A Study To Assess The Safety And Efficacy Of SU11248 In Patients With Gastrointestinal Stromal Tumor(GIST)

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00075218
First received: January 6, 2004
Last updated: August 31, 2009
Last verified: August 2009
Results First Received: May 6, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Gastrointestinal Stromal Tumor
Interventions: Drug: Placebo
Drug: SU011248

  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
Enrollment began (medical clinic) in December 2003. Study was unblinded on 27 January 2005 (end of Double-blind treatment). Subjects experiencing disease progression could crossover to Open-label treatment. Open-label data collection ended May 2008.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

361 subjects randomized to double-blind treatment in 2:1 ratio (sunitinib vs. Placebo).

255 subjects continued on or crossed over to Open-label treatment.


Reporting Groups
  Description
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.
Sunitinib Open-Label Treatment Subjects experiencing disease progression could have their treatment assignment unblinded, and subjects who had been receiving placebo could crossover to open-label treatment with sunitinib; subjects who had been receiving sunitinib during double-blind treatment of the study could continue to do so after unblinding if, in the opinion of the investigator, there was sufficient evidence of clinical benefit.

Participant Flow for 2 periods

Period 1:   Double-Blind Treatment
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment     Sunitinib Open-Label Treatment  
STARTED     243 [1]   118 [1]   0  
Received Double-Blind Treatment     228 [2]   114 [2]   0  
Crossed Over to Open-Label Treatment     152     103     0  
COMPLETED     152 [3]   103 [3]   0  
NOT COMPLETED     91     15     0  
Adverse Event                 23                 4                 0  
Withdrawal by Subject                 7                 4                 0  
Lost to Follow-up                 1                 0                 0  
Lack of Efficacy                 58                 6                 0  
Decision of Sponsor                 0                 1                 0  
No study medication taken                 2                 0                 0  
[1] Intent To Treat Population (ITT)
[2] As Treated Population (AT)
[3] Defined:subjects completed double-blind treatment phase and/or entered open-label treatment phase.

Period 2:   Open-Label Treatment
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment     Sunitinib Open-Label Treatment  
STARTED     0     0     255  
COMPLETED     0     0     0  
NOT COMPLETED     0     0     255  
Lack of Efficacy                 0                 0                 174  
Adverse Event                 0                 0                 51  
Withdrawal by Subject                 0                 0                 12  
Decision of Sponsor                 0                 0                 8  
Protocol Violation                 0                 0                 1  
enrolled in a separate continuation                 0                 0                 9  



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

Reporting Groups
  Description
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.
Total Total of all reporting groups

Baseline Measures
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment     Total  
Number of Participants  
[units: participants]
  243     118     361  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     170     81     251  
>=65 years     73     37     110  
Gender  
[units: participants]
     
Female     91     71     162  
Male     152     47     199  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Time to Tumor Progression (TTP) as Assessed by Imaging Studies at End of Double-blind Treatment Phase   [ Time Frame: Day 28 of each 6-week cycle : duration of double-blind treatment phase ]

2.  Primary:   Time to Tumor Progression (TTP) as Assessed in the Double-blind Treatment Phase at End of Study   [ Time Frame: Day 28 of each 6-week cycle : duration of double-blind treatment phase after Last Subject Last Visit (LSLV) ]

3.  Secondary:   Progression Free Survival (PFS)   [ Time Frame: Day 28 of each cycle : duration of double-blind treatment phase ]

4.  Secondary:   Overall Survival Status of Subjects   [ Time Frame: clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug ]

5.  Secondary:   Overall Survival   [ Time Frame: clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug ]

6.  Secondary:   Overall Survival Based on the Rank Preserving Structural Failure Time Method   [ Time Frame: clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug ]

7.  Secondary:   Best Overall Tumor Response During Double-blind Treatment Phase   [ Time Frame: Day 28 of each cycle : duration of double-blind treatment phase ]

8.  Secondary:   Confirmed Objective Response (CR or PR) in Subjects   [ Time Frame: Day 28 of each cycle : duration of double-blind treatment phase ]

9.  Secondary:   Time to Tumor Response (TTR)   [ Time Frame: Day 28 of each cycle : duration of double-blind treatment phase ]

10.  Secondary:   Duration of Performance Status Maintenance   [ Time Frame: Day 28 of each cycle : duration of double-blind treatment phase ]

11.  Secondary:   Time to Pain Progression Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI)   [ Time Frame: Day 1 & 28 of each cycle : duration of double-blind treatment phase ]

12.  Secondary:   Subjects With Pain Relief Response Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI)   [ Time Frame: Day 1 & 28 of each cycle : duration of double-blind treatment phase ]

13.  Secondary:   Change From Baseline Score in EuroQoL Visual Analog Scale (EQ-VAS)   [ Time Frame: Day 1 & 28 of each cycle : duration of double-blind treatment phase ]

14.  Secondary:   Change From Baseline in EQ-5D Health State Profile Index   [ Time Frame: Day 1 & 28 of each cycle : duration of double-blind treatment phase ]


  Serious Adverse Events
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Time Frame No text entered.
Additional Description No text entered.

Reporting Groups
  Description
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.
Sunitinib Open-Label Treatment Subjects experiencing disease progression could have their treatment assignment unblinded, and subjects who had been receiving placebo could crossover to open-label treatment with sunitinib; subjects who had been receiving sunitinib during double-blind treatment of the study could continue to do so after unblinding if, in the opinion of the investigator, there was sufficient evidence of clinical benefit.

Serious Adverse Events
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment     Sunitinib Open-Label Treatment  
Total, serious adverse events        
# participants affected     83     27     122  
Blood and lymphatic system disorders        
Anaemia † 1      
# participants affected / at risk     11/228 (4.82%)     1/114 (0.88%)     10/255 (3.92%)  
Thrombocytopenia      
# participants affected / at risk     5/228 (2.19%)     0/114 (0.00%)     4/255 (1.57%)  
Neutropenia      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     1/255 (0.39%)  
Febrile neutropenia      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Leukopenia      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Haemolytic anaemia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Lymphopenia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Cardiac disorders        
Cardiac arrest      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     0/255 (0.00%)  
Cardiac disorder      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Cardiac failure      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     0/255 (0.00%)  
Cardiomyopathy      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Ejection fraction decreased      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Left ventricular failure      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Mitral valve imcompetence      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Cardio-respiratory arrest      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Angina pectoris      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Bradycardia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Cardiac failure congestive      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Myocardial infarction      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Pericardial effusion      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Ventricular hypokinesia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Congenital, familial and genetic disorders        
Pyloric stenosis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Epidermolysis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Endocrine disorders        
Hypothyroidism      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     4/255 (1.57%)  
Gastrointestinal disorders        
Abdominal pain      
# participants affected / at risk     13/228 (5.70%)     6/114 (5.26%)     29/255 (11.37%)  
Nausea      
# participants affected / at risk     5/228 (2.19%)     3/114 (2.63%)     8/255 (3.14%)  
Vomiting      
# participants affected / at risk     5/228 (2.19%)     4/114 (3.51%)     12/255 (4.71%)  
Ascites      
# participants affected / at risk     4/228 (1.75%)     1/114 (0.88%)     3/255 (1.18%)  
Diarrhoea      
# participants affected / at risk     4/228 (1.75%)     0/114 (0.00%)     4/255 (1.57%)  
Abdominal distension      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     3/255 (1.18%)  
Constipation      
# participants affected / at risk     2/228 (0.88%)     1/114 (0.88%)     5/255 (1.96%)  
Gastrointestinal haemorrhage      
# participants affected / at risk     2/228 (0.88%)     3/114 (2.63%)     4/255 (1.57%)  
Intestinal obstruction      
# participants affected / at risk     2/228 (0.88%)     1/114 (0.88%)     2/255 (0.78%)  
Melaena      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     1/255 (0.39%)  
Abdominal pain upper      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Anal fistula      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Gastric haemorrhage      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Gastric ulcer      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Gastritis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Gastritis haemorrhagic      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Gastrointestinal obstruction      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     0/255 (0.00%)  
Haematemesis      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     3/255 (1.18%)  
Haemorrhoids      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Intestinal haemorrhage      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Oesophageal haemorrhage      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Rectal haemorrhage      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     5/255 (1.96%)  
Small intestinal obstruction      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     3/255 (1.18%)  
Ileus      
# participants affected / at risk     0/228 (0.00%)     2/114 (1.75%)     2/255 (0.78%)  
Subileus      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     1/255 (0.39%)  
Abdominal discomfort      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Anal haemorrhage      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Duodenal fistula      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Duodenal ulcer      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Dyspepsia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Enterocutaneous fistula      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Gastrooesophageal reflux disease      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Inguinal hernia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Intra-abdominal haemorrhage      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Large intestinal haemorrhage      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Peritoneal haemorrhage      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Tongue haemorrhage      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Upper gastrointestinal haemorrhage      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
General disorders        
Disease progression      
# participants affected / at risk     8/228 (3.51%)     4/114 (3.51%)     33/255 (12.94%)  
Pyrexia      
# participants affected / at risk     8/228 (3.51%)     1/114 (0.88%)     11/255 (4.31%)  
Fatigue      
# participants affected / at risk     2/228 (0.88%)     1/114 (0.88%)     3/255 (1.18%)  
Oedema peripheral      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     0/255 (0.00%)  
Asthenia      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     3/255 (1.18%)  
Chills      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     2/255 (0.78%)  
Drug interaction      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
General physical health deterioration      
# participants affected / at risk     1/228 (0.44%)     3/114 (2.63%)     4/255 (1.57%)  
Multi-organ failure      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Oedema      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Chest pain      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     3/255 (1.18%)  
Performance status decreased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Catheter related complication      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Impaired healing      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Infusion site extravasation      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Mucosal inflammation      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Pain      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Pneumatosis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Ulcer haemorrhage      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Hepatobiliary disorders        
Acute hepatic failure      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Bile duct stone      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Cholecystitis acute      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Cholelithiasis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Cholestasis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Hepatic failure      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     2/255 (0.78%)  
Hepatic function abnormal      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Hepatic haemorrhage      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Cholecystitis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Hepatotoxicity      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Infections and infestations        
Catheter sepsis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Central line infection      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Infection      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     3/255 (1.18%)  
Mediastinitis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Pneumonia      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     4/255 (1.57%)  
Staphylococcal sepsis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Urinary tract infection      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     2/255 (0.78%)  
Viral infection      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     0/255 (0.00%)  
Bacteraemia      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     2/255 (0.78%)  
Cystitis      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Lower respiratory tract infection      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     1/255 (0.39%)  
Gastroenteritis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Abdominal abscess      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Bacterial infection      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Campylobacter infection      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Cellulitis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Empyema      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Gastrointestinal infection      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Liver abscess      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Perirectal abscess      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Respiratory tract infection      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Sepsis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Urosepsis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Injury, poisoning and procedural complications        
Wound dehiscence      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Device malfunction      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Feeding tube complication      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Medication error      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Neck injury      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Skin laceration      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Investigations        
Aspartate aminotransferase increased      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Blood creatinine increased      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     3/255 (1.18%)  
Haemoglobin decreased      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     2/255 (0.78%)  
Ammonia increased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Blood bilirubin increased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Blood creatine phosphokinase increased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Blood potassium decreased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Blood pressure increased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Weight decreased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Metabolism and nutrition disorders        
Dehydration      
# participants affected / at risk     4/228 (1.75%)     0/114 (0.00%)     10/255 (3.92%)  
Hypoglycaemia      
# participants affected / at risk     4/228 (1.75%)     0/114 (0.00%)     0/255 (0.00%)  
Food intolerance      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Hypercalcaemia      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     1/255 (0.39%)  
Hypocalcaemia      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Hypokalaemia      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Anorexia      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     3/255 (1.18%)  
Appetite disorder      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Cachexia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Hypochloraemia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Hyponatraemia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Musculoskeletal and connective tissue disorders        
Back pain      
# participants affected / at risk     1/228 (0.44%)     2/114 (1.75%)     1/255 (0.39%)  
Fistula      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Flank pain      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Muscle spasms      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Pain in extremity      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Bone pain      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Intervertebral disc protrusion      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Mobility decreased      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Musculoskeletal pain      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     3/255 (1.18%)  
Myalgia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Neck pain      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Rotator cuff syndrome      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)        
Tumour haemorrhage      
# participants affected / at risk     3/228 (1.32%)     0/114 (0.00%)     3/255 (1.18%)  
Haemorrhagic tumour necrosis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Multiple myeloma      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Tumour associated fever      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Tumour lysis syndrome      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Cancer pain      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Hepatic neoplasm malignant      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Metastases to liver      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Neurilemmoma benign      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Tumour perforation      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Nervous system disorders        
Cerebral ischaemia      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Encephalopathy      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Myoclonus      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Somnolence      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     2/255 (0.78%)  
Syncope      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     3/255 (1.18%)  
Transient ischaemic attack      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Cerebrovascular accident      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     1/255 (0.39%)  
Paralysis      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Hepatic encephalopathy      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     3/255 (1.18%)  
Lethargy      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     3/255 (1.18%)  
Cerebral haemorrhage      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Coma      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Convulsion      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Dizziness      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Guillain-Barre syndrome      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Intracranial venous sinus thrombosis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Lacunar infarction      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Loss of consciousness      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Paraesthesia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Psychiatric disorders        
Insomnia      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Nervousness      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Confusional state      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     4/255 (1.57%)  
Agitation      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Completed suicide      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Renal and urinary disorders        
Haematuria      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Nephrotic syndrome      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Oliguria      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Renal colic      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Renal failure acute      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     1/255 (0.39%)  
Urinary retention      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     2/255 (0.78%)  
Hydronephrosis      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Renal failure      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Renal impairment      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Dysuria      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Renal failure      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Reproductive system and breast disorders        
Pelvic pain      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Uterine polyp      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Vaginal haemorrhage      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Respiratory, thoracic and mediastinal disorders        
Pulmonary embolism      
# participants affected / at risk     4/228 (1.75%)     1/114 (0.88%)     2/255 (0.78%)  
Pneumothorax      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Pulmonary hypertension      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Epistaxis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     3/255 (1.18%)  
Dyspnoea      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Pleural effusion      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Lung consolidation      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Skin and subcutaneous tissue disorders        
Rash      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Diabetic ulcer      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Palmar-plantar erythrodysaesthesia syndrome      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Surgical and medical procedures        
Hepatic embolisation      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Stent placement      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Vascular disorders        
Deep vein thrombosis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     3/255 (1.18%)  
Haemorrhage      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Hypertensive crisis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Thrombosis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Circulatory collapse      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Hypertension      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     4/255 (1.57%)  
Hypotension      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     3/255 (1.18%)  
Thrombophlebitis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Embolism      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Jugular vein thrombosis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (11.1)




  Other Adverse Events


  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
Duration of Tumor Response could not be reliably estimated at the time of analysis.


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