Study of Dovitinib Versus Sorafenib in Patients With Metastatic Renal Cell Carcinoma

An Open-label, Randomized, Multi-center, Phase III Study to Compare the Safety and Efficacy of Dovitinib Versus Sorafenib in Patients With Metastatic Renal Cell Carcinoma After Failure of Anti-angiogenic (VEGF-targeted and mTOR Inhibitor) Therapies

This study will evaluate the safety and efficacy of Dovitinib versus sorafenib in patients with metastatic renal cell cancer.

Study Overview

• Status: Completed
• Conditions: Metastatic Renal Cell Carcinoma
• Intervention / Treatment: Drug: Dovitinib; Drug: Sorafenib

• Study Type: Interventional
• Enrollment (Actual): 564
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1050AAK
    • Novartis Investigative Site
  • Sante Fe
    • Rosario, Sante Fe, Argentina, S200DSK
      • Novartis Investigative Site
• Australia
  • New South Wales
    • St. Leonards, New South Wales, Australia, 2065
      • Novartis Investigative Site
    • Westmead, New South Wales, Australia, 2145
      • Novartis Investigative Site
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Novartis Investigative Site
  • South Australia
    • Woodville, South Australia, Australia, 5011
      • Novartis Investigative Site
  • Victoria
    • Footscray, Victoria, Australia, 3011
      • Novartis Investigative Site
    • Heidelberg, Victoria, Australia, 3084
      • Novartis Investigative Site
• Austria
  • Linz, Austria, A-4020
    • Novartis Investigative Site
  • Wien, Austria, 1090
    • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1200
    • Novartis Investigative Site
  • Bruxelles, Belgium, 1000
    • Novartis Investigative Site
  • Gent, Belgium, 9000
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
  • Liège, Belgium, 4000
    • Novartis Investigative Site
• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Novartis Investigative Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Novartis Investigative Site
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Novartis Investigative Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Novartis Investigative Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Novartis Investigative Site
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • Novartis Investigative Site
    • London, Ontario, Canada, N6A 4L6
      • Novartis Investigative Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H2L 4M1
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H2X 1N8
      • Novartis Investigative Site
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Novartis Investigative Site
• Colombia
  • Bogota, Colombia
    • Novartis Investigative Site
• Czech Republic
  • Brno, Czech Republic, 656 53
    • Novartis Investigative Site
  • Olomouc, Czech Republic, 775 20
    • Novartis Investigative Site
  • Praha 5, Czech Republic, 150 06
    • Novartis Investigative Site
• France
  • Besancon Cedex, France, 25030
    • Novartis Investigative Site
  • Bordeaux Cedex, France, 33075
    • Novartis Investigative Site
  • Caen Cedex, France, 14021
    • Novartis Investigative Site
  • Clermont-Ferrand, France, 63011
    • Novartis Investigative Site
  • Grenoble, France, 38043
    • Novartis Investigative Site
  • Lyon Cedex, France, 69373
    • Novartis Investigative Site
  • Marseille, France, 13273
    • Novartis Investigative Site
  • Nice Cedex 2, France, 06189
    • Novartis Investigative Site
  • Paris, France, 75015
    • Novartis Investigative Site
  • Paris Cedex 13, France, 75651
    • Novartis Investigative Site
  • Rennes Cedex, France, 35062
    • Novartis Investigative Site
  • Saint Priest en Jarez Cedex, France, 42271
    • Novartis Investigative Site
  • Saint-Herblain Cédex, France, 44805
    • Novartis Investigative Site
  • Strasbourg Cedex, France, F-67098
    • Novartis Investigative Site
  • Suresnes, France, 92150
    • Novartis Investigative Site
  • Toulouse Cedex 9, France, 31059
    • Novartis Investigative Site
  • Vandoeuvre-Les-Nancy Cede, France, 54511
    • Novartis Investigative Site
  • Villejuif Cedex, France, 94805
    • Novartis Investigative Site
• Germany
  • Aschaffenburg, Germany, 63739
    • Novartis Investigative Site
  • Berlin, Germany, 10098
    • Novartis Investigative Site
  • Chemnitz, Germany, 09119
    • Novartis Investigative Site
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
  • Greifswald, Germany, 17475
    • Novartis Investigative Site
  • Hamburg, Germany, 20246
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
  • Jena, Germany, 07740
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Marburg, Germany, 35039
    • Novartis Investigative Site
  • Muenster, Germany, 48149
    • Novartis Investigative Site
  • München, Germany, 81675
    • Novartis Investigative Site
  • Nuernberg, Germany, 90419
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
  • Weiden, Germany, 92637
    • Novartis Investigative Site
• Greece
  • Athens, Greece, 115 28
    • Novartis Investigative Site
  • GR
    • Athens, GR, Greece, 115 27
      • Novartis Investigative Site
    • Thessaloniki, GR, Greece, 546 45
      • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, H-1122
    • Novartis Investigative Site
  • Budapest, Hungary, 1086
    • Novartis Investigative Site
  • Debrecen, Hungary, 4032
    • Novartis Investigative Site
  • Pecs, Hungary, 7624
    • Novartis Investigative Site
  • Szolnok, Hungary, H-5000
    • Novartis Investigative Site
• Israel
  • Petach Tikva, Israel, 49100
    • Novartis Investigative Site
  • Ramat Gan, Israel, 5266202
    • Novartis Investigative Site
  • Zrifin, Israel, 70300
    • Novartis Investigative Site
• Italy
  • Napoli, Italy, 80132
    • Novartis Investigative Site
  • AR
    • Arezzo, AR, Italy, 52100
      • Novartis Investigative Site
  • CR
    • Cremona, CR, Italy, 26100
      • Novartis Investigative Site
  • FC
    • Meldola, FC, Italy, 47014
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20133
      • Novartis Investigative Site
  • MO
    • Modena, MO, Italy, 41100
      • Novartis Investigative Site
  • PV
    • Pavia, PV, Italy, 27100
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00152
      • Novartis Investigative Site
  • TO
    • Candiolo, TO, Italy, 10060
      • Novartis Investigative Site
• Japan
  • Chiba, Japan, 260-8717
    • Novartis Investigative Site
  • Osaka, Japan, 537-8511
    • Novartis Investigative Site
  • Yamagata, Japan, 990-9585
    • Novartis Investigative Site
  • Aichi
    • Nagoya-city, Aichi, Japan, 466-8560
      • Novartis Investigative Site
  • Ehime
    • Toon-city, Ehime, Japan, 791-0295
      • Novartis Investigative Site
  • Fukuoka
    • Fukuoka-city, Fukuoka, Japan, 812-8582
      • Novartis Investigative Site
  • Hiroshima
    • Hiroshima-city, Hiroshima, Japan, 734-8551
      • Novartis Investigative Site
  • Hokkaido
    • Obihiro, Hokkaido, Japan, 080-0016
      • Novartis Investigative Site
    • Sapporo-city, Hokkaido, Japan, 060-8648
      • Novartis Investigative Site
  • Hyogo
    • Kobe-city, Hyogo, Japan, 650-0017
      • Novartis Investigative Site
    • Kobe-city, Hyogo, Japan, 650-0047
      • Novartis Investigative Site
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-8515
      • Novartis Investigative Site
    • Yokohama-city, Kanagawa, Japan, 236 0037
      • Novartis Investigative Site
  • Kyoto
    • Kyoto-city, Kyoto, Japan, 602-8566
      • Novartis Investigative Site
  • Nagano
    • Matsumoto, Nagano, Japan, 390-8621
      • Novartis Investigative Site
  • Osaka
    • Osaka-city, Osaka, Japan, 545-8586
      • Novartis Investigative Site
    • OsakaSayama, Osaka, Japan, 589-8511
      • Novartis Investigative Site
    • Suita-city, Osaka, Japan, 565-0871
      • Novartis Investigative Site
    • Takatsuki-city, Osaka, Japan, 569-8686
      • Novartis Investigative Site
  • Saitama
    • Hidaka, Saitama, Japan, 350-1298
      • Novartis Investigative Site
    • Kitaadachi-gun, Saitama, Japan, 362-0806
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8603
      • Novartis Investigative Site
    • Koto, Tokyo, Japan, 135-8550
      • Novartis Investigative Site
    • Minato-ku, Tokyo, Japan, 105-8470
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 162-8666
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 160-8582
      • Novartis Investigative Site
• Korea, Republic of
  • Korea
    • Seoul, Korea, Korea, Republic of, 05505
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 06351
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 110 744
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 03722
      • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Novartis Investigative Site
  • Breda, Netherlands, 4818 CK
    • Novartis Investigative Site
  • Dordrecht, Netherlands, 3318AT
    • Novartis Investigative Site
  • Maastricht, Netherlands, 6229 HX
    • Novartis Investigative Site
  • Rotterdam, Netherlands, 3075 EA
    • Novartis Investigative Site
  • KR
    • Meerssen, KR, Netherlands, 6231
      • Novartis Investigative Site
• Norway
  • Bergen, Norway, -N5021
    • Novartis Investigative Site
  • Ålesund, Norway, NO-6026
    • Novartis Investigative Site
• Poland
  • Warszawa, Poland, 02-781
    • Novartis Investigative Site
  • Warszawa, Poland, 04-141
    • Novartis Investigative Site
• Saudi Arabia
  • Riyadh, Saudi Arabia, 11211
    • Novartis Investigative Site
• Slovakia
  • Slovak Republic
    • Bratislava, Slovak Republic, Slovakia, 83310
      • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Madrid, Spain, 28007
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Andalucia
    • Cordoba, Andalucia, Spain, 14004
      • Novartis Investigative Site
    • Malaga, Andalucia, Spain, 29010
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41014
      • Novartis Investigative Site
  • Asturias
    • Oviedo, Asturias, Spain, 33006
      • Novartis Investigative Site
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Novartis Investigative Site
  • Catalunya
    • Badalona, Catalunya, Spain, 08916
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08003
      • Novartis Investigative Site
    • Hospitalet de LLobregat, Catalunya, Spain, 08907
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Benidorm, Comunidad Valenciana, Spain, 03501
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46010
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46009
      • Novartis Investigative Site
  • Galicia
    • Santiago de Compostela, Galicia, Spain, 15706
      • Novartis Investigative Site
  • Islas Baleares
    • Palma De Mallorca, Islas Baleares, Spain, 07120
      • Novartis Investigative Site
  • Las Palmas de Gran Canaria
    • Las Palmas de Gran Canarias, Las Palmas de Gran Canaria, Spain, 35016
      • Novartis Investigative Site
  • Madrid
    • Alcorcon, Madrid, Spain, 28922
      • Novartis Investigative Site
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Novartis Investigative Site
• Sweden
  • Stockholm, Sweden, SE-171 76
    • Novartis Investigative Site
  • Sundsvall, Sweden, 851 86
    • Novartis Investigative Site
  • Umeå, Sweden, SE-901 85
    • Novartis Investigative Site
  • Uppsala, Sweden, SE-751 85
    • Novartis Investigative Site
• Switzerland
  • St. Gallen, Switzerland, 9007
    • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
• United Kingdom
  • Colchester, United Kingdom, CO3 3NB
    • Novartis Investigative Site
  • Leicester, United Kingdom, LE1 5WW
    • Novartis Investigative Site
  • London, United Kingdom, SW17 0QT
    • Novartis Investigative Site
  • London, United Kingdom, NW3 4QG
    • Novartis Investigative Site
  • Manchester, United Kingdom, M20 9BX
    • Novartis Investigative Site
  • Southampton, United Kingdom, SO16 6YD
    • Novartis Investigative Site
  • Avon
    • Bristol, Avon, United Kingdom, BS2 8ED
      • Novartis Investigative Site
  • Middlesex
    • Northwood, Middlesex, United Kingdom, HA6 2RN
      • Novartis Investigative Site
• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group Dept of Highlands Oncology Grp
  • California
    • La Jolla, California, United States, 92093-0658
      • University of California San Diego - Moores Cancer Center Dept of Moores Cancer Ctr (5)
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center Cedars Sinai Medical Ctr. (SC)
    • Los Angeles, California, United States, 90095
      • University of California at Los Angeles UCLA (4)
    • Stanford, California, United States, 94304
      • Stanford University Medical Center Cancer Clinical Trials Office
  • Colorado
    • Greenwood Village, Colorado, United States
      • Rocky Mountain Cancer Centers RMCC
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists DeptofFloridaCancerSpecialists
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer & Blood Center, LLC
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Straub Clinic & Hospital Straub
    • Honolulu, Hawaii, United States, 96817
      • Moanalua Medical Center. Attn: Oncology Dept
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center Univ of KS
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center UMMC
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute Dept.of KarmanosCancerInst (5)
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center - Fairview Univ of MN
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Comprehensive Cancer Centers of Nevada CCC of Nevada (1)
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • CINJ at Cooper University Hospital Cooper
  • New York
    • NY, New York, United States, 90033
      • Memorial Sloan Kettering Cancer Center Dept. of MSKCC
    • Syracuse, New York, United States, 13210
      • SUNY - Upstate Medical University Div. of Hematology-Oncology
    • Troy, New York, United States, 12180
      • New York Oncology Hematology, P.C. Dept. of New York Oncology. PC
  • Oregon
    • Eugene, Oregon, United States, 97404
      • Willamette Valley Clinical Studies Williamette Valley Cancer
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States
      • St. Luke's Hospital and Health Network St Luke's
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina -Hollings Cancer Center Med Univ SC
    • Greenville, South Carolina, United States, 29605
      • Cancer Centers of the Carolinas CC of C -Eastside
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Sarah Cannon Research Institute SC - 3
    • Memphis, Tennessee, United States, 38120
      • The West Clinic
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center SC
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Health Care System/Sammons Cancer Center Dept. of Sammons Cancer (4)
    • Dallas, Texas, United States, 75251
      • Texas Oncology Texas Onc - Austin
    • Dallas, Texas, United States, 75251
      • Texas Oncology Texas Oncology - Houston
    • Dallas, Texas, United States, 75390-9034
      • University of Texas Southwestern Medical Center UTSW
    • Webster, Texas, United States, 77598
      • Deke Slayton Cancer Center Deke Slayton Cancer Center (2)
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists Dept.of Utah Cancer Spec. (3)
  • Virginia
    • Charlottesville, Virginia, United States, 22908-0334
      • University of Virginia Health Systems Univ Virginia
  • Washington
    • Spokane, Washington, United States, 99202
      • Rockwood Clinic Spokane Location

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients with metastatic renal cell carcinoma (mRCC) with histological or cytological confirmation of clear cell carcinoma or a component of clear cell
• Patients must have received one and only one prior VEGF-targeted therapy and one and only one prior mTOR inhibitor therapy in the metastatic setting. One VEGF targeted therapy (e.g. sunitinib, or pazopanib, or axitinib, or tivozanib or bevacizumab) and one prior mTOR inhibitor therapy (everolimus, or temsirolimus or ridaforolimus)
• Prior cytokines therapy and prior vaccines in the adjuvant setting is permitted.
• Patients must have had disease progression on or within 6 months of stopping the last therapy.
• Patients must have at least one measurable lesion at baseline (by RECIST Criteria Guidelines v1.1) assessed by Computer Tomography (CT) Scan or Magnetic Resonance Imaging (MRI).
• Karnofsky performance status ≥ 70%

• Patients must have the following laboratory values:

  • Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
  • Platelets ≥ 100 x 109/L
  • Hemoglobin (Hgb) > 9 g/dL
  • Serum total bilirubin: ≤ 1.5 x ULN
  • ALT and AST ≤ 3.0 x ULN (Patients with known liver metastases: AST and ALT ≤ 5.0 x ULN)
  • Serum creatinine ≤ 1.5 x ULN

Exclusion Criteria:

• Patients who have previously received sorafenib therapy in the neoadjuvant, adjuvant or metastatic setting.
• Patients who have previously received Dovitinib or brivanib in the neoadjuvant, adjuvant or metastatic setting.
• Patients with brain metastases. Radiological imaging (e.g. CT or MRI scan) of the brain is required at screening/baseline
• Patients with another primary malignancy within 3 years prior to starting study treatment, with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma or non-melanomatous skin cancer, or in-situ carcinoma of the uterine cervix
• Patients who have received the last administration of an anticancer targeted small molecule therapy ≤ 2 weeks prior to starting study treatment (e.g. sunitinib, pazopanib, axitinib, everolimus, temsirolimus), or who have not recovered from the side effects of such therapy
• Patients who have received the last administration of nitrosurea or mitomycin-C ≤ 6 weeks prior to starting study treatment, or who have not recovered from the side effects of such therapy
• Patients who have undergone major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) ≤ 4 weeks prior to starting study treatment or who have not recovered from side effects of such therapy
• Patients with a history of pulmonary embolism (PE), or untreated deep venous thrombosis (DVT) within the past 6 months
• Patients with concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dovitinib + best supportive care (BSC); Patients randomized to the dovitinib treatment arm received 500 mg of dovitinib orally on 5 days on/2 days off dosing schedule.	Drug: Dovitinib; Dovitinib is formulated as an oral gelatin capsule of 100 mg strength and was dosed on a flat scale of 500 mg on a 5 days on/2 days off dosing schedule. Medication labels complied withthe legal requirements of each country and were printed in the local language.; Other Names: TKI258
Active Comparator: Sorafenib + BSC; Patients in the sorafenib control arm received400 mg of sorafenib (2 x 200 mg tablets) orally taken twice daily.	Drug: Sorafenib; Sorafenib is formulated as a round, oral, biconvex, red film-coated tablet that contains 200 mg of sorafenib (tosylate). Sorafenib was administered twice daily without food at least 1 hour before or 2 hours after a meal. Sorafenib was supplied according to local practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) Per Independent Central Radiology Review	Assessed according to RECIST 1.1. PFS was defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause. If a patient had not progressed or died, on the date of the analysis cut-off or when he/she received any further anti-neoplastic therapy, PFS was censored on the date of last tumor assessment before the cutoff date or the anti-neoplastic therapy date. The distribution of PFS was estimated using the Kaplan-Meier method. The median PFS along with 95% confidence intervals was presented by treatment group.	Until disease progression or discontinuation of treatment due to unacceptable toxicity up to 30-Jun-2014 (discontinuation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall survival (OS) was the key secondary endpoint and was defined as the time from date of randomization to the date of death due to any cause. If a patient was not known to have died, survival was censored on the date of last contact.	until at least 386 deaths are documented in the clinical database.
Progression Free Survival (PFS) Per Investigator's Radiology Review	PFS was defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause. The primary analysis for PFS (based on central review) was also to be repeated on FAS considering the Investigator assessments and using the same analytical conventions as the primary analysis.	Until disease progression or discontinuation of treatment due to unacceptable toxicity
Percentage of Participants With Overall Response Rate (ORR) by Central Radiology Review	Overall response rate (ORR) was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR). Best overall esponse (BOR) for each patient was determined from the sequence of overall (lesion) responses according to the following rules: CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required. CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required. SD = at least one SD assessment (or better) > 6 weeks after randomization (and not qualifying for CR or PR). PD = progression ≤ 17 weeks after randomization (and not qualifying for CR, PR or SD).	Until disease progression or discontinuation of treatment due to unacceptable toxicity
Time to Definitive Worsening of Karnofsky Performance Status (KPS)	Time to definitive worsening of Karnofsky performance status (KPS) was defined as the time from date of randomization to the date of definitive worsening of KPS or to the date of death whichever occurred earlier. Definitive worsening was defined as a definitive decrease in performance status by at least one Karnofsky category (i.e. at least 10 points less) compared to Baseline. Worsening was considered definitive if no later increase above the defined threshold was observed within the course of the study. A single measure reporting a decrease in Karnofsky performance status was sufficient to consider it as definitive only if it was the last one available for this patient. Time to definitive worsening of KPS was analyzed at the time of the final analysis for PFS.	from date of randomization to the date of definitive worsening of KPS or to the date of death whichever occurred earlier
Patient-reported Outcomes (PROs): Time to Deterioration of Functional Assessment of Cancer Therapy-Kidney Symptom Index, Disease Related Symptoms (FKSI-DRS) by at Least 2 Scores	The Kidney Cancer Symptom Index - Disease Related Symptoms (FKSI-DRS) is a validated symptom scale used in studies of patients with kidney cancer. It includes 9-items that assess pain, bone pain, fatigue, lack of energy, shortness of breath, fevers, weight loss, coughing, and blood in urine and responses to each question are answered on a 5-point Likert-type scale ranging from 0 to 4 (e.g., 0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). FKSI-DRS scores range from 0 to 36, where higher scores correspond to better outcomes (eg, fewer symptoms).	from date of randomization, at least 2 score units
Patient-reported Outcomes (PROs): Time to Definitive Deterioration of the Physical Functioning (PF) Scale of EORTC QLQ-C30 by at Least 10%	The EORTC QLQ-C30 contains 30 items and is composed of both multi-item scales and single-item measures. These include five functional scales (physical, role, emotional, social and cognitive functioning), three symptom scales (fatigue, pain, nausea, and vomiting), a global health status/QoL scale, and six single items (dyspnea, diarrhea, constipation, anorexia, insomnia and financial impact). Each of the multiitem scales includes a different set of items - no item occurs in more than one scale. Each item in the EORTC QLQ-C30 has 4 response categories (1=Not at all, 2= A little, 3= Quite a bit, 4= Very much) with the higher number representing a worse outcome.	from date of randomization
Patient-reported Outcomes (PROs): Time to Definitive Deterioration of the Quality of Life (QoL) Scale Scores of EORTC QLQ-C30 by at Least 10%	The EORTC QLQ-C30 contains 30 items and is composed of both multi-item scales and single-item measures. These include five functional scales (physical, role, emotional, social and cognitive functioning), three symptom scales (fatigue, pain, nausea, and vomiting), a global health status/QoL scale, and six single items (dyspnea, diarrhea, constipation, anorexia, insomnia and financial impact). Each of the multiitem scales includes a different set of items - no item occurs in more than one scale. Each item in the EORTC QLQ-C30 has 4 response categories (1=Not at all, 2= A little, 3= Quite a bit, 4= Very much) with the higher number representing a worse outcome.	from date of randomization
Pre-dose Concentration in Plasma in Dovitinib	Predose concentrations of dovitinib were summarized by visit using PAS. All concentration data was listed by patient and time point using FAS. Mean pre-dose concentrations along with standard deviation (SD) was plotted over time if appropriate.	Week 2 Day 5, Week 4 Day 5, Week 6 Day 5

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Motzer RJ, Porta C, Vogelzang NJ, Sternberg CN, Szczylik C, Zolnierek J, Kollmannsberger C, Rha SY, Bjarnason GA, Melichar B, De Giorgi U, Grunwald V, Davis ID, Lee JL, Esteban E, Urbanowitz G, Cai C, Squires M, Marker M, Shi MM, Escudier B. Dovitinib versus sorafenib for third-line targeted treatment of patients with metastatic renal cell carcinoma: an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Mar;15(3):286-96. doi: 10.1016/S1470-2045(14)70030-0. Epub 2014 Feb 17.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: September 30, 2010
• First Submitted That Met QC Criteria: October 15, 2010
• First Posted (Estimate): October 18, 2010

Study Record Updates

• Last Update Posted (Estimate): December 7, 2015
• Last Update Submitted That Met QC Criteria: November 5, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: mRCC; TKI; Renal cell cancer; Dovitinib; RCC
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: CTKI258A2302; 2009-015459-25 (EudraCT Number)