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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:
ClinicalTrials.gov Identifier:
NCT01271712
First Posted: January 7, 2011
Last Update Posted: October 5, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Bayer
Results First Submitted: May 24, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, 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   91 [1]   58 [2] 
NOT COMPLETED   42   8 
Death                2                0 
Lack of Efficacy                1                0 
Adverse Event                9                4 
Progressive disease                23                3 
Withdrawal by Subject                4                1 
Non compliance with study drug                2                0 
receive no study drug                1                0 
[1] 91 participants started open-label treatment with regorafenib
[2] 58 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   91   58 
COMPLETED   0   0 
NOT COMPLETED   91   58 
Death                6                5 
Withdrawal by Subject                6                11 
Physician Decision                2                0 
Adverse Event                12                8 
Progressive disease                56                31 
Ongoing with open-label treatment                6                1 
Non-compliance with study drug                1                0 
Protocol Violation                0                1 
Switching to other therapy                2                1 

Period 3:   Safety Follow-up
    Regorafenib (Stivarga, BAY73-4506)   Placebo First, Then Option of Open Label Regorafenib Treatment
STARTED   118 [1]   52 [1] 
COMPLETED   97   37 
NOT COMPLETED   21   15 
Death                11                7 
Withdrawal by Subject                4                2 
Protocol Violation                1                1 
Ongoing safety follow-up                3                4 
No follow-up                1                1 
Progressive disease                1                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   100 [1]   39 [1] 
COMPLETED   85 [2]   33 [3] 
NOT COMPLETED   15   6 
Ongoing survival follow-up                15                6 
[1] All participants entered Survival Follow-up immediately after safety follow-up
[2] 85 participants died and completed survival follow-up.
[3] 33 participants died and completed survival follow-up.



  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 
Overall Participants Analyzed 
[Units: Participants]
 133   66   199 
Age 
[Units: Years]
Mean (Standard Deviation)
 58.2  (12.5)   58.1  (13.9)   58.2  (12.9) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      48  36.1%      24  36.4%      72  36.2% 
Male      85  63.9%      42  63.6%      127  63.8% 
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 
[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).
Prior anti-cancer drug group [1] 
[Units: Participants]
     
3rd line   74   39   113 
4th line and beyond   59   27   86 
[1] 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
  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 (08 Jun 2015) ]

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. ]

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 ]
  Hide Outcome Measure 6

Measure Type Secondary
Measure Title Disease Control Rate (DCR)
Measure Description Disease Control Rate (DCR) 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).), 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.), or Stable Disease (SD: steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.) according to RECIST v1.1 criteria. SD had to be maintained for at least 12 weeks from the first demonstration of that rating. 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  

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 
Disease Control Rate (DCR) 
[Units: Percentage of Participants]
Number (95% Confidence Interval)
 52.6 
 (43.8 to 61.3) 
 9.1 
 (3.4 to 18.7) 

No statistical analysis provided for Disease Control Rate (DCR)



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
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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
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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 Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


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


Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01271712     History of Changes
Other Study ID Numbers: 14874
2009-017957-37 ( EudraCT Number )
First Submitted: December 17, 2010
First Posted: January 7, 2011
Results First Submitted: May 24, 2013
Results First Posted: October 25, 2013
Last Update Posted: October 5, 2017