ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Avastin (Bevacizumab) in Combination With Platinum-Containing Chemotherapy in Patients With Advanced or Recurrent Non-Squamous Cell Lung Cancer.

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: NCT00451906
Recruitment Status : Completed
First Posted : March 26, 2007
Results First Posted : April 25, 2016
Last Update Posted : May 24, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non-Squamous Non-Small Cell Lung Cancer
Interventions Drug: Platinum-based chemotherapy
Drug: Bevacizumab [Avastin]
Enrollment 2252
Recruitment Details This study was conducted at 384 sites in 39 countries from 21 August 2006 to 30 June 2009.
Pre-assignment Details A total of 2252 participants were enrolled into the study, of which 2172 received the study drug. A total of 80 randomized participants did not receive study drug.
Arm/Group Title Bevacizumab + Chemotherapy
Hide Arm/Group Description Eligible participants with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) were administered bevacizumab infusions at a dose of 7.5 milligram per kilogram (mg/kg) or 15 mg/kg (investigator’s choice) on Day 1 and then every 3 weeks, intravenously (IV) for a maximum of 6 cycles in combination with the standard of care NSCLC first-line chemotherapy in line with the licensed national prescribing information, during the treatment period. The initial dose of bevacizumab was to be administered following chemotherapy; all subsequent doses could be given before or after chemotherapy. After the end of chemotherapy participants without disease progression could continue bevacizumab as maintenance therapy until confirmed disease progression, unacceptable toxicity or participant consent withdrawal. Participants were followed-up through a final-visit (28 days after last bevacizumab infusion) and then every 3 months until death.
Period Title: Overall Study
Started 2252
Completed 13
Not Completed 2239
Reason Not Completed
Adverse Event             515
Lost to Follow-up             31
Withdrawal by Subject             111
Protocol Violation             21
Progressive disease             1328
Termination of the study             108
Other Reasons             121
Did not complete final visit             4
Arm/Group Title Bevacizumab + Chemotherapy
Hide Arm/Group Description Eligible participants with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) were administered bevacizumab infusions at a dose of 7.5 milligram per kilogram (mg/kg) or 15 mg/kg (investigator’s choice) on Day 1 and then every 3 weeks, intravenously (IV) for a maximum of 6 cycles in combination with the standard of care NSCLC first-line chemotherapy in line with the licensed national prescribing information, during the treatment period. The initial dose of bevacizumab was to be administered following chemotherapy; all subsequent doses could be given before or after chemotherapy. After the end of chemotherapy participants without disease progression could continue bevacizumab as maintenance therapy until confirmed disease progression, unacceptable toxicity or participant consent withdrawal. Participants were followed-up through a final-visit (28 days after last bevacizumab infusion) and then every 3 months until death.
Overall Number of Baseline Participants 2172
Hide Baseline Analysis Population Description
Baseline characteristics were described for the intent-to-treat (ITT) population, which included all participants with at least one valid post-baseline (Day -28 to -1) assessment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2172 participants
58.8  (10.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2172 participants
Female
866
  39.9%
Male
1306
  60.1%
1.Primary Outcome
Title Number of Participants With Adverse Events of Special Interest
Hide Description Participants with adverse events (AEs) of special interest (hypertension, proteinuria, wound healing complications, gastrointestinal perforation, arterial and venous thromboembolic events, hemoptysis, Central Nervous System (CNS) bleeding, other hemorrhage events and congestive heart failure) were reported.
Time Frame Up to 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants with at least one valid post-baseline (Day -28 to -1) assessment.
Arm/Group Title Bevacizumab + Chemotherapy
Hide Arm/Group Description:
Eligible participants with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) were administered bevacizumab infusions at a dose of 7.5 milligram per kilogram (mg/kg) or 15 mg/kg (investigator’s choice) on Day 1 and then every 3 weeks, intravenously (IV) for a maximum of 6 cycles in combination with the standard of care NSCLC first-line chemotherapy in line with the licensed national prescribing information, during the treatment period. The initial dose of bevacizumab was to be administered following chemotherapy; all subsequent doses could be given before or after chemotherapy. After the end of chemotherapy participants without disease progression could continue bevacizumab as maintenance therapy until confirmed disease progression, unacceptable toxicity or participant consent withdrawal. Participants were followed-up through a final-visit (28 days after last bevacizumab infusion) and then every 3 months until death.
Overall Number of Participants Analyzed 2172
Measure Type: Number
Unit of Measure: participants
Hypertension 687
Proteinuria 672
Wound healing complication 26
Gastrointestinal perforation 30
Arterial/Venous thromboembolic events 274
Hemoptysis 176
CNS bleeding 7
Other hemorrhage events 744
Congestive heart failure 17
2.Primary Outcome
Title Number of Participants With Serious Adverse Events Related to Bevacizumab
Hide Description Participants with serious adverse events (SAEs) related to bevacizumab were reported for the duration of the study.
Time Frame Up to 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants with at least one valid post-baseline (Day -28 to -1) assessment.
Arm/Group Title Bevacizumab + Chemotherapy
Hide Arm/Group Description:
Eligible participants with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) were administered bevacizumab infusions at a dose of 7.5 milligram per kilogram (mg/kg) or 15 mg/kg (investigator’s choice) on Day 1 and then every 3 weeks, intravenously (IV) for a maximum of 6 cycles in combination with the standard of care NSCLC first-line chemotherapy in line with the licensed national prescribing information, during the treatment period. The initial dose of bevacizumab was to be administered following chemotherapy; all subsequent doses could be given before or after chemotherapy. After the end of chemotherapy participants without disease progression could continue bevacizumab as maintenance therapy until confirmed disease progression, unacceptable toxicity or participant consent withdrawal. Participants were followed-up through a final-visit (28 days after last bevacizumab infusion) and then every 3 months until death.
Overall Number of Participants Analyzed 2172
Measure Type: Number
Unit of Measure: participants
283
3.Secondary Outcome
Title Duration of Overall Survival
Hide Description Overall survival time was defined as time between first bevacizumab administration and date of death, irrespective of the cause of death. Participants for whom no death was captured on the clinical database were censored at the most recent date they were known to be alive.
Time Frame Up to 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants with at least one valid post-baseline (Day -28 to -1) assessment. Participants available at the time of assessment were included in the analysis.
Arm/Group Title Bevacizumab + Chemotherapy
Hide Arm/Group Description:
Eligible participants with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) were administered bevacizumab infusions at a dose of 7.5 milligram per kilogram (mg/kg) or 15 mg/kg (investigator’s choice) on Day 1 and then every 3 weeks, intravenously (IV) for a maximum of 6 cycles in combination with the standard of care NSCLC first-line chemotherapy in line with the licensed national prescribing information, during the treatment period. The initial dose of bevacizumab was to be administered following chemotherapy; all subsequent doses could be given before or after chemotherapy. After the end of chemotherapy participants without disease progression could continue bevacizumab as maintenance therapy until confirmed disease progression, unacceptable toxicity or participant consent withdrawal. Participants were followed-up through a final-visit (28 days after last bevacizumab infusion) and then every 3 months until death.
Overall Number of Participants Analyzed 1258
Median (95% Confidence Interval)
Unit of Measure: Months
14.6
(13.8 to 15.3)
4.Secondary Outcome
Title Time to Disease Progression
Hide Description Time to disease progression was defined as time between first bevacizumab administration and date of first occurrence of progressive disease. Participants who had not progressed at the time of study completion (including participants who died before progressive disease) or who were lost to follow-up were censored at the last bevacizumab administration date. Progressive disease is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Time to disease progression was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0.
Time Frame Up to 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population was considered for analysis, which included all participants with at least one valid post-baseline (Day -28 to -1) assessment. Participants available at the time of assessment were included in the analysis.
Arm/Group Title Bevacizumab + Chemotherapy
Hide Arm/Group Description:
Eligible participants with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) were administered bevacizumab infusions at a dose of 7.5 milligram per kilogram (mg/kg) or 15 mg/kg (investigator’s choice) on Day 1 and then every 3 weeks, intravenously (IV) for a maximum of 6 cycles in combination with the standard of care NSCLC first-line chemotherapy in line with the licensed national prescribing information, during the treatment period. The initial dose of bevacizumab was to be administered following chemotherapy; all subsequent doses could be given before or after chemotherapy. After the end of chemotherapy participants without disease progression could continue bevacizumab as maintenance therapy until confirmed disease progression, unacceptable toxicity or participant consent withdrawal. Participants were followed-up through a final-visit (28 days after last bevacizumab infusion) and then every 3 months until death.
Overall Number of Participants Analyzed 1501
Median (95% Confidence Interval)
Unit of Measure: Months
7.8
(7.5 to 8.1)
5.Secondary Outcome
Title Number of Participants With Central Nervous System Bleeding
Hide Description The incidence of central nervous system (CNS) bleeding was reported for participants who developed CNS metastases during the study period and who did not have Computed Tomography (CT) or magnetic resonance imaging (MRI) techniques of the head performed at baseline.
Time Frame Up to 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population was used for analysis, which included all participants with at least one valid post-baseline (Day -28 to -1) assessment. n = number of participants available at the time of assessment who were included in the analysis.
Arm/Group Title Bevacizumab + Chemotherapy
Hide Arm/Group Description:
Eligible participants with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) were administered bevacizumab infusions at a dose of 7.5 milligram per kilogram (mg/kg) or 15 mg/kg (investigator’s choice) on Day 1 and then every 3 weeks, intravenously (IV) for a maximum of 6 cycles in combination with the standard of care NSCLC first-line chemotherapy in line with the licensed national prescribing information, during the treatment period. The initial dose of bevacizumab was to be administered following chemotherapy; all subsequent doses could be given before or after chemotherapy. After the end of chemotherapy participants without disease progression could continue bevacizumab as maintenance therapy until confirmed disease progression, unacceptable toxicity or participant consent withdrawal. Participants were followed-up through a final-visit (28 days after last bevacizumab infusion) and then every 3 months until death.
Overall Number of Participants Analyzed 367
Measure Type: Number
Unit of Measure: participants
With CNS metastases (n = 281) 12
Without CT/MRI scans (n = 367) 16
Time Frame Up to 3 years
Adverse Event Reporting Description The ITT population was used for the safety analysis, which included all participants who had been treated with bevacizumab and chemotherapy at least once.
 
Arm/Group Title Bevacizumab + Chemotherapy
Hide Arm/Group Description Eligible participants with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) were administered bevacizumab infusions at a dose of 7.5 milligram per kilogram (mg/kg) or 15 mg/kg (investigator’s choice) on Day 1 and then every 3 weeks, intravenously (IV) for a maximum of 6 cycles in combination with the standard of care NSCLC first-line chemotherapy in line with the licensed national prescribing information, during the treatment period. The initial dose of bevacizumab was to be administered following chemotherapy; all subsequent doses could be given before or after chemotherapy. After the end of chemotherapy participants without disease progression could continue bevacizumab as maintenance therapy until confirmed disease progression, unacceptable toxicity or participant consent withdrawal. Participants were followed-up through a final-visit (28 days after last bevacizumab infusion) and then every 3 months until death.
All-Cause Mortality
Bevacizumab + Chemotherapy
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Bevacizumab + Chemotherapy
Affected / at Risk (%)
Total   834/2212 (37.70%) 
Blood and lymphatic system disorders   
Anaemia  1  36/2212 (1.63%) 
Anaemia haemolytic autoimmune  1  1/2212 (0.05%) 
Febrile bone marrow aplasia  1  5/2212 (0.23%) 
Febrile neutropenia  1  52/2212 (2.35%) 
Leukopenia  1  10/2212 (0.45%) 
Neutropenia  1  84/2212 (3.80%) 
Pancytopenia  1  11/2212 (0.50%) 
Thrombocythaemia  1  1/2212 (0.05%) 
Thrombocytopenia  1  44/2212 (1.99%) 
Cardiac disorders   
Acute coronary syndrome  1  1/2212 (0.05%) 
Acute myocardial infarction  1  2/2212 (0.09%) 
Angina unstable  1  2/2212 (0.09%) 
Arrhythmia  1  1/2212 (0.05%) 
Atrial fibrillation  1  8/2212 (0.36%) 
Atrial flutter  1  1/2212 (0.05%) 
Bradycardia  1  1/2212 (0.05%) 
Cardiac arrest  1  2/2212 (0.09%) 
Cardiac disorder  1  1/2212 (0.05%) 
Cardiac failure  1  4/2212 (0.18%) 
Cardiac failure congestive  1  4/2212 (0.18%) 
Cardiac flutter  1  1/2212 (0.05%) 
Cardiac tamponade  1  1/2212 (0.05%) 
Cardio-respiratory arrest  1  3/2212 (0.14%) 
Cardiogenic shock  1  1/2212 (0.05%) 
Cardiomyopathy  1  1/2212 (0.05%) 
Cardiopulmonary failure  1  1/2212 (0.05%) 
Coronary artery disease  1  1/2212 (0.05%) 
Left ventricular failure  1  1/2212 (0.05%) 
Myocardial infarction  1  17/2212 (0.77%) 
Myocardial ischaemia  1  4/2212 (0.18%) 
Pericardial effusion  1  1/2212 (0.05%) 
Pericarditis  1  2/2212 (0.09%) 
Tachyarrhythmia  1  1/2212 (0.05%) 
Tachycardia  1  2/2212 (0.09%) 
Ear and labyrinth disorders   
Tympanic membrane disorder  1  1/2212 (0.05%) 
Eye disorders   
Angle closure glaucoma  1  1/2212 (0.05%) 
Optic ischaemic neuropathy  1  1/2212 (0.05%) 
Retinal vein thrombosis  1  1/2212 (0.05%) 
Visual acuity reduced  1  1/2212 (0.05%) 
Visual disturbance  1  1/2212 (0.05%) 
Gastrointestinal disorders   
Abdominal pain  1  13/2212 (0.59%) 
Abdominal pain upper  1  3/2212 (0.14%) 
Anal fistula  1  1/2212 (0.05%) 
Anal stenosis  1  1/2212 (0.05%) 
Anal ulcer  1  1/2212 (0.05%) 
Appendicitis perforated  1  2/2212 (0.09%) 
Colitis  1  3/2212 (0.14%) 
Colitis ischaemic  1  2/2212 (0.09%) 
Constipation  1  12/2212 (0.54%) 
Diarrhoea  1  18/2212 (0.81%) 
Diverticular perforation  1  3/2212 (0.14%) 
Duodenal ulcer  1  1/2212 (0.05%) 
Duodenal ulcer haemorrhage  1  1/2212 (0.05%) 
Dysphagia  1  2/2212 (0.09%) 
Enteritis  1  1/2212 (0.05%) 
Faeces discoloured  1  1/2212 (0.05%) 
Gastric haemorrhage  1  1/2212 (0.05%) 
Gastric ulcer  1  1/2212 (0.05%) 
Gastric ulcer haemorrhage  1  1/2212 (0.05%) 
Gastritis  1  1/2212 (0.05%) 
Gastrointestinal disorder  1  1/2212 (0.05%) 
Gastrointestinal haemorrhage  1  8/2212 (0.36%) 
Gastrointestinal perforation  1  9/2212 (0.41%) 
Gingival disorder  1  1/2212 (0.05%) 
Glossodynia  1  1/2212 (0.05%) 
Haematemesis  1  3/2212 (0.14%) 
Haemorrhoids  1  2/2212 (0.09%) 
Ileus  1  4/2212 (0.18%) 
Ileus paralytic  1  1/2212 (0.05%) 
Intestinal obstruction  1  2/2212 (0.09%) 
Intestinal perforation  1  2/2212 (0.09%) 
Jejunal perforation  1  1/2212 (0.05%) 
Large intestine perforation  1  7/2212 (0.32%) 
Lower gastrointestinal haemorrhage  1  1/2212 (0.05%) 
Mechanical ileus  1  1/2212 (0.05%) 
Nausea  1  25/2212 (1.13%) 
Oesophagitis  1  1/2212 (0.05%) 
Pancreatitis acute  1  1/2212 (0.05%) 
Peptic ulcer perforation  1  1/2212 (0.05%) 
Peritonitis  1  3/2212 (0.14%) 
Rectal haemorrhage  1  7/2212 (0.32%) 
Small intestinal perforation  1  3/2212 (0.14%) 
Stomatitis  1  1/2212 (0.05%) 
Subileus  1  3/2212 (0.14%) 
Upper gastrointestinal haemorrhage  1  2/2212 (0.09%) 
Vomiting  1  26/2212 (1.18%) 
General disorders   
Aplasia  1  1/2212 (0.05%) 
Asthenia  1  2/2212 (0.09%) 
Catheter thrombosis  1  4/2212 (0.18%) 
Chest pain  1  19/2212 (0.86%) 
Chills  1  1/2212 (0.05%) 
Cyst rupture  1  1/2212 (0.05%) 
Death  1  14/2212 (0.63%) 
Extravasation  1  1/2212 (0.05%) 
Fatigue  1  19/2212 (0.86%) 
Feeling abnormal  1  1/2212 (0.05%) 
Gait disturbance  1  1/2212 (0.05%) 
General physical health deterioration  1  13/2212 (0.59%) 
Hyperpyrexia  1  1/2212 (0.05%) 
Ill-defined disorder  1  2/2212 (0.09%) 
Impaired healing  1  1/2212 (0.05%) 
Infusion related reaction  1  1/2212 (0.05%) 
Mucosal inflammation  1  1/2212 (0.05%) 
Multi-organ failure  1  1/2212 (0.05%) 
Pain  1  3/2212 (0.14%) 
Performance status decreased  1  2/2212 (0.09%) 
Pyrexia  1  37/2212 (1.67%) 
Sudden death  1  4/2212 (0.18%) 
Hepatobiliary disorders   
Alcoholic liver disease  1  1/2212 (0.05%) 
Bile duct stone  1  1/2212 (0.05%) 
Cholecystitis  1  2/2212 (0.09%) 
Cholecystitis acute  1  1/2212 (0.05%) 
Cholelithiasis  1  1/2212 (0.05%) 
Cholestasis  1  3/2212 (0.14%) 
Hepatic failure  1  2/2212 (0.09%) 
Hepatitis acute  1  1/2212 (0.05%) 
Hepatorenal syndrome  1  1/2212 (0.05%) 
Jaundice  1  2/2212 (0.09%) 
Immune system disorders   
Drug hypersensitivity  1  1/2212 (0.05%) 
Hypersensitivity  1  2/2212 (0.09%) 
Infections and infestations   
Abscess  1  3/2212 (0.14%) 
Abscess bacterial  1  1/2212 (0.05%) 
Anal abscess  1  4/2212 (0.18%) 
Anal infection  1  1/2212 (0.05%) 
Appendicitis  1  1/2212 (0.05%) 
Bronchitis  1  2/2212 (0.09%) 
Bronchopneumonia  1  2/2212 (0.09%) 
Candidiasis  1  1/2212 (0.05%) 
Catheter related infection  1  2/2212 (0.09%) 
Catheter site infection  1  2/2212 (0.09%) 
Cellulitis  1  2/2212 (0.09%) 
Central line infection  1  3/2212 (0.14%) 
Clostridial infection  1  2/2212 (0.09%) 
Device related infection  1  2/2212 (0.09%) 
Diverticulitis  1  2/2212 (0.09%) 
Empyema  1  6/2212 (0.27%) 
Enterocolitis infectious  1  1/2212 (0.05%) 
Erysipelas  1  1/2212 (0.05%) 
Febrile infection  1  1/2212 (0.05%) 
Gastroenteritis  1  6/2212 (0.27%) 
Herpes zoster  1  1/2212 (0.05%) 
Infection  1  7/2212 (0.32%) 
Lobar pneumonia  1  1/2212 (0.05%) 
Lower respiratory tract infection  1  2/2212 (0.09%) 
Lung abscess  1  1/2212 (0.05%) 
Lung infection  1  5/2212 (0.23%) 
Mumps  1  1/2212 (0.05%) 
Nasopharyngitis  1  1/2212 (0.05%) 
Neutropenic infection  1  1/2212 (0.05%) 
Neutropenic sepsis  1  2/2212 (0.09%) 
Penile abscess  1  1/2212 (0.05%) 
Peridiverticular abscess  1  1/2212 (0.05%) 
Perirectal abscess  1  2/2212 (0.09%) 
Pneumonia  1  52/2212 (2.35%) 
Pneumonia necrotising  1  1/2212 (0.05%) 
Pneumonia primary atypical  1  1/2212 (0.05%) 
Psoas abscess  1  1/2212 (0.05%) 
Pyopneumothorax  1  1/2212 (0.05%) 
Respiratory tract infection  1  10/2212 (0.45%) 
Sepsis  1  8/2212 (0.36%) 
Septic shock  1  4/2212 (0.18%) 
Sinusitis  1  2/2212 (0.09%) 
Staphylococcal infection  1  1/2212 (0.05%) 
Superinfection  1  1/2212 (0.05%) 
Tonsillitis  1  1/2212 (0.05%) 
Upper respiratory tract infection  1  4/2212 (0.18%) 
Urinary tract infection  1  4/2212 (0.18%) 
Urosepsis  1  1/2212 (0.05%) 
Viral infection  1  2/2212 (0.09%) 
Viral skin infection  1  1/2212 (0.05%) 
Not Codable  1 [1]  1/2212 (0.05%) 
Injury, poisoning and procedural complications   
Accidental overdose  1  1/2212 (0.05%) 
Alcohol poisoning  1  1/2212 (0.05%) 
Allergic transfusion reaction  1  1/2212 (0.05%) 
Ankle fracture  1  1/2212 (0.05%) 
Bone fissure  1  1/2212 (0.05%) 
Femur fracture  1  2/2212 (0.09%) 
Incision site haemorrhage  1  1/2212 (0.05%) 
Overdose  1  1/2212 (0.05%) 
Post procedural haemorrhage  1  1/2212 (0.05%) 
Postoperative thoracic procedure complication  1  1/2212 (0.05%) 
Radiation oesophagitis  1  1/2212 (0.05%) 
Rib fracture  1  1/2212 (0.05%) 
Wound  1  1/2212 (0.05%) 
Wound dehiscence  1  1/2212 (0.05%) 
Investigations   
Activated partial thromboplastin time prolonged  1  1/2212 (0.05%) 
Aspiration bronchial  1  1/2212 (0.05%) 
Blood bilirubin increased  1  1/2212 (0.05%) 
Blood creatinine increased  1  9/2212 (0.41%) 
Blood potassium decreased  1  1/2212 (0.05%) 
C-reactive protein increased  1  3/2212 (0.14%) 
Creatinine renal clearance decreased  1  1/2212 (0.05%) 
Gamma-glutamyltransferase increased  1  1/2212 (0.05%) 
Haematology test abnormal  1  1/2212 (0.05%) 
Haemoglobin decreased  1  5/2212 (0.23%) 
Neutrophil count decreased  1  9/2212 (0.41%) 
Platelet count decreased  1  11/2212 (0.50%) 
Transaminases abnormal  1  1/2212 (0.05%) 
Weight decreased  1  1/2212 (0.05%) 
White blood cell count decreased  1  8/2212 (0.36%) 
Metabolism and nutrition disorders   
Anorexia  1  4/2212 (0.18%) 
Cachexia  1  3/2212 (0.14%) 
Dehydration  1  9/2212 (0.41%) 
Electrolyte imbalance  1  1/2212 (0.05%) 
Hypercalcaemia  1  5/2212 (0.23%) 
Hypercreatininaemia  1  2/2212 (0.09%) 
Hyperglycaemia  1  2/2212 (0.09%) 
Hypoalbuminaemia  1  1/2212 (0.05%) 
Hypokalaemia  1  3/2212 (0.14%) 
Hyponatraemia  1  3/2212 (0.14%) 
Hypoproteinaemia  1  1/2212 (0.05%) 
Starvation  1  1/2212 (0.05%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  3/2212 (0.14%) 
Arthritis  1  2/2212 (0.09%) 
Back pain  1  5/2212 (0.23%) 
Bone pain  1  5/2212 (0.23%) 
Fistula  1  1/2212 (0.05%) 
Muscle haemorrhage  1  1/2212 (0.05%) 
Muscular weakness  1  2/2212 (0.09%) 
Musculoskeletal chest pain  1  1/2212 (0.05%) 
Musculoskeletal pain  1  1/2212 (0.05%) 
Osteolysis  1  1/2212 (0.05%) 
Pain in extremity  1  2/2212 (0.09%) 
Pathological fracture  1  2/2212 (0.09%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Bladder cancer  1  1/2212 (0.05%) 
Bladder neoplasm  1  1/2212 (0.05%) 
Colon cancer  1  1/2212 (0.05%) 
Infected neoplasm  1  2/2212 (0.09%) 
Lung neoplasm  1  1/2212 (0.05%) 
Metastases to bone  1  1/2212 (0.05%) 
Metastases to meninges  1  1/2212 (0.05%) 
Metastatic pain  1  1/2212 (0.05%) 
Paraneoplastic syndrome  1  3/2212 (0.14%) 
Tumour haemorrhage  1  1/2212 (0.05%) 
Nervous system disorders   
Aphonia  1  1/2212 (0.05%) 
Autonomic nervous system imbalance * 1  1/2212 (0.05%) 
Brain stem infarction  1  1/2212 (0.05%) 
Cerebral haematoma  1  1/2212 (0.05%) 
Cerebral haemorrhage  1  2/2212 (0.09%) 
Cerebral infarction  1  4/2212 (0.18%) 
Cerebral ischaemia  1  4/2212 (0.18%) 
Cerebral microangiopathy  1  1/2212 (0.05%) 
Cerebrovascular accident  1  7/2212 (0.32%) 
Coma  1  1/2212 (0.05%) 
Convulsion  1  6/2212 (0.27%) 
Dizziness  1  2/2212 (0.09%) 
Encephalopathy  1  1/2212 (0.05%) 
Epilepsy  1  2/2212 (0.09%) 
Headache  1  8/2212 (0.36%) 
Hemiparesis  1  1/2212 (0.05%) 
Hydrocephalus  1  1/2212 (0.05%) 
Hypertensive encephalopathy  1  1/2212 (0.05%) 
Intracranial aneurysm  1  1/2212 (0.05%) 
Ischaemic stroke  1  1/2212 (0.05%) 
Lacunar infarction  1  1/2212 (0.05%) 
Leukoencephalopathy  1  2/2212 (0.09%) 
Nervous system disorder  1  2/2212 (0.09%) 
Neuralgia  1  2/2212 (0.09%) 
Neuropathy peripheral  1  1/2212 (0.05%) 
Optic neuritis  1  1/2212 (0.05%) 
Peroneal nerve palsy  1  1/2212 (0.05%) 
Polyneuropathy  1  1/2212 (0.05%) 
Presyncope  1  1/2212 (0.05%) 
Sciatica  1  1/2212 (0.05%) 
Status epilepticus  1  1/2212 (0.05%) 
Syncope  1  11/2212 (0.50%) 
Toxic encephalopathy  1  1/2212 (0.05%) 
Transient ischaemic attack  1  1/2212 (0.05%) 
Psychiatric disorders   
Confusional state  1  7/2212 (0.32%) 
Emotional disorder  1  1/2212 (0.05%) 
Renal and urinary disorders   
Haematuria  1  1/2212 (0.05%) 
Nephritic syndrome  1  1/2212 (0.05%) 
Nephrolithiasis  1  2/2212 (0.09%) 
Nephrotic syndrome  1  3/2212 (0.14%) 
Proteinuria  1  3/2212 (0.14%) 
Renal failure  1  11/2212 (0.50%) 
Renal failure acute * 1  8/2212 (0.36%) 
Renal haemorrhage  1  1/2212 (0.05%) 
Renal impairment  1  1/2212 (0.05%) 
Urinary retention  1  1/2212 (0.05%) 
Reproductive system and breast disorders   
Benign prostatic hyperplasia  1  1/2212 (0.05%) 
Pelvic pain  1  1/2212 (0.05%) 
Respiratory, thoracic and mediastinal disorders   
Acute pulmonary oedema  1  1/2212 (0.05%) 
Acute respiratory failure  1  1/2212 (0.05%) 
Alveolitis  1  1/2212 (0.05%) 
Bronchopleural fistula  1  1/2212 (0.05%) 
Bronchospasm  1  1/2212 (0.05%) 
Chronic obstructive pulmonary disease  1  1/2212 (0.05%) 
Dysphonia  1  1/2212 (0.05%) 
Dyspnoea  1  32/2212 (1.45%) 
Epistaxis  1  21/2212 (0.95%) 
Haemoptysis  1  18/2212 (0.81%) 
Haemothorax  1  2/2212 (0.09%) 
Hydropneumothorax  1  1/2212 (0.05%) 
Interstitial lung disease  1  1/2212 (0.05%) 
Lung disorder  1  4/2212 (0.18%) 
Lung infiltration  1  1/2212 (0.05%) 
Pharyngolaryngeal pain  1  2/2212 (0.09%) 
Pleural effusion  1  5/2212 (0.23%) 
Pleuritic pain  1  1/2212 (0.05%) 
Pneumonitis  1  2/2212 (0.09%) 
Pneumothorax  1  12/2212 (0.54%) 
Pulmonary congestion  1  1/2212 (0.05%) 
Pulmonary embolism  1  55/2212 (2.49%) 
Pulmonary haemorrhage  1  4/2212 (0.18%) 
Pulmonary infarction  1  1/2212 (0.05%) 
Pulmonary thrombosis  1  1/2212 (0.05%) 
Pulmonary venous thrombosis  1  1/2212 (0.05%) 
Respiratory distress  1  2/2212 (0.09%) 
Respiratory failure  1  5/2212 (0.23%) 
Thoracic haemorrhage  1  1/2212 (0.05%) 
Skin and subcutaneous tissue disorders   
Angioedema  1  1/2212 (0.05%) 
Drug eruption  1  1/2212 (0.05%) 
Leukocytoclastic vasculitis  1  1/2212 (0.05%) 
Rash  1  1/2212 (0.05%) 
Skin lesion  1  1/2212 (0.05%) 
Skin ulcer  1  2/2212 (0.09%) 
Skin ulcer haemorrhage  1  1/2212 (0.05%) 
Stevens-johnson syndrome  1  1/2212 (0.05%) 
Surgical and medical procedures   
Astringent therapy  1  1/2212 (0.05%) 
Catheter placement  1  1/2212 (0.05%) 
Knee operation  1  1/2212 (0.05%) 
Lung lobectomy  1  1/2212 (0.05%) 
Pleurodesis  1  1/2212 (0.05%) 
Tumour excision  1  1/2212 (0.05%) 
Vascular disorders   
Aortic aneurysm  1  1/2212 (0.05%) 
Capillary leak syndrome  1  1/2212 (0.05%) 
Deep vein thrombosis  1  29/2212 (1.31%) 
Embolism  1  3/2212 (0.14%) 
Embolism venous  1  1/2212 (0.05%) 
Haemorrhage  1  2/2212 (0.09%) 
Hypertension  1  9/2212 (0.41%) 
Hypertensive crisis  1  4/2212 (0.18%) 
Infarction  1  1/2212 (0.05%) 
Jugular vein thrombosis  1  2/2212 (0.09%) 
Orthostatic hypotension  1  1/2212 (0.05%) 
Peripheral arterial occlusive disease  1  1/2212 (0.05%) 
Peripheral ischaemia  1  2/2212 (0.09%) 
Peripheral vascular disorder  1  1/2212 (0.05%) 
Phlebitis superficial  1  1/2212 (0.05%) 
Shock  1  1/2212 (0.05%) 
Subclavian vein thrombosis  1  2/2212 (0.09%) 
Thrombosis  1  7/2212 (0.32%) 
Vena cava thrombosis  1  1/2212 (0.05%) 
Venous insufficiency  1  1/2212 (0.05%) 
Venous thrombosis  1  3/2212 (0.14%) 
Venous thrombosis limb  1  2/2212 (0.09%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (10.1)
[1]
Neutropenia Due to Respiratory Infection
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bevacizumab + Chemotherapy
Affected / at Risk (%)
Total   1982/2212 (89.60%) 
Gastrointestinal disorders   
Constipation  1  423/2212 (19.12%) 
Diarrhoea  1  347/2212 (15.69%) 
Nausea  1  827/2212 (37.39%) 
Stomatitis  1  260/2212 (11.75%) 
Vomiting  1  516/2212 (23.33%) 
General disorders   
Chest pain  1  224/2212 (10.13%) 
Fatigue  1  893/2212 (40.37%) 
Pyrexia  1  263/2212 (11.89%) 
Investigations   
Alanine aminotransferase increased  1  159/2212 (7.19%) 
Aspartate aminotransferase increased  1  141/2212 (6.37%) 
Blood creatinine increased  1  186/2212 (8.41%) 
Gamma-glutamyltransferase increased  1  121/2212 (5.47%) 
Haemoglobin decreased  1  788/2212 (35.62%) 
Neutrophil count decreased  1  696/2212 (31.46%) 
Platelet count decreased  1  573/2212 (25.90%) 
Protein urine present  1  111/2212 (5.02%) 
White blood cell count decreased  1  623/2212 (28.16%) 
Metabolism and nutrition disorders   
Anorexia  1  462/2212 (20.89%) 
Hyperglycaemia  1  122/2212 (5.52%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  182/2212 (8.23%) 
Back pain  1  219/2212 (9.90%) 
Musculoskeletal pain  1  134/2212 (6.06%) 
Myalgia  1  135/2212 (6.10%) 
Pain in extremity  1  189/2212 (8.54%) 
Nervous system disorders   
Dizziness  1  128/2212 (5.79%) 
Headache  1  309/2212 (13.97%) 
Neuropathy  1  179/2212 (8.09%) 
Psychiatric disorders   
Insomnia  1  112/2212 (5.06%) 
Renal and urinary disorders   
Proteinuria  1  568/2212 (25.68%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  328/2212 (14.83%) 
Dysphonia  1  130/2212 (5.88%) 
Dyspnoea  1  279/2212 (12.61%) 
Epistaxis  1  589/2212 (26.63%) 
Haemoptysis  1  167/2212 (7.55%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  526/2212 (23.78%) 
Rash  1  167/2212 (7.55%) 
Vascular disorders   
Hypertension  1  680/2212 (30.74%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.1)
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.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor’s intellectual property rights.
Results Point of Contact
Name/Title: Roche Trial Information Hotline
Organization: F. Hoffmann-La Roche AG
Phone: +41 616878333
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00451906     History of Changes
Other Study ID Numbers: MO19390
First Submitted: March 22, 2007
First Posted: March 26, 2007
Results First Submitted: March 23, 2016
Results First Posted: April 25, 2016
Last Update Posted: May 24, 2016