Clinical trial NCT01223027: Study of Dovitinib Versus Sorafenib in Patients With Metastatic Renal Cell Carcinoma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Renal Cell Carcinoma
Keywords: Dovitinib
TKI
Renal cell cancer
RCC
mRCC
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-10-18
Enrollment: 564
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Progression Free Survival (PFS) Per Independent Central Radiology Review
timeFrame: Until disease progression or discontinuation of treatment due to unacceptable toxicity up to 30-Jun-2014 (discontinuation)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: until at least 386 deaths are documented in the clinical database.
measure: Progression Free Survival (PFS) Per Investigator's Radiology Review
timeFrame: Until disease progression or discontinuation of treatment due to unacceptable toxicity
measure: Percentage of Participants With Overall Response Rate (ORR) by Central Radiology Review
timeFrame: Until disease progression or discontinuation of treatment due to unacceptable toxicity
measure: Time to Definitive Worsening of Karnofsky Performance Status (KPS)
timeFrame: from date of randomization to the date of definitive worsening of KPS or to the date of death whichever occurred earlier
measure: 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
timeFrame: from date of randomization, at least 2 score units
measure: Patient-reported Outcomes (PROs): Time to Definitive Deterioration of the Physical Functioning (PF) Scale of EORTC QLQ-C30 by at Least 10%
timeFrame: from date of randomization
measure: Patient-reported Outcomes (PROs): Time to Definitive Deterioration of the Quality of Life (QoL) Scale Scores of EORTC QLQ-C30 by at Least 10%
timeFrame: from date of randomization
measure: Pre-dose Concentration in Plasma in Dovitinib
timeFrame: Week 2 Day 5, Week 4 Day 5, Week 6 Day 5
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group Dept of Highlands Oncology Grp
state: Arkansas
city: La Jolla
country: United States
facility: University of California San Diego - Moores Cancer Center Dept of Moores Cancer Ctr (5)
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center Cedars Sinai Medical Ctr. (SC)
state: California
city: Los Angeles
country: United States
facility: University of California at Los Angeles UCLA (4)
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center Cancer Clinical Trials Office
state: California
city: Greenwood Village
country: United States
facility: Rocky Mountain Cancer Centers RMCC
state: Colorado
city: Fort Myers
country: United States
facility: Florida Cancer Specialists DeptofFloridaCancerSpecialists
state: Florida
city: Athens
country: United States
facility: University Cancer & Blood Center, LLC
state: Georgia
city: Honolulu
country: United States
facility: Straub Clinic & Hospital Straub
state: Hawaii
city: Honolulu
country: United States
facility: Moanalua Medical Center. Attn: Oncology Dept
state: Hawaii
city: Kansas City
country: United States
facility: University of Kansas Cancer Center Univ of KS
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland Medical Center UMMC
state: Maryland
city: Detroit
country: United States
facility: Karmanos Cancer Institute Dept.of KarmanosCancerInst (5)
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center - Fairview Univ of MN
state: Minnesota
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada CCC of Nevada (1)
state: Nevada
city: Voorhees
country: United States
facility: CINJ at Cooper University Hospital Cooper
state: New Jersey
city: NY
country: United States
facility: Memorial Sloan Kettering Cancer Center Dept. of MSKCC
state: New York
city: Syracuse
country: United States
facility: SUNY - Upstate Medical University Div. of Hematology-Oncology
state: New York
city: Troy
country: United States
facility: New York Oncology Hematology, P.C. Dept. of New York Oncology. PC
state: New York
city: Eugene
country: United States
facility: Willamette Valley Clinical Studies Williamette Valley Cancer
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's Hospital and Health Network St Luke's
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina -Hollings Cancer Center Med Univ SC
state: South Carolina
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas CC of C -Eastside
state: South Carolina
city: Chattanooga
country: United States
facility: Sarah Cannon Research Institute SC - 3
state: Tennessee
city: Memphis
country: United States
facility: The West Clinic
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center SC
state: Tennessee
city: Dallas
country: United States
facility: Baylor Health Care System/Sammons Cancer Center Dept. of Sammons Cancer (4)
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Texas Onc - Austin
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Texas Oncology - Houston
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center UTSW
state: Texas
city: Webster
country: United States
facility: Deke Slayton Cancer Center Deke Slayton Cancer Center (2)
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists Dept.of Utah Cancer Spec. (3)
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health Systems Univ Virginia
state: Virginia
city: Spokane
country: United States
facility: Rockwood Clinic Spokane Location
state: Washington
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Sante Fe
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: St. Leonards
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Westmead
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: South Brisbane
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Woodville
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: Footscray
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Heidelberg
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Linz
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Liège
country: Belgium
facility: Novartis Investigative Site
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Calgary
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Halifax
country: Canada
facility: Novartis Investigative Site
state: Nova Scotia
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: London
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Saskatoon
country: Canada
facility: Novartis Investigative Site
state: Saskatchewan
city: Bogota
country: Colombia
facility: Novartis Investigative Site
city: Brno
country: Czech Republic
facility: Novartis Investigative Site
city: Olomouc
country: Czech Republic
facility: Novartis Investigative Site
city: Praha 5
country: Czech Republic
facility: Novartis Investigative Site
city: Besancon Cedex
country: France
facility: Novartis Investigative Site
city: Bordeaux Cedex
country: France
facility: Novartis Investigative Site
city: Caen Cedex
country: France
facility: Novartis Investigative Site
city: Clermont-Ferrand
country: France
facility: Novartis Investigative Site
city: Grenoble
country: France
facility: Novartis Investigative Site
city: Lyon Cedex
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Nice Cedex 2
country: France
facility: Novartis Investigative Site
city: Paris Cedex 13
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Rennes Cedex
country: France
facility: Novartis Investigative Site
city: Saint Priest en Jarez Cedex
country: France
facility: Novartis Investigative Site
city: Saint-Herblain Cédex
country: France
facility: Novartis Investigative Site
city: Strasbourg Cedex
country: France
facility: Novartis Investigative Site
city: Suresnes
country: France
facility: Novartis Investigative Site
city: Toulouse Cedex 9
country: France
facility: Novartis Investigative Site
city: Vandoeuvre-Les-Nancy Cede
country: France
facility: Novartis Investigative Site
city: Villejuif Cedex
country: France
facility: Novartis Investigative Site
city: Aschaffenburg
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Chemnitz
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Greifswald
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Jena
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Marburg
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: München
country: Germany
facility: Novartis Investigative Site
city: Nuernberg
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Weiden
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
state: GR
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Pecs
country: Hungary
facility: Novartis Investigative Site
city: Szolnok
country: Hungary
facility: Novartis Investigative Site
city: Petach Tikva
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Zrifin
country: Israel
facility: Novartis Investigative Site
city: Arezzo
country: Italy
facility: Novartis Investigative Site
state: AR
city: Cremona
country: Italy
facility: Novartis Investigative Site
state: CR
city: Meldola
country: Italy
facility: Novartis Investigative Site
state: FC
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Modena
country: Italy
facility: Novartis Investigative Site
state: MO
city: Pavia
country: Italy
facility: Novartis Investigative Site
state: PV
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Candiolo
country: Italy
facility: Novartis Investigative Site
state: TO
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Nagoya-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Toon-city
country: Japan
facility: Novartis Investigative Site
state: Ehime
city: Fukuoka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Hiroshima-city
country: Japan
facility: Novartis Investigative Site
state: Hiroshima
city: Obihiro
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Sapporo-city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Kobe-city
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Kobe-city
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Kyoto-city
country: Japan
facility: Novartis Investigative Site
state: Kyoto
city: Matsumoto
country: Japan
facility: Novartis Investigative Site
state: Nagano
city: Osaka-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: OsakaSayama
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Suita-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Takatsuki-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Hidaka
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Kitaadachi-gun
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Bunkyo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Koto
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Minato-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chiba
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Yamagata
country: Japan
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Meerssen
country: Netherlands
facility: Novartis Investigative Site
state: KR
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Breda
country: Netherlands
facility: Novartis Investigative Site
city: Dordrecht
country: Netherlands
facility: Novartis Investigative Site
city: Maastricht
country: Netherlands
facility: Novartis Investigative Site
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
city: Bergen
country: Norway
facility: Novartis Investigative Site
city: Ålesund
country: Norway
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Riyadh
country: Saudi Arabia
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Cordoba
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Oviedo
country: Spain
facility: Novartis Investigative Site
state: Asturias
city: Sabadell
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Badalona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Benidorm
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Palma De Mallorca
country: Spain
facility: Novartis Investigative Site
state: Islas Baleares
city: Las Palmas de Gran Canarias
country: Spain
facility: Novartis Investigative Site
state: Las Palmas de Gran Canaria
city: Alcorcon
country: Spain
facility: Novartis Investigative Site
state: Madrid
city: Pamplona
country: Spain
facility: Novartis Investigative Site
state: Navarra
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Sundsvall
country: Sweden
facility: Novartis Investigative Site
city: Umeå
country: Sweden
facility: Novartis Investigative Site
city: Uppsala
country: Sweden
facility: Novartis Investigative Site
city: St. Gallen
country: Switzerland
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bristol
country: United Kingdom
facility: Novartis Investigative Site
state: Avon
city: Northwood
country: United Kingdom
facility: Novartis Investigative Site
state: Middlesex
city: Colchester
country: United Kingdom
facility: Novartis Investigative Site
city: Leicester
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Southampton
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.