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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: August 22, 2016
Last verified: August 2016
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
  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
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


  Outcome Measures
  Show All Outcome Measures

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) ]

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 ]

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 ]

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 ]

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. ]
  Hide Outcome Measure 5

Measure Type Secondary
Measure Title Objective Response Rate
Measure Description Objective response rate was defined as the percentage of subjects whose best response was Complete Response (CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target).) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Results are based on central evaluation.
Time Frame From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 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 
Participants Analyzed 
[Units: Participants]
 133   66 
Objective Response Rate 
[Units: Percentage of Participants]
Number (95% Confidence Interval)
 4.5 
 (1.7 to 9.6) 
 1.5 
 (0.0 to 8.2) 

No statistical analysis provided for Objective Response Rate



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 ]

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 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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
Overall survival results are confounded by the fact that 85% of the participants initially randomized to placebo switched to open-label regorafenib.


  More Information