Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01271712
First received: December 17, 2010
Last updated: August 22, 2016
Last verified: August 2016
Results First Received: May 24, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Gastrointestinal Stromal Tumors
Interventions: Drug: Regorafenib (Stivarga, BAY73-4506)
Drug: Placebo
Drug: Best supportive care

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 240 participants with metastatic and/or unresectable GIST whose disease had progressed despite prior treatments with at least imatinib and sunitinib were screened; 199 were randomized. Patients must have shown objective disease progression or intolerance to imatinib, as well as disease progression while on sunitinib treatment.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were randomized in a 2:1 ratio to receive either regorafenib (133 patients) or placebo (66 patients). Randomization was stratified according 3rd vs. 4th line of therapy (at least 50% of patients were to be 3rd line), and geographical region (Asia vs.rest of world).

Reporting Groups
  Description
Regorafenib (Stivarga, BAY73-4506) Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
Placebo First, Then Option of Open Label Regorafenib Treatment Double blind phase: participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks. Open Label phase: participants on placebo who switched to Regorafenib, received Regorafenib 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks.

Participant Flow for 4 periods

Period 1:   Double Blind Treatment
    Regorafenib (Stivarga, BAY73-4506)   Placebo First, Then Option of Open Label Regorafenib Treatment
STARTED   133   66 
Participants Received Treatment   132   66 
COMPLETED   41 [1]   56 [2] 
NOT COMPLETED   92   10 
Death                2                0 
Lack of Efficacy                1                0 
Adverse Event                8                4 
Progressive disease                21                3 
Withdrawal by Subject                4                0 
Non compliance with study drug                2                0 
Ongoing in double-blind treatment                53                3 
receive no study drug                1                0 
[1] 41 participants started open-label treatment with regorafenib
[2] 56 participants started open-label treatment with regorafenib

Period 2:   Open Label Treatment
    Regorafenib (Stivarga, BAY73-4506)   Placebo First, Then Option of Open Label Regorafenib Treatment
STARTED   41   56 
Participants Received Treatment   41   56 
COMPLETED   0   0 
NOT COMPLETED   41   56 
Death                1                1 
Withdrawal by Subject                0                5 
Physician Decision                2                0 
Adverse Event                2                4 
Progressive disease                12                13 
Ongoing with open-label treatment                24                33 

Period 3:   Safety Follow-up
    Regorafenib (Stivarga, BAY73-4506)   Placebo First, Then Option of Open Label Regorafenib Treatment
STARTED   36 [1]   7 [1] 
COMPLETED   27   4 
NOT COMPLETED   9   3 
Death                4                2 
Withdrawal by Subject                1                1 
Protocol Violation                1                0 
Ongoing with open-label treatment                3                0 
[1] All participants who discontinued study drug entered 30-day Safety Follow-up

Period 4:   Survival Follow-up
    Regorafenib (Stivarga, BAY73-4506)   Placebo First, Then Option of Open Label Regorafenib Treatment
STARTED   27 [1]   4 [1] 
COMPLETED   0   0 
NOT COMPLETED   27   4 
Death                13                3 
Ongoing with open-label treatment                14                1 
[1] All participants entered Survival Follow-up 30 days after discontinuation of study drug



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Regorafenib (Stivarga, BAY73-4506) Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
Placebo Participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
Total Total of all reporting groups

Baseline Measures
   Regorafenib (Stivarga, BAY73-4506)   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 133   66   199 
Age 
[Units: Years]
Mean (Standard Deviation)
 58.2  (12.5)   58.1  (13.9)   58.2  (12.9) 
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 
[1] ECOG = Eastern cooperative oncology group PS levels are 0 (Fully active, able to carry on all pre-disease performance), 1 (ambulatory and able to carry out work of a light or sedentary), 2 (Ambulatory and capable of all selfcare but unable to carry out any work activities), 3 (Capable of only limited selfcare, confined to bed or chair more than 50% of awake time), 4 (Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair) and 5 (death).
Prior anti-cancer drug group [1] 
[Units: Participants]
     
3rd line   74   39   113 
4th line and beyond   59   27   86 
[1] 3rd line: 3rd in sequence of multiple therapies: imatinib (1st); sunitinib (2nd). 4th line and beyond: 4th in sequence of multiple therapies: imatinib (1st); sunitinib (2nd); other (3rd).


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Progression-free Survival   [ Time Frame: From randomization of the first subject until approximately 144 progression-free survival events had occurred (study duration approximately one year) ]

2.  Secondary:   Overall Survival   [ Time Frame: From randomization of the first subject until date of database cutoff (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


  Other Adverse Events
  Hide Other Adverse Events

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

Frequency Threshold
Threshold above which other adverse events are reported   5  

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

Other Adverse Events
    Regorafenib (Double Blind Only)   Placebo ( Double Blind Only)   Regorafenib, Open Label Only (Regorafenib Continued)   Placebo, Open Label Only (Switch to Regorafenib)
Total, other (not including serious) adverse events         
# participants affected / at risk   131/132 (99.24%)   60/66 (90.91%)   31/41 (75.61%)   55/56 (98.21%) 
Blood and lymphatic system disorders         
Anemia * 1         
# participants affected / at risk   14/132 (10.61%)   4/66 (6.06%)   2/41 (4.88%)   7/56 (12.50%) 
Endocrine disorders         
Hypothyroidism * 1         
# participants affected / at risk   19/132 (14.39%)   2/66 (3.03%)   2/41 (4.88%)   4/56 (7.14%) 
Gastrointestinal disorders         
Abdominal pain * 1         
# participants affected / at risk   33/132 (25.00%)   10/66 (15.15%)   6/41 (14.63%)   11/56 (19.64%) 
Constipation * 1         
# participants affected / at risk   36/132 (27.27%)   15/66 (22.73%)   7/41 (17.07%)   12/56 (21.43%) 
Diarrhea * 1         
# participants affected / at risk   60/132 (45.45%)   6/66 (9.09%)   8/41 (19.51%)   15/56 (26.79%) 
Dyspepsia * 1         
# participants affected / at risk   7/132 (5.30%)   2/66 (3.03%)   2/41 (4.88%)   2/56 (3.57%) 
Dry mouth * 1         
# participants affected / at risk   8/132 (6.06%)   3/66 (4.55%)   0/41 (0.00%)   3/56 (5.36%) 
Mucositis oral * 1         
# participants affected / at risk   54/132 (40.91%)   5/66 (7.58%)   2/41 (4.88%)   17/56 (30.36%) 
Nausea * 1         
# participants affected / at risk   26/132 (19.70%)   8/66 (12.12%)   6/41 (14.63%)   13/56 (23.21%) 
Gastrointestinal disorders - Other * 1         
# participants affected / at risk   8/132 (6.06%)   3/66 (4.55%)   0/41 (0.00%)   1/56 (1.79%) 
Vomiting * 1         
# participants affected / at risk   22/132 (16.67%)   5/66 (7.58%)   4/41 (9.76%)   3/56 (5.36%) 
General disorders         
Edema limbs * 1         
# participants affected / at risk   6/132 (4.55%)   7/66 (10.61%)   3/41 (7.32%)   8/56 (14.29%) 
Fatigue * 1         
# participants affected / at risk   66/132 (50.00%)   25/66 (37.88%)   5/41 (12.20%)   22/56 (39.29%) 
Fever * 1         
# participants affected / at risk   28/132 (21.21%)   7/66 (10.61%)   3/41 (7.32%)   9/56 (16.07%) 
Flu like symptoms * 1         
# participants affected / at risk   7/132 (5.30%)   1/66 (1.52%)   2/41 (4.88%)   1/56 (1.79%) 
Pain * 1         
# participants affected / at risk   20/132 (15.15%)   13/66 (19.70%)   3/41 (7.32%)   11/56 (19.64%) 
Infections and infestations         
Infections and infestations - Other * 1         
# participants affected / at risk   8/132 (6.06%)   0/66 (0.00%)   3/41 (7.32%)   2/56 (3.57%) 
Rash pustular * 1         
# participants affected / at risk   9/132 (6.82%)   0/66 (0.00%)   0/41 (0.00%)   2/56 (3.57%) 
Upper respiratory infection * 1         
# participants affected / at risk   12/132 (9.09%)   0/66 (0.00%)   1/41 (2.44%)   4/56 (7.14%) 
Urinary tract infection * 1         
# participants affected / at risk   7/132 (5.30%)   2/66 (3.03%)   2/41 (4.88%)   1/56 (1.79%) 
Investigations         
Alanine aminotransferase increased * 1         
# participants affected / at risk   9/132 (6.82%)   1/66 (1.52%)   4/41 (9.76%)   5/56 (8.93%) 
Alkaline phosphatase increased * 1         
# participants affected / at risk   6/132 (4.55%)   3/66 (4.55%)   3/41 (7.32%)   2/56 (3.57%) 
Aspartate aminotransferase increased * 1         
# participants affected / at risk   12/132 (9.09%)   3/66 (4.55%)   5/41 (12.20%)   8/56 (14.29%) 
Blood bilirubin increased * 1         
# participants affected / at risk   13/132 (9.85%)   2/66 (3.03%)   2/41 (4.88%)   7/56 (12.50%) 
Neutrophil count decreased * 1         
# participants affected / at risk   6/132 (4.55%)   3/66 (4.55%)   2/41 (4.88%)   4/56 (7.14%) 
Investigations - Other * 1         
# participants affected / at risk   6/132 (4.55%)   3/66 (4.55%)   3/41 (7.32%)   1/56 (1.79%) 
Platelet count decreased * 1         
# participants affected / at risk   8/132 (6.06%)   0/66 (0.00%)   0/41 (0.00%)   3/56 (5.36%) 
Weight loss * 1         
# participants affected / at risk   18/132 (13.64%)   5/66 (7.58%)   2/41 (4.88%)   5/56 (8.93%) 
Metabolism and nutrition disorders         
Anorexia * 1         
# participants affected / at risk   40/132 (30.30%)   14/66 (21.21%)   5/41 (12.20%)   13/56 (23.21%) 
Hypoalbuminemia * 1         
# participants affected / at risk   6/132 (4.55%)   0/66 (0.00%)   1/41 (2.44%)   3/56 (5.36%) 
Hypokalemia * 1         
# participants affected / at risk   5/132 (3.79%)   2/66 (3.03%)   0/41 (0.00%)   7/56 (12.50%) 
Hyponatremia * 1         
# participants affected / at risk   4/132 (3.03%)   3/66 (4.55%)   0/41 (0.00%)   3/56 (5.36%) 
Hypophosphatemia * 1         
# participants affected / at risk   7/132 (5.30%)   0/66 (0.00%)   0/41 (0.00%)   1/56 (1.79%) 
Hyperglycemia * 1         
# participants affected / at risk   5/132 (3.79%)   4/66 (6.06%)   1/41 (2.44%)   3/56 (5.36%) 
Musculoskeletal and connective tissue disorders         
Back pain * 1         
# participants affected / at risk   12/132 (9.09%)   3/66 (4.55%)   2/41 (4.88%)   1/56 (1.79%) 
Myalgia * 1         
# participants affected / at risk   21/132 (15.91%)   8/66 (12.12%)   3/41 (7.32%)   9/56 (16.07%) 
Pain in extremity * 1         
# participants affected / at risk   14/132 (10.61%)   3/66 (4.55%)   1/41 (2.44%)   3/56 (5.36%) 
Nervous system disorders         
Dysgeusia * 1         
# participants affected / at risk   11/132 (8.33%)   2/66 (3.03%)   0/41 (0.00%)   3/56 (5.36%) 
Headache * 1         
# participants affected / at risk   20/132 (15.15%)   6/66 (9.09%)   2/41 (4.88%)   8/56 (14.29%) 
Peripheral sensory neuropathy * 1         
# participants affected / at risk   8/132 (6.06%)   1/66 (1.52%)   1/41 (2.44%)   2/56 (3.57%) 
Renal and urinary disorders         
Proteinuria * 1         
# participants affected / at risk   10/132 (7.58%)   1/66 (1.52%)   8/41 (19.51%)   5/56 (8.93%) 
Respiratory, thoracic and mediastinal disorders         
Cough * 1         
# participants affected / at risk   11/132 (8.33%)   6/66 (9.09%)   1/41 (2.44%)   8/56 (14.29%) 
Dyspnea * 1         
# participants affected / at risk   8/132 (6.06%)   3/66 (4.55%)   2/41 (4.88%)   4/56 (7.14%) 
Epistaxis * 1         
# participants affected / at risk   3/132 (2.27%)   0/66 (0.00%)   2/41 (4.88%)   3/56 (5.36%) 
Hoarseness * 1         
# participants affected / at risk   32/132 (24.24%)   4/66 (6.06%)   2/41 (4.88%)   9/56 (16.07%) 
Voice alteration * 1         
# participants affected / at risk   16/132 (12.12%)   2/66 (3.03%)   0/41 (0.00%)   8/56 (14.29%) 
Skin and subcutaneous tissue disorders         
Alopecia * 1         
# participants affected / at risk   32/132 (24.24%)   1/66 (1.52%)   5/41 (12.20%)   16/56 (28.57%) 
Dry skin * 1         
# participants affected / at risk   8/132 (6.06%)   0/66 (0.00%)   1/41 (2.44%)   1/56 (1.79%) 
Erythema multiforme * 1         
# participants affected / at risk   7/132 (5.30%)   1/66 (1.52%)   0/41 (0.00%)   1/56 (1.79%) 
Erythroderma * 1         
# participants affected / at risk   5/132 (3.79%)   0/66 (0.00%)   0/41 (0.00%)   3/56 (5.36%) 
Skin and subcutaneous tissue disorders - Other * 1         
# participants affected / at risk   11/132 (8.33%)   1/66 (1.52%)   3/41 (7.32%)   5/56 (8.93%) 
Pain of skin * 1         
# participants affected / at risk   8/132 (6.06%)   1/66 (1.52%)   0/41 (0.00%)   1/56 (1.79%) 
Palmar-plantar erythrodysesthesia syndrome * 1         
# participants affected / at risk   75/132 (56.82%)   9/66 (13.64%)   12/41 (29.27%)   33/56 (58.93%) 
Pruritus * 1         
# participants affected / at risk   11/132 (8.33%)   8/66 (12.12%)   2/41 (4.88%)   4/56 (7.14%) 
Rash acneiform * 1         
# participants affected / at risk   7/132 (5.30%)   0/66 (0.00%)   0/41 (0.00%)   1/56 (1.79%) 
Rash maculo-papular * 1         
# participants affected / at risk   24/132 (18.18%)   2/66 (3.03%)   3/41 (7.32%)   6/56 (10.71%) 
Vascular disorders         
Hypertension * 1         
# participants affected / at risk   77/132 (58.33%)   18/66 (27.27%)   9/41 (21.95%)   29/56 (51.79%) 
* Events were collected by non-systematic assessment
1 Term from vocabulary, NCI-CTCAE v.4.0



  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Overall survival results are confounded by the fact that 85% of the participants initially randomized to placebo switched to open-label regorafenib.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


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


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

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01271712     History of Changes
Other Study ID Numbers: 14874
2009-017957-37 ( EudraCT Number )
Study First Received: December 17, 2010
Results First Received: May 24, 2013
Last Updated: August 22, 2016
Health Authority: United States: Food and Drug Administration
Austria:AGES-PharmMed LCM
Belgium:Agence Fédérale des Médicaments et des Produits de Santé
Canada: Health Canada
China: Food and Drug Administration
Finland: Finnish Medicines Agency
France: Agence française de sécurité sanitaire des produits de santé (Afssaps)
Germany: Federal Institute for Drugs and Medical Devices
Israel: Ministry of Health
Italy: Agenzia Italiana del Farmaco
Japan: Pharmaceuticals and Medical Devices Agency
Netherlands: College ter Beoordeling van Geneesmiddelen Medicines Evaluation Board
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Singapore: Health Sciences Authority
South Korea: Korea Food and Drug Administration
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency