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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
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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 
Overall Participants Analyzed 
[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
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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
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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
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  More Information
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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Communications
Organization: Genentech, Inc.
phone: 800 821-8590



Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00281697     History of Changes
Other Study ID Numbers: AVF3693g
Study First Received: January 23, 2006
Results First Received: August 23, 2012
Last Updated: July 5, 2013
Health Authority: United States: Food and Drug Administration