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Trial record 72 of 179 for:    colon cancer | ( Map: New Jersey, United States )

First Line Metastatic Colorectal Cancer Therapy in Combination With FOLFOX (HORIZON III)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00384176
Recruitment Status : Completed
First Posted : October 5, 2006
Results First Posted : November 28, 2012
Last Update Posted : April 14, 2017
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Colorectal Cancer
Interventions Drug: Cediranib
Drug: Bevacizumab
Drug: 5-fluorouracil ( in FOLFOX)
Drug: Leucovorin (in FOLFOX)
Drug: Oxaliplatin (in FOLFOX)
Enrollment 1814
Recruitment Details Enrolled = 1814 though not all patient randomised. Randomised= Intent to treat (ITT): Cediranib 20mg 709, Cediranib 30mg 192 Bevacizumab 713; Safety: Cediranib 20mg 705, Cediranib 30mg 191 Bevacizumab 704
Pre-assignment Details

Cediranib 30mg discontinued following Phase II, Cediranib 20mg chosen dose for comparing with Bevacizumab.

200 patients dropped prior to treatment. Study was set up as a phase II/III study. Participants were enrolled into both phases if they participated in both Phase II/III, but are only counted once in the Enrollment Number and in the Results.

Arm/Group Title Cediranib 20 mg Bevacizumab 5 mg/kg Cediranib 30 mg
Hide Arm/Group Description

Cediranib 20 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.

Bevacizumab 5 mg/kg on Day 1 and every 2 weeks + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.

Cediranib 30 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.
Period Title: Overall Study
Started 709 713 192
Completed 397 394 60
Not Completed 312 319 132
Reason Not Completed
Death             239             247             105
Withdrawal by Subject             52             48             22
Lost to Follow-up             16             18             4
Incorrect enrol/elig crit not fulfilled             2             3             0
Longer QTC as Visit 1             1             0             0
Toxicity of treatment             1             0             0
Did not receive study treatment             0             1             1
Physician Decision             0             2             0
Liver metastases, colon resec. planned             1             0             0
Arm/Group Title Cediranib 20 mg Bevacizumab 5 mg/kg Cediranib 30 mg Total
Hide Arm/Group Description

Cediranib 20 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.

Bevacizumab 5 mg/kg on Day 1 and every 2 weeks

+ FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.

Cediranib 30 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.
Total of all reporting groups
Overall Number of Baseline Participants 709 713 192 1614
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 709 participants 713 participants 192 participants 1614 participants
58.1  (11.37) 59.0  (10.82) 59.2  (10.59) 58.6  (11.1)
[1]
Measure Description: Age at informed consent
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 709 participants 713 participants 192 participants 1614 participants
Female
297
  41.9%
299
  41.9%
73
  38.0%
669
  41.4%
Male
412
  58.1%
414
  58.1%
119
  62.0%
945
  58.6%
[1]
Measure Description: Gender at informed consent
1.Primary Outcome
Title Progression Free Survival
Hide Description Progression is defined as the number of months from randomisation until progressive disease based on RECIST (progression of target lesions, clear progression of existing non-target lesions or the appearance of one or more new lesions) or death in the absence of progression.
Time Frame Baseline then at Weeks 8, 16, 24 and then every 12 weeks until progression
Hide Outcome Measure Data
Hide Analysis Population Description
Two cediranib doses (20 mg and 30 mg) were initially included in this study; however, it was intended that one dose would be selected for continuation. The decision was taken to continue with cediranib 20 mg. No statistical analyses were performed on the 30mg group.
Arm/Group Title Cediranib 20 mg Bevacizumab 5 mg/kg Cediranib 30 mg
Hide Arm/Group Description:

Cediranib 20 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.

Bevacizumab 5 mg/kg on Day 1 and every 2 weeks

+ FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.

Cediranib 30 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.
Overall Number of Participants Analyzed 709 713 0
Median (Inter-Quartile Range)
Unit of Measure: Months
9.9
(6.3 to 13.5)
10.3
(6.5 to 14.1)
2.Secondary Outcome
Title Overall Survival
Hide Description Number of months from randomisation to the date of death from any cause
Time Frame Randomisation until data cut-off
Hide Outcome Measure Data
Hide Analysis Population Description
Two cediranib doses (20 mg and 30 mg) were initially included in this study; however, it was intended that one dose would be selected for continuation. The decision was taken to continue with cediranib 20 mg. No statistical analyses were performed on the 30mg group.
Arm/Group Title Cediranib 20 mg Bevacizumab 5 mg/kg Cediranib 30 mg
Hide Arm/Group Description:

Cediranib 20 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.

Bevacizumab 5 mg/kg on Day 1 and every 2 weeks

+ FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.

Cediranib 30 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.
Overall Number of Participants Analyzed 709 713 0
Median (Inter-Quartile Range)
Unit of Measure: Months
22.8
(13.3 to 32.3)
21.3
(12.2 to 32.8)
3.Secondary Outcome
Title Objective Response Rate
Hide Description

Objective response rate is Complete Response (CR) + Partial Response (PR) as defined below:

CR = Disappearance of all target lesions. PR = At least a 30% decrease in the sum of longest diameters (LDs) of target lesions, taking as reference the baseline sum of LDs.

Time Frame Up until data cut-off
Hide Outcome Measure Data
Hide Analysis Population Description
Two cediranib doses (20 mg and 30 mg) were initially included in this study; however, it was intended that one dose would be selected for continuation. The decision was taken to continue with cediranib 20 mg. No statistical analyses were performed on the 30mg group.
Arm/Group Title Cediranib 20 mg Bevacizumab 5 mg/kg Cediranib 30 mg
Hide Arm/Group Description:

Cediranib 20 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.

Bevacizumab 5 mg/kg on Day 1 and every 2 weeks

+ FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.

Cediranib 30 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.
Overall Number of Participants Analyzed 709 713 0
Measure Type: Number
Unit of Measure: Participants
328 337
4.Secondary Outcome
Title Duration of Response
Hide Description Duration of Response is calculated as the time from the first recording of CR/PR until the patient progresses, regardless of whether the patient was still taking study medication. Only confirmed responses are included in the calculation. For patients who had not progressed, the end date used in the calculation of duration of response is the data cut-off date of 15th November 2009.
Time Frame Up until data cut-off date of 15/11/2007
Hide Outcome Measure Data
Hide Analysis Population Description
Two cediranib doses (20 mg and 30 mg) were initially included in this study; however, it was intended that one dose would be selected for continuation. The decision was taken to continue with cediranib 20 mg. No statistical analyses were performed on the 30mg group.
Arm/Group Title Cediranib 20 mg Bevacizumab 5 mg/kg Cediranib 30 mg
Hide Arm/Group Description:

Cediranib 20 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.

Bevacizumab 5 mg/kg on Day 1 and every 2 weeks

+ FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.

Cediranib 30 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.
Overall Number of Participants Analyzed 328 337 0
Median (Inter-Quartile Range)
Unit of Measure: Months
8.6
(6.1 to 12.1)
9.6
(6.5 to 13.6)
5.Secondary Outcome
Title Percentage Change in Tumour Size
Hide Description Percentage change in tumour size from baseline to first RECIST assessment (Week 8) ((Week 8 - baseline)/baseline)*100
Time Frame Baseline to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
No statistical analyses were performed on the 30mg group. Patients had to have both a baseline and post-baseline (week 8) value to be included in the analysis. If patients did not have a week 8 assessment they were not included.
Arm/Group Title Cediranib 20 mg Bevacizumab 5 mg/kg Cediranib 30 mg
Hide Arm/Group Description:

Cediranib 20 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.

Bevacizumab 5 mg/kg on Day 1 and every 2 weeks

+ FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.

Cediranib 30 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.
Overall Number of Participants Analyzed 634 649 0
Mean (Standard Deviation)
Unit of Measure: Percentage change in tumour size
-23.2  (21.8) -22.1  (19.55)
6.Secondary Outcome
Title Time to Worsening of Health Related Quality of Life (QOL) Based on the FACT Colorectal Symptom Index (FCSI)
Hide Description Time to worsening of symptoms, as measured by the FACT colorectal symptom index (FCSI), will be defined as the time when a sustained clinically important deterioration in the total score from the FCSI has been recorded.
Time Frame Baseline through to data cut-off
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cediranib 20 mg Bevacizumab 5 mg/kg Cediranib 30 mg
Hide Arm/Group Description:

Cediranib 20 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.

Bevacizumab 5 mg/kg on Day 1 and every 2 weeks

+ FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.

Cediranib 30 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.
Overall Number of Participants Analyzed 709 713 0
Median (Inter-Quartile Range)
Unit of Measure: Days
170
(56 to 328)
245
(112 to 348)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cediranib 20 mg Cediranib 30 mg 1Bevacizumab 5mg/kg
Hide Arm/Group Description

Cediranib 20 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.

Cediranib 30 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.
Bevacizumab 5 mg/kg on Day 1 and every 2 weeks
All-Cause Mortality
Cediranib 20 mg Cediranib 30 mg 1Bevacizumab 5mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Cediranib 20 mg Cediranib 30 mg 1Bevacizumab 5mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   275/705 (39.01%)   90/191 (47.12%)   231/704 (32.81%) 
Blood and lymphatic system disorders       
Febrile Neutropenia  1  11/705 (1.56%)  1/191 (0.52%)  13/704 (1.85%) 
Neutropenia  1  8/705 (1.13%)  5/191 (2.62%)  11/704 (1.56%) 
Thrombocytopenia  1  6/705 (0.85%)  1/191 (0.52%)  1/704 (0.14%) 
Anaemia  1  1/705 (0.14%)  0/191 (0.00%)  3/704 (0.43%) 
Idiopathic Thrombocytopenic Purpura  1  0/705 (0.00%)  0/191 (0.00%)  2/704 (0.28%) 
Agranulocytosis  1  0/705 (0.00%)  1/191 (0.52%)  1/704 (0.14%) 
Coagulopathy  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Disseminated Intravascular Coagulation  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Leukopenia  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Pancytopenia  1  0/705 (0.00%)  1/191 (0.52%)  1/704 (0.14%) 
Cardiac disorders       
Acute Myocardial Infarction  1  1/705 (0.14%)  0/191 (0.00%)  3/704 (0.43%) 
Cardiac Failure  1  3/705 (0.43%)  0/191 (0.00%)  1/704 (0.14%) 
Myocardial Ischaemia  1  3/705 (0.43%)  1/191 (0.52%)  2/704 (0.28%) 
Atrial Fibrillation  1  1/705 (0.14%)  0/191 (0.00%)  2/704 (0.28%) 
Myocardial Infarction  1  2/705 (0.28%)  0/191 (0.00%)  1/704 (0.14%) 
Angina Pectoris  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Angina Unstable  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Arrhythmia  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Arteriospasm Coronary  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Atrial Flutter  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Atrial Thrombosis  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Atrioventricular Block  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Bradycardia  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Cardiomyopathy  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Cardiopulmonary Failure  1  1/705 (0.14%)  1/191 (0.52%)  0/704 (0.00%) 
Coronary Artery Disease  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Intracardiac Thrombus  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Left Ventricular Dysfunction  1  1/705 (0.14%)  1/191 (0.52%)  0/704 (0.00%) 
Left Ventricular Failure  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Mitral Valve Incompetence  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Pericarditis Constrictive  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Supraventricular Tachycardia  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Congenital, familial and genetic disorders       
Dihydropyrimidine Dehydrogenase Deficiency  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Ear and labyrinth disorders       
Deafness  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Vertigo  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Endocrine disorders       
Adrenal Insufficiency  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Hypothyroidism  1  0/705 (0.00%)  1/191 (0.52%)  1/704 (0.14%) 
Eye disorders       
Diplopia  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Ulcerative Keratitis  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Gastrointestinal disorders       
Diarrhoea  1  30/705 (4.26%)  11/191 (5.76%)  13/704 (1.85%) 
Intestinal Obstruction  1  9/705 (1.28%)  2/191 (1.05%)  12/704 (1.70%) 
Vomiting  1  11/705 (1.56%)  3/191 (1.57%)  12/704 (1.70%) 
Abdominal Pain  1  9/705 (1.28%)  2/191 (1.05%)  10/704 (1.42%) 
Nausea  1  10/705 (1.42%)  1/191 (0.52%)  4/704 (0.57%) 
Ileus  1  7/705 (0.99%)  2/191 (1.05%)  6/704 (0.85%) 
Small Intestinal Obstruction  1  7/705 (0.99%)  0/191 (0.00%)  7/704 (0.99%) 
Stomatitis  1  7/705 (0.99%)  2/191 (1.05%)  1/704 (0.14%) 
Intestinal Perforation  1  0/705 (0.00%)  1/191 (0.52%)  6/704 (0.85%) 
Rectal Haemorrhage  1  5/705 (0.71%)  1/191 (0.52%)  0/704 (0.00%) 
Anal Fistula  1  0/705 (0.00%)  0/191 (0.00%)  4/704 (0.57%) 
Constipation  1  3/705 (0.43%)  1/191 (0.52%)  4/704 (0.57%) 
Abdominal Pain Upper  1  2/705 (0.28%)  2/191 (1.05%)  3/704 (0.43%) 
Colitis  1  0/705 (0.00%)  0/191 (0.00%)  3/704 (0.43%) 
Subileus  1  3/705 (0.43%)  0/191 (0.00%)  0/704 (0.00%) 
Gastrooesophageal Reflux Disease  1  0/705 (0.00%)  0/191 (0.00%)  2/704 (0.28%) 
Abdominal Pain Lower  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Anal Fissure  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Ascites  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Colonic Obstruction  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Duodenal Ulcer  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Duodenal Ulcer Perforation  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Duodenitis  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Enteritis  1  0/705 (0.00%)  1/191 (0.52%)  1/704 (0.14%) 
Enterovesical Fistula  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Gastric Ulcer Haemorrhage  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Gastritis  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Gastrointestinal Haemorrhage  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Gastrointestinal Inflammation  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Gastrointestinal Pain  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Gastrointestinal Toxicity  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Ileus Paralytic  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Inguinal Hernia  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Intestinal Haemorrhage  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Large Intestinal Haemorrhage  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Large Intestinal Obstruction  1  1/705 (0.14%)  1/191 (0.52%)  1/704 (0.14%) 
Large Intestine Perforation  1  1/705 (0.14%)  1/191 (0.52%)  1/704 (0.14%) 
Melaena  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Mesenteric Artery Thrombosis  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Mouth Ulceration  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Oesophageal Varices Haemorrhage  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Oesophagitis  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Pancreatitis  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Pancreatitis Acute  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Periproctitis  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Peritonitis  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Proctalgia  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Rectal Perforation  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Reflux Oesophagitis  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Varices Oesophageal  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
General disorders       
Pyrexia  1  21/705 (2.98%)  9/191 (4.71%)  11/704 (1.56%) 
Fatigue  1  6/705 (0.85%)  7/191 (3.66%)  0/704 (0.00%) 
Asthenia  1  3/705 (0.43%)  2/191 (1.05%)  1/704 (0.14%) 
Malaise  1  3/705 (0.43%)  0/191 (0.00%)  0/704 (0.00%) 
Non-Cardiac Chest Pain  1  3/705 (0.43%)  2/191 (1.05%)  1/704 (0.14%) 
Catheter Related Complication  1  2/705 (0.28%)  0/191 (0.00%)  0/704 (0.00%) 
Catheter Thrombosis  1  2/705 (0.28%)  0/191 (0.00%)  1/704 (0.14%) 
Chills  1  2/705 (0.28%)  0/191 (0.00%)  0/704 (0.00%) 
Multi-Organ Failure  1  2/705 (0.28%)  0/191 (0.00%)  0/704 (0.00%) 
Death  1  1/705 (0.14%)  1/191 (0.52%)  0/704 (0.00%) 
General Physical Health Deterioration  1  1/705 (0.14%)  1/191 (0.52%)  0/704 (0.00%) 
Infusion Site Extravasation  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Infusion Site Inflammation  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Mucosal Inflammation  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Oedema  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Oedema Peripheral  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Pain  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Sudden Death  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Hepatobiliary disorders       
Hyperbilirubinaemia  1  2/705 (0.28%)  0/191 (0.00%)  1/704 (0.14%) 
Portal Vein Thrombosis  1  2/705 (0.28%)  0/191 (0.00%)  1/704 (0.14%) 
Bile Duct Obstruction  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Cholecystitis  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Hepatic Failure  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Hepatic Pain  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Immune system disorders       
Drug Hypersensitivity  1  2/705 (0.28%)  1/191 (0.52%)  5/704 (0.71%) 
Hypersensitivity  1  0/705 (0.00%)  0/191 (0.00%)  2/704 (0.28%) 
Food Allergy  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Infections and infestations       
Pneumonia  1  10/705 (1.42%)  2/191 (1.05%)  5/704 (0.71%) 
Catheter Related Infection  1  6/705 (0.85%)  1/191 (0.52%)  6/704 (0.85%) 
Sepsis  1  6/705 (0.85%)  1/191 (0.52%)  6/704 (0.85%) 
Urinary Tract Infection  1  6/705 (0.85%)  1/191 (0.52%)  3/704 (0.43%) 
Central Line Infection  1  4/705 (0.57%)  0/191 (0.00%)  4/704 (0.57%) 
Infection  1  4/705 (0.57%)  0/191 (0.00%)  1/704 (0.14%) 
Catheter Sepsis  1  1/705 (0.14%)  0/191 (0.00%)  3/704 (0.43%) 
Lower Respiratory Tract Infection  1  1/705 (0.14%)  0/191 (0.00%)  3/704 (0.43%) 
Abscess  1  0/705 (0.00%)  0/191 (0.00%)  2/704 (0.28%) 
Anal Abscess  1  2/705 (0.28%)  0/191 (0.00%)  1/704 (0.14%) 
Diverticulitis  1  0/705 (0.00%)  0/191 (0.00%)  2/704 (0.28%) 
Gastroenteritis  1  2/705 (0.28%)  0/191 (0.00%)  2/704 (0.28%) 
Herpes Zoster  1  0/705 (0.00%)  0/191 (0.00%)  2/704 (0.28%) 
Septic Shock  1  1/705 (0.14%)  0/191 (0.00%)  2/704 (0.28%) 
Sinusitis  1  0/705 (0.00%)  0/191 (0.00%)  2/704 (0.28%) 
Staphylococcal Infection  1  1/705 (0.14%)  0/191 (0.00%)  2/704 (0.28%) 
Abdominal Abscess  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Abdominal Infection  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Abdominal Sepsis  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Appendicitis  1  1/705 (0.14%)  1/191 (0.52%)  0/704 (0.00%) 
Breast Abscess  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Bronchitis  1  1/705 (0.14%)  1/191 (0.52%)  1/704 (0.14%) 
Bronchopneumonia  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Catheter Site Cellulitis  1  1/705 (0.14%)  1/191 (0.52%)  0/704 (0.00%) 
Cellulitis  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Clostridial Infection  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Cystitis  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Endocarditis  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Enterococcal Infection  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Gas Gangrene  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Gastroenteritis Viral  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Gingival Infection  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Hepatitis C  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Herpes Virus Infection  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Influenza  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Infusion Site Infection  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Liver Abscess  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Lobar Pneumonia  1  1/705 (0.14%)  1/191 (0.52%)  0/704 (0.00%) 
Lung Infection  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Mucormycosis  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Nasopharyngitis  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Necrotising Fasciitis  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Neutropenic Sepsis  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Oesophageal Candidiasis  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Pelvic Abscess  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Perirectal Abscess  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Pulmonary Tuberculosis  1  1/705 (0.14%)  1/191 (0.52%)  0/704 (0.00%) 
Pyelonephritis  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Respiratory Tract Infection  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Retroperitoneal Abscess  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Tooth Abscess  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Upper Respiratory Tract Infection  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Urosepsis  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Viral Diarrhoea  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Viral Infection  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Wound Infection  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Injury, poisoning and procedural complications       
Post Procedural Complication  1  3/705 (0.43%)  0/191 (0.00%)  0/704 (0.00%) 
Abdominal Wound Dehiscence  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Cardiac Valve Replacement Complication  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Drug Toxicity  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Femur Fracture  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Gastrointestinal Stoma Complication  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Hip Fracture  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Joint Dislocation  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Lumbar Vertebral Fracture  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Multiple Fractures  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Patella Fracture  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Post Procedural Haemorrhage  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Procedural Pain  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Wound Dehiscence  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Wrist Fracture  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Investigations       
Alanine Aminotransferase Increased  1  2/705 (0.28%)  0/191 (0.00%)  0/704 (0.00%) 
Blood Pressure Increased  1  2/705 (0.28%)  0/191 (0.00%)  2/704 (0.28%) 
Aspartate Aminotransferase Increased  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Body Temperature Increased  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
C-Reactive Protein Increased  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Electrocardiogram Qt Prolonged  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Gamma-Glutamyltransferase Increased  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Glomerular Filtration Rate Decreased  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Haemoglobin Decreased  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Lipase Increased  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Transaminases Increased  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Viral Test Positive  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Weight Decreased  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Metabolism and nutrition disorders       
Dehydration  1  6/705 (0.85%)  5/191 (2.62%)  8/704 (1.14%) 
Hypokalaemia  1  4/705 (0.57%)  0/191 (0.00%)  1/704 (0.14%) 
Hyperglycaemia  1  0/705 (0.00%)  0/191 (0.00%)  3/704 (0.43%) 
Decreased Appetite  1  2/705 (0.28%)  2/191 (1.05%)  0/704 (0.00%) 
Hyponatraemia  1  2/705 (0.28%)  0/191 (0.00%)  0/704 (0.00%) 
Electrolyte Imbalance  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Fluid Intake Reduced  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Gout  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Hypercalcaemia  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Hyperkalaemia  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Hypoalbuminaemia  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Hypocalcaemia  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Hypoglycaemia  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Ketoacidosis  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Musculoskeletal and connective tissue disorders       
Back Pain  1  2/705 (0.28%)  0/191 (0.00%)  3/704 (0.43%) 
Chondrocalcinosis Pyrophosphate  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Flank Pain  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Intervertebral Disc Protrusion  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Musculoskeletal Pain  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Myalgia  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Neck Pain  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Osteoporosis  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Pain In Extremity  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Pathological Fracture  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Periostitis  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Metastatic Pain  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Osteoma  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Tumour Haemorrhage  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Tumour Pain  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Nervous system disorders       
Cerebral Haemorrhage  1  3/705 (0.43%)  2/191 (1.05%)  1/704 (0.14%) 
Syncope  1  3/705 (0.43%)  1/191 (0.52%)  1/704 (0.14%) 
Transient Ischaemic Attack  1  3/705 (0.43%)  1/191 (0.52%)  1/704 (0.14%) 
Convulsion  1  0/705 (0.00%)  2/191 (1.05%)  0/704 (0.00%) 
Aphasia  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Cerebral Infarction  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Cerebral Ischaemia  1  1/705 (0.14%)  1/191 (0.52%)  1/704 (0.14%) 
Cerebrovascular Accident  1  0/705 (0.00%)  1/191 (0.52%)  1/704 (0.14%) 
Cognitive Disorder  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Depressed Level Of Consciousness  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Dizziness  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Facial Palsy  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Grand Mal Convulsion  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Haemorrhagic Cerebral Infarction  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Haemorrhagic Stroke  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Headache  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Hemiparesis  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Hypertensive Encephalopathy  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Ischaemic Cerebral Infarction  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Lethargy  1  1/705 (0.14%)  1/191 (0.52%)  0/704 (0.00%) 
Loss Of Consciousness  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Nerve Root Lesion  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Neuropathy Peripheral  1  1/705 (0.14%)  1/191 (0.52%)  0/704 (0.00%) 
Partial Seizures  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Peroneal Nerve Palsy  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Reversible Posterior Leukoencephalopathy Syndrome  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Somnolence  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Toxic Encephalopathy  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Vascular Encephalopathy  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Psychiatric disorders       
Bradyphrenia  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Depression  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Dissociative Disorder  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Suicidal Ideation  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Renal and urinary disorders       
Hydronephrosis  1  0/705 (0.00%)  0/191 (0.00%)  2/704 (0.28%) 
Renal Failure  1  2/705 (0.28%)  1/191 (0.52%)  1/704 (0.14%) 
Bladder Obstruction  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Haematuria  1  1/705 (0.14%)  1/191 (0.52%)  0/704 (0.00%) 
Renal Colic  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Renal Failure Acute  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Renal Pain  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Ureteric Obstruction  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Urinary Incontinence  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Urinary Retention  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Reproductive system and breast disorders       
Female Genital Tract Fistula  1  0/705 (0.00%)  0/191 (0.00%)  2/704 (0.28%) 
Fibrocystic Breast Disease  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Respiratory, thoracic and mediastinal disorders       
Pulmonary Embolism  1  13/705 (1.84%)  6/191 (3.14%)  21/704 (2.98%) 
Dyspnoea  1  3/705 (0.43%)  2/191 (1.05%)  4/704 (0.57%) 
Pneumothorax  1  0/705 (0.00%)  0/191 (0.00%)  3/704 (0.43%) 
Epistaxis  1  2/705 (0.28%)  0/191 (0.00%)  0/704 (0.00%) 
Laryngospasm  1  2/705 (0.28%)  0/191 (0.00%)  0/704 (0.00%) 
Pneumonia Aspiration  1  2/705 (0.28%)  0/191 (0.00%)  0/704 (0.00%) 
Bronchospasm  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Chronic Obstructive Pulmonary Disease  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Haemoptysis  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Lung Disorder  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Organising Pneumonia  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Pharyngeal Oedema  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Pleural Effusion  1  1/705 (0.14%)  1/191 (0.52%)  0/704 (0.00%) 
Skin and subcutaneous tissue disorders       
Palmar-Plantar Erythrodysaesthesia Syndrome  1  0/705 (0.00%)  2/191 (1.05%)  0/704 (0.00%) 
Dermatitis Contact  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Subcutaneous Emphysema  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Swelling Face  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Vascular disorders       
Deep Vein Thrombosis  1  9/705 (1.28%)  2/191 (1.05%)  9/704 (1.28%) 
Hypertension  1  9/705 (1.28%)  4/191 (2.09%)  2/704 (0.28%) 
Jugular Vein Thrombosis  1  3/705 (0.43%)  0/191 (0.00%)  0/704 (0.00%) 
Hypertensive Crisis  1  2/705 (0.28%)  2/191 (1.05%)  0/704 (0.00%) 
Hypotension  1  1/705 (0.14%)  0/191 (0.00%)  2/704 (0.28%) 
Arterial Thrombosis Limb  1  0/705 (0.00%)  0/191 (0.00%)  1/704 (0.14%) 
Circulatory Collapse  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Embolism Venous  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Haematoma  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Orthostatic Hypotension  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Shock Haemorrhagic  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Subclavian Vein Thrombosis  1  1/705 (0.14%)  1/191 (0.52%)  0/704 (0.00%) 
Thrombosis  1  0/705 (0.00%)  1/191 (0.52%)  0/704 (0.00%) 
Vasospasm  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Vena Cava Thrombosis  1  1/705 (0.14%)  1/191 (0.52%)  1/704 (0.14%) 
Venous Thrombosis  1  1/705 (0.14%)  0/191 (0.00%)  1/704 (0.14%) 
Venous Thrombosis Limb  1  1/705 (0.14%)  0/191 (0.00%)  0/704 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cediranib 20 mg Cediranib 30 mg 1Bevacizumab 5mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   684/705 (97.02%)   187/191 (97.91%)   672/704 (95.45%) 
Blood and lymphatic system disorders       
Neutropenia  1  302/705 (42.84%)  85/191 (44.50%)  228/704 (32.39%) 
Thrombocytopenia  1  186/705 (26.38%)  55/191 (28.80%)  85/704 (12.07%) 
Anaemia  1  50/705 (7.09%)  16/191 (8.38%)  79/704 (11.22%) 
Leukopenia  1  56/705 (7.94%)  20/191 (10.47%)  52/704 (7.39%) 
Endocrine disorders       
Hypothyroidism  1  35/705 (4.96%)  24/191 (12.57%)  8/704 (1.14%) 
Gastrointestinal disorders       
Diarrhoea  1  486/705 (68.94%)  147/191 (76.96%)  354/704 (50.28%) 
Nausea  1  355/705 (50.35%)  100/191 (52.36%)  349/704 (49.57%) 
Stomatitis  1  252/705 (35.74%)  77/191 (40.31%)  187/704 (26.56%) 
Vomiting  1  221/705 (31.35%)  64/191 (33.51%)  192/704 (27.27%) 
Constipation  1  145/705 (20.57%)  34/191 (17.80%)  187/704 (26.56%) 
Abdominal Pain  1  161/705 (22.84%)  49/191 (25.65%)  124/704 (17.61%) 
Abdominal Pain Upper  1  82/705 (11.63%)  21/191 (10.99%)  59/704 (8.38%) 
Dyspepsia  1  45/705 (6.38%)  11/191 (5.76%)  56/704 (7.95%) 
Dry Mouth  1  33/705 (4.68%)  10/191 (5.24%)  30/704 (4.26%) 
Dysphagia  1  22/705 (3.12%)  11/191 (5.76%)  10/704 (1.42%) 
General disorders       
Fatigue  1  314/705 (44.54%)  89/191 (46.60%)  299/704 (42.47%) 
Pyrexia  1  92/705 (13.05%)  26/191 (13.61%)  123/704 (17.47%) 
Asthenia  1  96/705 (13.62%)  31/191 (16.23%)  73/704 (10.37%) 
Oedema Peripheral  1  28/705 (3.97%)  14/191 (7.33%)  39/704 (5.54%) 
Immune system disorders       
Drug Hypersensitivity  1  41/705 (5.82%)  10/191 (5.24%)  50/704 (7.10%) 
Infections and infestations       
Nasopharyngitis  1  42/705 (5.96%)  21/191 (10.99%)  50/704 (7.10%) 
Urinary Tract Infection  1  42/705 (5.96%)  15/191 (7.85%)  43/704 (6.11%) 
Upper Respiratory Tract Infection  1  18/705 (2.55%)  4/191 (2.09%)  36/704 (5.11%) 
Investigations       
Weight Decreased  1  80/705 (11.35%)  32/191 (16.75%)  56/704 (7.95%) 
Alanine Aminotransferase Increased  1  18/705 (2.55%)  11/191 (5.76%)  13/704 (1.85%) 
Metabolism and nutrition disorders       
Decreased Appetite  1  177/705 (25.11%)  71/191 (37.17%)  160/704 (22.73%) 
Hypokalaemia  1  59/705 (8.37%)  16/191 (8.38%)  38/704 (5.40%) 
Musculoskeletal and connective tissue disorders       
Back Pain  1  54/705 (7.66%)  20/191 (10.47%)  63/704 (8.95%) 
Pain In Extremity  1  46/705 (6.52%)  16/191 (8.38%)  38/704 (5.40%) 
Arthralgia  1  34/705 (4.82%)  15/191 (7.85%)  40/704 (5.68%) 
Musculoskeletal Pain  1  40/705 (5.67%)  7/191 (3.66%)  35/704 (4.97%) 
Myalgia  1  18/705 (2.55%)  11/191 (5.76%)  22/704 (3.13%) 
Nervous system disorders       
Neuropathy Peripheral  1  218/705 (30.92%)  49/191 (25.65%)  212/704 (30.11%) 
Paraesthesia  1  157/705 (22.27%)  46/191 (24.08%)  158/704 (22.44%) 
Peripheral Sensory Neuropathy  1  135/705 (19.15%)  37/191 (19.37%)  144/704 (20.45%) 
Headache  1  117/705 (16.60%)  46/191 (24.08%)  90/704 (12.78%) 
Dysgeusia  1  82/705 (11.63%)  24/191 (12.57%)  84/704 (11.93%) 
Dizziness  1  51/705 (7.23%)  16/191 (8.38%)  33/704 (4.69%) 
Lethargy  1  40/705 (5.67%)  12/191 (6.28%)  30/704 (4.26%) 
Psychiatric disorders       
Insomnia  1  49/705 (6.95%)  16/191 (8.38%)  55/704 (7.81%) 
Depression  1  23/705 (3.26%)  11/191 (5.76%)  23/704 (3.27%) 
Renal and urinary disorders       
Proteinuria  1  48/705 (6.81%)  23/191 (12.04%)  40/704 (5.68%) 
Respiratory, thoracic and mediastinal disorders       
Epistaxis  1  169/705 (23.97%)  45/191 (23.56%)  172/704 (24.43%) 
Dysphonia  1  124/705 (17.59%)  47/191 (24.61%)  81/704 (11.51%) 
Cough  1  71/705 (10.07%)  22/191 (11.52%)  68/704 (9.66%) 
Dyspnoea  1  60/705 (8.51%)  27/191 (14.14%)  43/704 (6.11%) 
Oropharyngeal Pain  1  44/705 (6.24%)  13/191 (6.81%)  37/704 (5.26%) 
Skin and subcutaneous tissue disorders       
Palmar-Plantar Erythrodysaesthesia Syndrome  1  104/705 (14.75%)  31/191 (16.23%)  68/704 (9.66%) 
Alopecia  1  65/705 (9.22%)  18/191 (9.42%)  64/704 (9.09%) 
Rash  1  51/705 (7.23%)  14/191 (7.33%)  38/704 (5.40%) 
Vascular disorders       
Hypertension  1  292/705 (41.42%)  92/191 (48.17%)  183/704 (25.99%) 
Phlebitis  1  22/705 (3.12%)  10/191 (5.24%)  31/704 (4.40%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
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.
If a Study Site, or an investigator, requests permission to publish data from this study, any such publication (including oral presentations) is to be agreed with AstraZeneca prior to publication.
Results Point of Contact
Name/Title: Gerard Lynch
Organization: AstraZeneca
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00384176     History of Changes
Other Study ID Numbers: D8480C00013
Eudract Number 2005-003440-66
First Submitted: October 3, 2006
First Posted: October 5, 2006
Results First Submitted: March 7, 2012
Results First Posted: November 28, 2012
Last Update Posted: April 14, 2017