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: May 20, 2014
Last verified: May 2014
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


  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) ]

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. ]

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
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Time Frame From randomization of the first subject until date of database cutoff (26 Jan 2012).
Additional Description Acronyms used: International Normalized Ratio (INR).

Reporting Groups
  Description
Regorafenib (Double Blind Only) Regorafenib (Double Blind study phase only): 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 ( Double Blind Only) Placebo (Double Blind study phase only): 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
Regorafenib, Open Label Only (Regorafenib Continued) Continue Regorafenib (Open Label study phase only): Participants continue to receive 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, Open Label Only (Switch to Regorafenib) Switch to Regorafenib (Open Label study phase only): Participants switched to Open label Regorafenib treatment from Placebo. 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

Serious Adverse Events
    Regorafenib (Double Blind Only)     Placebo ( Double Blind Only)     Regorafenib, Open Label Only (Regorafenib Continued)     Placebo, Open Label Only (Switch to Regorafenib)  
Total, serious adverse events          
# participants affected / at risk     38/132 (28.79%)     14/66 (21.21%)     9/41 (21.95%)     20/56 (35.71%)  
Blood and lymphatic system disorders          
Anemia * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Cardiac disorders          
Acute coronary syndrome * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Cardiac arrest * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Cardiac disorders - Other * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Ear and labyrinth disorders          
Vertigo * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     1/41 (2.44%)     0/56 (0.00%)  
Gastrointestinal disorders          
Abdominal pain * 1        
# participants affected / at risk     5/132 (3.79%)     1/66 (1.52%)     0/41 (0.00%)     1/56 (1.79%)  
Ascites * 1        
# participants affected / at risk     3/132 (2.27%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Colonic fistula * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Colonic obstruction * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     0/41 (0.00%)     1/56 (1.79%)  
Colonic perforation * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     0/41 (0.00%)     1/56 (1.79%)  
Constipation * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Diarrhea * 1        
# participants affected / at risk     2/132 (1.52%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Gastric hemorrhage * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Intra-abdominal hemorrhage * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     1/41 (2.44%)     0/56 (0.00%)  
Ileus * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     1/56 (1.79%)  
Lower gastrointestinal hemorrhage * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Nausea * 1        
# participants affected / at risk     1/132 (0.76%)     1/66 (1.52%)     0/41 (0.00%)     1/56 (1.79%)  
Obstruction gastric * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     1/41 (2.44%)     0/56 (0.00%)  
Gastrointestinal disorders - Other * 1        
# participants affected / at risk     1/132 (0.76%)     1/66 (1.52%)     0/41 (0.00%)     0/56 (0.00%)  
Peritoneal necrosis * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Retroperitoneal hemorrhage * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Upper gastrointestinal hemorrhage * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Vomiting * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     0/41 (0.00%)     1/56 (1.79%)  
General disorders          
Death NOS * 1        
# participants affected / at risk     1/132 (0.76%)     2/66 (3.03%)     0/41 (0.00%)     0/56 (0.00%)  
Fatigue * 1        
# participants affected / at risk     2/132 (1.52%)     2/66 (3.03%)     0/41 (0.00%)     2/56 (3.57%)  
Fever * 1        
# participants affected / at risk     3/132 (2.27%)     0/66 (0.00%)     0/41 (0.00%)     1/56 (1.79%)  
Malaise * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Multi-organ failure * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     0/41 (0.00%)     1/56 (1.79%)  
Non-cardiac chest pain * 1        
# participants affected / at risk     0/132 (0.00%)     1/66 (1.52%)     0/41 (0.00%)     0/56 (0.00%)  
General disorders and administration site conditions - Other * 1        
# participants affected / at risk     1/132 (0.76%)     1/66 (1.52%)     0/41 (0.00%)     1/56 (1.79%)  
Pain * 1        
# participants affected / at risk     1/132 (0.76%)     2/66 (3.03%)     0/41 (0.00%)     1/56 (1.79%)  
Hepatobiliary disorders          
Bile duct stenosis * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     0/41 (0.00%)     1/56 (1.79%)  
Cholecystitis * 1        
# participants affected / at risk     0/132 (0.00%)     1/66 (1.52%)     0/41 (0.00%)     0/56 (0.00%)  
Hepatic failure * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     1/41 (2.44%)     0/56 (0.00%)  
Hepatic hemorrhage * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     1/41 (2.44%)     0/56 (0.00%)  
Hepatobiliary disorders - Other * 1        
# participants affected / at risk     1/132 (0.76%)     1/66 (1.52%)     0/41 (0.00%)     0/56 (0.00%)  
Portal vein thrombosis * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     0/41 (0.00%)     1/56 (1.79%)  
Infections and infestations          
Abdominal infection * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Catheter related infection * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     0/41 (0.00%)     1/56 (1.79%)  
Enterocolitis infectious * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     0/41 (0.00%)     2/56 (3.57%)  
Lung infection * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     0/41 (0.00%)     1/56 (1.79%)  
Infections and infestations - Other * 1        
# participants affected / at risk     2/132 (1.52%)     0/66 (0.00%)     0/41 (0.00%)     1/56 (1.79%)  
Sepsis * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     1/41 (2.44%)     0/56 (0.00%)  
Upper respiratory infection * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Urinary tract infection * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Wound infection * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Investigations          
Alanine aminotransferase increased * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     2/56 (3.57%)  
Aspartate aminotransferase increased * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     0/41 (0.00%)     1/56 (1.79%)  
Blood bilirubin increased * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     1/41 (2.44%)     1/56 (1.79%)  
Creatinine increased * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
INR increased * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Neutrophil count decreased * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     0/41 (0.00%)     1/56 (1.79%)  
Investigations - Other * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Platelet count decreased * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     0/41 (0.00%)     1/56 (1.79%)  
Metabolism and nutrition disorders          
Acidosis * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Dehydration * 1        
# participants affected / at risk     3/132 (2.27%)     1/66 (1.52%)     0/41 (0.00%)     0/56 (0.00%)  
Hyperglycemia * 1        
# participants affected / at risk     0/132 (0.00%)     1/66 (1.52%)     0/41 (0.00%)     0/56 (0.00%)  
Hyperkalemia * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Musculoskeletal and connective tissue disorders          
Back pain * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     0/41 (0.00%)     2/56 (3.57%)  
Generalized muscle weakness * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Muscle weakness right-sided * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)          
Tumor pain * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     0/41 (0.00%)     2/56 (3.57%)  
Nervous system disorders          
Hypoglossal nerve disorder * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Nervous system disorders - Other * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     0/41 (0.00%)     1/56 (1.79%)  
Paresthesia * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Reversible posterior leukoencephalopathy syndrome * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Somnolence * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Psychiatric disorders          
Confusion * 1        
# participants affected / at risk     0/132 (0.00%)     1/66 (1.52%)     0/41 (0.00%)     0/56 (0.00%)  
Mania * 1        
# participants affected / at risk     0/132 (0.00%)     1/66 (1.52%)     0/41 (0.00%)     0/56 (0.00%)  
Psychiatric disorders - Other * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Renal and urinary disorders          
Acute kidney injury * 1        
# participants affected / at risk     2/132 (1.52%)     0/66 (0.00%)     0/41 (0.00%)     1/56 (1.79%)  
Renal and urinary disorders - Other * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Respiratory, thoracic and mediastinal disorders          
Adult respiratory distress syndrome * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     1/41 (2.44%)     0/56 (0.00%)  
Dyspnea * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Pneumonitis * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Skin and subcutaneous tissue disorders          
Rash maculo-papular * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     0/41 (0.00%)     1/56 (1.79%)  
Surgical and medical procedures          
Surgical and medical procedures - Other * 1        
# participants affected / at risk     0/132 (0.00%)     0/66 (0.00%)     2/41 (4.88%)     0/56 (0.00%)  
Vascular disorders          
Hypertension * 1        
# participants affected / at risk     1/132 (0.76%)     0/66 (0.00%)     0/41 (0.00%)     0/56 (0.00%)  
Thromboembolic event * 1        
# participants affected / at risk     2/132 (1.52%)     0/66 (0.00%)     1/41 (2.44%)     1/56 (1.79%)  
* Events were collected by non-systematic assessment
1 Term from vocabulary, NCI-CTCAE v.4.0




  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.


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