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: May 28, 2015
Last verified: May 2015
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
Other: Best Supportive Care (BSC)

  Participant Flow
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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)+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).
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). Period 1 is placebo and placebo-regorafenib with placebo period only before unblinding. Period 2 is placebo-regorafenib with regorafenib period only.

Participant Flow for 2 periods

Period 1:   Without/Before Drug Switch
    Regorafenib (Stivarga, BAY73-4506)+BSC     Placebo+BSC  
STARTED     505     255  
Participants Received Treatment     500     253  
COMPLETED     429     237  
NOT COMPLETED     76     18  
Adverse Event                 50                 7  
Withdrawal by Subject                 17                 5  
Protocol Violation                 2                 0  
Physician Decision                 2                 0  
did not receive study treatment                 5                 2  
Switch to Regorafenib                 0                 4  

Period 2:   Switched From Placebo to Regorafenib
    Regorafenib (Stivarga, BAY73-4506)+BSC     Placebo+BSC  
STARTED     0     4 [1]
COMPLETED     0     3  
NOT COMPLETED     0     1  
Adverse Event                 0                 1  
[1] Participants in the placebo+BSC group switched to Regorafenib treatment after unblinding.



  Baseline Characteristics
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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)+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).
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).
Total Total of all reporting groups

Baseline Measures
    Regorafenib (Stivarga, BAY73-4506)+BSC     Placebo+BSC     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
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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 (19May2010 - 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 (19May2010 - 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 (19May2010 - 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 (19May2010 - 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)+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).
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)

Measured Values
    Regorafenib (Stivarga, BAY73-4506)+BSC     Placebo+BSC  
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 (19May2010 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats


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