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

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01223027
Collaborator
(none)
564
Enrollment
199
Locations
2
Arms
39
Duration (Months)
2.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
564 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Study Start Date :
Mar 1, 2011
Actual Primary Completion Date :
Jun 1, 2014
Actual Study Completion Date :
Jun 1, 2014

Arms and Interventions

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.

    Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival (PFS) Per Independent Central Radiology Review [Until disease progression or discontinuation of treatment due to unacceptable toxicity up to 30-Jun-2014 (discontinuation)]

      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.

    Secondary Outcome Measures

    1. Overall Survival (OS) [until at least 386 deaths are documented in the clinical database.]

      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.

    2. Progression Free Survival (PFS) Per Investigator's Radiology Review [Until disease progression or discontinuation of treatment due to unacceptable toxicity]

      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.

    3. Percentage of Participants With Overall Response Rate (ORR) by Central Radiology Review [Until disease progression or discontinuation of treatment due to unacceptable toxicity]

      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).

    4. Time to Definitive Worsening of Karnofsky Performance Status (KPS) [from date of randomization to the date of definitive worsening of KPS or to the date of death whichever occurred earlier]

      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.

    5. 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 [from date of randomization, at least 2 score units]

      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).

    6. Patient-reported Outcomes (PROs): Time to Definitive Deterioration of the Physical Functioning (PF) Scale of EORTC QLQ-C30 by at Least 10% [from date of randomization]

      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.

    7. Patient-reported Outcomes (PROs): Time to Definitive Deterioration of the Quality of Life (QoL) Scale Scores of EORTC QLQ-C30 by at Least 10% [from date of randomization]

      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.

    8. Pre-dose Concentration in Plasma in Dovitinib [Week 2 Day 5, Week 4 Day 5, Week 6 Day 5]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Highlands Oncology Group Dept of Highlands Oncology Grp Fayetteville Arkansas United States 72703
    2 University of California San Diego - Moores Cancer Center Dept of Moores Cancer Ctr (5) La Jolla California United States 92093-0658
    3 Cedars Sinai Medical Center Cedars Sinai Medical Ctr. (SC) Los Angeles California United States 90048
    4 University of California at Los Angeles UCLA (4) Los Angeles California United States 90095
    5 Stanford University Medical Center Cancer Clinical Trials Office Stanford California United States 94304
    6 Rocky Mountain Cancer Centers RMCC Greenwood Village Colorado United States
    7 Florida Cancer Specialists DeptofFloridaCancerSpecialists Fort Myers Florida United States 33901
    8 University Cancer & Blood Center, LLC Athens Georgia United States 30607
    9 Straub Clinic & Hospital Straub Honolulu Hawaii United States 96813
    10 Moanalua Medical Center. Attn: Oncology Dept Honolulu Hawaii United States 96817
    11 University of Kansas Cancer Center Univ of KS Kansas City Kansas United States 66160
    12 University of Maryland Medical Center UMMC Baltimore Maryland United States 21201
    13 Karmanos Cancer Institute Dept.of KarmanosCancerInst (5) Detroit Michigan United States 48201
    14 University of Minnesota Medical Center - Fairview Univ of MN Minneapolis Minnesota United States 55455
    15 Comprehensive Cancer Centers of Nevada CCC of Nevada (1) Las Vegas Nevada United States 89109
    16 CINJ at Cooper University Hospital Cooper Voorhees New Jersey United States 08043
    17 Memorial Sloan Kettering Cancer Center Dept. of MSKCC NY New York United States 90033
    18 SUNY - Upstate Medical University Div. of Hematology-Oncology Syracuse New York United States 13210
    19 New York Oncology Hematology, P.C. Dept. of New York Oncology. PC Troy New York United States 12180
    20 Willamette Valley Clinical Studies Williamette Valley Cancer Eugene Oregon United States 97404
    21 St. Luke's Hospital and Health Network St Luke's Bethlehem Pennsylvania United States
    22 Medical University of South Carolina -Hollings Cancer Center Med Univ SC Charleston South Carolina United States 29425
    23 Cancer Centers of the Carolinas CC of C -Eastside Greenville South Carolina United States 29605
    24 Sarah Cannon Research Institute SC - 3 Chattanooga Tennessee United States 37404
    25 The West Clinic Memphis Tennessee United States 38120
    26 Vanderbilt University Medical Center SC Nashville Tennessee United States 37232
    27 Baylor Health Care System/Sammons Cancer Center Dept. of Sammons Cancer (4) Dallas Texas United States 75246
    28 Texas Oncology Texas Onc - Austin Dallas Texas United States 75251
    29 Texas Oncology Texas Oncology - Houston Dallas Texas United States 75251
    30 University of Texas Southwestern Medical Center UTSW Dallas Texas United States 75390-9034
    31 Deke Slayton Cancer Center Deke Slayton Cancer Center (2) Webster Texas United States 77598
    32 Utah Cancer Specialists Dept.of Utah Cancer Spec. (3) Salt Lake City Utah United States 84106
    33 University of Virginia Health Systems Univ Virginia Charlottesville Virginia United States 22908-0334
    34 Rockwood Clinic Spokane Location Spokane Washington United States 99202
    35 Novartis Investigative Site Rosario Sante Fe Argentina S200DSK
    36 Novartis Investigative Site Buenos Aires Argentina C1050AAK
    37 Novartis Investigative Site St. Leonards New South Wales Australia 2065
    38 Novartis Investigative Site Westmead New South Wales Australia 2145
    39 Novartis Investigative Site South Brisbane Queensland Australia 4101
    40 Novartis Investigative Site Woodville South Australia Australia 5011
    41 Novartis Investigative Site Footscray Victoria Australia 3011
    42 Novartis Investigative Site Heidelberg Victoria Australia 3084
    43 Novartis Investigative Site Linz Austria A-4020
    44 Novartis Investigative Site Wien Austria 1090
    45 Novartis Investigative Site Bruxelles Belgium 1000
    46 Novartis Investigative Site Bruxelles Belgium 1200
    47 Novartis Investigative Site Gent Belgium 9000
    48 Novartis Investigative Site Leuven Belgium 3000
    49 Novartis Investigative Site Liège Belgium 4000
    50 Novartis Investigative Site Porto Alegre RS Brazil 90610-000
    51 Novartis Investigative Site Calgary Alberta Canada T2N 4N2
    52 Novartis Investigative Site Edmonton Alberta Canada T6G 1Z2
    53 Novartis Investigative Site Vancouver British Columbia Canada V5Z 4E6
    54 Novartis Investigative Site Halifax Nova Scotia Canada B3H 2Y9
    55 Novartis Investigative Site Hamilton Ontario Canada L8N 4A6
    56 Novartis Investigative Site London Ontario Canada N6A 4L6
    57 Novartis Investigative Site Ottawa Ontario Canada K1H 8L6
    58 Novartis Investigative Site Toronto Ontario Canada M4N 3M5
    59 Novartis Investigative Site Toronto Ontario Canada M5G 2M9
    60 Novartis Investigative Site Montreal Quebec Canada H2L 4M1
    61 Novartis Investigative Site Montreal Quebec Canada H2X 1N8
    62 Novartis Investigative Site Montreal Quebec Canada H3T 1E2
    63 Novartis Investigative Site Saskatoon Saskatchewan Canada S7N 4H4
    64 Novartis Investigative Site Bogota Colombia
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    66 Novartis Investigative Site Olomouc Czech Republic 775 20
    67 Novartis Investigative Site Praha 5 Czech Republic 150 06
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    89 Novartis Investigative Site Erlangen Germany 91054
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    94 Novartis Investigative Site Jena Germany 07740
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    97 Novartis Investigative Site Muenster Germany 48149
    98 Novartis Investigative Site München Germany 81675
    99 Novartis Investigative Site Nuernberg Germany 90419
    100 Novartis Investigative Site Ulm Germany 89081
    101 Novartis Investigative Site Weiden Germany 92637
    102 Novartis Investigative Site Athens GR Greece 115 27
    103 Novartis Investigative Site Thessaloniki GR Greece 546 45
    104 Novartis Investigative Site Athens Greece 115 28
    105 Novartis Investigative Site Budapest Hungary 1086
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    107 Novartis Investigative Site Debrecen Hungary 4032
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    110 Novartis Investigative Site Petach Tikva Israel 49100
    111 Novartis Investigative Site Ramat Gan Israel 5266202
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    114 Novartis Investigative Site Cremona CR Italy 26100
    115 Novartis Investigative Site Meldola FC Italy 47014
    116 Novartis Investigative Site Milano MI Italy 20133
    117 Novartis Investigative Site Modena MO Italy 41100
    118 Novartis Investigative Site Pavia PV Italy 27100
    119 Novartis Investigative Site Roma RM Italy 00152
    120 Novartis Investigative Site Candiolo TO Italy 10060
    121 Novartis Investigative Site Napoli Italy 80132
    122 Novartis Investigative Site Nagoya-city Aichi Japan 466-8560
    123 Novartis Investigative Site Toon-city Ehime Japan 791-0295
    124 Novartis Investigative Site Fukuoka-city Fukuoka Japan 812-8582
    125 Novartis Investigative Site Hiroshima-city Hiroshima Japan 734-8551
    126 Novartis Investigative Site Obihiro Hokkaido Japan 080-0016
    127 Novartis Investigative Site Sapporo-city Hokkaido Japan 060-8648
    128 Novartis Investigative Site Kobe-city Hyogo Japan 650-0017
    129 Novartis Investigative Site Kobe-city Hyogo Japan 650-0047
    130 Novartis Investigative Site Yokohama-city Kanagawa Japan 236 0037
    131 Novartis Investigative Site Yokohama Kanagawa Japan 241-8515
    132 Novartis Investigative Site Kyoto-city Kyoto Japan 602-8566
    133 Novartis Investigative Site Matsumoto Nagano Japan 390-8621
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    137 Novartis Investigative Site Takatsuki-city Osaka Japan 569-8686
    138 Novartis Investigative Site Hidaka Saitama Japan 350-1298
    139 Novartis Investigative Site Kitaadachi-gun Saitama Japan 362-0806
    140 Novartis Investigative Site Bunkyo-ku Tokyo Japan 113-8603
    141 Novartis Investigative Site Koto Tokyo Japan 135-8550
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    145 Novartis Investigative Site Chiba Japan 260-8717
    146 Novartis Investigative Site Osaka Japan 537-8511
    147 Novartis Investigative Site Yamagata Japan 990-9585
    148 Novartis Investigative Site Seoul Korea Korea, Republic of 03722
    149 Novartis Investigative Site Seoul Korea Korea, Republic of 05505
    150 Novartis Investigative Site Seoul Korea Korea, Republic of 06351
    151 Novartis Investigative Site Seoul Korea Korea, Republic of 110 744
    152 Novartis Investigative Site Meerssen KR Netherlands 6231
    153 Novartis Investigative Site Amsterdam Netherlands 1081 HV
    154 Novartis Investigative Site Breda Netherlands 4818 CK
    155 Novartis Investigative Site Dordrecht Netherlands 3318AT
    156 Novartis Investigative Site Maastricht Netherlands 6229 HX
    157 Novartis Investigative Site Rotterdam Netherlands 3075 EA
    158 Novartis Investigative Site Bergen Norway -N5021
    159 Novartis Investigative Site Ålesund Norway NO-6026
    160 Novartis Investigative Site Warszawa Poland 02-781
    161 Novartis Investigative Site Warszawa Poland 04-141
    162 Novartis Investigative Site Riyadh Saudi Arabia 11211
    163 Novartis Investigative Site Bratislava Slovak Republic Slovakia 83310
    164 Novartis Investigative Site Cordoba Andalucia Spain 14004
    165 Novartis Investigative Site Malaga Andalucia Spain 29010
    166 Novartis Investigative Site Sevilla Andalucia Spain 41014
    167 Novartis Investigative Site Oviedo Asturias Spain 33006
    168 Novartis Investigative Site Sabadell Barcelona Spain 08208
    169 Novartis Investigative Site Badalona Catalunya Spain 08916
    170 Novartis Investigative Site Barcelona Catalunya Spain 08003
    171 Novartis Investigative Site Barcelona Catalunya Spain 08035
    172 Novartis Investigative Site Barcelona Catalunya Spain 08036
    173 Novartis Investigative Site Hospitalet de LLobregat Catalunya Spain 08907
    174 Novartis Investigative Site Benidorm Comunidad Valenciana Spain 03501
    175 Novartis Investigative Site Valencia Comunidad Valenciana Spain 46009
    176 Novartis Investigative Site Valencia Comunidad Valenciana Spain 46010
    177 Novartis Investigative Site Santiago de Compostela Galicia Spain 15706
    178 Novartis Investigative Site Palma De Mallorca Islas Baleares Spain 07120
    179 Novartis Investigative Site Las Palmas de Gran Canarias Las Palmas de Gran Canaria Spain 35016
    180 Novartis Investigative Site Alcorcon Madrid Spain 28922
    181 Novartis Investigative Site Pamplona Navarra Spain 31008
    182 Novartis Investigative Site Barcelona Spain 08041
    183 Novartis Investigative Site Madrid Spain 28007
    184 Novartis Investigative Site Madrid Spain 28040
    185 Novartis Investigative Site Madrid Spain 28041
    186 Novartis Investigative Site Stockholm Sweden SE-171 76
    187 Novartis Investigative Site Sundsvall Sweden 851 86
    188 Novartis Investigative Site Umeå Sweden SE-901 85
    189 Novartis Investigative Site Uppsala Sweden SE-751 85
    190 Novartis Investigative Site St. Gallen Switzerland 9007
    191 Novartis Investigative Site Bangkok Thailand 10700
    192 Novartis Investigative Site Bristol Avon United Kingdom BS2 8ED
    193 Novartis Investigative Site Northwood Middlesex United Kingdom HA6 2RN
    194 Novartis Investigative Site Colchester United Kingdom CO3 3NB
    195 Novartis Investigative Site Leicester United Kingdom LE1 5WW
    196 Novartis Investigative Site London United Kingdom NW3 4QG
    197 Novartis Investigative Site London United Kingdom SW17 0QT
    198 Novartis Investigative Site Manchester United Kingdom M20 9BX
    199 Novartis Investigative Site Southampton United Kingdom SO16 6YD

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01223027
    Other Study ID Numbers:
    • CTKI258A2302
    • 2009-015459-25
    First Posted:
    Oct 18, 2010
    Last Update Posted:
    Dec 7, 2015
    Last Verified:
    Nov 1, 2015
    Keywords provided by Novartis Pharmaceuticals
    Dovitinib
    TKI
    Renal cell cancer
    RCC
    mRCC
    Additional relevant MeSH terms:
    Carcinoma
    Carcinoma, Renal Cell
    Sorafenib

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Dovitinib + Best Supportive Care (BSC) Sorafenib + BSC
    Arm/Group Description Patients randomized to the dovitinib treatment arm received 500 mg of dovitinib taken orally on 5 days on/2 days off dosing schedule. Patients in the sorafenib control arm received 400 mg of sorafenib (2 x 200 mg tablets) taken orally twice daily.
    Period Title: Overall Study
    STARTED 284 286
    COMPLETED 10 9
    NOT COMPLETED 274 277

    Baseline Characteristics

    Arm/Group Title Dovitinib + Best Supportive Care (BSC) Sorafenib + BSC Total
    Arm/Group Description Patients randomized to the dovitinib treatment arm received 500 mg of dovitinib taken orally on 5 days on/2 days off dosing schedule. Patients in the sorafenib control arm received 400 mg of sorafenib (2 x 200 mg tablets) taken orally twice daily. Total of all reporting groups
    Overall Participants 284 286 570
    Age, Customized (Number) [Number]
    < 65 years
    187
    65.8%
    165
    57.7%
    352
    61.8%
    >= 65 years
    97
    34.2%
    121
    42.3%
    218
    38.2%
    Sex: Female, Male (Count of Participants)
    Female
    71
    25%
    67
    23.4%
    138
    24.2%
    Male
    213
    75%
    219
    76.6%
    432
    75.8%
    Race/Ethnicity, Customized (Number) [Number]
    Caucasian
    233
    82%
    232
    81.1%
    465
    81.6%
    Asian
    42
    14.8%
    40
    14%
    82
    14.4%
    Black
    3
    1.1%
    5
    1.7%
    8
    1.4%
    Unknown
    1
    0.4%
    6
    2.1%
    7
    1.2%
    Other
    5
    1.8%
    3
    1%
    8
    1.4%
    Weight (kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg]
    74.9
    (15.39)
    75.5
    (15.96)
    75.2
    (15.67)
    Karnofsky performance score (Number) [Number]
    100 -Normal no complaints; no evidence of disease
    83
    29.2%
    73
    25.5%
    156
    27.4%
    90 - Able to carry on normal activity
    93
    32.7%
    101
    35.3%
    194
    34%
    80 - Normal activity with efforts
    73
    25.7%
    83
    29%
    156
    27.4%
    70 - Cares for self
    35
    12.3%
    29
    10.1%
    64
    11.2%
    Memorial Sloan Kettering Cancer Center Risk Criteria (MSKCC) risk group (Number) [Number]
    Favorable
    70
    24.6%
    65
    22.7%
    135
    23.7%
    Intermediate
    156
    54.9%
    155
    54.2%
    311
    54.6%
    Poor
    54
    19%
    61
    21.3%
    115
    20.2%
    Missing
    4
    1.4%
    5
    1.7%
    9
    1.6%

    Outcome Measures

    1. Primary Outcome
    Title Progression Free Survival (PFS) Per Independent Central Radiology Review
    Description 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.
    Time Frame Until disease progression or discontinuation of treatment due to unacceptable toxicity up to 30-Jun-2014 (discontinuation)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS) consisted of all randomized patients.
    Arm/Group Title Dovitinib + Best Supportive Care (BSC) Sorafenib + BSC
    Arm/Group Description Patients randomized to the dovitinib treatment arm received 500 mg of dovitinib taken orally on 5 days on/2 days off dosing schedule. Patients in the sorafenib control arm received 400 mg of sorafenib (2 x 200 mg tablets) taken orally twice daily.
    Measure Participants 284 286
    Median (95% Confidence Interval) [Months]
    3.7
    3.6
    2. Secondary Outcome
    Title Overall Survival (OS)
    Description 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.
    Time Frame until at least 386 deaths are documented in the clinical database.

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS) consisted of all randomized patients.
    Arm/Group Title Dovitinib + Best Supportive Care (BSC) Sorafenib + BSC
    Arm/Group Description Patients randomized to the dovitinib treatment arm received 500 mg of dovitinib taken orally on 5 days on/2 days off dosing schedule. Patients in the sorafenib control arm received 400 mg of sorafenib (2 x 200 mg tablets) taken orally twice daily.
    Measure Participants 284 286
    Median (95% Confidence Interval) [Months]
    11.1
    11.0
    3. Secondary Outcome
    Title Progression Free Survival (PFS) Per Investigator's Radiology Review
    Description 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.
    Time Frame Until disease progression or discontinuation of treatment due to unacceptable toxicity

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS) consisted of all randomized patients.
    Arm/Group Title Dovitinib + Best Supportive Care (BSC) Sorafenib + BSC
    Arm/Group Description Patients randomized to the dovitinib treatment arm received 500 mg of dovitinib taken orally on 5 days on/2 days off dosing schedule. Patients in the sorafenib control arm received 400 mg of sorafenib (2 x 200 mg tablets) taken orally twice daily.
    Measure Participants 284 286
    Median (95% Confidence Interval) [Months]
    3.9
    3.9
    4. Secondary Outcome
    Title Percentage of Participants With Overall Response Rate (ORR) by Central Radiology Review
    Description 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).
    Time Frame Until disease progression or discontinuation of treatment due to unacceptable toxicity

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS) consisted of all randomized patients.
    Arm/Group Title Dovitinib + Best Supportive Care (BSC) Sorafenib + BSC
    Arm/Group Description Patients randomized to the dovitinib treatment arm received 500 mg of dovitinib taken orally on 5 days on/2 days off dosing schedule. Patients in the sorafenib control arm received 400 mg of sorafenib (2 x 200 mg tablets) taken orally twice daily.
    Measure Participants 284 286
    Number [Percentage of Participants]
    3.9
    1.4%
    3.8
    1.3%
    5. Secondary Outcome
    Title Time to Definitive Worsening of Karnofsky Performance Status (KPS)
    Description 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.
    Time Frame from date of randomization to the date of definitive worsening of KPS or to the date of death whichever occurred earlier

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS) consited of all randomized patients.
    Arm/Group Title Dovitinib + Best Supportive Care (BSC) Sorafenib + BSC
    Arm/Group Description Patients randomized to the dovitinib treatment arm received 500 mg of dovitinib taken orally on 5 days on/2 days off dosing schedule. Patients in the sorafenib control arm received 400 mg of sorafenib (2 x 200 mg tablets) taken orally twice daily.
    Measure Participants 284 286
    Median (95% Confidence Interval) [Months]
    5.1
    5.7
    6. Secondary Outcome
    Title 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
    Description 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).
    Time Frame from date of randomization, at least 2 score units

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS) consisted of all randomized patients.
    Arm/Group Title Dovitinib + Best Supportive Care (BSC) Sorafenib + BSC
    Arm/Group Description Patients randomized to the dovitinib treatment arm received 500 mg of dovitinib taken orally on 5 days on/2 days off dosing schedule. Patients in the sorafenib control arm received 400 mg of sorafenib (2 x 200 mg tablets) taken orally twice daily.
    Measure Participants 284 286
    Median (95% Confidence Interval) [Months]
    4.9
    6.4
    7. Secondary Outcome
    Title Patient-reported Outcomes (PROs): Time to Definitive Deterioration of the Physical Functioning (PF) Scale of EORTC QLQ-C30 by at Least 10%
    Description 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.
    Time Frame from date of randomization

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS) consisted of all randomized patients.
    Arm/Group Title Dovitinib + Best Supportive Care (BSC) Sorafenib + BSC
    Arm/Group Description Patients randomized to the dovitinib treatment arm received 500 mg of dovitinib taken orally on 5 days on/2 days off dosing schedule. Patients in the sorafenib control arm received 400 mg of sorafenib (2 x 200 mg tablets) taken orally twice daily.
    Measure Participants 284 286
    Median (95% Confidence Interval) [Months]
    3.8
    5.6
    8. Secondary Outcome
    Title Patient-reported Outcomes (PROs): Time to Definitive Deterioration of the Quality of Life (QoL) Scale Scores of EORTC QLQ-C30 by at Least 10%
    Description 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.
    Time Frame from date of randomization

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS) consisted of all randomized patients.
    Arm/Group Title Dovitinib + Best Supportive Care (BSC) Sorafenib + BSC
    Arm/Group Description Patients randomized to the dovitinib treatment arm received 500 mg of dovitinib taken orally on 5 days on/2 days off dosing schedule. Patients in the sorafenib control arm received 400 mg of sorafenib (2 x 200 mg tablets) taken orally twice daily.
    Measure Participants 284 286
    Median (95% Confidence Interval) [Months]
    3.7
    4.5
    9. Secondary Outcome
    Title Pre-dose Concentration in Plasma in Dovitinib
    Description 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.
    Time Frame Week 2 Day 5, Week 4 Day 5, Week 6 Day 5

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set (PAS) consisted of all patients who received at least one dose of dovitinib and had at least one evaluable post-Baseline dovitinib concentration measurement.
    Arm/Group Title Dovitinib + Best Supportive Care (BSC)
    Arm/Group Description Patients randomized to the dovitinib treatment arm received 500 mg of dovitinib taken orally on 5 days on/2 days off dosing schedule.
    Measure Participants 284
    Week 2 Day 5 (n: 205)
    128.06
    (92.571)
    Week 4 Day 5 (n: 202)
    114.08
    (77.884)
    Week 6 Day 5 (n: 170)
    118.27
    (84.246)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description 570 patients randomized, 564 patients included in the Safety Set. AEs were reported based on this set which consisted of all patients who received at least 1 dose of study treatment. Patients were analyzed according to treatment actually received which was defined as the treatment the patient received at the first day of study medication.
    Arm/Group Title Dovitinib Sorafenib
    Arm/Group Description Patients randomized to the dovitinib treatment arm received 500 mg of dovitinib taken orally on 5 days on/2 days off dosing schedule. Patients in the sorafenib control arm received 400 mg of sorafenib (2 x 200 mg tablets) taken orally twice daily.
    All Cause Mortality
    Dovitinib Sorafenib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Dovitinib Sorafenib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 133/280 (47.5%) 112/284 (39.4%)
    Blood and lymphatic system disorders
    ANAEMIA 7/280 (2.5%) 7/284 (2.5%)
    LEUKOPENIA 2/280 (0.7%) 0/284 (0%)
    LYMPHOPENIA 1/280 (0.4%) 0/284 (0%)
    NEUTROPENIA 1/280 (0.4%) 0/284 (0%)
    THROMBOCYTOPENIA 2/280 (0.7%) 1/284 (0.4%)
    Cardiac disorders
    ACUTE MYOCARDIAL INFARCTION 1/280 (0.4%) 0/284 (0%)
    ATRIAL FIBRILLATION 0/280 (0%) 1/284 (0.4%)
    CARDIAC FAILURE 0/280 (0%) 1/284 (0.4%)
    CARDIAC FAILURE CONGESTIVE 1/280 (0.4%) 0/284 (0%)
    CARDIAC TAMPONADE 1/280 (0.4%) 0/284 (0%)
    CARDIOPULMONARY FAILURE 0/280 (0%) 1/284 (0.4%)
    CORONARY ARTERY OCCLUSION 1/280 (0.4%) 0/284 (0%)
    LEFT VENTRICULAR DYSFUNCTION 1/280 (0.4%) 0/284 (0%)
    MYOCARDIAL INFARCTION 3/280 (1.1%) 0/284 (0%)
    MYOCARDIAL ISCHAEMIA 0/280 (0%) 1/284 (0.4%)
    SUPRAVENTRICULAR TACHYCARDIA 0/280 (0%) 2/284 (0.7%)
    TACHYCARDIA 1/280 (0.4%) 0/284 (0%)
    ACUTE CORONARY SYNDROME 1/280 (0.4%) 1/284 (0.4%)
    CARDIO-RESPIRATORY ARREST 0/280 (0%) 1/284 (0.4%)
    Endocrine disorders
    HYPERCALCAEMIA OF MALIGNANCY 0/280 (0%) 1/284 (0.4%)
    Eye disorders
    DIPLOPIA 1/280 (0.4%) 0/284 (0%)
    CONJUNCTIVITIS 1/280 (0.4%) 0/284 (0%)
    Gastrointestinal disorders
    ABDOMINAL HERNIA 0/280 (0%) 1/284 (0.4%)
    ABDOMINAL PAIN 7/280 (2.5%) 1/284 (0.4%)
    ABDOMINAL PAIN UPPER 2/280 (0.7%) 2/284 (0.7%)
    ABDOMINAL TENDERNESS 0/280 (0%) 1/284 (0.4%)
    ANAL FISSURE 0/280 (0%) 1/284 (0.4%)
    ASCITES 0/280 (0%) 2/284 (0.7%)
    COLONIC FISTULA 1/280 (0.4%) 0/284 (0%)
    CONSTIPATION 1/280 (0.4%) 2/284 (0.7%)
    DIARRHOEA 10/280 (3.6%) 4/284 (1.4%)
    DYSPEPSIA 1/280 (0.4%) 0/284 (0%)
    DYSPHAGIA 3/280 (1.1%) 0/284 (0%)
    FAECAL INCONTINENCE 1/280 (0.4%) 0/284 (0%)
    GASTRIC PERFORATION 0/280 (0%) 1/284 (0.4%)
    GASTROINTESTINAL HAEMORRHAGE 1/280 (0.4%) 1/284 (0.4%)
    GASTROINTESTINAL MOTILITY DISORDER 0/280 (0%) 1/284 (0.4%)
    ILEUS 2/280 (0.7%) 2/284 (0.7%)
    ILEUS PARALYTIC 0/280 (0%) 1/284 (0.4%)
    INTESTINAL OBSTRUCTION 3/280 (1.1%) 0/284 (0%)
    LARGE INTESTINAL HAEMORRHAGE 1/280 (0.4%) 0/284 (0%)
    LARGE INTESTINE PERFORATION 1/280 (0.4%) 0/284 (0%)
    LOWER GASTROINTESTINAL HAEMORRHAGE 1/280 (0.4%) 0/284 (0%)
    NAUSEA 6/280 (2.1%) 3/284 (1.1%)
    OBSTRUCTION GASTRIC 0/280 (0%) 3/284 (1.1%)
    ODYNOPHAGIA 0/280 (0%) 1/284 (0.4%)
    ORAL PAIN 1/280 (0.4%) 0/284 (0%)
    PANCREATITIS 2/280 (0.7%) 0/284 (0%)
    PNEUMOPERITONEUM 0/280 (0%) 1/284 (0.4%)
    RECTAL HAEMORRHAGE 0/280 (0%) 1/284 (0.4%)
    RETROPERITONEAL HAEMATOMA 0/280 (0%) 1/284 (0.4%)
    RETROPERITONEAL HAEMORRHAGE 1/280 (0.4%) 0/284 (0%)
    STOMATITIS 1/280 (0.4%) 3/284 (1.1%)
    VOMITING 8/280 (2.9%) 3/284 (1.1%)
    General disorders
    ASTHENIA 3/280 (1.1%) 6/284 (2.1%)
    DEATH 1/280 (0.4%) 0/284 (0%)
    FATIGUE 4/280 (1.4%) 5/284 (1.8%)
    GENERAL PHYSICAL HEALTH DETERIORATION 7/280 (2.5%) 14/284 (4.9%)
    MALAISE 2/280 (0.7%) 0/284 (0%)
    MULTI-ORGAN FAILURE 1/280 (0.4%) 2/284 (0.7%)
    NON-CARDIAC CHEST PAIN 1/280 (0.4%) 1/284 (0.4%)
    OEDEMA PERIPHERAL 1/280 (0.4%) 0/284 (0%)
    PAIN 3/280 (1.1%) 3/284 (1.1%)
    PERFORMANCE STATUS DECREASED 1/280 (0.4%) 3/284 (1.1%)
    PYREXIA 7/280 (2.5%) 5/284 (1.8%)
    SUDDEN DEATH 0/280 (0%) 1/284 (0.4%)
    GENERALISED OEDEMA 2/280 (0.7%) 0/284 (0%)
    Hepatobiliary disorders
    CHOLECYSTITIS 0/280 (0%) 1/284 (0.4%)
    HEPATIC FAILURE 1/280 (0.4%) 1/284 (0.4%)
    JAUNDICE CHOLESTATIC 1/280 (0.4%) 0/284 (0%)
    Immune system disorders
    SERUM SICKNESS 1/280 (0.4%) 0/284 (0%)
    Infections and infestations
    ANAL ABSCESS 0/280 (0%) 1/284 (0.4%)
    CYSTITIS 1/280 (0.4%) 0/284 (0%)
    EMPHYSEMATOUS CYSTITIS 1/280 (0.4%) 0/284 (0%)
    GASTROENTERITIS 0/280 (0%) 1/284 (0.4%)
    INFECTIVE GLOSSITIS 1/280 (0.4%) 0/284 (0%)
    PNEUMONIA 7/280 (2.5%) 8/284 (2.8%)
    ERYSIPELAS 1/280 (0.4%) 0/284 (0%)
    LOBAR PNEUMONIA 1/280 (0.4%) 0/284 (0%)
    LUNG INFECTION 1/280 (0.4%) 1/284 (0.4%)
    MENINGITIS CRYPTOCOCCAL 1/280 (0.4%) 0/284 (0%)
    PYELONEPHRITIS ACUTE 1/280 (0.4%) 0/284 (0%)
    RESPIRATORY TRACT INFECTION 1/280 (0.4%) 0/284 (0%)
    SEPSIS 7/280 (2.5%) 0/284 (0%)
    URINARY TRACT INFECTION 1/280 (0.4%) 2/284 (0.7%)
    Injury, poisoning and procedural complications
    CONTRAST MEDIA REACTION 1/280 (0.4%) 0/284 (0%)
    FEMORAL NECK FRACTURE 1/280 (0.4%) 0/284 (0%)
    FEMUR FRACTURE 1/280 (0.4%) 1/284 (0.4%)
    HUMERUS FRACTURE 1/280 (0.4%) 0/284 (0%)
    OVERDOSE 1/280 (0.4%) 0/284 (0%)
    SUBDURAL HAEMATOMA 1/280 (0.4%) 0/284 (0%)
    TOXICITY TO VARIOUS AGENTS 1/280 (0.4%) 0/284 (0%)
    UPPER LIMB FRACTURE 1/280 (0.4%) 0/284 (0%)
    WRIST FRACTURE 1/280 (0.4%) 0/284 (0%)
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED 0/280 (0%) 1/284 (0.4%)
    AMYLASE INCREASED 1/280 (0.4%) 0/284 (0%)
    ASPARTATE AMINOTRANSFERASE INCREASED 0/280 (0%) 1/284 (0.4%)
    BLOOD ALKALINE PHOSPHATASE INCREASED 1/280 (0.4%) 0/284 (0%)
    BLOOD CREATININE INCREASED 0/280 (0%) 1/284 (0.4%)
    HAEMATOCRIT DECREASED 0/280 (0%) 1/284 (0.4%)
    LIPASE INCREASED 1/280 (0.4%) 0/284 (0%)
    LIVER FUNCTION TEST ABNORMAL 0/280 (0%) 1/284 (0.4%)
    PLATELET COUNT DECREASED 2/280 (0.7%) 0/284 (0%)
    TROPONIN INCREASED 1/280 (0.4%) 0/284 (0%)
    WEIGHT DECREASED 2/280 (0.7%) 0/284 (0%)
    Metabolism and nutrition disorders
    HYPONATRAEMIA 3/280 (1.1%) 4/284 (1.4%)
    HYPOPROTEINAEMIA 1/280 (0.4%) 0/284 (0%)
    LACTIC ACIDOSIS 0/280 (0%) 1/284 (0.4%)
    TUMOUR LYSIS SYNDROME 0/280 (0%) 1/284 (0.4%)
    CACHEXIA 2/280 (0.7%) 0/284 (0%)
    DECREASED APPETITE 2/280 (0.7%) 4/284 (1.4%)
    DEHYDRATION 6/280 (2.1%) 5/284 (1.8%)
    HYPERCALCAEMIA 3/280 (1.1%) 2/284 (0.7%)
    HYPERKALAEMIA 2/280 (0.7%) 2/284 (0.7%)
    HYPERTRIGLYCERIDAEMIA 1/280 (0.4%) 0/284 (0%)
    HYPOCALCAEMIA 1/280 (0.4%) 0/284 (0%)
    HYPOGLYCAEMIA 0/280 (0%) 1/284 (0.4%)
    HYPOKALAEMIA 2/280 (0.7%) 0/284 (0%)
    HYPOMAGNESAEMIA 1/280 (0.4%) 0/284 (0%)
    HYPOPHAGIA 2/280 (0.7%) 0/284 (0%)
    Musculoskeletal and connective tissue disorders
    AMYOTROPHY 1/280 (0.4%) 0/284 (0%)
    ARTHRALGIA 2/280 (0.7%) 3/284 (1.1%)
    BACK PAIN 5/280 (1.8%) 7/284 (2.5%)
    BONE PAIN 2/280 (0.7%) 2/284 (0.7%)
    FLANK PAIN 1/280 (0.4%) 0/284 (0%)
    INTERVERTEBRAL DISC DISORDER 1/280 (0.4%) 0/284 (0%)
    MUSCULAR WEAKNESS 0/280 (0%) 1/284 (0.4%)
    MUSCULOSKELETAL CHEST PAIN 1/280 (0.4%) 0/284 (0%)
    MUSCULOSKELETAL PAIN 0/280 (0%) 1/284 (0.4%)
    MYALGIA 1/280 (0.4%) 0/284 (0%)
    MYOPATHY 1/280 (0.4%) 0/284 (0%)
    NECK PAIN 0/280 (0%) 1/284 (0.4%)
    OSTEONECROSIS OF JAW 1/280 (0.4%) 0/284 (0%)
    PAIN IN EXTREMITY 1/280 (0.4%) 1/284 (0.4%)
    PATHOLOGICAL FRACTURE 0/280 (0%) 2/284 (0.7%)
    SPINAL COLUMN STENOSIS 0/280 (0%) 1/284 (0.4%)
    SPINAL OSTEOARTHRITIS 1/280 (0.4%) 0/284 (0%)
    INTERVERTEBRAL DISC COMPRESSION 1/280 (0.4%) 0/284 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    CANCER PAIN 0/280 (0%) 1/284 (0.4%)
    INFECTED NEOPLASM 1/280 (0.4%) 0/284 (0%)
    MALIGNANT PLEURAL EFFUSION 0/280 (0%) 1/284 (0.4%)
    METASTASES TO CENTRAL NERVOUS SYSTEM 1/280 (0.4%) 1/284 (0.4%)
    METASTATIC PAIN 1/280 (0.4%) 1/284 (0.4%)
    OESOPHAGEAL CARCINOMA 0/280 (0%) 1/284 (0.4%)
    PERICARDIAL EFFUSION MALIGNANT 1/280 (0.4%) 1/284 (0.4%)
    TUMOUR PAIN 3/280 (1.1%) 0/284 (0%)
    RENAL CELL CARCINOMA 1/280 (0.4%) 0/284 (0%)
    Nervous system disorders
    APHASIA 1/280 (0.4%) 0/284 (0%)
    CEREBROVASCULAR ACCIDENT 0/280 (0%) 1/284 (0.4%)
    CONVULSION 2/280 (0.7%) 0/284 (0%)
    DEPRESSED LEVEL OF CONSCIOUSNESS 1/280 (0.4%) 0/284 (0%)
    DIZZINESS 1/280 (0.4%) 0/284 (0%)
    EPILEPSY 1/280 (0.4%) 0/284 (0%)
    HEMIPARESIS 1/280 (0.4%) 1/284 (0.4%)
    LOSS OF CONSCIOUSNESS 1/280 (0.4%) 0/284 (0%)
    NEURALGIA 1/280 (0.4%) 0/284 (0%)
    NEUROLOGICAL DECOMPENSATION 1/280 (0.4%) 0/284 (0%)
    PARAESTHESIA 0/280 (0%) 1/284 (0.4%)
    PRESYNCOPE 1/280 (0.4%) 0/284 (0%)
    SCIATICA 1/280 (0.4%) 0/284 (0%)
    SPINAL CORD COMPRESSION 2/280 (0.7%) 2/284 (0.7%)
    SYNCOPE 2/280 (0.7%) 1/284 (0.4%)
    TRANSIENT ISCHAEMIC ATTACK 1/280 (0.4%) 0/284 (0%)
    EPIDURITIS 1/280 (0.4%) 0/284 (0%)
    Psychiatric disorders
    APATHY 1/280 (0.4%) 0/284 (0%)
    CONFUSIONAL STATE 3/280 (1.1%) 2/284 (0.7%)
    DELIRIUM 1/280 (0.4%) 0/284 (0%)
    Renal and urinary disorders
    AZOTAEMIA 2/280 (0.7%) 0/284 (0%)
    HAEMATURIA 0/280 (0%) 3/284 (1.1%)
    POLLAKIURIA 0/280 (0%) 1/284 (0.4%)
    RENAL FAILURE 0/280 (0%) 1/284 (0.4%)
    RENAL FAILURE ACUTE 0/280 (0%) 1/284 (0.4%)
    URINARY BLADDER HAEMORRHAGE 0/280 (0%) 1/284 (0.4%)
    URINARY INCONTINENCE 1/280 (0.4%) 0/284 (0%)
    URINARY RETENTION 1/280 (0.4%) 1/284 (0.4%)
    Reproductive system and breast disorders
    GENITAL HAEMORRHAGE 0/280 (0%) 1/284 (0.4%)
    Respiratory, thoracic and mediastinal disorders
    ACUTE PULMONARY OEDEMA 1/280 (0.4%) 0/284 (0%)
    ACUTE RESPIRATORY FAILURE 1/280 (0.4%) 0/284 (0%)
    ATELECTASIS 0/280 (0%) 1/284 (0.4%)
    BRONCHIAL OBSTRUCTION 1/280 (0.4%) 0/284 (0%)
    COUGH 1/280 (0.4%) 0/284 (0%)
    DYSPNOEA 16/280 (5.7%) 15/284 (5.3%)
    EPISTAXIS 0/280 (0%) 1/284 (0.4%)
    HAEMOPTYSIS 0/280 (0%) 1/284 (0.4%)
    HYDROTHORAX 1/280 (0.4%) 0/284 (0%)
    HYPOXIA 0/280 (0%) 1/284 (0.4%)
    PLEURAL EFFUSION 10/280 (3.6%) 10/284 (3.5%)
    PNEUMONIA ASPIRATION 1/280 (0.4%) 0/284 (0%)
    PNEUMONITIS 1/280 (0.4%) 2/284 (0.7%)
    PNEUMOTHORAX 0/280 (0%) 1/284 (0.4%)
    PRODUCTIVE COUGH 0/280 (0%) 1/284 (0.4%)
    PULMONARY EMBOLISM 3/280 (1.1%) 0/284 (0%)
    RESPIRATORY ARREST 1/280 (0.4%) 1/284 (0.4%)
    RESPIRATORY DISTRESS 1/280 (0.4%) 0/284 (0%)
    RESPIRATORY FAILURE 4/280 (1.4%) 3/284 (1.1%)
    HYDROPNEUMOTHORAX 1/280 (0.4%) 0/284 (0%)
    Skin and subcutaneous tissue disorders
    ANGIOEDEMA 0/280 (0%) 1/284 (0.4%)
    DIABETIC FOOT 0/280 (0%) 1/284 (0.4%)
    PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME 0/280 (0%) 1/284 (0.4%)
    PRURITUS GENERALISED 1/280 (0.4%) 0/284 (0%)
    RASH 1/280 (0.4%) 0/284 (0%)
    RASH ERYTHEMATOUS 1/280 (0.4%) 0/284 (0%)
    RASH GENERALISED 1/280 (0.4%) 0/284 (0%)
    SKIN LESION 0/280 (0%) 1/284 (0.4%)
    TOXIC EPIDERMAL NECROLYSIS 0/280 (0%) 1/284 (0.4%)
    TOXIC SKIN ERUPTION 0/280 (0%) 1/284 (0.4%)
    Vascular disorders
    EMBOLISM 2/280 (0.7%) 0/284 (0%)
    HYPERTENSION 0/280 (0%) 1/284 (0.4%)
    HYPOTENSION 0/280 (0%) 2/284 (0.7%)
    PHLEBITIS 1/280 (0.4%) 0/284 (0%)
    SHOCK 1/280 (0.4%) 0/284 (0%)
    THROMBOSIS 1/280 (0.4%) 0/284 (0%)
    VASCULAR FRAGILITY 1/280 (0.4%) 0/284 (0%)
    Other (Not Including Serious) Adverse Events
    Dovitinib Sorafenib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 268/280 (95.7%) 271/284 (95.4%)
    Blood and lymphatic system disorders
    ANAEMIA 27/280 (9.6%) 28/284 (9.9%)
    Endocrine disorders
    HYPOTHYROIDISM 14/280 (5%) 8/284 (2.8%)
    Eye disorders
    LACRIMATION INCREASED 19/280 (6.8%) 2/284 (0.7%)
    Gastrointestinal disorders
    ABDOMINAL PAIN 34/280 (12.1%) 37/284 (13%)
    ABDOMINAL PAIN UPPER 28/280 (10%) 23/284 (8.1%)
    CONSTIPATION 49/280 (17.5%) 67/284 (23.6%)
    DIARRHOEA 184/280 (65.7%) 126/284 (44.4%)
    DRY MOUTH 23/280 (8.2%) 12/284 (4.2%)
    DYSPEPSIA 30/280 (10.7%) 14/284 (4.9%)
    NAUSEA 146/280 (52.1%) 81/284 (28.5%)
    STOMATITIS 31/280 (11.1%) 53/284 (18.7%)
    VOMITING 120/280 (42.9%) 44/284 (15.5%)
    General disorders
    ASTHENIA 63/280 (22.5%) 44/284 (15.5%)
    FATIGUE 113/280 (40.4%) 94/284 (33.1%)
    NON-CARDIAC CHEST PAIN 22/280 (7.9%) 18/284 (6.3%)
    OEDEMA PERIPHERAL 26/280 (9.3%) 17/284 (6%)
    PYREXIA 40/280 (14.3%) 37/284 (13%)
    Investigations
    BLOOD ALKALINE PHOSPHATASE INCREASED 25/280 (8.9%) 5/284 (1.8%)
    GAMMA-GLUTAMYLTRANSFERASE INCREASED 25/280 (8.9%) 8/284 (2.8%)
    LIPASE INCREASED 16/280 (5.7%) 11/284 (3.9%)
    WEIGHT DECREASED 61/280 (21.8%) 87/284 (30.6%)
    Metabolism and nutrition disorders
    DECREASED APPETITE 90/280 (32.1%) 96/284 (33.8%)
    HYPERTRIGLYCERIDAEMIA 55/280 (19.6%) 2/284 (0.7%)
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 26/280 (9.3%) 26/284 (9.2%)
    BACK PAIN 37/280 (13.2%) 32/284 (11.3%)
    MUSCLE SPASMS 18/280 (6.4%) 24/284 (8.5%)
    MUSCULAR WEAKNESS 15/280 (5.4%) 6/284 (2.1%)
    MUSCULOSKELETAL CHEST PAIN 15/280 (5.4%) 13/284 (4.6%)
    MYALGIA 27/280 (9.6%) 17/284 (6%)
    PAIN IN EXTREMITY 35/280 (12.5%) 29/284 (10.2%)
    Nervous system disorders
    DIZZINESS 27/280 (9.6%) 7/284 (2.5%)
    DYSGEUSIA 31/280 (11.1%) 8/284 (2.8%)
    HEADACHE 26/280 (9.3%) 24/284 (8.5%)
    Psychiatric disorders
    INSOMNIA 15/280 (5.4%) 19/284 (6.7%)
    Respiratory, thoracic and mediastinal disorders
    COUGH 50/280 (17.9%) 48/284 (16.9%)
    DYSPHONIA 22/280 (7.9%) 25/284 (8.8%)
    DYSPNOEA 51/280 (18.2%) 48/284 (16.9%)
    Skin and subcutaneous tissue disorders
    ALOPECIA 2/280 (0.7%) 61/284 (21.5%)
    DERMATITIS ACNEIFORM 23/280 (8.2%) 6/284 (2.1%)
    DRY SKIN 22/280 (7.9%) 26/284 (9.2%)
    ERYTHEMA 1/280 (0.4%) 15/284 (5.3%)
    PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME 32/280 (11.4%) 114/284 (40.1%)
    PRURITUS 15/280 (5.4%) 30/284 (10.6%)
    RASH 54/280 (19.3%) 47/284 (16.5%)
    Vascular disorders
    HYPERTENSION 54/280 (19.3%) 78/284 (27.5%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 862-778-8300
    Email trialandresults.registry@novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01223027
    Other Study ID Numbers:
    • CTKI258A2302
    • 2009-015459-25
    First Posted:
    Oct 18, 2010
    Last Update Posted:
    Dec 7, 2015
    Last Verified:
    Nov 1, 2015