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

May 28, 2015 updated by: Bayer

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

760

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Capital Federal-Buenos Aires, Argentina, C1426ANZ
    • Ciudad Auton. de Buenos Aires
      • Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1122AAL
      • Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1264AAA
    • Santa Fe
      • Rosario, Santa Fe, Argentina, S2000PBJ
    • Tucuman
      • San Miguel de Tucumán, Tucuman, Argentina, T4000GTB
  • Australia
    • New South Wales
      • Concord, New South Wales, Australia, 2139
      • St Leonards, New South Wales, Australia, 2065
    • Queensland
      • Woolloogabba, Queensland, Australia, 4102
    • South Australia
      • Woodville South, South Australia, Australia, 5011
    • 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
    • Bahia
      • Salvador, Bahia, Brazil, 41830-492
    • Ceará
      • Fortaleza, Ceará, Brazil, 60160-230
    • Minas Gerais
      • Belo Horizonte, Minas Gerais, Brazil, 30110-090
    • Rio Grande do Sul
      • Ijuí, Rio Grande do Sul, Brazil, 98700-000
  • Canada
      • Quebec, Canada, G1R 2J6
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
    • Manitoba
      • Winnipeg, Manitoba, Canada, R2H 2A6
    • New Brunswick
      • Moncton, New Brunswick, Canada, E1C 6Z8
    • Ontario
      • London, Ontario, Canada, N6A 4L6
      • Mississauga, Ontario, Canada, L5M 2N1
      • Oshawa, Ontario, Canada, L1G 2B9
      • Toronto, Ontario, Canada, M4N 3M5
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
  • China
      • Beijing, China, 100021
      • Beijing, China, 100071
      • Changchun, China, 130021
      • Chongqing, China, 400038
      • Chongqing, China, 400042
      • Fuzhou, China, 350014
      • Fuzhou, China, 350025
      • Ha'erbin, China, 150040
      • Hanghzou, China, 310009
      • Shanghai, China, 200001
      • Shanghai, China, 200030
      • Tianjin, China, 300060
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
      • Guangzhou, Guangdong, China, 510515
    • Jiangsu
      • Nanjing, Jiangsu, China, 210003
      • Nanjing, Jiangsu, China, 210009
    • Shandong
      • Qingdao, Shandong, China, 266100
  • 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
      • Berlin, Germany, 13125
    • Baden-Württemberg
      • Freiburg, Baden-Württemberg, Germany, 79106
      • Karlsruhe, Baden-Württemberg, Germany, 76137
      • Mannheim, Baden-Württemberg, Germany, 68167
      • Stuttgart, Baden-Württemberg, Germany, 70199
    • Bayern
      • München, Bayern, Germany, 81925
      • München, Bayern, Germany, 81377
      • München, Bayern, Germany, 81737
    • Niedersachsen
      • Hannover, Niedersachsen, Germany, 30625
      • Oldenburg, Niedersachsen, Germany, 26133
    • Nordrhein-Westfalen
      • Essen, Nordrhein-Westfalen, Germany, 45122
      • Köln, Nordrhein-Westfalen, Germany, 50924
      • Leverkusen, Nordrhein-Westfalen, Germany, 51375
      • Porta Westfalica, Nordrhein-Westfalen, Germany, 32457
    • Rheinland-Pfalz
      • Trier, Rheinland-Pfalz, Germany, 54290
    • Sachsen
      • Dresden, Sachsen, Germany, 01307
    • Sachsen-Anhalt
      • Halle, Sachsen-Anhalt, Germany, 06120
      • Magdeburg, Sachsen-Anhalt, Germany, 39104
  • 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, 20162
      • Milano, Italy, 20133
      • Modena, Italy, 41124
      • Napoli, Italy, 80131
      • Pisa, Italy, 56126
      • Reggio Emilia, Italy, 42100
      • Roma, Italy, 00168
  • Japan
      • Chiba, Japan, 260-8717
      • Fukuoka, Japan, 812-8582
      • Kochi, Japan, 781-8555
      • Kumamoto, Japan, 860-8556
      • Osaka, Japan, 540-0006
    • Aichi
      • Nagoya, Aichi, Japan, 464-8681
    • Chiba
      • Kashiwa, Chiba, Japan, 277-8577
    • Ehime
      • Matsuyama, Ehime, Japan, 791-0280
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 060-8648
    • Osaka
      • Osakasayama, Osaka, Japan, 589-8511
      • Takatsuki, Osaka, Japan, 569-8686
    • Saitama
      • Hidaka, Saitama, Japan, 350-1298
      • Kita-Adachigun, Saitama, Japan, 362-0806
    • Shizuoka
      • Sunto, Shizuoka, Japan, 411-8777
    • Tochigi
      • Shimotsuke, Tochigi, Japan, 329-0498
      • Utsunomiya, Tochigi, Japan, 320-0834
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan, 113-8519
      • Chuo-ku, Tokyo, Japan, 104-0045
      • Koto-ku, Tokyo, Japan, 135-8550
      • Mitaka, Tokyo, Japan, 181-8611
  • 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
      • Barcelona, Spain, 08035
      • Madrid, Spain, 28040
      • Madrid, Spain, 28046
      • Madrid, Spain, 28041
      • Málaga, Spain, 29010
      • Sevilla, Spain, 41013
    • Barcelona
      • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Sabadell, Barcelona, Spain, 08208
  • Switzerland
      • Genève, Switzerland, 1211
    • Graubünden
      • Chur, Graubünden, Switzerland, 7000
  • Turkey
      • Ankara, Turkey, 06500
      • Instanbul, Turkey, 34662
      • Istanbul, Turkey, 34390
      • Izmir, Turkey, 35100
  • 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
    • Florida
      • Aventura, Florida, United States, 33180
      • Jacksonville, Florida, United States, 32224
    • Illinois
      • Peoria, Illinois, United States, 61615-7828
    • Iowa
      • Cedar Rapids, Iowa, United States, 52403
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
    • Minnesota
      • Rochester, Minnesota, United States, 55905
      • St. Cloud, Minnesota, United States, 56303
    • Missouri
      • Jefferson City, Missouri, United States, 65109
    • New Jersey
      • Neptune, New Jersey, United States, 07754
    • New York
      • New York, New York, United States, 10011
    • North Dakota
      • Fargo, North Dakota, United States, 58122
    • Ohio
      • Toledo, Ohio, United States, 43623
    • Pennsylvania
      • Scranton, Pennsylvania, United States, 18510
    • South Carolina
      • Charleston, South Carolina, United States, 29414
      • Sumter, South Carolina, United States, 29150
    • Texas
      • Dallas, Texas, United States, 75390-9110
    • Utah
      • Salt Lake City, Utah, United States, 84106
    • Wisconsin
      • Green Bay, Wisconsin, United States, 54303

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Regorafenib (Stivarga, BAY73-4506)+BSC
Participants received Regorafenib 160 mg per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus Best Supportive Care(BSC).
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)
Other: Best Supportive Care (BSC)
BSC includes any concomitant medications or treatments: antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any other symptomatic therapy necessary to provide BSC, except other investigational anti-tumor agents or anti-neoplastic chemo/hormonal/immuno-therapy.
PLACEBO_COMPARATOR: Placebo+BSC
Participants received matching placebo tablets per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus Best Supportive Care (BSC).
Other: Best Supportive Care (BSC)
BSC includes any concomitant medications or treatments: antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any other symptomatic therapy necessary to provide BSC, except other investigational anti-tumor agents or anti-neoplastic chemo/hormonal/immuno-therapy.
Drug: Placebo
matching placebo tablets for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 (19May2010 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals.
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.
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.
Objective Tumor Response
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. Tumor assessed at 8 week intervals.
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.
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.
Disease Control
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. Tumor assessed at 8 week intervals.
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.
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.
Tumor Response
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. Tumor assessed at 8 week intervals.
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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bayer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2010

Primary Completion (ACTUAL)

July 1, 2011

Study Completion (ACTUAL)

January 1, 2014

Study Registration Dates

First Submitted

April 8, 2010

First Submitted That Met QC Criteria

April 13, 2010

First Posted (ESTIMATE)

April 14, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

June 24, 2015

Last Update Submitted That Met QC Criteria

May 28, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14387
  • 2009-012787-14 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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