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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01103323
First received: April 8, 2010
Last updated: January 23, 2014
Last verified: January 2014
Results First Received: October 19, 2012  
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
Condition: Metastatic Colorectal Cancer
Interventions: Drug: Regorafenib (Stivarga, BAY73-4506)
Drug: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
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
Placebo Participants received matching placebo tablets per oral once daily for 3 weeks on 1 week off of every 4 week cycle

Participant Flow:   Overall Study
    Regorafenib (Stivarga, BAY73-4506)     Placebo  
STARTED     505     255  
Participants Received Treatment     500     253  
COMPLETED     386     232  
NOT COMPLETED     119     23  
Adverse Event                 42                 7  
Withdrawal by Subject                 16                 5  
Protocol Violation                 2                 0  
Physician Decision                 2                 0  
ongoing with treatment                 52                 9  
did not receive study treatment                 5                 2  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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
Placebo Participants received matching placebo tablets per oral once daily for 3 weeks on 1 week off of every 4 week cycle
Total Total of all reporting groups

Baseline Measures
    Regorafenib (Stivarga, BAY73-4506)     Placebo     Total  
Number of Participants  
[units: participants]
  505     255     760  
Age [1]
[units: Years]
Mean ( Full Range )
  60.7  
  ( 22 to 82 )  
  60.1  
  ( 25 to 85 )  
  60.5  
  ( 22 to 85 )  
Gender  
[units: Participants]
     
Female     194     102     296  
Male     311     153     464  
Eastern Cooperative Oncology Group (ECOG) performance status (PS) before treatment [2]
[units: Participants]
     
0     265     146     411  
1     240     109     349  
KRAS mutation [3]
[units: Participants]
     
No     205     94     299  
Yes     273     157     430  
Unknown     27     4     31  
[1] The age of the patient in years at enrollment in the study.
[2] ECOG PS is a scale that measures how cancer affects the daily life of a patient on an ordinal scale from grade 0 (best) to grade 5 (worst). 0=Fully active without restriction; 1= Restricted in physically strenuous activity; 2= Ambulatory, capable of all selfcare; 3= Capable of limited selfcare; 4= Completely disabled; 5= Dead
[3] KRAS - Kirsten rat sarcoma viral oncogene homolog (protein), member of the RAS family of GTPases (guanosine triphosphate hydrolases)



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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). ]

2.  Secondary:   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. ]

3.  Secondary:   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. ]

4.  Secondary:   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. ]
  Hide Outcome Measure 4

Measure Type Secondary
Measure Title Disease Control
Measure Description 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.
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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT

Reporting Groups
  Description
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
Placebo Participants received matching placebo tablets per oral once daily for 3 weeks on 1 week off of every 4 week cycle

Measured Values
    Regorafenib (Stivarga, BAY73-4506)     Placebo  
Number of Participants Analyzed  
[units: participants]
  505     255  
Disease Control  
[units: Percentage¬†of¬†participants]
  41.0     14.9  


Statistical Analysis 1 for Disease Control
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.000001
Difference [4] -25.94
95% Confidence Interval ( -32.06 to -19.82 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Two treatment groups compared using Cochran-Mantel-Haenszel (CMH) test adjusting for same stratification factors as at randomization.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Comparison based on pre-specified alpha level of 0.025 (1-sided).
[4] Other relevant estimation information:
  Difference = Placebo - Regorafenib 160 mg



5.  Secondary:   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. ]


  Serious Adverse Events


  Other Adverse Events


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
At 2nd IA, pre-specified O’Brien-Fleming-type efficacy boundary was crossed. DMC concluded OS result positive and after positive risk benefit assessment, recommended unblinding of study. OS from 2nd IA are the final formal and definitive results.  


Results Point of Contact:  
Name/Title: Therapeutic Area Head
Organization: BAYER
e-mail: clinical-trials-contact@bayerhealthcare.com


Publications of Results:

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: January 23, 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