A Study to Evaluate the Efficacy of Bevacizumab in Combination With Tarceva for Advanced Non-Small Cell Lung Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech
ClinicalTrials.gov Identifier:
NCT00130728
First received: August 12, 2005
Last updated: September 26, 2011
Last verified: September 2011
Results First Received: November 16, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Non-Small Cell Lung Cancer
Interventions: Drug: bevacizumab
Drug: erlotinib HCl
Drug: placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Erlotinib HCl + Bevacizumab oral erlotinib HCl 150 mg/day orally + intravenous infusion of bevacizumab at a dose of 15 mg/kg on the first day of each 3-week cycle
Erlotinib HCl + Placebo oral erlotinib HCl 150 mg/day orally + intravenous infusion of placebo at a dose of 15 mg/kg on the first day of each 3-week cycle

Participant Flow:   Overall Study
    Erlotinib HCl + Bevacizumab     Erlotinib HCl + Placebo  
STARTED     319     317  
Received Study Drug (Safety Population)     313     313  
COMPLETED     108     104  
NOT COMPLETED     211     213  
Death                 207                 211  
Lost to Follow-up                 4                 0  
Withdrawal by Subject                 0                 2  



  Baseline Characteristics
  Hide Baseline Characteristics

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

Reporting Groups
  Description
Erlotinib HCl + Bevacizumab oral erlotinib HCl 150 mg/day orally + intravenous infusion of bevacizumab at a dose of 15 mg/kg on the first day of each 3-week cycle
Erlotinib HCl + Placebo oral erlotinib HCl 150 mg/day orally + intravenous infusion of placebo at a dose of 15 mg/kg on the first day of each 3-week cycle
Total Total of all reporting groups

Baseline Measures
    Erlotinib HCl + Bevacizumab     Erlotinib HCl + Placebo     Total  
Number of Participants  
[units: participants]
  319     317     636  
Age  
[units: years]
Mean ± Standard Deviation
  64.8  ± 10.4     65.0  ± 10.3     64.9  ± 10.4  
Age, Customized  
[units: participants]
     
Between 18 and 59 years     91     90     181  
Between 60 and 64 years     62     66     128  
Between 65 and 69 years     59     53     112  
>= 70 years     107     108     215  
Gender  
[units: participants]
     
Female     148     147     295  
Male     171     170     341  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Overall Survival (OS) Among All Randomized Patients   [ Time Frame: From the date of randomization until the date of patient death from any cause, or the date of last contact. (Up to 3.1 years) ]

2.  Secondary:   Progression-free Survival (PFS)   [ Time Frame: From randomization to documented disease progression or death on study treatment, whichever occurred first. (Up to 3.1 years) ]

3.  Secondary:   Percentage of Participants With Objective Response   [ Time Frame: The median duration of Objective response was up to 9.7 months ]

4.  Secondary:   Duration of Objective Response   [ Time Frame: Period from Objective response until disease progression or death on study treatment. (Up to 29.5 months) ]


  Serious Adverse Events
  Hide Serious Adverse Events

Time Frame Up to 3 years
Additional Description Safety Evaluable Population

Reporting Groups
  Description
Erlotinib HCl + Bevacizumab oral erlotinib HCl 150 mg/day orally + intravenous infusion of bevacizumab at a dose of 15 mg/kg on the first day of each 3-week cycle
Erlotinib HCl + Placebo oral erlotinib HCl 150 mg/day orally + intravenous infusion of placebo at a dose of 15 mg/kg on the first day of each 3-week cycle

Serious Adverse Events
    Erlotinib HCl + Bevacizumab     Erlotinib HCl + Placebo  
Total, serious adverse events      
# participants affected / at risk     130/313 (41.53%)     114/313 (36.42%)  
Blood and lymphatic system disorders      
Anaemia † 1    
# participants affected / at risk     2/313 (0.64%)     1/313 (0.32%)  
Cardiac disorders      
Acute Myocardial Infarction † 1    
# participants affected / at risk     3/313 (0.96%)     0/313 (0.00%)  
Angina Pectoris † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Atrial Fibrillation † 1    
# participants affected / at risk     3/313 (0.96%)     4/313 (1.28%)  
Atrial Flutter † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Cardiac Arrest † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Cardiac Failure Congestive † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Cardiomyopathy † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Cardiopulmonary Failure † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Coronary Artery Disease † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Coronary Artery Stenosis † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Myocardial Infarction † 1    
# participants affected / at risk     5/313 (1.60%)     0/313 (0.00%)  
Pericardial Effusion † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Pericarditis † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Ear and labyrinth disorders      
Vertigo † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Eye disorders      
Blindness Unilateral † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Retinal Haemorrhage † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Vision Blurred † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Gastrointestinal disorders      
Abdominal Pain † 1    
# participants affected / at risk     6/313 (1.92%)     1/313 (0.32%)  
Abdominal Pain Upper † 1    
# participants affected / at risk     1/313 (0.32%)     1/313 (0.32%)  
Constipation † 1    
# participants affected / at risk     3/313 (0.96%)     0/313 (0.00%)  
Diarrhoea † 1    
# participants affected / at risk     6/313 (1.92%)     4/313 (1.28%)  
Diverticulum † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Duodenal Ulcer † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Duodenal Ulcer Haemorrhage † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Dysphagia † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Faecaloma † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Gastritis Erosive † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Gastrointestinal Haemorrhage † 1    
# participants affected / at risk     1/313 (0.32%)     2/313 (0.64%)  
Gastrointestinal Perforation † 1    
# participants affected / at risk     2/313 (0.64%)     0/313 (0.00%)  
Haemorrhoidal Haemorrhage † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Ileus † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Inguinal Hernia, Obstructive † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Intestinal Perforation † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Large Intestine Perforation † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Lower Gastrointestinal Haemorrhage † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Nausea † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Oesophageal Obstruction † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Oesophageal Perforation † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Oesophageal Stenosis † 1    
# participants affected / at risk     1/313 (0.32%)     1/313 (0.32%)  
Pancreatitis † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Pancreatitis Acute † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Peritonitis † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Rectal Haemorrhage † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Small Intestinal Obstruction † 1    
# participants affected / at risk     2/313 (0.64%)     0/313 (0.00%)  
Upper Gastrointestinal Haemorrhage † 1    
# participants affected / at risk     3/313 (0.96%)     0/313 (0.00%)  
Vomiting † 1    
# participants affected / at risk     3/313 (0.96%)     4/313 (1.28%)  
General disorders      
Asthenia † 1    
# participants affected / at risk     2/313 (0.64%)     1/313 (0.32%)  
Chest Discomfort † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Chest Pain † 1    
# participants affected / at risk     3/313 (0.96%)     2/313 (0.64%)  
Death † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Influenza Like Illness † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Non-Cardiac Chest Pain † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Oedema Peripheral † 1    
# participants affected / at risk     1/313 (0.32%)     1/313 (0.32%)  
Pain † 1    
# participants affected / at risk     0/313 (0.00%)     4/313 (1.28%)  
Pyrexia † 1    
# participants affected / at risk     2/313 (0.64%)     3/313 (0.96%)  
Hepatobiliary disorders      
Cholestasis † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Hepatic Function Abnormal † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Immune system disorders      
Food Allergy † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Infections and infestations      
Appendicitis † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Breast Cellulitis † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Bronchitis † 1    
# participants affected / at risk     2/313 (0.64%)     1/313 (0.32%)  
Cellulitis † 1    
# participants affected / at risk     1/313 (0.32%)     3/313 (0.96%)  
Clostridium Difficile Colitis † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Diverticulitis † 1    
# participants affected / at risk     2/313 (0.64%)     0/313 (0.00%)  
Empyema † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Infection † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Lobar Pneumonia † 1    
# participants affected / at risk     1/313 (0.32%)     1/313 (0.32%)  
Lower Respiratory Tract Infection † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Lung Infection † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Perirectal Abscess † 1    
# participants affected / at risk     2/313 (0.64%)     0/313 (0.00%)  
Pneumonia † 1    
# participants affected / at risk     15/313 (4.79%)     9/313 (2.88%)  
Pyelonephritis † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Sepsis † 1    
# participants affected / at risk     1/313 (0.32%)     1/313 (0.32%)  
Septic Shock † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Tracheitis † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Urinary Tract Infection † 1    
# participants affected / at risk     3/313 (0.96%)     2/313 (0.64%)  
Injury, poisoning and procedural complications      
Fall † 1    
# participants affected / at risk     1/313 (0.32%)     3/313 (0.96%)  
Femur Fracture † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Hip Fracture † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Radiation Retinopathy † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Spinal Compression Fracture † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Tibia Fracture † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Tracheal Injury † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Wound Dehiscence † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Investigations      
Alanine Aminotransferase Increased † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Blood Culture Positive † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Heart Rate Increased † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
International Normalised Ratio Increased † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Liver Function Test Abnormal † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Platelet Count Decreased † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Metabolism and nutrition disorders      
Anorexia † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Dehydration † 1    
# participants affected / at risk     6/313 (1.92%)     3/313 (0.96%)  
Diabetic Ketoacidosis † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Failure to Thrive † 1    
# participants affected / at risk     1/313 (0.32%)     1/313 (0.32%)  
Hypercalcaemia † 1    
# participants affected / at risk     1/313 (0.32%)     1/313 (0.32%)  
Hyperglycaemia † 1    
# participants affected / at risk     0/313 (0.00%)     2/313 (0.64%)  
Musculoskeletal and connective tissue disorders      
Arthralgia † 1    
# participants affected / at risk     2/313 (0.64%)     0/313 (0.00%)  
Back Pain † 1    
# participants affected / at risk     0/313 (0.00%)     5/313 (1.60%)  
Bone Pain † 1    
# participants affected / at risk     1/313 (0.32%)     2/313 (0.64%)  
Flank Pain † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Muscular Weakness † 1    
# participants affected / at risk     1/313 (0.32%)     1/313 (0.32%)  
Musculoskeletal Chest Pain † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Musculoskeletal Pain † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Pain in Extremity † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Malignant Pleural Effusion † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Nervous system disorders      
Ataxia † 1    
# participants affected / at risk     1/313 (0.32%)     1/313 (0.32%)  
Cerebral Infarction † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Cerebral Ischaemia † 1    
# participants affected / at risk     2/313 (0.64%)     0/313 (0.00%)  
Haemorrhage Intracranial † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Intracranial Pressure Increased † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Ischaemic Stroke † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Neuralgia † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Neuropathy Peripheral † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Reversible Posterior Leukoencephalopathy Syndrome † 1    
# participants affected / at risk     2/313 (0.64%)     0/313 (0.00%)  
Spinal Cord Compression † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Syncope † 1    
# participants affected / at risk     2/313 (0.64%)     0/313 (0.00%)  
Toxic Encephalopathy † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Transient Ischaemic Attack † 1    
# participants affected / at risk     2/313 (0.64%)     0/313 (0.00%)  
Vocal Cord Paralysis † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Psychiatric disorders      
Confusional State † 1    
# participants affected / at risk     2/313 (0.64%)     2/313 (0.64%)  
Mental Status Changes † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Renal and urinary disorders      
Nephrolithiasis † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Renal Failure † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Respiratory, thoracic and mediastinal disorders      
Bronchial Obstruction † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Chronic Obstructive Pulmonary Disease † 1    
# participants affected / at risk     6/313 (1.92%)     0/313 (0.00%)  
Dyspnoea † 1    
# participants affected / at risk     11/313 (3.51%)     24/313 (7.67%)  
Dyspnoea at Rest † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Epistaxis † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Haemoptysis † 1    
# participants affected / at risk     2/313 (0.64%)     4/313 (1.28%)  
Hydropneumothorax † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Hypoxia † 1    
# participants affected / at risk     1/313 (0.32%)     4/313 (1.28%)  
Lung Infiltration † 1    
# participants affected / at risk     0/313 (0.00%)     2/313 (0.64%)  
Pleural Effusion † 1    
# participants affected / at risk     3/313 (0.96%)     8/313 (2.56%)  
Pneumonitis † 1    
# participants affected / at risk     2/313 (0.64%)     0/313 (0.00%)  
Pneumothorax † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Pulmonary Embolism † 1    
# participants affected / at risk     11/313 (3.51%)     8/313 (2.56%)  
Pulmonary Haemorrhage † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Pulmonary Oedema † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Respiratory Distress † 1    
# participants affected / at risk     1/313 (0.32%)     1/313 (0.32%)  
Respiratory Failure † 1    
# participants affected / at risk     2/313 (0.64%)     0/313 (0.00%)  
Upper Respiratory Tract Congestion † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Wheezing † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Skin and subcutaneous tissue disorders      
Exfoliative Rash † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Rash † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Skin Ulcer † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Vascular disorders      
Deep Vein Thrombosis † 1    
# participants affected / at risk     1/313 (0.32%)     6/313 (1.92%)  
Hypertension † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Hypertensive Crisis † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Hypotension † 1    
# participants affected / at risk     1/313 (0.32%)     1/313 (0.32%)  
Jugular Vein Thrombosis † 1    
# participants affected / at risk     1/313 (0.32%)     1/313 (0.32%)  
Pelvic Venous Thrombosis † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Shock † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Thrombosis † 1    
# participants affected / at risk     2/313 (0.64%)     0/313 (0.00%)  
Trousseau's Syndrome † 1    
# participants affected / at risk     1/313 (0.32%)     0/313 (0.00%)  
Venous Thrombosis Limb † 1    
# participants affected / at risk     0/313 (0.00%)     1/313 (0.32%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedRA




  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
No text entered.


  More Information