Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Bevacizumab in Previously Untreated Extensive-Stage Small Cell Lung Cancer (SALUTE)

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: NCT00403403
Recruitment Status : Completed
First Posted : November 23, 2006
Results First Posted : February 25, 2011
Last Update Posted : April 29, 2011
Sponsor:
Information provided by:
Genentech, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Small Cell Lung Cancer
Interventions Drug: Bevacizumab
Drug: Chemotherapy
Drug: Placebo
Enrollment 102
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo+Chemotherapy Bevacizumab+Chemotherapy
Hide Arm/Group Description Chemotherapy = cisplatin (or carboplatin) + etoposide. Placebo 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve [AUC]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles. Chemotherapy = cisplatin (or carboplatin) + etoposide. Bevacizumab 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve [AUC]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles.
Period Title: Overall Study
Started 50 52
Safety-Evaluable Patients 47 51
Completed 50 52
Not Completed 0 0
Arm/Group Title Placebo+Chemotherapy Bevacizumab+Chemotherapy Total
Hide Arm/Group Description Chemotherapy = cisplatin (or carboplatin) + etoposide. Placebo 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve [AUC]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles. Chemotherapy = cisplatin (or carboplatin) + etoposide. Bevacizumab 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve [AUC]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles. Total of all reporting groups
Overall Number of Baseline Participants 50 52 102
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 50 participants 52 participants 102 participants
64.0  (10.0) 61.3  (8.5) 62.7  (9.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 52 participants 102 participants
Female
20
  40.0%
26
  50.0%
46
  45.1%
Male
30
  60.0%
26
  50.0%
56
  54.9%
1.Primary Outcome
Title Progression-free Survival (PFS)
Hide Description Duration of PFS, defined as the time from randomization to disease progression or on-study death, whichever occurred first.
Time Frame Randomization until progression or lost to follow-up (up to 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Placebo+Chemotherapy Bevacizumab+Chemotherapy
Hide Arm/Group Description:
Chemotherapy = cisplatin (or carboplatin) + etoposide. Placebo 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve [AUC]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles.
Chemotherapy = cisplatin (or carboplatin) + etoposide. Bevacizumab 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve [AUC]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles.
Overall Number of Participants Analyzed 50 52
Median (95% Confidence Interval)
Unit of Measure: Months
4.4
(4.2 to 4.9)
5.5
(4.5 to 6.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo+Chemotherapy, Bevacizumab+Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0097
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.528
Confidence Interval 95%
0.323 to 0.862
Estimation Comments HR estimated from a stratified Cox regression model, stratified for ECOG performance (0-1 vs. 2) and chemotherapy type (cisplatin vs. carboplatin)
2.Secondary Outcome
Title Overall Survival
Hide Description Duration of overall survival from randomization until death or loss to follow-up
Time Frame Randomization until death or lost of follow-up (up to 27 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Placebo+Chemotherapy Bevacizumab+Chemotherapy
Hide Arm/Group Description:
Chemotherapy = cisplatin (or carboplatin) + etoposide. Placebo 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve [AUC]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles.
Chemotherapy = cisplatin (or carboplatin) + etoposide. Bevacizumab 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve [AUC]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles.
Overall Number of Participants Analyzed 50 52
Median (95% Confidence Interval)
Unit of Measure: Months
10.9
(8.1 to 14.7)
9.4
(8.7 to 11.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo+Chemotherapy, Bevacizumab+Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6054
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.160
Confidence Interval (2-Sided) 95%
0.660 to 2.039
Estimation Comments HR estimated from a stratified Cox regression model, stratified for ECOG performance (0-1 vs. 2) and chemotherapy type (cisplatin vs. carboplatin)
3.Secondary Outcome
Title Percentage of Participants With an Objective Response
Hide Description

Objective response was defined as a complete or partial response (per RECIST) determined by two investigator assessments conducted at least 4 weeks apart.

Complete Response (CR), Partial Response (PR), Incomplete Response (IR), Stable Disease (SD) (per RECIST):

Target Lesions Non-Target Lesions New Lesions Overall Response CR CR No CR CR IR/SD No PR PR Non-PD No PR

Time Frame Randomization until progression or lost to follow-up (up to 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Placebo+Chemotherapy Bevacizumab+Chemotherapy
Hide Arm/Group Description:
Chemotherapy = cisplatin (or carboplatin) + etoposide. Placebo 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve [AUC]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles.
Chemotherapy = cisplatin (or carboplatin) + etoposide. Bevacizumab 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve [AUC]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles.
Overall Number of Participants Analyzed 50 52
Measure Type: Number
Unit of Measure: Percentage of participants
48.0 57.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo+Chemotherapy, Bevacizumab+Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3269
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 9.7
Confidence Interval 95%
-9.6 to 29.0
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Number of Participants With an Objective Response
Hide Description

Objective response was defined as a complete or partial response (per RECIST) determined by two investigator assessments conducted at least 4 weeks apart.

Complete Response (CR), Partial Response (PR), Incomplete Response (IR), Stable Disease (SD) (per RECIST):

Target Lesions Non-Target Lesions New Lesions Overall Response CR CR No CR CR IR/SD No PR PR Non-PD No PR

Time Frame Randomization until progression or lost to follow-up (up to 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo+Chemotherapy Bevacizumab+Chemotherapy
Hide Arm/Group Description:
Chemotherapy = cisplatin (or carboplatin) + etoposide. Placebo 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve [AUC]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles.
Chemotherapy = cisplatin (or carboplatin) + etoposide. Bevacizumab 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve [AUC]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles.
Overall Number of Participants Analyzed 50 52
Measure Type: Number
Unit of Measure: number of participants
24 30
5.Secondary Outcome
Title Duration of Objective Response
Hide Description Duration of response was defined as time from the first response date to disease progression or on-study death (i.e., death occurring any time from randomization to 30 days after the final treatment with bevacizumab/placebo). Objective response was defined as a complete or partial response (per RECIST) determined by two investigator assessments conducted at least 4 weeks apart.
Time Frame Randomization until progression or lost to follow-up (up to 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized patients with measurable disease at baseline.
Arm/Group Title Placebo+Chemotherapy Bevacizumab+Chemotherapy
Hide Arm/Group Description:
Chemotherapy = cisplatin (or carboplatin) + etoposide. Placebo 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve [AUC]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles.
Chemotherapy = cisplatin (or carboplatin) + etoposide. Bevacizumab 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve [AUC]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles.
Overall Number of Participants Analyzed 24 30
Median (95% Confidence Interval)
Unit of Measure: Months
3.2
(2.9 to 4.2)
4.7
(4.2 to 5.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo+Chemotherapy, Bevacizumab+Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0011
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.305
Confidence Interval (2-Sided) 95%
0.144 to 0.644
Estimation Comments HR estimated from a stratified Cox regression model, stratified for ECOG performance (0-1 vs. 2) and chemotherapy type (cisplatin vs. carboplatin)
Time Frame Overall duration of study
Adverse Event Reporting Description

Safety analyses were performed on the safety evaluable population, which included 98 patients who received at least one dose of chemotherapy, bevacizumab, or placebo.

National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)

 
Arm/Group Title Placebo+Chemotherapy Bevacizumab+Chemotherapy
Hide Arm/Group Description Chemotherapy = cisplatin (or carboplatin) + etoposide. Placebo 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve [AUC]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles. Chemotherapy = cisplatin (or carboplatin) + etoposide. Bevacizumab 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve [AUC]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles.
All-Cause Mortality
Placebo+Chemotherapy Bevacizumab+Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Placebo+Chemotherapy Bevacizumab+Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   11/47 (23.40%)   20/51 (39.22%) 
Blood and lymphatic system disorders     
Pancytopenia * 1  2/47 (4.26%)  0/51 (0.00%) 
Febrile Neutropenia * 1  0/47 (0.00%)  1/51 (1.96%) 
Cardiac disorders     
Cardiac Failure Congestive * 1  0/47 (0.00%)  1/51 (1.96%) 
Myocardial Infarction * 1  1/47 (2.13%)  0/51 (0.00%) 
Pericardial Effusion * 1  0/47 (0.00%)  1/51 (1.96%) 
Tachycardia * 1  0/47 (0.00%)  1/51 (1.96%) 
Atrial Fibrillation * 1  0/47 (0.00%)  1/51 (1.96%) 
Cardiac Arrest * 1  0/47 (0.00%)  1/51 (1.96%) 
Gastrointestinal disorders     
Diarrhea * 1  0/47 (0.00%)  2/51 (3.92%) 
Gastrointestinal Perforation * 1  0/47 (0.00%)  2/51 (3.92%) 
Nausea * 1  1/47 (2.13%)  0/51 (0.00%) 
Vomiting * 1  0/47 (0.00%)  1/51 (1.96%) 
Gastrointestinal Hemorrhage * 1  0/47 (0.00%)  2/51 (3.92%) 
Abdominal Pain * 1  0/47 (0.00%)  1/51 (1.96%) 
Constipation * 1  1/47 (2.13%)  0/51 (0.00%) 
Ileus * 1  1/47 (2.13%)  0/51 (0.00%) 
General disorders     
Death * 1  0/47 (0.00%)  1/51 (1.96%) 
Infections and infestations     
Pneumonia * 1  2/47 (4.26%)  3/51 (5.88%) 
Lobar Pneumonia * 1  1/47 (2.13%)  0/51 (0.00%) 
Injury, poisoning and procedural complications     
Road Traffic Accident * 1  1/47 (2.13%)  0/51 (0.00%) 
Investigations     
Hemoglobin Decreased * 1  1/47 (2.13%)  0/51 (0.00%) 
Metabolism and nutrition disorders     
Dehydration * 1  2/47 (4.26%)  0/51 (0.00%) 
Electrolyte Imbalance * 1  1/47 (2.13%)  0/51 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back Pain * 1  0/47 (0.00%)  1/51 (1.96%) 
Nervous system disorders     
Depressed Level of Consciousness * 1  0/47 (0.00%)  1/51 (1.96%) 
Reversible Posterior Leukoencephalopathy Syndrome * 1  0/47 (0.00%)  1/51 (1.96%) 
Psychiatric disorders     
Mental Status Changes * 1  0/47 (0.00%)  1/51 (1.96%) 
Renal and urinary disorders     
Renal Failure * 1  1/47 (2.13%)  1/51 (1.96%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnea * 1  2/47 (4.26%)  2/51 (3.92%) 
Pulmonary Embolism * 1  2/47 (4.26%)  0/51 (0.00%) 
Chronic Obstructive Pulmonary Disease * 1  0/47 (0.00%)  1/51 (1.96%) 
Hemoptysis * 1  0/47 (0.00%)  1/51 (1.96%) 
Stridor * 1  1/47 (2.13%)  0/51 (0.00%) 
Hydropneumothorax * 1  0/47 (0.00%)  1/51 (1.96%) 
Pneumothorax * 1  0/47 (0.00%)  1/51 (1.96%) 
Respiratory Failure * 1  0/47 (0.00%)  1/51 (1.96%) 
Vascular disorders     
Deep Vein Thrombosis * 1  1/47 (2.13%)  0/51 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, NCI CTCAE 3.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo+Chemotherapy Bevacizumab+Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   31/47 (65.96%)   35/51 (68.63%) 
Blood and lymphatic system disorders     
Neutropenia * 1  20/47 (42.55%)  20/51 (39.22%) 
Thrombocytopenia * 1  2/47 (4.26%)  4/51 (7.84%) 
Vascular disorders     
Hypertension * 1  12/47 (25.53%)  15/51 (29.41%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, NCI CTCAE 3.0
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
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Genentech, Inc.
Phone: 800-821-8590
Layout table for additonal information
Responsible Party: David Karlin, M.D., Study Director, Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00403403    
Other Study ID Numbers: AVF3995g
First Submitted: November 21, 2006
First Posted: November 23, 2006
Results First Submitted: January 28, 2010
Results First Posted: February 25, 2011
Last Update Posted: April 29, 2011