Clinical trial NCT01103323: Patients With Metastatic Colorectal Cancer Treated With Regorafenib or Placebo After Failure of Standard Therapy
Official title: A Randomized, Double-blind, Placebo-controlled Phase III Study of Regorafenib Plus BSC Versus Placebo Plus BSC in Patients With Metastatic Colorectal Cancer (CRC) Who Have Progressed After Standard Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Keywords: Metastatic Colorectal Cancer
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2010-04-14
Enrollment: 760
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 is a randomized, double-blind, placebo-controlled multi-center phase III study to evaluate efficacy and safety of regorafenib in patients with metastatic colorectal cancer (CRC) who have progressed on/after all approved drugs for CRC

Detailed description: All participants received Best Supportive Care. Acronyms used in Adverse events section: Gastrointestinal (GI), Genitourinary (GU), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Common Terminology Criteria for Adverse Events (CTCAE), International Normalized Ratio (INR), Central nervous system (CNS), Acute respiratory distress syndrome (ARDS), Cranial nerves (CN), Disseminated Intravascular Coagulation (DIC), Cardiac troponin T (cTnT).

Abbreviation used in Results section: Data Monitoring Committee (DMC). Adverse event collection will be covered in Adverse events section.

Eligibility criteria: Inclusion Criteria:

* Histological or cytological documentation of adenocarcinoma of the colon or rectum
* Progression during or within 3 months following the last administration of approved standard therapies. Patients treated with oxaliplatin in an adjuvant setting should have progressed during or within 6 months of completion of adjuvant therapy
* Patients with measurable or non measurable disease
* Eastern Cooperative Oncology Group (ECOG) Performance Status of \</= 1
* Life expectancy of at least 3 months
* Adequate bone marrow, liver and renal function

Exclusion Criteria:

* Unstable/uncontrolled cardiac disease
* History of arterial or venous thrombotic or embolic events
* Symptomatic metastatic brain or meningeal tumors
* Patients with evidence or history of bleeding diathesis
* Interstitial lung disease - Persistent proteinuria \>/= grade 3
* Unresolved toxicity \> grade 1 attributed to any prior therapy/procedure excluding alopecia and oxaliplatin induced neurotoxicity \</= Grade 2

Primary outcomes:
measure: Overall Survival
timeFrame: From randomization of the first subject until the database cut-off approximately 14 months later (19May2010 - 21Jul2011) used for 2nd planned formal interim analysis (IA).
Secondary outcomes:
measure: Progression-free Survival (Based on Investigator's Assessment)
timeFrame: From randomization of the first subject until the database cut-off approximately 14 months later (19May2010 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals.
measure: Objective Tumor Response
timeFrame: From randomization of the first subject until the database cut-off approximately 14 months later (19May2010 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals.
measure: Disease Control
timeFrame: From randomization of the first subject until the database cut-off approximately 14 months later (19May2010 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals.
measure: Tumor Response
timeFrame: From randomization of the first subject until the database cut-off approximately 14 months later (19May2010 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals.
Other outcomes:
Locations:
city: Beverly Hills
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Mission Hills
country: United States
state: California
city: Orange
country: United States
state: California
city: Redlands
country: United States
state: California
city: Santa Maria
country: United States
state: California
city: Aventura
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Peoria
country: United States
state: Illinois
city: Cedar Rapids
country: United States
state: Iowa
city: New Orleans
country: United States
state: Louisiana
city: Ann Arbor
country: United States
state: Michigan
city: Rochester
country: United States
state: Minnesota
city: St. Cloud
country: United States
state: Minnesota
city: Jefferson City
country: United States
state: Missouri
city: Neptune
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Fargo
country: United States
state: North Dakota
city: Toledo
country: United States
state: Ohio
city: Scranton
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Sumter
country: United States
state: South Carolina
city: Dallas
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Green Bay
country: United States
state: Wisconsin
city: Buenos Aires
country: Argentina
state: Ciudad Auton. de Buenos Aires
city: Buenos Aires
country: Argentina
state: Ciudad Auton. de Buenos Aires
city: Rosario
country: Argentina
state: Santa Fe
city: San Miguel de Tucumán
country: Argentina
state: Tucuman
city: Capital Federal-Buenos Aires
country: Argentina
city: Concord
country: Australia
state: New South Wales
city: St Leonards
country: Australia
state: New South Wales
city: Woolloogabba
country: Australia
state: Queensland
city: Woodville South
country: Australia
state: South Australia
city: Footscray
country: Australia
state: Victoria
city: Parkville
country: Australia
state: Victoria
city: Bruxelles - Brussel
country: Belgium
city: Bruxelles - Brussel
country: Belgium
city: Bruxelles - Brussel
country: Belgium
city: Edegem
country: Belgium
city: Leuven
country: Belgium
city: Roeselare
country: Belgium
city: Salvador
country: Brazil
state: Bahia
city: Fortaleza
country: Brazil
state: Ceará
city: Belo Horizonte
country: Brazil
state: Minas Gerais
city: Ijuí
country: Brazil
state: Rio Grande do Sul
city: Vancouver
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: Moncton
country: Canada
state: New Brunswick
city: London
country: Canada
state: Ontario
city: Mississauga
country: Canada
state: Ontario
city: Oshawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Quebec
country: Canada
city: Guangzhou
country: China
state: Guangdong
city: Guangzhou
country: China
state: Guangdong
city: Nanjing
country: China
state: Jiangsu
city: Nanjing
country: China
state: Jiangsu
city: Qingdao
country: China
state: Shandong
city: Beijing
country: China
city: Beijing
country: China
city: Changchun
country: China
city: Chongqing
country: China
city: Chongqing
country: China
city: Fuzhou
country: China
city: Fuzhou
country: China
city: Ha'erbin
country: China
city: Hanghzou
country: China
city: Shanghai
country: China
city: Shanghai
country: China
city: Tianjin
country: China
city: Brno
country: Czech Republic
city: Hradec Kralove
country: Czech Republic
city: Olomouc
country: Czech Republic
city: Praha
country: Czech Republic
city: Avignon
country: France
city: Le Mans Cedex 2
country: France
city: Lille Cedex
country: France
city: Lille Cedex
country: France
city: Marseille
country: France
city: Montpellier
country: France
city: Paris
country: France
city: Reims
country: France
city: Rennes
country: France
city: Strasbourg Cedex
country: France
city: Freiburg
country: Germany
state: Baden-Württemberg
city: Karlsruhe
country: Germany
state: Baden-Württemberg
city: Mannheim
country: Germany
state: Baden-Württemberg
city: Stuttgart
country: Germany
state: Baden-Württemberg
city: München
country: Germany
state: Bayern
city: München
country: Germany
state: Bayern
city: München
country: Germany
state: Bayern
city: Hannover
country: Germany
state: Niedersachsen
city: Oldenburg
country: Germany
state: Niedersachsen
city: Essen
country: Germany
state: Nordrhein-Westfalen
city: Köln
country: Germany
state: Nordrhein-Westfalen
city: Leverkusen
country: Germany
state: Nordrhein-Westfalen
city: Porta Westfalica
country: Germany
state: Nordrhein-Westfalen
city: Trier
country: Germany
state: Rheinland-Pfalz
city: Halle
country: Germany
state: Sachsen-Anhalt
city: Magdeburg
country: Germany
state: Sachsen-Anhalt
city: Dresden
country: Germany
state: Sachsen
city: Berlin
country: Germany
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Nyiregyhaza
country: Hungary
city: Szeged
country: Hungary
city: Ashkelon
country: Israel
city: Beer Sheva
country: Israel
city: Haifa
country: Israel
city: Holon
country: Israel
city: Jerusalem
country: Israel
city: Petach Tikva
country: Israel
city: Rehovot
country: Israel
city: Tel Aviv
country: Israel
city: Tel Hashomer
country: Israel
city: Zrifin
country: Israel
city: Brescia
country: Italy
city: Genova
country: Italy
city: Milano
country: Italy
city: Milano
country: Italy
city: Modena
country: Italy
city: Napoli
country: Italy
city: Pisa
country: Italy
city: Reggio Emilia
country: Italy
city: Roma
country: Italy
city: Nagoya
country: Japan
state: Aichi
city: Kashiwa
country: Japan
state: Chiba
city: Matsuyama
country: Japan
state: Ehime
city: Sapporo
country: Japan
state: Hokkaido
city: Osakasayama
country: Japan
state: Osaka
city: Takatsuki
country: Japan
state: Osaka
city: Hidaka
country: Japan
state: Saitama
city: Kita-Adachigun
country: Japan
state: Saitama
city: Sunto
country: Japan
state: Shizuoka
city: Shimotsuke
country: Japan
state: Tochigi
city: Utsunomiya
country: Japan
state: Tochigi
city: Bunkyo-ku
country: Japan
state: Tokyo
city: Chuo-ku
country: Japan
state: Tokyo
city: Koto-ku
country: Japan
state: Tokyo
city: Mitaka
country: Japan
state: Tokyo
city: Chiba
country: Japan
city: Fukuoka
country: Japan
city: Kochi
country: Japan
city: Kumamoto
country: Japan
city: Osaka
country: Japan
city: Amsterdam
country: Netherlands
city: Hoofddorp
country: Netherlands
city: Leeuwarden
country: Netherlands
city: Leiden
country: Netherlands
city: Aveiro
country: Portugal
city: Coimbra
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Porto
country: Portugal
city: Hospitalet de Llobregat
country: Spain
state: Barcelona
city: Sabadell
country: Spain
state: Barcelona
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Málaga
country: Spain
city: Sevilla
country: Spain
city: Chur
country: Switzerland
state: Graubünden
city: Genève
country: Switzerland
city: Ankara
country: Turkey
city: Instanbul
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, Humblet Y, Bouche O, Mineur L, Barone C, Adenis A, Tabernero J, Yoshino T, Lenz HJ, Goldberg RM, Sargent DJ, Cihon F, Cupit L, Wagner A, Laurent D; CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):303-12. doi: 10.1016/S0140-6736(12)61900-X. Epub 2012 Nov 22.
citation: Mross K, Frost A, Steinbild S, Hedbom S, Buchert M, Fasol U, Unger C, Kratzschmar J, Heinig R, Boix O, Christensen O. A phase I dose-escalation study of regorafenib (BAY 73-4506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors. Clin Cancer Res. 2012 May 1;18(9):2658-67. doi: 10.1158/1078-0432.CCR-11-1900. Epub 2012 Mar 15.
citation: Tabernero J, Lenz HJ, Siena S, Sobrero A, Falcone A, Ychou M, Humblet Y, Bouche O, Mineur L, Barone C, Adenis A, Yoshino T, Goldberg RM, Sargent DJ, Wagner A, Laurent D, Teufel M, Jeffers M, Grothey A, Van Cutsem E. Analysis of circulating DNA and protein biomarkers to predict the clinical activity of regorafenib and assess prognosis in patients with metastatic colorectal cancer: a retrospective, exploratory analysis of the CORRECT trial. Lancet Oncol. 2015 Aug;16(8):937-48. doi: 10.1016/S1470-2045(15)00138-2. Epub 2015 Jul 13.