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

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ClinicalTrials.gov Identifier: NCT01271712
Recruitment Status : Active, not recruiting
First Posted : January 7, 2011
Results First Posted : October 25, 2013
Last Update Posted : October 10, 2018
Sponsor:
Information provided by (Responsible Party):
Bayer

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
Enrollment 199

Recruitment Details 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 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).
Arm/Group Title Regorafenib (Stivarga, BAY73-4506) Placebo First, Then Option of Open Label Regorafenib Treatment
Hide Arm/Group Description 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 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.
Period Title: Double Blind Treatment
Started 133 66
Participants Received Treatment 132 66
Completed 91 [1] 58 [2]
Not Completed 42 8
Reason Not Completed
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 Title: Open Label Treatment
Started 91 58
Completed 0 0
Not Completed 91 58
Reason Not Completed
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 Title: Safety Follow-up
Started 118 [1] 52 [1]
Completed 97 37
Not Completed 21 15
Reason Not Completed
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 Title: Survival Follow-up
Started 100 [1] 39 [1]
Completed 85 [2] 33 [3]
Not Completed 15 6
Reason Not Completed
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.
Arm/Group Title Regorafenib (Stivarga, BAY73-4506) Placebo Total
Hide Arm/Group Description 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 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 of all reporting groups
Overall Number of Baseline Participants 133 66 199
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 133 participants 66 participants 199 participants
58.2  (12.5) 58.1  (13.9) 58.2  (12.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 133 participants 66 participants 199 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] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 133 participants 66 participants 199 participants
PS 0 73 37 110
PS 1 60 29 89
PS 2 0 0 0
Missing 0 0 0
[1]
Measure Description: 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] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 133 participants 66 participants 199 participants
3rd line 74 39 113
4th line and beyond 59 27 86
[1]
Measure Description: 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).
1.Primary Outcome
Title Progression-free Survival
Hide Description Progression-free Survival (PFS) was defined as the time from date of randomization to radiological disease progression or death due to any cause, whichever occurs first. PFS was based on central radiological assessment using modified RECIST (Response Evaluation Criteria in Solid Tumors) v.1.1. Progression is defined as at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study; or unequivocal progression of existing non-target lesions; or appearance of new lesions. Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation. Results are based on central evaluation.
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 DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) - defined as all randomized participants.
Arm/Group Title Regorafenib (Stivarga, BAY73-4506) Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 133 66
Median (95% Confidence Interval)
Unit of Measure: Days
147
(122 to 173)
28
(28 to 32)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Regorafenib (Stivarga, BAY73-4506), Placebo
Comments The two treatment groups were compared using a stratified log rank test with a one-sided alpha of 0.01 stratified by (3rd vs 4th-line; and geographical region). The null hypothesis that both treatment arms have the same PFS distribution was tested against the alternative hypothesis that the distribution of PFS in the regorafenib arm is different from the control arm according to a proportional hazards relation between the treatment arms.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.000001
Comments [Not Specified]
Method Log Rank
Comments stratified
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Regorafenib (Stivarga, BAY73-4506), Placebo
Comments Hazard ratio and its 95% CI (Confidence Interval) was based on stratified Cox Regression Model
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Cox
Comments stratified
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.268
Confidence Interval (2-Sided) 95%
0.185 to 0.388
Estimation Comments regorafenib over placebo
2.Secondary Outcome
Title Overall Survival
Hide 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. Median OS was not observed at the time of PFS analysis and first analysis of OS, therefore only the proportion of death events was reported in the results posting system. This approach was maintained for the subsequent updates in the results posting system.
Time Frame From randomization of the first subject until date of database cutoff (08 Jun 2015)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS). 58 (87.9%) patients in placebo group and 91 (68.4%) patients in regorafenib had started open-label treatment with regorafenib before time of final database cutoff 08 Jun 2015
Arm/Group Title Regorafenib (Stivarga, BAY73-4506) Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 133 66
Measure Type: Number
Unit of Measure: Percentage of patients with death
82.0 80.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Regorafenib (Stivarga, BAY73-4506), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.285777
Comments [Not Specified]
Method Log Rank
Comments stratified
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Regorafenib (Stivarga, BAY73-4506), Placebo
Comments Hazard ratio and its 95% CI was based on stratified Cox Regression Model
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Cox
Comments stratified
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.909
Confidence Interval (2-Sided) 95%
0.653 to 1.265
Estimation Comments regorafenib over control. 58 (87.9%) patients in placebo group and 91 (68.4%) patients in regorafenib had started open-label treatment with regorafenib before time of final database cutoff 08 Jun 2015.
3.Secondary Outcome
Title Time to Progression (TTP)
Hide Description Time to progression (TTP) was defined as the time from date of randomization to disease progression (based on central radiological assessment using modified RECIST [Response Evaluation Criteria in Solid Tumors] v.1.1). Progression is defined as at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study; or unequivocal progression of existing non-target lesions; or appearance of new lesions. Subjects without progression at the time of analysis were censored at their last date of tumor evaluation. Results are based on central evaluation.
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 DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS)
Arm/Group Title Regorafenib (Stivarga, BAY73-4506) Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 133 66
Median (95% Confidence Interval)
Unit of Measure: Days
165
(125 to 174)
28
(28 to 34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Regorafenib (Stivarga, BAY73-4506), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.000001
Comments [Not Specified]
Method Log Rank
Comments stratified
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Regorafenib (Stivarga, BAY73-4506), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Cox
Comments stratified
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.248
Confidence Interval (2-Sided) 95%
0.170 to 0.364
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Tumor Response
Hide Description Tumor Response of a subject was defined as the best tumor response (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.], 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.], or Progressive Disease [PD: at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study or unequivocal progression of existing non-target lesions, or appearance of new lesions.]) observed during the trial period and assessed according to RECIST v1.1 criteria. 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS)
Arm/Group Title Regorafenib (Stivarga, BAY73-4506) Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 133 66
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Complete Response (CR)
0
(0 to 0)
0
(0 to 0)
Partial Response (PR)
4.5
(1.7 to 9.6)
1.5
(0 to 8.2)
Stable Disease (SD)
71.4
(63.0 to 78.9)
33.3
(22.2 to 46.0)
Progressive Disease (PD)
21.1
(14.5 to 29.0)
63.6
(50.9 to 75.1)
Not Assessable
3.0
(0.8 to 7.5)
1.5
(0 to 8.2)
5.Secondary Outcome
Title Objective Response Rate
Hide 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS)
Arm/Group Title Regorafenib (Stivarga, BAY73-4506) Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 133 66
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
4.5
(1.7 to 9.6)
1.5
(0.0 to 8.2)
6.Secondary Outcome
Title Disease Control Rate (DCR)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS)
Arm/Group Title Regorafenib (Stivarga, BAY73-4506) Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 133 66
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
52.6
(43.8 to 61.3)
9.1
(3.4 to 18.7)
7.Secondary Outcome
Title Duration of Response (DOR)
Hide Description Duration of Response was defined as the time from date of first response (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.]) to the date when Progressive Disease (PD: at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study or unequivocal progression of existing non-target lesions, or appearance of new lesions.) is first documented, or to the date of death, whichever occurs first, according to RECIST v1.1. Subjects still having CR or PR and have not died at the time of analysis were censored at their last date of tumor evaluation. Duration of response defined for responders only, i.e CR or PR. 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set with response participants
Arm/Group Title Regorafenib (Stivarga, BAY73-4506) Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 6 1
Median (95% Confidence Interval)
Unit of Measure: Days
99 [1] 
(42 to NA)
30 [2] 
(NA to NA)
[1]
A complete confidence interval (CI) cannot be calculated because there are too few patients in the data set.
[2]
CI cannot be calculated because there is only 1 patient in the data set.
Time Frame From randomization of the first subject until date of database cutoff (08 Jun 2015).
Adverse Event Reporting Description At primary completion (cutoff 26JAN2012) blinded patients who received either regorafenib or placebo were reported in “Regorafenib (DoubleBlindOnly)” and “Placebo (DoubleBlindOnly)” respectively; patients who received regorafenib after unblinding were reported in "Regorafenib, OpenLabelOnly(RegorafenibCont.)" and "Placebo, OpenLabelOnly(Switch to Regorafenib)". This safety update (cutoff 08JUN2015) was reported in “Treated with Regorafenib at any time” and “Treated with Regorafenib for>1 year”.
 
Arm/Group Title Regorafenib (Double Blind Only) Placebo (Double Blind Only) Placebo, Open Label Only (Switch to Regorafenib) Treated With Regorafenib at Any Time Treated With Regorafenib for > 1 Year
Hide Arm/Group Description 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. Data cut-off date 26 JAN 2012. 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. Data cut-off date 26 JAN 2012. 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. Data cut-off date 08 JUN 2015. Treated with Regorafenib at any time (including placebo switched to regorafenib): At any time, 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. Data cut-off date 08 JUN 2015. Treated with Regorafenib for > 1 year (including placebo switched to regorafenib): For more than a year, 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. Data cut-off date 08 JUN 2015.
All-Cause Mortality
Regorafenib (Double Blind Only) Placebo (Double Blind Only) Placebo, Open Label Only (Switch to Regorafenib) Treated With Regorafenib at Any Time Treated With Regorafenib for > 1 Year
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Regorafenib (Double Blind Only) Placebo (Double Blind Only) Placebo, Open Label Only (Switch to Regorafenib) Treated With Regorafenib at Any Time Treated With Regorafenib for > 1 Year
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   23/41 (56.10%)      8/8 (100.00%)      31/58 (53.45%)      103/190 (54.21%)      39/75 (52.00%)    
Blood and lymphatic system disorders           
Anemia * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  2 2/190 (1.05%)  3 0/75 (0.00%)  0
Cardiac disorders           
Acute coronary syndrome * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 7/190 (3.68%)  7 6/75 (8.00%)  6
Atrial fibrillation * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 1/190 (0.53%)  1 1/75 (1.33%)  1
Cardiac arrest * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Chest pain - cardiac * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  2 1/75 (1.33%)  2
Conduction disorder * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 1/75 (1.33%)  1
Heart failure * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 1/75 (1.33%)  1
Cardiac disorders - Other * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Congenital, familial and genetic disorders           
Congenital, familial and genetic disorders - Other * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Ear and labyrinth disorders           
Vertigo * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Eye disorders           
Eye disorders - Other * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 1/190 (0.53%)  1 1/75 (1.33%)  1
Gastrointestinal disorders           
Abdominal pain * 1  5/41 (12.20%)  5 0/8 (0.00%)  0 2/58 (3.45%)  2 9/190 (4.74%)  10 1/75 (1.33%)  1
Anal fistula * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 1/75 (1.33%)  1
Ascites * 1  3/41 (7.32%)  4 0/8 (0.00%)  0 0/58 (0.00%)  0 3/190 (1.58%)  4 0/75 (0.00%)  0
Colonic fistula * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Colonic obstruction * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  2 1/190 (0.53%)  2 0/75 (0.00%)  0
Colonic perforation * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  2 2/190 (1.05%)  4 1/75 (1.33%)  2
Constipation * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 2/190 (1.05%)  2 2/75 (2.67%)  2
Diarrhea * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 3/190 (1.58%)  4 2/75 (2.67%)  3
Gastric hemorrhage * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 1/58 (1.72%)  1 2/190 (1.05%)  2 0/75 (0.00%)  0
Intra-abdominal hemorrhage * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 3/190 (1.58%)  3 0/75 (0.00%)  0
Ileus * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 1/58 (1.72%)  1 2/190 (1.05%)  2 0/75 (0.00%)  0
Lower gastrointestinal hemorrhage * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Nausea * 1  0/41 (0.00%)  0 1/8 (12.50%)  1 1/58 (1.72%)  1 2/190 (1.05%)  2 1/75 (1.33%)  1
Obstruction gastric * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Gastrointestinal disorders - Other * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Peritoneal necrosis * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Retroperitoneal hemorrhage * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Small intestinal obstruction * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  2 1/75 (1.33%)  2
Upper gastrointestinal hemorrhage * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Vomiting * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 2/190 (1.05%)  2 1/75 (1.33%)  1
General disorders           
Death NOS * 1  1/41 (2.44%)  1 2/8 (25.00%)  2 1/58 (1.72%)  1 3/190 (1.58%)  3 2/75 (2.67%)  2
Edema limbs * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  2 1/190 (0.53%)  2 0/75 (0.00%)  0
Fatigue * 1  2/41 (4.88%)  4 1/8 (12.50%)  2 2/58 (3.45%)  2 5/190 (2.63%)  7 2/75 (2.67%)  2
Fever * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 2/58 (3.45%)  2 5/190 (2.63%)  5 2/75 (2.67%)  2
Malaise * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Multi-organ failure * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 2/190 (1.05%)  2 0/75 (0.00%)  0
Non-cardiac chest pain * 1  0/41 (0.00%)  0 1/8 (12.50%)  1 0/58 (0.00%)  0 0/190 (0.00%)  0 0/75 (0.00%)  0
General disorders and administration site conditions - Other * 1  1/41 (2.44%)  1 1/8 (12.50%)  1 2/58 (3.45%)  3 5/190 (2.63%)  6 3/75 (4.00%)  3
Pain * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 2/58 (3.45%)  3 3/190 (1.58%)  4 1/75 (1.33%)  1
Hepatobiliary disorders           
Bile duct stenosis * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 2/190 (1.05%)  2 1/75 (1.33%)  1
Cholecystitis * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 1/75 (1.33%)  1
Hepatic failure * 1  1/41 (2.44%)  2 0/8 (0.00%)  0 1/58 (1.72%)  1 3/190 (1.58%)  4 0/75 (0.00%)  0
Hepatic hemorrhage * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 2/190 (1.05%)  3 1/75 (1.33%)  1
Hepatobiliary disorders - Other * 1  0/41 (0.00%)  0 1/8 (12.50%)  1 1/58 (1.72%)  1 2/190 (1.05%)  2 1/75 (1.33%)  1
Portal vein thrombosis * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 1/190 (0.53%)  1 0/75 (0.00%)  0
Infections and infestations           
Abdominal infection * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 2/190 (1.05%)  2 0/75 (0.00%)  0
Bronchial infection * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 2/190 (1.05%)  3 1/75 (1.33%)  2
Catheter related infection * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  2 1/190 (0.53%)  2 0/75 (0.00%)  0
Enterocolitis infectious * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 2/58 (3.45%)  3 2/190 (1.05%)  3 1/75 (1.33%)  2
Lung infection * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 2/190 (1.05%)  2 1/75 (1.33%)  1
Infections and infestations - Other * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 4/58 (6.90%)  4 8/190 (4.21%)  9 3/75 (4.00%)  4
Sepsis * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 2/58 (3.45%)  2 3/190 (1.58%)  3 1/75 (1.33%)  1
Upper respiratory infection * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 3/190 (1.58%)  3 3/75 (4.00%)  3
Urinary tract infection * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 1/75 (1.33%)  1
Wound infection * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Injury, poisoning and procedural complications           
Fracture * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  2 3/190 (1.58%)  4 2/75 (2.67%)  3
Hip fracture * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 1/190 (0.53%)  1 1/75 (1.33%)  1
Investigations           
Alanine aminotransferase increased * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  2 3/190 (1.58%)  6 1/75 (1.33%)  3
Aspartate aminotransferase increased * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 1/190 (0.53%)  1 0/75 (0.00%)  0
Blood bilirubin increased * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 2/58 (3.45%)  2 3/190 (1.58%)  3 1/75 (1.33%)  1
Creatinine increased * 1  1/41 (2.44%)  2 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  2 0/75 (0.00%)  0
INR increased * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 1/75 (1.33%)  1
Neutrophil count decreased * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 1/190 (0.53%)  1 0/75 (0.00%)  0
Investigations - Other * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 2/190 (1.05%)  2 0/75 (0.00%)  0
Platelet count decreased * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  2 1/190 (0.53%)  2 0/75 (0.00%)  0
Metabolism and nutrition disorders           
Acidosis * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Anorexia * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Dehydration * 1  0/41 (0.00%)  0 1/8 (12.50%)  1 0/58 (0.00%)  0 3/190 (1.58%)  3 3/75 (4.00%)  3
Hyperglycemia * 1  0/41 (0.00%)  0 1/8 (12.50%)  1 0/58 (0.00%)  0 0/190 (0.00%)  0 0/75 (0.00%)  0
Hyperkalemia * 1  1/41 (2.44%)  3 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  3 0/75 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Back pain * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 2/58 (3.45%)  2 2/190 (1.05%)  2 1/75 (1.33%)  1
Generalized muscle weakness * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 1/75 (1.33%)  1
Musculoskeletal and connective tissue disorder - Other * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 1/190 (0.53%)  1 1/75 (1.33%)  1
Muscle weakness right-sided * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 3/58 (5.17%)  3 6/190 (3.16%)  6 3/75 (4.00%)  3
Tumor pain * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 2/58 (3.45%)  4 3/190 (1.58%)  5 1/75 (1.33%)  1
Nervous system disorders           
Amnesia * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 1/75 (1.33%)  1
Hypoglossal nerve disorder * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Intracranial hemorrhage * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 1/75 (1.33%)  1
Nervous system disorders - Other * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 2/58 (3.45%)  2 2/190 (1.05%)  2 0/75 (0.00%)  0
Paresthesia * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Reversible posterior leukoencephalopathy syndrome * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Somnolence * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Stroke * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 2/190 (1.05%)  2 2/75 (2.67%)  2
Transient ischemic attacks * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 1/75 (1.33%)  1
Psychiatric disorders           
Confusion * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 1/190 (0.53%)  1 1/75 (1.33%)  1
Mania * 1  0/41 (0.00%)  0 1/8 (12.50%)  4 0/58 (0.00%)  0 0/190 (0.00%)  0 0/75 (0.00%)  0
Psychiatric disorders - Other * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Renal and urinary disorders           
Acute kidney injury * 1  2/41 (4.88%)  2 0/8 (0.00%)  0 1/58 (1.72%)  2 3/190 (1.58%)  4 0/75 (0.00%)  0
Renal and urinary disorders - Other * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 3/190 (1.58%)  4 1/75 (1.33%)  2
Renal colic * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 1/75 (1.33%)  1
Urinary retention * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 2/190 (1.05%)  2 1/75 (1.33%)  1
Respiratory, thoracic and mediastinal disorders           
Adult respiratory distress syndrome * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Dyspnea * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 2/190 (1.05%)  2 0/75 (0.00%)  0
Pleural effusion * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 1/75 (1.33%)  1
Pneumonitis * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Respiratory failure * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 1/75 (1.33%)  1
Skin and subcutaneous tissue disorders           
Rash maculo-papular * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 1/190 (0.53%)  1 1/75 (1.33%)  1
Surgical and medical procedures           
Surgical and medical procedures - Other * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 4/190 (2.11%)  4 2/75 (2.67%)  2
Vascular disorders           
Hypertension * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Vascular disorders - Other * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 0/75 (0.00%)  0
Peripheral ischemia * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 0/58 (0.00%)  0 1/190 (0.53%)  1 1/75 (1.33%)  1
Thromboembolic event * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 1/58 (1.72%)  2 4/190 (2.11%)  5 0/75 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, NCI-CTCAE (4.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Regorafenib (Double Blind Only) Placebo (Double Blind Only) Placebo, Open Label Only (Switch to Regorafenib) Treated With Regorafenib at Any Time Treated With Regorafenib for > 1 Year
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   40/41 (97.56%)      7/8 (87.50%)      58/58 (100.00%)      189/190 (99.47%)      75/75 (100.00%)    
Blood and lymphatic system disorders           
Anemia * 1  4/41 (9.76%)  7 0/8 (0.00%)  0 11/58 (18.97%)  25 32/190 (16.84%)  72 14/75 (18.67%)  30
Blood and lymphatic system disorders - Other * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 2/58 (3.45%)  9 6/190 (3.16%)  17 4/75 (5.33%)  9
Ear and labyrinth disorders           
Hearing impaired * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 1/58 (1.72%)  1 7/190 (3.68%)  7 5/75 (6.67%)  5
Ear and labyrinth disorders - Other * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 4/58 (6.90%)  4 7/190 (3.68%)  7 4/75 (5.33%)  4
Endocrine disorders           
Hypothyroidism * 1  4/41 (9.76%)  4 0/8 (0.00%)  0 6/58 (10.34%)  6 37/190 (19.47%)  48 23/75 (30.67%)  30
Eye disorders           
Blurred vision * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 2/58 (3.45%)  2 6/190 (3.16%)  6 6/75 (8.00%)  6
Eye disorders - Other * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 6/190 (3.16%)  6 4/75 (5.33%)  4
Gastrointestinal disorders           
Abdominal pain * 1  14/41 (34.15%)  18 0/8 (0.00%)  0 16/58 (27.59%)  23 61/190 (32.11%)  118 25/75 (33.33%)  56
Ascites * 1  2/41 (4.88%)  2 1/8 (12.50%)  1 2/58 (3.45%)  2 6/190 (3.16%)  8 1/75 (1.33%)  3
Bloating * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 7/190 (3.68%)  10 6/75 (8.00%)  9
Constipation * 1  10/41 (24.39%)  14 5/8 (62.50%)  6 16/58 (27.59%)  30 63/190 (33.16%)  100 28/75 (37.33%)  51
Diarrhea * 1  15/41 (36.59%)  20 1/8 (12.50%)  1 24/58 (41.38%)  66 96/190 (50.53%)  350 53/75 (70.67%)  278
Dyspepsia * 1  4/41 (9.76%)  4 1/8 (12.50%)  2 6/58 (10.34%)  9 19/190 (10.00%)  38 11/75 (14.67%)  29
Dry mouth * 1  5/41 (12.20%)  5 0/8 (0.00%)  0 5/58 (8.62%)  6 15/190 (7.89%)  16 5/75 (6.67%)  6
Flatulence * 1  4/41 (9.76%)  4 0/8 (0.00%)  0 3/58 (5.17%)  3 10/190 (5.26%)  11 5/75 (6.67%)  6
Mucositis oral * 1  14/41 (34.15%)  18 2/8 (25.00%)  3 21/58 (36.21%)  48 81/190 (42.63%)  174 38/75 (50.67%)  111
Nausea * 1  9/41 (21.95%)  12 3/8 (37.50%)  4 18/58 (31.03%)  32 61/190 (32.11%)  109 32/75 (42.67%)  65
Gastrointestinal disorders - Other * 1  4/41 (9.76%)  4 0/8 (0.00%)  0 4/58 (6.90%)  7 16/190 (8.42%)  20 10/75 (13.33%)  14
Stomach pain * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 2/58 (3.45%)  2 7/190 (3.68%)  7 5/75 (6.67%)  5
Vomiting * 1  10/41 (24.39%)  11 3/8 (37.50%)  5 12/58 (20.69%)  24 48/190 (25.26%)  85 21/75 (28.00%)  54
General disorders           
Chills * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 4/58 (6.90%)  4 11/190 (5.79%)  19 8/75 (10.67%)  16
Edema limbs * 1  3/41 (7.32%)  4 3/8 (37.50%)  3 11/58 (18.97%)  20 33/190 (17.37%)  71 17/75 (22.67%)  52
Fatigue * 1  18/41 (43.90%)  32 3/8 (37.50%)  4 32/58 (55.17%)  83 104/190 (54.74%)  250 46/75 (61.33%)  136
Fever * 1  10/41 (24.39%)  17 1/8 (12.50%)  1 18/58 (31.03%)  24 52/190 (27.37%)  83 25/75 (33.33%)  46
Flu like symptoms * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 3/58 (5.17%)  3 17/190 (8.95%)  21 13/75 (17.33%)  16
Localized edema * 1  2/41 (4.88%)  2 1/8 (12.50%)  1 3/58 (5.17%)  5 7/190 (3.68%)  9 4/75 (5.33%)  6
Non-cardiac chest pain * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 7/190 (3.68%)  8 6/75 (8.00%)  7
General disorders and administration site conditions - Other * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 4/58 (6.90%)  5 10/190 (5.26%)  11 5/75 (6.67%)  6
Pain * 1  5/41 (12.20%)  8 1/8 (12.50%)  1 18/58 (31.03%)  43 53/190 (27.89%)  110 27/75 (36.00%)  68
Immune system disorders           
Allergic reaction * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 4/190 (2.11%)  4 4/75 (5.33%)  4
Infections and infestations           
Bronchial infection * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 4/58 (6.90%)  4 10/190 (5.26%)  11 8/75 (10.67%)  9
Infections and infestations - Other * 1  2/41 (4.88%)  3 0/8 (0.00%)  0 5/58 (8.62%)  7 21/190 (11.05%)  38 13/75 (17.33%)  25
Rash pustular * 1  2/41 (4.88%)  2 0/8 (0.00%)  0 2/58 (3.45%)  16 13/190 (6.84%)  48 10/75 (13.33%)  41
Sinusitis * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 1/58 (1.72%)  1 6/190 (3.16%)  6 5/75 (6.67%)  5
Skin infection * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 3/58 (5.17%)  4 6/190 (3.16%)  7 4/75 (5.33%)  4
Tooth infection * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 5/190 (2.63%)  5 4/75 (5.33%)  4
Upper respiratory infection * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 9/58 (15.52%)  12 25/190 (13.16%)  37 20/75 (26.67%)  32
Urinary tract infection * 1  2/41 (4.88%)  3 0/8 (0.00%)  0 2/58 (3.45%)  4 12/190 (6.32%)  17 6/75 (8.00%)  9
Investigations           
Alanine aminotransferase increased * 1  4/41 (9.76%)  9 1/8 (12.50%)  2 6/58 (10.34%)  15 20/190 (10.53%)  41 4/75 (5.33%)  10
Alkaline phosphatase increased * 1  1/41 (2.44%)  1 1/8 (12.50%)  1 3/58 (5.17%)  6 11/190 (5.79%)  21 3/75 (4.00%)  4
Aspartate aminotransferase increased * 1  4/41 (9.76%)  9 2/8 (25.00%)  2 8/58 (13.79%)  15 23/190 (12.11%)  58 6/75 (8.00%)  24
Blood bilirubin increased * 1  4/41 (9.76%)  6 1/8 (12.50%)  3 9/58 (15.52%)  15 22/190 (11.58%)  52 7/75 (9.33%)  27
GGT increased * 1  0/41 (0.00%)  0 1/8 (12.50%)  2 2/58 (3.45%)  2 4/190 (2.11%)  4 1/75 (1.33%)  1
Lipase increased * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 3/58 (5.17%)  11 6/190 (3.16%)  19 3/75 (4.00%)  14
Neutrophil count decreased * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 6/58 (10.34%)  8 13/190 (6.84%)  25 6/75 (8.00%)  12
Investigations - Other * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 2/58 (3.45%)  14 14/190 (7.37%)  49 10/75 (13.33%)  28
Platelet count decreased * 1  1/41 (2.44%)  5 0/8 (0.00%)  0 6/58 (10.34%)  25 15/190 (7.89%)  46 10/75 (13.33%)  34
White blood cell decreased * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 2/58 (3.45%)  2 6/190 (3.16%)  17 4/75 (5.33%)  15
Weight gain * 1  0/41 (0.00%)  0 1/8 (12.50%)  1 2/58 (3.45%)  3 3/190 (1.58%)  4 2/75 (2.67%)  3
Weight loss * 1  4/41 (9.76%)  5 2/8 (25.00%)  2 11/58 (18.97%)  20 40/190 (21.05%)  72 22/75 (29.33%)  44
Metabolism and nutrition disorders           
Anorexia * 1  15/41 (36.59%)  21 3/8 (37.50%)  5 20/58 (34.48%)  42 76/190 (40.00%)  133 31/75 (41.33%)  71
Dehydration * 1  0/41 (0.00%)  0 1/8 (12.50%)  1 5/58 (8.62%)  5 6/190 (3.16%)  8 4/75 (5.33%)  6
Hypoalbuminemia * 1  2/41 (4.88%)  2 0/8 (0.00%)  0 3/58 (5.17%)  3 9/190 (4.74%)  10 2/75 (2.67%)  2
Hypocalcemia * 1  1/41 (2.44%)  2 0/8 (0.00%)  0 3/58 (5.17%)  8 9/190 (4.74%)  15 4/75 (5.33%)  4
Hypokalemia * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 12/58 (20.69%)  18 20/190 (10.53%)  31 13/75 (17.33%)  22
Hyponatremia * 1  0/41 (0.00%)  0 2/8 (25.00%)  2 3/58 (5.17%)  4 8/190 (4.21%)  11 2/75 (2.67%)  2
Hypophosphatemia * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 1/58 (1.72%)  1 10/190 (5.26%)  13 5/75 (6.67%)  7
Hypercalcemia * 1  0/41 (0.00%)  0 1/8 (12.50%)  1 3/58 (5.17%)  3 4/190 (2.11%)  4 4/75 (5.33%)  4
Hyperglycemia * 1  1/41 (2.44%)  3 0/8 (0.00%)  0 5/58 (8.62%)  5 13/190 (6.84%)  18 9/75 (12.00%)  10
Hyperuricemia * 1  1/41 (2.44%)  1 1/8 (12.50%)  1 2/58 (3.45%)  2 7/190 (3.68%)  7 2/75 (2.67%)  2
Musculoskeletal and connective tissue disorders           
Arthralgia * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 4/58 (6.90%)  7 14/190 (7.37%)  20 8/75 (10.67%)  14
Back pain * 1  2/41 (4.88%)  2 1/8 (12.50%)  1 4/58 (6.90%)  6 21/190 (11.05%)  29 14/75 (18.67%)  20
Bone pain * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  3 5/190 (2.63%)  9 5/75 (6.67%)  9
Flank pain * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 5/190 (2.63%)  5 4/75 (5.33%)  4
Generalized muscle weakness * 1  1/41 (2.44%)  1 1/8 (12.50%)  1 4/58 (6.90%)  7 6/190 (3.16%)  14 3/75 (4.00%)  11
Myalgia * 1  5/41 (12.20%)  5 3/8 (37.50%)  3 10/58 (17.24%)  17 33/190 (17.37%)  75 16/75 (21.33%)  48
Neck pain * 1  0/41 (0.00%)  0 1/8 (12.50%)  1 0/58 (0.00%)  0 2/190 (1.05%)  2 1/75 (1.33%)  1
Musculoskeletal and connective tissue disorder - Other * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 4/58 (6.90%)  5 14/190 (7.37%)  17 10/75 (13.33%)  12
Pain in extremity * 1  5/41 (12.20%)  5 1/8 (12.50%)  2 7/58 (12.07%)  15 28/190 (14.74%)  51 17/75 (22.67%)  37
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Tumor pain * 1  1/41 (2.44%)  2 1/8 (12.50%)  1 3/58 (5.17%)  4 7/190 (3.68%)  9 2/75 (2.67%)  2
Nervous system disorders           
Dizziness * 1  0/41 (0.00%)  0 1/8 (12.50%)  1 1/58 (1.72%)  1 6/190 (3.16%)  16 6/75 (8.00%)  16
Dysgeusia * 1  2/41 (4.88%)  2 0/8 (0.00%)  0 4/58 (6.90%)  4 17/190 (8.95%)  19 9/75 (12.00%)  11
Headache * 1  4/41 (9.76%)  4 0/8 (0.00%)  0 11/58 (18.97%)  21 37/190 (19.47%)  66 23/75 (30.67%)  49
Paresthesia * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 3/58 (5.17%)  5 11/190 (5.79%)  19 9/75 (12.00%)  13
Peripheral sensory neuropathy * 1  5/41 (12.20%)  7 0/8 (0.00%)  0 4/58 (6.90%)  8 16/190 (8.42%)  22 6/75 (8.00%)  7
Somnolence * 1  0/41 (0.00%)  0 1/8 (12.50%)  1 0/58 (0.00%)  0 0/190 (0.00%)  0 0/75 (0.00%)  0
Psychiatric disorders           
Anxiety * 1  4/41 (9.76%)  4 0/8 (0.00%)  0 3/58 (5.17%)  4 9/190 (4.74%)  10 4/75 (5.33%)  5
Confusion * 1  0/41 (0.00%)  0 1/8 (12.50%)  1 1/58 (1.72%)  1 2/190 (1.05%)  2 0/75 (0.00%)  0
Depression * 1  2/41 (4.88%)  2 0/8 (0.00%)  0 2/58 (3.45%)  2 10/190 (5.26%)  11 4/75 (5.33%)  5
Insomnia * 1  3/41 (7.32%)  3 1/8 (12.50%)  1 3/58 (5.17%)  4 21/190 (11.05%)  22 14/75 (18.67%)  15
Renal and urinary disorders           
Hematuria * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 3/58 (5.17%)  3 7/190 (3.68%)  9 3/75 (4.00%)  3
Renal and urinary disorders - Other * 1  3/41 (7.32%)  3 0/8 (0.00%)  0 0/58 (0.00%)  0 9/190 (4.74%)  11 3/75 (4.00%)  4
Proteinuria * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 6/58 (10.34%)  11 22/190 (11.58%)  57 8/75 (10.67%)  20
Urinary frequency * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 2/58 (3.45%)  2 7/190 (3.68%)  8 4/75 (5.33%)  5
Respiratory, thoracic and mediastinal disorders           
Cough * 1  1/41 (2.44%)  1 1/8 (12.50%)  1 11/58 (18.97%)  18 27/190 (14.21%)  44 15/75 (20.00%)  32
Dyspnea * 1  4/41 (9.76%)  6 0/8 (0.00%)  0 7/58 (12.07%)  9 22/190 (11.58%)  32 11/75 (14.67%)  16
Epistaxis * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 4/58 (6.90%)  6 10/190 (5.26%)  15 7/75 (9.33%)  10
Hiccups * 1  0/41 (0.00%)  0 1/8 (12.50%)  1 0/58 (0.00%)  0 0/190 (0.00%)  0 0/75 (0.00%)  0
Hoarseness * 1  8/41 (19.51%)  8 0/8 (0.00%)  0 9/58 (15.52%)  11 42/190 (22.11%)  71 17/75 (22.67%)  36
Pneumonitis * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 3/58 (5.17%)  3 5/190 (2.63%)  5 4/75 (5.33%)  4
Voice alteration * 1  2/41 (4.88%)  2 1/8 (12.50%)  1 11/58 (18.97%)  12 28/190 (14.74%)  32 14/75 (18.67%)  17
Skin and subcutaneous tissue disorders           
Alopecia * 1  7/41 (17.07%)  9 0/8 (0.00%)  0 21/58 (36.21%)  26 62/190 (32.63%)  84 33/75 (44.00%)  49
Dry skin * 1  2/41 (4.88%)  3 0/8 (0.00%)  0 2/58 (3.45%)  3 13/190 (6.84%)  15 7/75 (9.33%)  8
Erythema multiforme * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 1/58 (1.72%)  3 10/190 (5.26%)  17 7/75 (9.33%)  12
Erythroderma * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 4/58 (6.90%)  5 9/190 (4.74%)  11 6/75 (8.00%)  6
Hyperhidrosis * 1  0/41 (0.00%)  0 1/8 (12.50%)  2 2/58 (3.45%)  2 6/190 (3.16%)  11 4/75 (5.33%)  9
Skin and subcutaneous tissue disorders - Other * 1  3/41 (7.32%)  3 0/8 (0.00%)  0 7/58 (12.07%)  10 27/190 (14.21%)  41 17/75 (22.67%)  28
Pain of skin * 1  0/41 (0.00%)  0 0/8 (0.00%)  0 1/58 (1.72%)  1 9/190 (4.74%)  38 6/75 (8.00%)  35
Palmar-plantar erythrodysesthesia syndrome * 1  17/41 (41.46%)  37 1/8 (12.50%)  1 39/58 (67.24%)  151 126/190 (66.32%)  664 58/75 (77.33%)  453
Pruritus * 1  4/41 (9.76%)  4 1/8 (12.50%)  2 7/58 (12.07%)  8 20/190 (10.53%)  27 10/75 (13.33%)  15
Rash acneiform * 1  2/41 (4.88%)  2 0/8 (0.00%)  0 3/58 (5.17%)  3 11/190 (5.79%)  11 6/75 (8.00%)  6
Rash maculo-papular * 1  6/41 (14.63%)  7 0/8 (0.00%)  0 8/58 (13.79%)  10 32/190 (16.84%)  71 16/75 (21.33%)  26
Vascular disorders           
Hypotension * 1  1/41 (2.44%)  1 0/8 (0.00%)  0 1/58 (1.72%)  1 7/190 (3.68%)  8 4/75 (5.33%)  5
Hypertension * 1  18/41 (43.90%)  32 3/8 (37.50%)  3 37/58 (63.79%)  97 123/190 (64.74%)  575 61/75 (81.33%)  430
Thromboembolic event * 1  0/41 (0.00%)  0 2/8 (25.00%)  2 1/58 (1.72%)  1 5/190 (2.63%)  6 4/75 (5.33%)  4
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, NCI-CTCAE (4.0)
Overall survival results are confounded by the fact that 85% of the participants initially randomized to placebo switched to open-label regorafenib.
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.
Results Point of Contact
Name/Title: Therapeutic Area Head
Organization: BAYER
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 10, 2018