Pazopanib Versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma

NCT ID: NCT00720941

Last Updated: 2025-03-30

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1110 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-08-14

Study Completion Date

2021-03-24

Brief Summary

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This was a randomized, open-label, parallel group Phase III non inferiority study to evaluate the efficacy and safety of pazopanib compared with sunitinib in subjects with advanced renal cell carcinoma (RCC) who had not received prior systemic therapy for advanced or metastatic RCC.

Detailed Description

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Approximately 876 eligible subjects (approximately 438 per treatment arm) were planned to be enrolled over the course of the study. However, due to higher than expected withdrawal rates and discordance rates between independent review committee (IRC) and investigator assessments of progression, the protocol was amended (Protocol Amendment 4) to increase the number of subjects to approximately 1100 total by including all subjects enrolled in CPZP034A2301 (hereafter referred as Study A2301) and CPZP034A2201 (a sub study of CPZP034A2301, hereafter referred as Study A2201 with NCT01147822).

The subjects were centrally randomized in 1:1 ratio to receive either 800mg pazopanib to be administered once daily orally continuous dosing or 50mg sunitinib to be administered in 6-week cycles: 50mg orally daily for 4 weeks followed by 2 weeks off treatment. Subjects were permitted to receive supportive care throughout the study including transfusion of blood and blood products, treatment with antibiotics, anti-emetics, anti-diarrheal agents, analgesics, erythropoietin, or bisphosphonates, when appropriate. The study treatment continued until subjects experience disease progression, unacceptable toxicity, withdraw consent, or death.

Conditions

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Carcinoma, Renal Cell

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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Sunitinib

Control arm

Group Type ACTIVE_COMPARATOR

Sunitinib

Intervention Type DRUG

50 mg sunitinib to be administered in 6-week cycles: 50mg orally daily for 4 weeks followed by 2 weeks off treatment

Pazopanib

Experimental arm

Group Type EXPERIMENTAL

Pazopanib

Intervention Type DRUG

800 mg administered once daily orally continuous dosing

Interventions

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Pazopanib

800 mg administered once daily orally continuous dosing

Intervention Type DRUG

Sunitinib

50 mg sunitinib to be administered in 6-week cycles: 50mg orally daily for 4 weeks followed by 2 weeks off treatment

Intervention Type DRUG

Other Intervention Names

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GW786034

Eligibility Criteria

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Inclusion Criteria

* Written informed consent
* Diagnosis of renal cell carcinoma with clear-cell component histology.
* Received no prior systemic therapy (interleukin-2, interferon-alpha, chemotherapy, bevacizumab, mTOR inhibitor, sunitinib, sorafenib or other VEGF TKI) for advanced or metastatic RCC
* Locally advanced or metastatic renal cell carcinoma
* Measurable disease by CT or MRI
* Karnofsky performance scale status of \>=70
* Age \>=18 years
* A female is eligible to enter and participate in this study if she is of: non-childbearing or agrees to use adequate contraception.
* Adequate organ system function
* Total serum calcium concentration \<12.0mg/dL
* Left ventricular ejection fraction \>= lower limit of institutional normal.

Exclusion Criteria

* Pregnant or lactating female (unless agrees to refrain from nursing throughout the treatment period and for 14 days following the last dose of study)
* History of another malignancy (unless have been disease-free for 3 years)
* History or clinical evidence of central nervous system (CNS) metastases (unless have previously-treated CNS metastases and meet all 3 of the following criteria are: are asymptomatic, have had no evidence of active CNS metastases for \>=6 months prior to enrolment, and have no requirement for steroids or enzyme-inducing anticonvulsants)
* Clinically significant gastrointestinal abnormalities including, but not limited to: malabsorption syndrome, major resection of the stomach or small bowel that could affect the absorption of study drug, active peptic ulcer disease, known intraluminal metastatic lesion/s with suspected bleeding, Inflammatory bowel disease, ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation, history of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
* Presence of uncontrolled infection.
* Prolongation of corrected QT interval (QTc) \> 480 milliseconds
* History of any one or more of the following cardiovascular conditions within the past 12 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery by-pass graft surgery, symptomatic peripheral vascular disease, Class III or IV congestive heart failure, as defined by the New York Heart Association
* History of cerebrovascular accident including transient ischemic attack within the past 12 months
* History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months (unless had recent DVT and have been treated with therapeutic anti-coagulating agents for at least 6 weeks)
* Poorly controlled hypertension (defined as systolic blood pressure of \>=150mmHg or diastolic blood pressure of \>=90mmHg). Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry
* Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
* Evidence of active bleeding or bleeding susceptibility
* Spitting/coughing up blood within 6 weeks of first dose of study drug
* Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
* Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with patient's safety, obtaining informed consent or compliance to the study.
* Use any prohibited medications within 14 days of the first dose of study medication.
* Use of an investigational agent, including an investigational anti-cancer agent, within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug.
* Prior use of an investigational or licensed drug that targets VEGF or VEGF receptors (eg. bevacizumab, sunitinib, sorafenib, etc), or are mTOR inhibitors (eg. temsirolimus, everolimus, etc).
* Is now undergoing and/or has undergone in the 14 days immediately prior to first dose of study drug, any cancer therapy (surgery, tumor embolization, chemotherapy, radiation therapy, immunotherapy, biological therapy, or hormonal therapy)
* Any ongoing toxicity from prior anti-cancer therapy that is \>Grade 1 and/or that is progressing in severity.
* Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or sunitinib.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Huntsville, Alabama, United States

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Tucson, Arizona, United States

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Little Rock, Arkansas, United States

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Beverly Hills, California, United States

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Escondido, California, United States

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Fresno, California, United States

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Greenbrae, California, United States

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Hayward, 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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Montebello, California, United States

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Oakland, California, United States

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Orange, California, United States

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Roseville, California, United States

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Sacramento, California, United States

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Sacramento, California, United States

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San Bernardino, California, United States

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San Francisco, California, United States

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San Jose, California, United States

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Santa Clara, California, United States

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South San Francisco, California, United States

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Vallejo, California, United States

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Walnut Creek, California, United States

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Denver, Colorado, United States

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Southington, Connecticut, United States

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Trumbull, Connecticut, United States

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

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Fort Myers, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Elk Grove Village, Illinois, United States

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Peoria, Illinois, United States

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Carmel, Indiana, United States

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Indianapolis, Indiana, United States

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Cedar Rapids, Iowa, United States

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Louisville, Kentucky, United States

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Paducah, Kentucky, United States

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Annapolis, Maryland, United States

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Boston, Massachusetts, United States

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Tupelo, Mississippi, United States

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Charlottesville, Virginia, United States

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Hampton, Virginia, United States

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Camperdown, New South Wales, Australia

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Westmead, New South Wales, Australia

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Bedford Park, South Australia, Australia

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Hobart, Tasmania, Australia

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Heidelberg, Victoria, Australia

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Wodonga, Victoria, Australia

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Calgary, Alberta, Canada

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Moncton, New Brunswick, Canada

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Guangzhou, Guangdong, China

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Nanjing, Jiangsu, China

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Beijing, , China

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Tianjin, , China

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Kirchheim, Baden-Wurttemberg, Germany

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Sigmaringen, Baden-Wurttemberg, Germany

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Stuttgart, Baden-Wurttemberg, Germany

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Munich, Bavaria, Germany

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Planegg, Bavaria, Germany

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Marburg, Hesse, Germany

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Offenbach, Hesse, Germany

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Hanover, Lower Saxony, Germany

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Aachen, North Rhine-Westphalia, Germany

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Bonn, North Rhine-Westphalia, Germany

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Dortmund, North Rhine-Westphalia, Germany

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Duisburg, North Rhine-Westphalia, Germany

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Düsseldorf, North Rhine-Westphalia, Germany

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Essen, North Rhine-Westphalia, Germany

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Homburg, Saarland, Germany

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Dresden, Saxony, Germany

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Leipzig, Saxony, Germany

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Plauen, Saxony, Germany

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Eisleben Lutherstadt, Saxony-Anhalt, Germany

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Magdeburg, Saxony-Anhalt, Germany

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Berlin, , Germany

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Berlin, , Germany

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Dublin, , Ireland

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Dublin, , Ireland

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Galway, , Ireland

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Tallaght, Dublin, , Ireland

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Napoli, Campania, Italy

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Meldola (FC), Emilia-Romagna, Italy

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Ravenna, Emilia-Romagna, Italy

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Pordenone, Friuli Venezia Giulia, Italy

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Rome, Lazio, Italy

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Milan, Lombardy, Italy

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Arezzo, Tuscany, Italy

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Ehime, , Japan

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Fukuoka, , Japan

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Hokkaido, , Japan

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Ibaraki, , Japan

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Okayama, , Japan

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Osaka, , Japan

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Shizuoka, , Japan

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Tokyo, , Japan

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Yamagata, , Japan

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Alkmaar, , Netherlands

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Amsterdam, , Netherlands

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Groningen, , Netherlands

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Sittard-geleen, , Netherlands

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The Hague, , Netherlands

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Tilburg, , Netherlands

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Utrecht, , Netherlands

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Daegu, , South Korea

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Daejeon, , South Korea

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Goyang-si, Gyeonggi-Do, , South Korea

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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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Seoul, , South Korea

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Badalona, , Spain

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Barakaldo (Vizcaya), , Spain

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Barcelona, , Spain

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Girona, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Pamplona, , Spain

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Lund, , Sweden

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Stockholm, , Sweden

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Uppsala, , Sweden

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Kaohsiung Hsien, , Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taoyuan District, , Taiwan

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Bristol, Gloucestershire, United Kingdom

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Northwood, Middlesex, United Kingdom

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Bebington, Wirral, , United Kingdom

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Birmingham, , United Kingdom

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Cambridge, , United Kingdom

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Glasgow, , United Kingdom

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Leeds, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Nottingham, , United Kingdom

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Sheffield, , United Kingdom

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Swansea, , United Kingdom

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Countries

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United States Australia Canada China Germany Ireland Italy Japan Netherlands South Korea Spain Sweden Taiwan United Kingdom

References

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Reference Type DERIVED
PMID: 26457466 (View on PubMed)

Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, Boleti E, Fife K, Jin J, Jones R, Uemura H, De Giorgi U, Harmenberg U, Wang J, Sternberg CN, Deen K, McCann L, Hackshaw MD, Crescenzo R, Pandite LN, Choueiri TK. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013 Aug 22;369(8):722-31. doi: 10.1056/NEJMoa1303989.

Reference Type DERIVED
PMID: 23964934 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2008-002102-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CPZP034A2301

Identifier Type: OTHER

Identifier Source: secondary_id

VEG108844

Identifier Type: OTHER

Identifier Source: secondary_id

108844

Identifier Type: -

Identifier Source: org_study_id

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