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Study of Regorafenib as a 3rd-line or Beyond Treatment for Gastrointestinal Stromal Tumors (GIST) (GRID)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01271712
First received: December 17, 2010
Last updated: November 24, 2014
Last verified: November 2014
History of Changes
Results First Received: May 24, 2013  
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: Gastrointestinal Stromal Tumors
Interventions: Drug: Regorafenib (Stivarga, BAY73-4506)
Drug: Placebo
Drug: Best supportive care

  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
A total of 240 participants with metastatic and/or unresectable GIST whose disease had progressed despite prior treatments with at least imatinib and sunitinib were screened; 199 were randomized. Patients must have shown objective disease progression or intolerance to imatinib, as well as disease progression while on sunitinib treatment.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were randomized in a 2:1 ratio to receive either regorafenib (133 patients) or placebo (66 patients). Randomization was stratified according 3rd vs. 4th line of therapy (at least 50% of patients were to be 3rd line), and geographical region (Asia vs.rest of world).

Reporting Groups
  Description
Regorafenib (Stivarga, BAY73-4506) Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
Placebo First, Then Option of Open Label Regorafenib Treatment Double blind phase: participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks. Open Label phase: participants on placebo who switched to Regorafenib, received Regorafenib 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks.

Participant Flow for 4 periods

 Period 1:   Double Blind Treatment
    Regorafenib (Stivarga, BAY73-4506)     Placebo First, Then Option of Open Label Regorafenib Treatment  
STARTED     133     66  
Participants Received Treatment     132     66  
COMPLETED     41 [1]   56 [2]
NOT COMPLETED     92     10  
Death                 2                 0  
Lack of Efficacy                 1                 0  
Adverse Event                 8                 4  
Progressive disease                 21                 3  
Withdrawal by Subject                 4                 0  
Non compliance with study drug                 2                 0  
Ongoing in double-blind treatment                 53                 3  
receive no study drug                 1                 0  
[1] 41 participants started open-label treatment with regorafenib
[2] 56 participants started open-label treatment with regorafenib

Period 2:   Open Label Treatment
    Regorafenib (Stivarga, BAY73-4506)     Placebo First, Then Option of Open Label Regorafenib Treatment  
STARTED     41     56  
Participants Received Treatment     41     56  
COMPLETED     0     0  
NOT COMPLETED     41     56  
Death                 1                 1  
Withdrawal by Subject                 0                 5  
Physician Decision                 2                 0  
Adverse Event                 2                 4  
Progressive disease                 12                 13  
Ongoing with open-label treatment                 24                 33  

Period 3:   Safety Follow-up
    Regorafenib (Stivarga, BAY73-4506)     Placebo First, Then Option of Open Label Regorafenib Treatment  
STARTED     36 [1]   7 [1]
COMPLETED     27     4  
NOT COMPLETED     9     3  
Death                 4                 2  
Withdrawal by Subject                 1                 1  
Protocol Violation                 1                 0  
Ongoing with open-label treatment                 3                 0  
[1] All participants who discontinued study drug entered 30-day Safety Follow-up

Period 4:   Survival Follow-up
    Regorafenib (Stivarga, BAY73-4506)     Placebo First, Then Option of Open Label Regorafenib Treatment  
STARTED     27 [1]   4 [1]
COMPLETED     0     0  
NOT COMPLETED     27     4  
Death                 13                 3  
Ongoing with open-label treatment                 14                 1  
[1] All participants entered Survival Follow-up 30 days after discontinuation of study drug



  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) Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
Placebo Participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
Total Total of all reporting groups

Baseline Measures
    Regorafenib (Stivarga, BAY73-4506)     Placebo     Total  
Number of Participants  
[units: participants]
 		  133     66     199  
Age  
[units: Years]
Mean ± Standard Deviation 		  58.2  ± 12.5     58.1  ± 13.9     58.2  ± 12.9  
Gender  
[units: Participants]
 		     
Female     48     24     72  
Male     85     42     127  
ECOG Performance Status (PS)] [1]
[units: Participants]
 		     
PS 0     73     37     110  
PS 1     60     29     89  
PS 2     0     0     0  
Missing     0     0     0  
Prior anti-cancer drug group [2]
[units: Participants]
 		     
3rd line     74     39     113  
4th line and beyond     59     27     86  
[1] ECOG = Eastern cooperative oncology group PS levels are 0 (Fully active, able to carry on all pre-disease performance), 1 (ambulatory and able to carry out work of a light or sedentary), 2 (Ambulatory and capable of all selfcare but unable to carry out any work activities), 3 (Capable of only limited selfcare, confined to bed or chair more than 50% of awake time), 4 (Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair) and 5 (death).
[2] 3rd line: 3rd in sequence of multiple therapies: imatinib (1st); sunitinib (2nd). 4th line and beyond: 4th in sequence of multiple therapies: imatinib (1st); sunitinib (2nd); other (3rd).



  Outcome Measures
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1.  Primary:   Progression-free Survival   [ Time Frame: From randomization of the first subject until approximately 144 progression-free survival events had occurred (study duration approximately one year) ]
  Show Outcome Measure 1

2.  Secondary:   Overall Survival   [ Time Frame: From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately one year ]
  Hide Outcome Measure 2

Measure Type Secondary
Measure Title Overall Survival
Measure Description Overall Survival (OS) was defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their date of last contact. Since the median value could not be estimated due to censored data, the number of participants with events is presented.
Time Frame From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately one year  
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.
Full Analysis Set (FAS)

Reporting Groups
  Description
Regorafenib (Stivarga, BAY73-4506) Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
Placebo Participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks

Measured Values
    Regorafenib (Stivarga, BAY73-4506)     Placebo  
Number of Participants Analyzed  
[units: participants]
 		  133     66  
Overall Survival  
[units: Percentage of participants]
 		  21.8     25.8  


Statistical Analysis 1 for Overall Survival
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.198896
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  stratified
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.

Statistical Analysis 2 for Overall Survival
Groups [1] All groups
Method [2] Regression, Cox
Hazard Ratio (HR) [3] 0.772
95% Confidence Interval ( 0.423 to 1.408 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Hazard ratio and its 95% CI was based on stratified Cox Regression Model
[2] Other relevant method information, such as adjustments or degrees of freedom:
  stratified
[3] Other relevant estimation information:
  regorafenib over control



3.  Secondary:   Time to Progression (TTP)   [ Time Frame: From randomization of the first subject until until date of database cutoff (26 Jan 2012); study duration approximately 1 year ]
  Show Outcome Measure 3

4.  Secondary:   Tumor Response   [ Time Frame: From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year ]
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5.  Secondary:   Objective Response Rate   [ Time Frame: From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year. ]
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6.  Secondary:   Disease Control Rate (DCR)   [ Time Frame: From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year ]
  Show Outcome Measure 6

7.  Secondary:   Duration of Response (DOR)   [ Time Frame: From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year ]
  Show Outcome Measure 7


  Serious Adverse Events
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  Other Adverse Events
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  Limitations and Caveats
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  More Information
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