A Study to Evaluate the Safety and Efficacy of Bevacizumab in Combination With Chemotherapy in Previously Treated Metastatic Breast Cancer (RIBBON 2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT00281697
First received: January 23, 2006
Last updated: July 5, 2013
Last verified: July 2013
Results First Received: August 23, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Metastatic Breast Cancer
Interventions: Drug: Bevacizumab
Drug: Placebo
Drug: Standard chemotherapy

  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
Standard Chemotherapy + Bevacizumab Patients received one of several standard chemotherapies for metastatic breast cancer plus bevacizumab in a dose of either 10 mg/kg intravenously (IV) every 2 weeks or 15 mg/kg IV every 3 weeks depending upon the schedule of chemotherapy chosen.
Standard Chemotherapy + Placebo Patients received one of several standard chemotherapies for metastatic breast cancer plus placebo to bevacizumab administered IV either every 2 weeks or every 3 weeks depending upon the schedule of chemotherapy chosen.

Participant Flow:   Overall Study
    Standard Chemotherapy + Bevacizumab     Standard Chemotherapy + Placebo  
STARTED     459     225  
COMPLETED     58     28  
NOT COMPLETED     401     197  
> 60 days since last dose of study drug                 4                 4  
Adverse Event                 54                 15  
Death                 8                 3  
Disease progression                 279                 149  
Not specified                 5                 6  
Physician's decision to withdraw                 15                 12  
Subject/guardian's decision to withdraw                 33                 6  
Did not receive study drug                 3                 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
Standard Chemotherapy + Bevacizumab Patients received one of several standard chemotherapies for metastatic breast cancer plus bevacizumab in a dose of either 10 mg/kg intravenously (IV) every 2 weeks or 15 mg/kg IV every 3 weeks depending upon the schedule of chemotherapy chosen.
Standard Chemotherapy + Placebo Patients received one of several standard chemotherapies for metastatic breast cancer plus placebo to bevacizumab administered IV either every 2 weeks or every 3 weeks depending upon the schedule of chemotherapy chosen.
Total Total of all reporting groups

Baseline Measures
    Standard Chemotherapy + Bevacizumab     Standard Chemotherapy + Placebo     Total  
Number of Participants  
[units: participants]
  459     225     684  
Age  
[units: years]
Mean ± Standard Deviation
  55.6  ± 11.0     55.0  ± 11.2     55.4  ± 11.1  
Gender  
[units: participants]
     
Female     457     225     682  
Male     2     0     2  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Progression-free Survival   [ Time Frame: Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months) ]

2.  Secondary:   Progression-free Survival Within Individual Standard Chemotherapy Cohorts (Taxanes, Gemcitabine, Capecitabine, and Vinorelbine)   [ Time Frame: Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months) ]

3.  Secondary:   Overall Survival   [ Time Frame: Baseline to the end of the study (up to 6 years, 7 months) ]

4.  Secondary:   One-year Survival   [ Time Frame: Baseline to the end of the study (up to 6 years, 7 months) ]

5.  Secondary:   Objective Response   [ Time Frame: Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months) ]

6.  Secondary:   Duration of Objective Response   [ Time Frame: Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months) ]


  Serious Adverse Events
  Hide Serious Adverse Events

Time Frame Adverse events were collected from Baseline to the end of the study (up to 6 years, 7 months).
Additional Description Adverse events are reported for safety-evaluable population defined as all randomized patients who received study treatment, defined as at least 1 full or partial dose of bevacizumab, placebo, or standard chemotherapy.

Reporting Groups
  Description
Standard Chemotherapy + Bevacizumab Patients received one of several standard chemotherapies for metastatic breast cancer plus bevacizumab in a dose of either 10 mg/kg intravenously (IV) every 2 weeks or 15 mg/kg IV every 3 weeks depending upon the schedule of chemotherapy chosen.
Standard Chemotherapy + Placebo Patients received one of several standard chemotherapies for metastatic breast cancer plus placebo to bevacizumab administered IV either every 2 weeks or every 3 weeks depending upon the schedule of chemotherapy chosen.

Serious Adverse Events
    Standard Chemotherapy + Bevacizumab     Standard Chemotherapy + Placebo  
Total, serious adverse events      
# participants affected / at risk     112/458 (24.45%)     39/221 (17.65%)  
Blood and lymphatic system disorders      
Febrile neutropenia † 1    
# participants affected / at risk     8/458 (1.75%)     5/221 (2.26%)  
Neutropenia † 1    
# participants affected / at risk     6/458 (1.31%)     1/221 (0.45%)  
Anaemia † 1    
# participants affected / at risk     3/458 (0.66%)     2/221 (0.90%)  
Thrombocytopenia † 1    
# participants affected / at risk     3/458 (0.66%)     0/221 (0.00%)  
Pancytopenia † 1    
# participants affected / at risk     2/458 (0.44%)     0/221 (0.00%)  
Cardiac disorders      
Myocardial infarction † 1    
# participants affected / at risk     0/458 (0.00%)     2/221 (0.90%)  
Pericardial effusion † 1    
# participants affected / at risk     0/458 (0.00%)     2/221 (0.90%)  
Tachycardia † 1    
# participants affected / at risk     0/458 (0.00%)     2/221 (0.90%)  
Acute myocardial infarction † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Atrial fibrillation † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Cardiac failure congestive † 1    
# participants affected / at risk     1/458 (0.22%)     1/221 (0.45%)  
Supraventricular tachycardia † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Eye disorders      
Diplopia † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Gastrointestinal disorders      
Vomiting † 1    
# participants affected / at risk     6/458 (1.31%)     1/221 (0.45%)  
Nausea † 1    
# participants affected / at risk     4/458 (0.87%)     1/221 (0.45%)  
Constipation † 1    
# participants affected / at risk     3/458 (0.66%)     1/221 (0.45%)  
Diarrhoea † 1    
# participants affected / at risk     2/458 (0.44%)     1/221 (0.45%)  
Gastrointestinal haemorrhage † 1    
# participants affected / at risk     3/458 (0.66%)     0/221 (0.00%)  
Gastric ulcer † 1    
# participants affected / at risk     1/458 (0.22%)     1/221 (0.45%)  
Lower gastrointestinal haemorrhage † 1    
# participants affected / at risk     2/458 (0.44%)     0/221 (0.00%)  
Oesophagitis † 1    
# participants affected / at risk     1/458 (0.22%)     1/221 (0.45%)  
Periproctitis † 1    
# participants affected / at risk     2/458 (0.44%)     0/221 (0.00%)  
Abdominal pain † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Abdominal pain lower † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Abdominal pain upper † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Colitis † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Enterovesical fistula † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Gastritis † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Gastrointestinal perforation † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Haematemesis † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Ileus † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Intestinal perforation † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Obstruction gastric † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Odynophagia † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Oesophageal varices haemorrhage † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Proctitis † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Small intestinal obstruction † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Upper gastrointestinal haemorrhage † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
General disorders      
Pyrexia † 1    
# participants affected / at risk     3/458 (0.66%)     2/221 (0.90%)  
Asthenia † 1    
# participants affected / at risk     1/458 (0.22%)     1/221 (0.45%)  
Chest pain † 1    
# participants affected / at risk     1/458 (0.22%)     1/221 (0.45%)  
Thrombosis in device † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Death † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Impaired healing † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Oedema peripheral † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Pain † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Performance status decreased † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Sudden death † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Device dislocation † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Hepatobiliary disorders      
Hepatitis † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Hepatitis cholestatic † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Hyperbilirubinaemia † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Infections and infestations      
Pneumonia † 1    
# participants affected / at risk     3/458 (0.66%)     3/221 (1.36%)  
Infection † 1    
# participants affected / at risk     4/458 (0.87%)     0/221 (0.00%)  
Cellulitis † 1    
# participants affected / at risk     2/458 (0.44%)     1/221 (0.45%)  
Urinary tract infection † 1    
# participants affected / at risk     0/458 (0.00%)     3/221 (1.36%)  
Bronchitis † 1    
# participants affected / at risk     2/458 (0.44%)     0/221 (0.00%)  
Herpes zoster † 1    
# participants affected / at risk     2/458 (0.44%)     0/221 (0.00%)  
Lower respiratory tract infection † 1    
# participants affected / at risk     1/458 (0.22%)     1/221 (0.45%)  
Septic shock † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Appendicitis † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Bronchopneumonia † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Device related infection † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Erysipelas † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Escherichia bacteraemia † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Gastroenteritis † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Neutropenic infection † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Neutropenic sepsis † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Rectal abscess † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Subcutaneous abscess † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Lobar pneumonia † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Injury, poisoning and procedural complications      
Hip fracture † 1    
# participants affected / at risk     3/458 (0.66%)     0/221 (0.00%)  
Post procedural haemorrhage † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Skull fracture † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Spinal compression fracture † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Wrist fracture † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Investigations      
Platelet count decreased † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Troponin increased † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Electrocardiogram abnormal † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Metabolism and nutrition disorders      
Dehydration † 1    
# participants affected / at risk     5/458 (1.09%)     0/221 (0.00%)  
Failure to thrive † 1    
# participants affected / at risk     1/458 (0.22%)     1/221 (0.45%)  
Hypoglycaemia † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Hypovolaemia † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Metabolic acidosis † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Hyperglycaemia † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Musculoskeletal and connective tissue disorders      
Back pain † 1    
# participants affected / at risk     3/458 (0.66%)     0/221 (0.00%)  
Bone pain † 1    
# participants affected / at risk     2/458 (0.44%)     0/221 (0.00%)  
Musculoskeletal pain † 1    
# participants affected / at risk     2/458 (0.44%)     0/221 (0.00%)  
Pathological fracture † 1    
# participants affected / at risk     2/458 (0.44%)     0/221 (0.00%)  
Arthropathy † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Fascitis † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Muscle twitching † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Muscular weakness † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Myopathy † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Pain in extremity † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Metastases to meninges † 1    
# participants affected / at risk     2/458 (0.44%)     0/221 (0.00%)  
Metastases to central nervous system † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Tumour haemorrhage † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Tumour necrosis † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Nervous system disorders      
Syncope † 1    
# participants affected / at risk     2/458 (0.44%)     0/221 (0.00%)  
Tremor † 1    
# participants affected / at risk     1/458 (0.22%)     1/221 (0.45%)  
Altered state of consciousness † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Cerebral ischaemia † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Convulsion † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Cranial nerve paralysis † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Headache † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Neuropathy peripheral † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Transient ischaemic attack † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Psychiatric disorders      
Mental status changes † 1    
# participants affected / at risk     1/458 (0.22%)     1/221 (0.45%)  
Conversion disorder † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Renal and urinary disorders      
Renal failure acute † 1    
# participants affected / at risk     3/458 (0.66%)     1/221 (0.45%)  
Nephrotic syndrome † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Proteinuria † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Renal tubular necrosis † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Reproductive system and breast disorders      
Vaginal haemorrhage † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Respiratory, thoracic and mediastinal disorders      
Dyspnoea † 1    
# participants affected / at risk     2/458 (0.44%)     3/221 (1.36%)  
Pulmonary embolism † 1    
# participants affected / at risk     3/458 (0.66%)     2/221 (0.90%)  
Pleural effusion † 1    
# participants affected / at risk     3/458 (0.66%)     1/221 (0.45%)  
Hypoxia † 1    
# participants affected / at risk     1/458 (0.22%)     1/221 (0.45%)  
Acute pulmonary oedema † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Acute respiratory distress syndrome † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Asthma † 1    
# participants affected / at risk     0/458 (0.00%)     2/221 (0.90%)  
Haemoptysis † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Pulmonary oedema † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Respiratory failure † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Skin and subcutaneous tissue disorders      
Rash † 1    
# participants affected / at risk     0/458 (0.00%)     1/221 (0.45%)  
Vascular disorders      
Deep vein thrombosis † 1    
# participants affected / at risk     4/458 (0.87%)     1/221 (0.45%)  
Hypertension † 1    
# participants affected / at risk     2/458 (0.44%)     0/221 (0.00%)  
Hypertensive crisis † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Hypotension † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Superior vena caval syndrome † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Thrombosis † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Embolism † 1    
# participants affected / at risk     1/458 (0.22%)     0/221 (0.00%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (12.0)




  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