A Study of Cabozantinib (XL184) vs Everolimus in Subjects With Metastatic Renal Cell Carcinoma

NCT ID: NCT01865747

Last Updated: 2021-04-27

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

658 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-06-30

Study Completion Date

2021-01-15

Brief Summary

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The purpose of this study is to evaluate the effect of Cabozantinib (XL184) compared with Everolimus (Afinitor) on progression-free survival (PFS) and overall survival (OS) in subjects with advanced renal cell cancer that has progressed after prior VEGFR tyrosine kinase inhibitor therapy.

Detailed Description

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Conditions

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Renal Cell Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cabozantinib (XL184)

Cabozantinib (XL184) 60 mg tablet once daily.

Group Type EXPERIMENTAL

Cabozantinib tablets

Intervention Type DRUG

Everolimus (Afinitor)

Everolimus (Afinitor) 10 mg tablet once daily.

Group Type ACTIVE_COMPARATOR

Everolimus (Afinitor) tablets

Intervention Type DRUG

Interventions

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Cabozantinib tablets

Intervention Type DRUG

Everolimus (Afinitor) tablets

Intervention Type DRUG

Other Intervention Names

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XL184

Eligibility Criteria

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Inclusion Criteria

1. Documented histological or cytological diagnosis of renal cell cancer with a clear-cell component.
2. Measurable disease as determined by the investigator.
3. Must have received at least one VEGFR-targeting TKI (eg, sorafenib, sunitinib, axitinib, pazopanib or tivozanib).
4. Recovery from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
5. Adequate organ and marrow function.
6. Sexually active fertile subjects(male and female)must agree to use medically accepted methods of contraception during the course of the study and for 4 months after the last dose of study treatment.
7. Female subjects of childbearing potential must not be pregnant at screening.

Exclusion Criteria

1. Prior treatment with everolimus, or any other specific or selective TORC1/PI3K/AKT inhibitor (eg, temsirolimus), or cabozantinib.
2. Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before randomization.
3. Receipt of any type of anticancer antibody (including investigational antibody) within 4 weeks before randomization.
4. Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before randomization. Systemic treatment with radionuclides within 6 weeks before randomization. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
5. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery and stable for at least 3 months before randomization.
6. Concomitant anticoagulation at therapeutic doses with oral anticoagulants or platelet inhibitors.
7. Chronic treatment with corticosteroids or other immunosuppressive agents.
8. Serious illness other than cancer.
9. Major surgery within 3 months before randomization. Complete wound healing from major surgery must have occurred 1 month before randomization and from minor surgery at least 10 days before randomization.
10. Pregnant or lactating females.
11. Diagnosis of another malignancy within 2 years before randomization, except for superficial skin cancers, or localized, low grade tumors.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Exelixis

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Birmingham, Alabama, United States

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Anchorage, Alaska, United States

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Gilbert, Arizona, United States

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Scottsdale, Arizona, United States

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Tucson, Arizona, United States

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Duarte, California, United States

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La Jolla, California, United States

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Los Angeles, California, United States

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Los Angeles, California, United States

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Vallejo, California, United States

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Aurora, Colorado, United States

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Denver, Colorado, United States

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New Haven, Connecticut, United States

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Washington D.C., District of Columbia, United States

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Boca Raton, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Iowa City, Iowa, United States

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Westwood, Kansas, United States

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Baltimore, Maryland, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Detroit, Michigan, United States

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Detroit, Michigan, United States

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Rochester, Minnesota, United States

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St Louis, Missouri, United States

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Las Vegas, Nevada, United States

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Albany, New York, United States

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New York, New York, United States

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Durham, North Carolina, United States

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Cleveland, Ohio, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Portland, Oregon, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Charleston, South Carolina, United States

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Knoxville, Tennessee, United States

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Memphis, Tennessee, United States

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Nashville, Tennessee, United States

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Nashville, Tennessee, United States

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Austin, Texas, United States

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Bedford, Texas, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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Salt Lake City, Utah, United States

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Seattle, Washington, United States

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Vancouver, Washington, United States

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Yakima, Washington, United States

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La Plata, Buenos Aires, Argentina

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Mar del Plata, , Argentina

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Concord, New South Wales, Australia

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Darlinghurst, New South Wales, Australia

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Kogarah, New South Wales, Australia

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Port Macquarie, New South Wales, Australia

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Randwick, New South Wales, Australia

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Wahroonga, New South Wales, Australia

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Westmead, New South Wales, Australia

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Milton, Queensland, Australia

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Wooloongabba, Queensland, Australia

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Adelaide, South Australia, Australia

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Hobart, Tasmania, Australia

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Bentleight East, Victoria, Australia

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Box Hill, Victoria, Australia

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Wodonga, Victoria, Australia

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Linz, Upper Austria, Austria

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Vienna, , Austria

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Vienna, , Austria

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Bonheiden, Antwerpen, Belgium

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Brasschaat, Antwerpen, Belgium

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Brussels, Brussels Capital, Belgium

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Leuven, Vlaams Brabant, Belgium

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Roeselare, West-Vlaanderen, Belgium

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Antwerp, , Belgium

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Liège, , Belgium

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Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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Vancouver, British Columbia, Canada

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Winnepeg, Manitoba, Canada

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Halifax, Nova Scotia, Canada

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Hamilton, Ontario, Canada

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Kingston, Ontario, Canada

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London, Ontario, Canada

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Oshawa, Ontario, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Saskatoon, Saskatchewan, Canada

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Santiago, , Chile

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Olomouc, Olomoucký kraj, Czechia

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Brno, , Czechia

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Prague, , Czechia

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Herlev, Capital Region, Denmark

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Aarhus, Central Jutland, Denmark

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Odense, Region Syddanmark, Denmark

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Turku, Länsi-Suomen Lääni, Finland

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Helsinki, , Finland

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Caen, Calvados, France

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Besançon, Doubs, France

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Bordeaux, Gironde, France

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Toulouse, Haute-Garonne, France

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Rennes, Ille-et-Vilaine, France

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Nantes, Loire-Atlantique, France

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Lyon, Rhône, France

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Le Mans, Sarthe, France

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Villejuif, Val-de-Marne, France

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Marseille, , France

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Paris, , France

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Freiburg im Breisgau, Baden Wuttemberg, Germany

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Tübingen, Baden-Wurttemberg, Germany

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Ulm, Baden-Wurttemberg, Germany

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Erlangen, Bavaria, Germany

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Aachen, North Rhine-Westphalia, Germany

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Essen, North Rhine-Westphalia, Germany

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Mainz, Rhineland-Palatinate, Germany

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Erfurt, Thuringia, Germany

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Jena, Thuringia, Germany

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Berlin, , Germany

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Dresden, , Germany

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Frankfurt am Main, , Germany

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Gütersloh, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Heidelberg, , Germany

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Munich, , Germany

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München, , Germany

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Budapest, , Hungary

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Szolnok, , Hungary

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Dublin, , Ireland

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Dublin, , Ireland

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Bari, Apulia, Italy

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Meldola, Emilia-Romagna, Italy

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Modena, Emilia-Romagna, Italy

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Ravenna, Emilia-Romagna, Italy

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Rome, Lazio, Italy

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Rome, Lazio, Italy

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Genoa, Liguria, Italy

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Cremona, Lombardy, Italy

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Arezzo, Tuscany, Italy

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Terni, Umbria, Italy

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Maastricht, Limburg, Netherlands

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Amsterdam, North Holland, Netherlands

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Leiden, South Holland, Netherlands

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Rotterdam, South Holland, Netherlands

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Poznan, Greater Poland Voivodeship, Poland

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Bialystok, Podlaskie Voivodeship, Poland

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Gdansk, Pomeranian Voivodeship, Poland

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Warsaw, , Poland

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Lisbon, , Portugal

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Lisbon, , Portugal

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Porto, , Portugal

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Moscow, , Russia

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Omsk, , Russia

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Saint Petersburg, , Russia

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Yaroslavl, , Russia

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Prešov, , Slovakia

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Žilina, , Slovakia

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Badalona, Catalonia, Spain

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Barcelona, Catalonia, Spain

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L'Hospitalet de Llobregat, Catalonia, Spain

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Pamplona, Navarre, Spain

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Oviedo, Principality of Asturias, Spain

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Barcelona, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Santiago de Compostela, , Spain

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Seville, , Spain

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Valencia, , Spain

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Lund, Skåne County, Sweden

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Stockholm, Södermanland County, Sweden

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Umeå, , Sweden

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Taichung, , Taiwan

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Taipei, , Taiwan

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Ankara, , Turkey (Türkiye)

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Gaziantep, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Birmingham, England, United Kingdom

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Derby, England, United Kingdom

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Guildford, England, United Kingdom

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London, England, United Kingdom

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London, England, United Kingdom

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London, England, United Kingdom

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Manchester, England, United Kingdom

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Metropolitan Borough of Wirral, England, United Kingdom

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Northwood, England, United Kingdom

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Aberdeen, Scotland, United Kingdom

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Edinburgh, Scotland, United Kingdom

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Glasgow, Scotland, United Kingdom

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Countries

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United States Argentina Australia Austria Belgium Canada Chile Czechia Denmark Finland France Germany Hungary Ireland Italy Netherlands Poland Portugal Russia Slovakia South Korea Spain Sweden Taiwan Turkey (Türkiye) United Kingdom

References

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Gong AJ, Ruchalski K, Kim HJ, Douek M, Gutierrez A, Patel M, Sai V, Coy H, Villegas B, Raman S, Goldin J. RECIST 1.1 Target Lesion Categorical Response in Metastatic Renal Cell Carcinoma: A Comparison of Conventional versus Volumetric Assessment. Radiol Imaging Cancer. 2023 Sep;5(5):e220166. doi: 10.1148/rycan.220166.

Reference Type DERIVED
PMID: 37656041 (View on PubMed)

Denize T, Farah S, Cimadamore A, Flaifel A, Walton E, Sticco-Ivins MA, Labaki C, Braun DA, Sun M, Wang E, Xie W, Choueiri TK, Signoretti S. Biomarkers of Angiogenesis and Clinical Outcomes to Cabozantinib and Everolimus in Patients with Metastatic Renal Cell Carcinoma from the Phase III METEOR Trial. Clin Cancer Res. 2022 Feb 15;28(4):748-755. doi: 10.1158/1078-0432.CCR-21-3088.

Reference Type DERIVED
PMID: 34921022 (View on PubMed)

Powles T, Choueiri TK, Motzer RJ, Jonasch E, Pal S, Tannir NM, Signoretti S, Kaldate R, Scheffold C, Wang E, Aftab DT, Escudier B, George DJ. Outcomes based on plasma biomarkers in METEOR, a randomized phase 3 trial of cabozantinib vs everolimus in advanced renal cell carcinoma. BMC Cancer. 2021 Aug 7;21(1):904. doi: 10.1186/s12885-021-08630-w.

Reference Type DERIVED
PMID: 34364385 (View on PubMed)

Donskov F, Motzer RJ, Voog E, Hovey E, Grullich C, Nott LM, Cuff K, Gil T, Jensen NV, Chevreau C, Negrier S, Depenbusch R, Bergmann L, Cornelio I, Champsaur A, Escudier B, Pal S, Powles T, Choueiri TK. Outcomes based on age in the phase III METEOR trial of cabozantinib versus everolimus in patients with advanced renal cell carcinoma. Eur J Cancer. 2020 Feb;126:1-10. doi: 10.1016/j.ejca.2019.10.032. Epub 2019 Dec 27.

Reference Type DERIVED
PMID: 31887537 (View on PubMed)

Flaifel A, Xie W, Braun DA, Ficial M, Bakouny Z, Nassar AH, Jennings RB, Escudier B, George DJ, Motzer RJ, Morris MJ, Powles T, Wang E, Huang Y, Freeman GJ, Choueiri TK, Signoretti S. PD-L1 Expression and Clinical Outcomes to Cabozantinib, Everolimus, and Sunitinib in Patients with Metastatic Renal Cell Carcinoma: Analysis of the Randomized Clinical Trials METEOR and CABOSUN. Clin Cancer Res. 2019 Oct 15;25(20):6080-6088. doi: 10.1158/1078-0432.CCR-19-1135. Epub 2019 Aug 1.

Reference Type DERIVED
PMID: 31371341 (View on PubMed)

Cella D, Escudier B, Tannir NM, Powles T, Donskov F, Peltola K, Schmidinger M, Heng DYC, Mainwaring PN, Hammers HJ, Lee JL, Roth BJ, Marteau F, Williams P, Baer J, Mangeshkar M, Scheffold C, Hutson TE, Pal S, Motzer RJ, Choueiri TK. Quality of Life Outcomes for Cabozantinib Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma: METEOR Phase III Randomized Trial. J Clin Oncol. 2018 Mar 10;36(8):757-764. doi: 10.1200/JCO.2017.75.2170. Epub 2018 Jan 29.

Reference Type DERIVED
PMID: 29377755 (View on PubMed)

Escudier B, Powles T, Motzer RJ, Olencki T, Aren Frontera O, Oudard S, Rolland F, Tomczak P, Castellano D, Appleman LJ, Drabkin H, Vaena D, Milwee S, Youkstetter J, Lougheed JC, Bracarda S, Choueiri TK. Cabozantinib, a New Standard of Care for Patients With Advanced Renal Cell Carcinoma and Bone Metastases? Subgroup Analysis of the METEOR Trial. J Clin Oncol. 2018 Mar 10;36(8):765-772. doi: 10.1200/JCO.2017.74.7352. Epub 2018 Jan 8.

Reference Type DERIVED
PMID: 29309249 (View on PubMed)

Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, Rini BI, Hammers HJ, Donskov F, Roth BJ, Peltola K, Lee JL, Heng DYC, Schmidinger M, Agarwal N, Sternberg CN, McDermott DF, Aftab DT, Hessel C, Scheffold C, Schwab G, Hutson TE, Pal S, Motzer RJ; METEOR investigators. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016 Jul;17(7):917-927. doi: 10.1016/S1470-2045(16)30107-3. Epub 2016 Jun 5.

Reference Type DERIVED
PMID: 27279544 (View on PubMed)

Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, Hammers H, Hutson TE, Lee JL, Peltola K, Roth BJ, Bjarnason GA, Geczi L, Keam B, Maroto P, Heng DY, Schmidinger M, Kantoff PW, Borgman-Hagey A, Hessel C, Scheffold C, Schwab GM, Tannir NM, Motzer RJ; METEOR Investigators. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015 Nov 5;373(19):1814-23. doi: 10.1056/NEJMoa1510016. Epub 2015 Sep 25.

Reference Type DERIVED
PMID: 26406150 (View on PubMed)

Other Identifiers

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XL184-308

Identifier Type: -

Identifier Source: org_study_id

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