Ohio
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	East Bay Radiation Oncology Center	Castro Valley	California
United States	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Physicians' Clinic of Iowa PC	Cedar Rapids	Iowa
United States	Saint Luke's Hospital	Cedar Rapids	Iowa
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Roper Hospital	Charleston	South Carolina
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	Saint Luke's Hospital	Chesterfield	Missouri
United States	Jesse Brown Veterans Affairs Medical Center	Chicago	Illinois
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	Presence Resurrection Medical Center	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Weiss Memorial Hospital	Chicago	Illinois
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	University of Cincinnati/Barrett Cancer Center	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	North Coast Cancer Care-Clyde	Clyde	Ohio
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	University of Missouri - Ellis Fischel	Columbia	Missouri
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Carolinas HealthCare System NorthEast	Concord	North Carolina
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton NCI Community Oncology Research Program	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Health Center	Dayton	Ohio
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Heartland Cancer Research NCORP	Decatur	Illinois
United States	Colorado Cancer Research Program NCORP	Denver	Colorado
United States	Kaiser Permanente-Franklin	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	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	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Greenville Health System Cancer Institute-Easley	Easley	South Carolina
United States	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York
United States	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin
United States	Fairview-Southdale Hospital	Edina	Minnesota
United States	Elkhart Clinic	Elkhart	Indiana
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Hematology Oncology Center Incorporated	Elyria	Ohio
United States	Mercy Cancer Center-Elyria	Elyria	Ohio
United States	Bay Area Breast Surgeons Inc	Emeryville	California
United States	Epic Care Partners in Cancer Care	Emeryville	California
United States	Swedish Medical Center	Englewood	Colorado
United States	Ephrata Cancer Center	Ephrata	Pennsylvania
United States	Green Bay Oncology - Escanaba	Escanaba	Michigan
United States	Eureka Hospital	Eureka	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Saint Francis Hospital	Federal Way	Washington
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	McLaren Cancer Institute-Flint	Flint	Michigan
United States	Singh and Arora Hematology Oncology PC	Flint	Michigan
United States	Kaiser Permanente-Fontana	Fontana	California
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana
United States	Radiation Oncology Associates PC	Fort Wayne	Indiana
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Aurora Cancer Care-Franklin	Franklin	Wisconsin
United States	Fredericksburg Oncology Inc	Fredericksburg	Virginia
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Valley Medical Oncology Consultants-Fremont	Fremont	California
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Mountain States Tumor Institute - Fruitland	Fruitland	Idaho
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	Aurora Cancer Care-Glendale	Glendale	Wisconsin
United States	Glens Falls Hospital	Glens Falls	New York
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Big Sky Oncology	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
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	Greenville Health System Cancer Institute-Butternut	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Eastside	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina
United States	Greenville Memorial Hospital	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Self Regional Healthcare	Greenwood	South Carolina
United States	Greenville Health System Cancer Institute-Greer	Greer	South Carolina
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Kaiser Permanente - Harbor City	Harbor City	California
United States	Hartford Hospital	Hartford	Connecticut
United States	Illinois CancerCare-Havana	Havana	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Northern Montana Hospital	Havre	Montana
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Hawaii Cancer Care Inc-POB II	Honolulu	Hawaii
United States	Hawaii Oncology Inc-Kuakini	Honolulu	Hawaii
United States	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	Edwards Comprehensive Cancer Center	Huntington	West Virginia
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Franciscan Health Indianapolis	Indianapolis	Indiana
United States	Iowa City VA Healthcare System	Iowa City	Iowa
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	Kaiser Permanente-Irvine	Irvine	California
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	Fowler Family Center for Cancer Care	Jonesboro	Arkansas
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Jupiter Medical Center	Jupiter	Florida
United States	Castle Medical Center	Kailua	Hawaii
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Glacier Oncology PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Presence Saint Mary's Hospital	Kankakee	Illinois
United States	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Providence Medical Center	Kansas City	Kansas
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Joseph Health Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Truman Medical Center	Kansas City	Missouri
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee
United States	Vidant Oncology-Kinston	Kinston	North Carolina
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	University of Tennessee - Knoxville	Knoxville	Tennessee
United States	Community Howard Regional Health	Kokomo	Indiana
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	AMITA Health Adventist Medical Center	La Grange	Illinois
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	IU Health La Porte Hospital	La Porte	Indiana
United States	Kaiser Permanente-Rock Creek	Lafayette	Colorado
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	McLaren Cancer Institute-Lapeer Region	Lapeer	Michigan
United States	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Beebe Medical Center	Lewes	Delaware
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Liberty Radiation Oncology Center	Liberty	Missouri
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Lima Memorial Hospital	Lima	Ohio
United States	Saint Rita's Medical Center	Lima	Ohio
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Kaiser Permanente-Cadillac	Los Angeles	California
United States	McKee Medical Center	Loveland	Colorado
United States	Centra Lynchburg Hematology-Oncology Clinic Inc	Lynchburg	Virginia
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Mcdonough District Hospital	Macomb	Illinois
United States	Medical Center of Central Georgia	Macon	Georgia
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	Bay Area Medical Center	Marinette	Wisconsin
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Contra Costa Regional Medical Center	Martinez	California
United States	Saint Luke's Hospital	Maumee	Ohio
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Riddle Memorial Hospital	Media	Pennsylvania
United States	Saint Luke's Mountain States Tumor Institute - Meridian	Meridian	Idaho
United States	Premier Oncology Hematology Associates	Merrillville	Indiana
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Orange Regional Medical Center	Middletown	New York
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Minneapolis Veterans 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	Montana Cancer Specialists	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Memorial Medical Center	Modesto	California
United States	Holy Family Medical Center	Monmouth	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	University Health-Conway	Monroe	Louisiana
United States	McLaren Cancer Institute-Macomb	Mount Clemens	Michigan
United States	Virtua Memorial	Mount Holly	New Jersey
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	El Camino Hospital	Mountain View	California
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	Saint Luke's Mountain States Tumor Institute - Nampa	Nampa	Idaho
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Louisiana State University Health Science Center	New Orleans	Louisiana
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Weill Medical College of Cornell University	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Lakeland Hospital Niles	Niles	Michigan
United States	Bromenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center Foundation	Normal	Illinois
United States	Illinois CancerCare-Community Cancer Center	Normal	Illinois
United States	Cancer Care Associates-Norman	Norman	Oklahoma
United States	Great Plains Health Callahan Cancer Center	North Platte	Nebraska
United States	Southwest VA Regional Cancer Center	Norton	Virginia
United States	Fisher-Titus Medical Center	Norwalk	Ohio
United States	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut
United States	Sutter Cancer Research Consortium	Novato	California
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Tumor Institute	Oakland	California
United States	Hematology and Oncology Associates-Oakland	Oakland	California
United States	Highland General Hospital	Oakland	California
United States	Kaiser Permanente Oakland-Broadway	Oakland	California
United States	Kaiser Permanente-Oakland	Oakland	California
United States	Tom K Lee Inc	Oakland	California
United States	Green Bay Oncology - Oconto Falls	Oconto Falls	Wisconsin
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	Mercy Physicians of Oklahoma-Lakeside	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Providence - Saint Peter Hospital	Olympia	Washington
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	21st Century Oncology-Orange Park	Orange Park	Florida
United States	Saint Charles Hospital	Oregon	Ohio
United States	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	Florida Hospital Orlando	Orlando	Florida
United States	UF Cancer Center at Orlando Health	Orlando	Florida
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	Kaiser Permanente - Panorama City	Panorama City	California
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Parker Adventist Hospital	Parker	Colorado
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Sacred Heart Hospital	Pensacola	Florida
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Illinois Valley Hospital	Peru	Illinois
United States	McLaren Cancer Institute-Northern Michigan	Petoskey	Michigan
United States	Berkshire Hematology Oncology PC	Pittsfield	Massachusetts
United States	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana
United States	Adventist Medical Center	Portland	Oregon
United States	Compass Oncology Rose Quarter	Portland	Oregon
United States	Kaiser Permanente Northwest	Portland	Oregon
United States	Legacy Emanuel Hospital and Health Center	Portland	Oregon
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	Kaiser Permanente-Rancho Cordova Cancer Center	Rancho Cordova	California
United States	Kaiser Permanente-Redwood City	Redwood City	California
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Clinic-Rice Lake Center	Rice Lake	Wisconsin
United States	Kaiser Permanente-Richmond	Richmond	California
United States	Reid Health	Richmond	Indiana
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	West Suburban Medical Center	River Forest	Illinois
United States	Kaiser Permanente-Riverside	Riverside	California
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Swedish American Hospital	Rockford	Illinois
United States	Rohnert Park Cancer Center	Rohnert Park	California
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Kaiser Permanente-Roseville	Roseville	California
United States	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California
United States	Kaiser Permanente - Sacramento	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	South Sacramento Cancer Center	Sacramento	California
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Saint Joseph Oncology Inc	Saint Joseph	Missouri
United States	Comprehensive Cancer Care PC	Saint Louis	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
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	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Kaiser Permanente-San Diego Mission	San Diego	California
United States	Kaiser Permanente-San Diego Zion	San Diego	California
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	UCSF Medical Center-Mount Zion	San Francisco	California
United States	Zuckerberg San Francisco General Hospital	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Kaiser Permanente-San Marcos	San Marcos	California
United States	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California
United States	Kaiser Permanente-San Rafael	San Rafael	California
United States	North Coast Cancer Care	Sandusky	Ohio
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Sutter Pacific Medical Foundation	Santa Rosa	California
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Hematology and Oncology Associates of North East Pennsylvania	Scranton	Pennsylvania
United States	Greenville Health System Cancer Institute-Seneca	Seneca	South Carolina
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Shawnee Mission Medical Center-KCCC	Shawnee Mission	Kansas
United States	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Highland Clinic	Shreveport	Louisiana
United States	Louisiana State University Health Sciences Center Shreveport	Shreveport	Louisiana
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	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Avera McKennan Hospital and University Health Center	Sioux Falls	South Dakota
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	Kaiser Permanente Cancer Treatment Center	South San Francisco	California
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina
United States	Rockwood Clinic	Spokane	Washington
United States	Illinois CancerCare-Spring Valley	Spring Valley	Illinois
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Cancer Research for the Ozarks NCORP	Springfield	Missouri
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Stamford Hospital/Bennett Cancer Center	Stamford	Connecticut
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Staten Island University Hospital	Staten Island	New York
United States	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	MultiCare Allenmore Hospital	Tacoma	Washington
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Northwest NCI Community Oncology Research Program	Tacoma	Washington
United States	Saint Joseph Medical Center	Tacoma	Washington
United States	Mid-Columbia Medical Center/Celilo Cancer Center	The Dalles	Oregon
United States	North Suburban Medical Center	Thornton	Colorado
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	Mercy Saint Anne Hospital	Toledo	Ohio
United States	Saint Vincent Mercy Medical Center	Toledo	Ohio
United States	The Toledo Hospital/Toledo Children's Hospital	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	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	Upper Valley Medical Center	Troy	Ohio
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	Saint Luke's Mountain States Tumor Institute-Twin Falls	Twin Falls	Idaho
United States	Associates In Hematology Oncology PC-Upland	Upland	Pennsylvania
United States	Carle Cancer Center	Urbana	Illinois
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	Compass Oncology Vancouver	Vancouver	Washington
United States	Legacy Salmon Creek Hospital	Vancouver	Washington
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Virtua Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Maui Memorial Medical Center	Wailuku	Hawaii
United States	Pacific Cancer Institute of Maui	Wailuku	Hawaii
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Marion L Shepard Cancer Center at Vidant Beaufort Hospital	Washington	North Carolina
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	Aurora Cancer Care-Waukesha	Waukesha	Wisconsin
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Fulton County Health Center	Wauseon	Ohio
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Cleveland Clinic-Weston	Weston	Florida
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin
United States	Michiana Hematology Oncology PC-Westville	Westville	Indiana
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	White River Junction Veteran Administration Medical Center	White River Junction	Vermont
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	UPMC Susquehanna	Williamsport	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Aspirus UW Cancer Center	Wisconsin Rapids	Wisconsin
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Kaiser Permanente-Woodland Hills	Woodland Hills	California
United States	University of Massachusetts Medical School	Worcester	Massachusetts
United States	Wright-Patterson Medical Center	Wright-Patterson Air Force Base	Ohio
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	Main Line Health NCORP	Wynnewood	Pennsylvania
United States	Metro Health Hospital	Wyoming	Michigan
United States	Greene Memorial Hospital	Xenia	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	Overall Survival (OS)	Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.	The time from date of randomization to date of death due to any cause, assessed up to 5.5 years
Secondary	Progression-free Survival (PFS)	Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.	The time from randomization to disease progression or death from any cause, assessed up to 5.5 years
Secondary	Objective Response Rate (CR + PR)	The response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients.	Up to 5.5 years
Secondary	Toxicities, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0	The number of patients reporting grade 3 or higher adverse events as graded by the NCI's Common Toxicity Criteria (CTCAE) Version 4 are reported here. A complete list of all reported adverse events is reported in the Adverse Events section of this report.	Up to 30 days after completion of study treatment