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 : June 12, 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

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.
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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

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

110

PS 1

PS 2

Missing

^[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

113

4th line and beyond

^[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

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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) ]

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2. Secondary:

Overall Survival [ Time Frame: From randomization of the first subject until date of database cutoff (08 Jun 2015) ]

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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 ]

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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 ]

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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 ]

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Serious Adverse Events

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Time Frame	From randomization of the first subject until date of database cutoff (08 Jun 2015).
Additional 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”.

Time Frame

From randomization of the first subject until date of database cutoff (08 Jun 2015).

Additional 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”.

Reporting Groups

	Description
Regorafenib (Double Blind 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. Data cut-off date 26 JAN 2012.
Placebo (Double Blind 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. Data cut-off date 26 JAN 2012.
Placebo, Open Label Only (Switch to Regorafenib)	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	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	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.

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
Total, Serious Adverse Events
# participants affected / at risk	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
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	2/190 (1.05%)	0/75 (0.00%)
# events	0	0	2	3	0
Cardiac disorders
Acute coronary syndrome ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	7/190 (3.68%)	6/75 (8.00%)
# events	0	0	0	7	6
Atrial fibrillation ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	1	1	1
Cardiac arrest ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	1	0	0	1	0
Chest pain - cardiac ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	0	2	2
Conduction disorder ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	0	1	1
Heart failure ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	0	1	1
Cardiac disorders - Other ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	0	0	0	1	0
Congenital, familial and genetic disorders
Congenital, familial and genetic disorders - Other ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	0	0	0	1	0
Ear and labyrinth disorders
Vertigo ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	0	0	0	1	0
Eye disorders
Eye disorders - Other ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	1	1	1
Gastrointestinal disorders
Abdominal pain ^* 1
# participants affected / at risk	5/41 (12.20%)	0/8 (0.00%)	2/58 (3.45%)	9/190 (4.74%)	1/75 (1.33%)
# events	5	0	2	10	1
Anal fistula ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	0	1	1
Ascites ^* 1
# participants affected / at risk	3/41 (7.32%)	0/8 (0.00%)	0/58 (0.00%)	3/190 (1.58%)	0/75 (0.00%)
# events	4	0	0	4	0
Colonic fistula ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	1	0	0	1	0
Colonic obstruction ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	1/190 (0.53%)	0/75 (0.00%)
# events	0	0	2	2	0
Colonic perforation ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	2/190 (1.05%)	1/75 (1.33%)
# events	0	0	2	4	2
Constipation ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	2/190 (1.05%)	2/75 (2.67%)
# events	0	0	1	2	2
Diarrhea ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	3/190 (1.58%)	2/75 (2.67%)
# events	1	0	0	4	3
Gastric hemorrhage ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	1/58 (1.72%)	2/190 (1.05%)	0/75 (0.00%)
# events	1	0	1	2	0
Intra-abdominal hemorrhage ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	3/190 (1.58%)	0/75 (0.00%)
# events	1	0	0	3	0
Ileus ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	1/58 (1.72%)	2/190 (1.05%)	0/75 (0.00%)
# events	1	0	1	2	0
Lower gastrointestinal hemorrhage ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	1	0	0	1	0
Nausea ^* 1
# participants affected / at risk	0/41 (0.00%)	1/8 (12.50%)	1/58 (1.72%)	2/190 (1.05%)	1/75 (1.33%)
# events	0	1	1	2	1
Obstruction gastric ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	0	0	0	1	0
Gastrointestinal disorders - Other ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	1	0	0	1	0
Peritoneal necrosis ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	1	0	0	1	0
Retroperitoneal hemorrhage ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	0	0	0	1	0
Small intestinal obstruction ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	0	2	2
Upper gastrointestinal hemorrhage ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	0	0	0	1	0
Vomiting ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	2/190 (1.05%)	1/75 (1.33%)
# events	0	0	1	2	1
General disorders
Death NOS ^* 1
# participants affected / at risk	1/41 (2.44%)	2/8 (25.00%)	1/58 (1.72%)	3/190 (1.58%)	2/75 (2.67%)
# events	1	2	1	3	2
Edema limbs ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	1/190 (0.53%)	0/75 (0.00%)
# events	0	0	2	2	0
Fatigue ^* 1
# participants affected / at risk	2/41 (4.88%)	1/8 (12.50%)	2/58 (3.45%)	5/190 (2.63%)	2/75 (2.67%)
# events	4	2	2	7	2
Fever ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	2/58 (3.45%)	5/190 (2.63%)	2/75 (2.67%)
# events	1	0	2	5	2
Malaise ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	1	0	0	1	0
Multi-organ failure ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	2/190 (1.05%)	0/75 (0.00%)
# events	0	0	1	2	0
Non-cardiac chest pain ^* 1
# participants affected / at risk	0/41 (0.00%)	1/8 (12.50%)	0/58 (0.00%)	0/190 (0.00%)	0/75 (0.00%)
# events	0	1	0	0	0
General disorders and administration site conditions - Other ^* 1
# participants affected / at risk	1/41 (2.44%)	1/8 (12.50%)	2/58 (3.45%)	5/190 (2.63%)	3/75 (4.00%)
# events	1	1	3	6	3
Pain ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	2/58 (3.45%)	3/190 (1.58%)	1/75 (1.33%)
# events	1	0	3	4	1
Hepatobiliary disorders
Bile duct stenosis ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	2/190 (1.05%)	1/75 (1.33%)
# events	0	0	1	2	1
Cholecystitis ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	0	1	1
Hepatic failure ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	1/58 (1.72%)	3/190 (1.58%)	0/75 (0.00%)
# events	2	0	1	4	0
Hepatic hemorrhage ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	2/190 (1.05%)	1/75 (1.33%)
# events	0	0	0	3	1
Hepatobiliary disorders - Other ^* 1
# participants affected / at risk	0/41 (0.00%)	1/8 (12.50%)	1/58 (1.72%)	2/190 (1.05%)	1/75 (1.33%)
# events	0	1	1	2	1
Portal vein thrombosis ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	1/190 (0.53%)	0/75 (0.00%)
# events	0	0	1	1	0
Infections and infestations
Abdominal infection ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	2/190 (1.05%)	0/75 (0.00%)
# events	1	0	0	2	0
Bronchial infection ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	2/190 (1.05%)	1/75 (1.33%)
# events	0	0	0	3	2
Catheter related infection ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	1/190 (0.53%)	0/75 (0.00%)
# events	0	0	2	2	0
Enterocolitis infectious ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	2/58 (3.45%)	2/190 (1.05%)	1/75 (1.33%)
# events	0	0	3	3	2
Lung infection ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	2/190 (1.05%)	1/75 (1.33%)
# events	0	0	1	2	1
Infections and infestations - Other ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	4/58 (6.90%)	8/190 (4.21%)	3/75 (4.00%)
# events	1	0	4	9	4
Sepsis ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	2/58 (3.45%)	3/190 (1.58%)	1/75 (1.33%)
# events	0	0	2	3	1
Upper respiratory infection ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	3/190 (1.58%)	3/75 (4.00%)
# events	0	0	0	3	3
Urinary tract infection ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	0	1	1
Wound infection ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	1	0	0	1	0
Injury, poisoning and procedural complications
Fracture ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	3/190 (1.58%)	2/75 (2.67%)
# events	0	0	2	4	3
Hip fracture ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	1	1	1
Investigations
Alanine aminotransferase increased ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	3/190 (1.58%)	1/75 (1.33%)
# events	0	0	2	6	3
Aspartate aminotransferase increased ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	1/190 (0.53%)	0/75 (0.00%)
# events	0	0	1	1	0
Blood bilirubin increased ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	2/58 (3.45%)	3/190 (1.58%)	1/75 (1.33%)
# events	0	0	2	3	1
Creatinine increased ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	2	0	0	2	0
INR increased ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	0	1	1
Neutrophil count decreased ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	1/190 (0.53%)	0/75 (0.00%)
# events	0	0	1	1	0
Investigations - Other ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	2/190 (1.05%)	0/75 (0.00%)
# events	1	0	0	2	0
Platelet count decreased ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	1/190 (0.53%)	0/75 (0.00%)
# events	0	0	2	2	0
Metabolism and nutrition disorders
Acidosis ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	1	0	0	1	0
Anorexia ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	1	0	0	1	0
Dehydration ^* 1
# participants affected / at risk	0/41 (0.00%)	1/8 (12.50%)	0/58 (0.00%)	3/190 (1.58%)	3/75 (4.00%)
# events	0	1	0	3	3
Hyperglycemia ^* 1
# participants affected / at risk	0/41 (0.00%)	1/8 (12.50%)	0/58 (0.00%)	0/190 (0.00%)	0/75 (0.00%)
# events	0	1	0	0	0
Hyperkalemia ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	3	0	0	3	0
Musculoskeletal and connective tissue disorders
Back pain ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	2/58 (3.45%)	2/190 (1.05%)	1/75 (1.33%)
# events	0	0	2	2	1
Generalized muscle weakness ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	0	1	1
Musculoskeletal and connective tissue disorder - Other ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	1	1	1
Muscle weakness right-sided ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	1	0	0	1	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	3/58 (5.17%)	6/190 (3.16%)	3/75 (4.00%)
# events	1	0	3	6	3
Tumor pain ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	2/58 (3.45%)	3/190 (1.58%)	1/75 (1.33%)
# events	0	0	4	5	1
Nervous system disorders
Amnesia ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	0	1	1
Hypoglossal nerve disorder ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	1	0	0	1	0
Intracranial hemorrhage ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	0	1	1
Nervous system disorders - Other ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	2/58 (3.45%)	2/190 (1.05%)	0/75 (0.00%)
# events	0	0	2	2	0
Paresthesia ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	1	0	0	1	0
Reversible posterior leukoencephalopathy syndrome ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	1	0	0	1	0
Somnolence ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	1	0	0	1	0
Stroke ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	2/190 (1.05%)	2/75 (2.67%)
# events	0	0	1	2	2
Transient ischemic attacks ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	0	1	1
Psychiatric disorders
Confusion ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	1	1	1
Mania ^* 1
# participants affected / at risk	0/41 (0.00%)	1/8 (12.50%)	0/58 (0.00%)	0/190 (0.00%)	0/75 (0.00%)
# events	0	4	0	0	0
Psychiatric disorders - Other ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	1	0	0	1	0
Renal and urinary disorders
Acute kidney injury ^* 1
# participants affected / at risk	2/41 (4.88%)	0/8 (0.00%)	1/58 (1.72%)	3/190 (1.58%)	0/75 (0.00%)
# events	2	0	2	4	0
Renal and urinary disorders - Other ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	3/190 (1.58%)	1/75 (1.33%)
# events	0	0	0	4	2
Renal colic ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	0	1	1
Urinary retention ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	2/190 (1.05%)	1/75 (1.33%)
# events	1	0	0	2	1
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	0	0	0	1	0
Dyspnea ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	2/190 (1.05%)	0/75 (0.00%)
# events	1	0	0	2	0
Pleural effusion ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	0	1	1
Pneumonitis ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	1	0	0	1	0
Respiratory failure ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	0	1	1
Skin and subcutaneous tissue disorders
Rash maculo-papular ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	1	1	1
Surgical and medical procedures
Surgical and medical procedures - Other ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	1/58 (1.72%)	4/190 (2.11%)	2/75 (2.67%)
# events	0	0	1	4	2
Vascular disorders
Hypertension ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	1	0	0	1	0
Vascular disorders - Other ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	0/75 (0.00%)
# events	0	0	0	1	0
Peripheral ischemia ^* 1
# participants affected / at risk	0/41 (0.00%)	0/8 (0.00%)	0/58 (0.00%)	1/190 (0.53%)	1/75 (1.33%)
# events	0	0	0	1	1
Thromboembolic event ^* 1
# participants affected / at risk	1/41 (2.44%)	0/8 (0.00%)	1/58 (1.72%)	4/190 (2.11%)	0/75 (0.00%)
# events	1	0	2	5	0

*	Events were collected by non-systematic assessment
1	Term from vocabulary, NCI-CTCAE (4.0)

Other Adverse Events

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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:

	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.
	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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	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:

Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, Hohenberger P, Leahy M, von Mehren M, Joensuu H, Badalamenti G, Blackstein M, Le Cesne A, Schöffski P, Maki RG, Bauer S, Nguyen BB, Xu J, Nishida T, Chung J, Kappeler C, Kuss I, Laurent D, Casali PG; GRID study investigators. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):295-302. doi: 10.1016/S0140-6736(12)61857-1. Epub 2012 Nov 22.

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

Poole CD, Connolly MP, Chang J, Currie CJ. Health utility of patients with advanced gastrointestinal stromal tumors (GIST) after failure of imatinib and sunitinib: findings from GRID, a randomized, double-blind, placebo-controlled phase III study of regorafenib versus placebo. Gastric Cancer. 2015 Jul;18(3):627-34. doi: 10.1007/s10120-014-0391-x. Epub 2014 Jun 24.

Mross K, Frost A, Steinbild S, Hedbom S, Büchert M, Fasol U, Unger C, Krätzschmar J, Heinig R, Boix O, Christensen O. A phase I dose-escalation study of regorafenib (BAY 73-4506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors. Clin Cancer Res. 2012 May 1;18(9):2658-67. doi: 10.1158/1078-0432.CCR-11-1900. Epub 2012 Mar 15.

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:	June 12, 2018

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