Patients With Metastatic Colorectal Cancer Treated With Regorafenib or Placebo After Failure of Standard Therapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01103323
First received: April 8, 2010
Last updated: April 29, 2014
Last verified: April 2014
  Purpose

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


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: Regorafenib (Stivarga, BAY73-4506)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: 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). ] [ Designated as safety issue: No ]
    Overall survival (OS) was defined as the time (days) from randomization to death due to any cause. Patients alive at the time of analysis were censored at the last date known to be alive. If a patient was lost to follow-up and there was no contact after randomization, this patient was censored at Day 1.


Secondary Outcome Measures:
  • Progression-free Survival (Based on Investigator's Assessment) [ Time Frame: From randomization of the first subject until the database cut-off approximately 14 months later (19May2012 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals. ] [ Designated as safety issue: No ]
    Progression-free survival was defined as the time (days) from date of randomization to date of first observed disease progression (radiological or clinical) or death due to any cause, if death occurred before progression was documented.

  • Objective Tumor Response [ Time Frame: From randomization of the first subject until the database cut-off approximately 14 months later (19May2012 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals. ] [ Designated as safety issue: No ]
    The objective tumor response was defined as the percentage of patients with complete response (CR, tumor disappears) or partial response (PR, sum of lesion sizes decreased at least 30% from baseline) as best overall response. A best overall response was defined for all patients, using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1. Patients whose best overall response was not CR or PR, and any patients with no post-baseline assessments were considered nonresponders for the analysis.

  • Disease Control [ Time Frame: From randomization of the first subject until the database cut-off approximately 14 months later (19May2012 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals. ] [ Designated as safety issue: No ]
    Disease control was defined as the percentage of patients whose best response was not PD [sum of lesion sizes increased at least 20% from smallest sum on study or new lesions] (ie, CR [tumor disappears], PR [sum of lesion sizes decreased at least 30% from baseline] or SD (stable disease)). SD included if at least 6 weeks after randomization.

  • Tumor Response [ Time Frame: From randomization of the first subject until the database cut-off approximately 14 months later (19May2012 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals. ] [ Designated as safety issue: No ]
    A tumor response (best overall response) was defined for all patients, using the RECIST criteria, version 1.1. Categories: complete response (CR, tumor disappears), partial response (PR, sum of lesion sizes decreased at least 30% from baseline), stable disease (SD, steady state of disease), progressive disease (PD, sum of lesion sizes increased at least 20% from smallest sum on study or new lesions). Clinical PD considered when radiographic imaging not possible.


Enrollment: 760
Study Start Date: April 2010
Study Completion Date: January 2014
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regorafenib (Stivarga, BAY73-4506)
Participants received Regorafenib 160 mg per oral once daily for 3 weeks on 1 week off of every 4 week cycle
Drug: Regorafenib (Stivarga, BAY73-4506)
160 mg per oral once daily for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off) plus Best Supportive Care
Placebo Comparator: Placebo
Participants received matching placebo tablets per oral once daily for 3 weeks on 1 week off of every 4 week cycle
Drug: Placebo
matching placebo tablets for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off) plus Best Supportive Care

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01103323

  Hide Study Locations
Locations
United States, California
Beverly Hills, California, United States, 90211
Los Angeles, California, United States, 90036
Los Angeles, California, United States, 90033
Mission Hills, California, United States, 91345
Orange, California, United States, 92868
Redlands, California, United States, 92374
Santa Maria, California, United States, 93454
United States, Florida
Aventura, Florida, United States, 33180
Jacksonville, Florida, United States, 32224
United States, Illinois
Peoria, Illinois, United States, 61615-7828
United States, Iowa
Cedar Rapids, Iowa, United States, 52403
United States, Louisiana
New Orleans, Louisiana, United States, 70121
United States, Michigan
Ann Arbor, Michigan, United States, 48106
United States, Minnesota
Rochester, Minnesota, United States, 55905
St. Cloud, Minnesota, United States, 56303
United States, Missouri
Jefferson City, Missouri, United States, 65109
United States, New Jersey
Neptune, New Jersey, United States, 07754
United States, New York
New York, New York, United States, 10011
United States, North Dakota
Fargo, North Dakota, United States, 58122
United States, Ohio
Toledo, Ohio, United States, 43623
United States, Pennsylvania
Scranton, Pennsylvania, United States, 18510
United States, South Carolina
Charleston, South Carolina, United States, 29414
Sumter, South Carolina, United States, 29150
United States, Texas
Dallas, Texas, United States, 75390-9110
United States, Utah
Salt Lake City, Utah, United States, 84106
United States, Wisconsin
Green Bay, Wisconsin, United States, 54303
Argentina
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1122AAL
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1264AAA
Rosario, Santa Fe, Argentina, S2000PBJ
San Miguel de Tucumán, Tucuman, Argentina, T4000GTB
Capital Federal-Buenos Aires, Argentina, C1426ANZ
Australia, New South Wales
Concord, New South Wales, Australia, 2139
St Leonards, New South Wales, Australia, 2065
Australia, Queensland
Woolloogabba, Queensland, Australia, 4102
Australia, South Australia
Woodville South, South Australia, Australia, 5011
Australia, Victoria
Footscray, Victoria, Australia, 3011
Parkville, Victoria, Australia, 3050
Belgium
Bruxelles - Brussel, Belgium, 1070
Bruxelles - Brussel, Belgium, 1200
Bruxelles - Brussel, Belgium, 1000
Edegem, Belgium, 2650
Leuven, Belgium, 3000
Roeselare, Belgium, 8800
Brazil
Salvador, Bahia, Brazil, 41830-492
Fortaleza, Ceará, Brazil, 60160-230
Belo Horizonte, Minas Gerais, Brazil, 30110-090
Ijuí, Rio Grande do Sul, Brazil, 98700-000
Canada, British Columbia
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Manitoba
Winnipeg, Manitoba, Canada, R2H 2A6
Canada, New Brunswick
Moncton, New Brunswick, Canada, E1C 6Z8
Canada, Ontario
London, Ontario, Canada, N6A 4L6
Mississauga, Ontario, Canada, L5M 2N1
Oshawa, Ontario, Canada, L1G 2B9
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
Montreal, Quebec, Canada, H3T 1E2
Canada
Quebec, Canada, G1R 2J6
China, Guangdong
Guangzhou, Guangdong, China, 510515
Guangzhou, Guangdong, China, 510060
China, Jiangsu
Nanjing, Jiangsu, China, 210009
Nanjing, Jiangsu, China, 210003
China, Shandong
Qingdao, Shandong, China, 266100
China
Beijing, China, 100021
Beijing, China, 100071
Changchun, China, 130021
Chongqing, China, 400042
Chongqing, China, 400038
Fuzhou, China, 350014
Fuzhou, China, 350025
Ha'erbin, China, 150040
Hanghzou, China, 310009
Shanghai, China, 200001
Shanghai, China, 200030
Tianjin, China, 300060
Czech Republic
Brno, Czech Republic, 65 653
Hradec Kralove, Czech Republic, 500 05
Olomouc, Czech Republic, 775 20
Praha, Czech Republic, 18081
France
Avignon, France, 84000
Le Mans Cedex 2, France, 72015
Lille Cedex, France, 59037
Lille Cedex, France, 59020
Marseille, France, 13005
Montpellier, France, 34298
Paris, France, 75651
Reims, France, 51092
Rennes, France, 35042
Strasbourg Cedex, France, 67085
Germany
Freiburg, Baden-Württemberg, Germany, 79106
Karlsruhe, Baden-Württemberg, Germany, 76137
Mannheim, Baden-Württemberg, Germany, 68167
Stuttgart, Baden-Württemberg, Germany, 70199
München, Bayern, Germany, 81377
München, Bayern, Germany, 81737
München, Bayern, Germany, 81925
Hannover, Niedersachsen, Germany, 30625
Oldenburg, Niedersachsen, Germany, 26133
Essen, Nordrhein-Westfalen, Germany, 45122
Köln, Nordrhein-Westfalen, Germany, 50924
Leverkusen, Nordrhein-Westfalen, Germany, 51375
Porta Westfalica, Nordrhein-Westfalen, Germany, 32457
Trier, Rheinland-Pfalz, Germany, 54290
Halle, Sachsen-Anhalt, Germany, 06120
Magdeburg, Sachsen-Anhalt, Germany, 39104
Dresden, Sachsen, Germany, 01307
Berlin, Germany, 13125
Hungary
Budapest, Hungary, 1082
Debrecen, Hungary, 4032
Nyiregyhaza, Hungary, 4400
Szeged, Hungary, 6725
Israel
Ashkelon, Israel, 7830604
Beer Sheva, Israel, 8410101
Haifa, Israel, 3109601
Holon, Israel
Jerusalem, Israel, 9112001
Petach Tikva, Israel, 4941492
Rehovot, Israel, 7610001
Tel Aviv, Israel, 6423906
Tel Hashomer, Israel, 5262000
Zrifin, Israel, 6093000
Italy
Brescia, Italy, 25124
Genova, Italy, 16132
Milano, Italy, 20133
Milano, Italy, 20162
Modena, Italy, 41124
Napoli, Italy, 80131
Pisa, Italy, 56126
Reggio Emilia, Italy, 42100
Roma, Italy, 00168
Japan
Nagoya, Aichi, Japan, 464-8681
Kashiwa, Chiba, Japan, 277-8577
Matsuyama, Ehime, Japan, 791-0280
Sapporo, Hokkaido, Japan, 060-8648
Osakasayama, Osaka, Japan, 589-8511
Takatsuki, Osaka, Japan, 569-8686
Hidaka, Saitama, Japan, 350-1298
Kita-Adachigun, Saitama, Japan, 362-0806
Sunto, Shizuoka, Japan, 411-8777
Shimotsuke, Tochigi, Japan, 329-0498
Utsunomiya, Tochigi, Japan, 320-0834
Bunkyo-ku, Tokyo, Japan, 113-8519
Chuo-ku, Tokyo, Japan, 104-0045
Koto-ku, Tokyo, Japan, 135-8550
Mitaka, Tokyo, Japan, 181-8611
Chiba, Japan, 260-8717
Fukuoka, Japan, 812-8582
Kochi, Japan, 781-8555
Kumamoto, Japan, 860-8556
Osaka, Japan, 540-0006
Netherlands
Amsterdam, Netherlands, 1081 HV
Hoofddorp, Netherlands, 2134 TM
Leeuwarden, Netherlands, 8901 BR
Leiden, Netherlands, 2333 ZA
Portugal
Aveiro, Portugal, 3810-096
Coimbra, Portugal, 3030-075
Lisboa, Portugal, 1649-035
Porto, Portugal, 4099-001
Porto, Portugal, 4200-072
Spain
Hospitalet de Llobregat, Barcelona, Spain, 08907
Sabadell, Barcelona, Spain, 08208
Barcelona, Spain, 08035
Madrid, Spain, 28040
Madrid, Spain, 28046
Madrid, Spain, 28041
Málaga, Spain, 29010
Sevilla, Spain, 41013
Switzerland
Chur, Graubünden, Switzerland, 7000
Genève, Switzerland, 1211
Turkey
Ankara, Turkey, 06500
Instanbul, Turkey, 34662
Istanbul, Turkey, 34390
Izmir, Turkey, 35100
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01103323     History of Changes
Other Study ID Numbers: 14387, 2009-012787-14
Study First Received: April 8, 2010
Results First Received: October 19, 2012
Last Updated: April 29, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: National Institute of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Czech Republic: State Institute for Drug Control
Hungary: National Institute of Pharmacy
Australia: Department of Health and Ageing Therapeutic Goods Administration
China: Food and Drug Administration
Japan: Pharmaceuticals and Medical Devices Agency
Brazil: National Health Surveillance Agency
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Switzerland: Swissmedic
Canada: Health Canada
Spain: Spanish Agency of Medicines
Portugal: National Pharmacy and Medicines Institute
Turkey: Ministry of Health
Israel: Ministry of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Belgium: Federal Agency for Medicinal Products and Health Products
United States: Food and Drug Administration

Keywords provided by Bayer:
Metastatic Colorectal Cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on September 29, 2014