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

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00403403
• Collaborator: (none)
• Enrollment: 102
• Arms: 2
• Duration (Months): 27

Study Details

Study Description

Brief Summary

This is a placebo-controlled, double-blind, multicenter, randomized study for preliminary evaluation of the efficacy and safety of combining bevacizumab with cisplatin (or carboplatin) and etoposide in patients with previously untreated extensive-stage small cell lung cancer (SCLC).

Condition or Disease	Intervention/Treatment	Phase
Small Cell Lung Cancer	Drug: Bevacizumab; Drug: Chemotherapy; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Placebo-Controlled, Double-Blind, Multicenter, Randomized, Phase II Study of Bevacizumab in Previously Untreated Extensive-Stage Small Cell Lung Cancer
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo+Chemotherapy Chemotherapy = cisplatin (or carboplatin) + etoposide	Drug: Chemotherapy; Chemotherapy = cisplatin (or carboplatin) + etoposide. 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.; Drug: Placebo; 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.
Experimental: Bevacizumab+Chemotherapy Chemotherapy = cisplatin (or carboplatin) + etoposide	Drug: Bevacizumab; 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.; Drug: Chemotherapy; Chemotherapy = cisplatin (or carboplatin) + etoposide. 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.

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) [Randomization until progression or lost to follow-up (up to 2 years)]

   Duration of PFS, defined as the time from randomization to disease progression or on-study death, whichever occurred first.

Secondary Outcome Measures

1. Overall Survival [Randomization until death or lost of follow-up (up to 27 months)]

   Duration of overall survival from randomization until death or loss to follow-up

2. Percentage of Participants With an Objective Response [Randomization until progression or lost to follow-up (up to 2 years)]

   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

3. Number of Participants With an Objective Response [Randomization until progression or lost to follow-up (up to 2 years)]

   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

4. Duration of Objective Response [Randomization until progression or lost to follow-up (up to 2 years)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically documented small cell carcinoma of the bronchus, classified as extensive-stage disease

• Measurable disease or lesions

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

Exclusion Criteria:

• Life expectancy of < 12 weeks

• Current, recent, or planned participation in another experimental drug study

• Ongoing or active infection

• Active malignancy other than SCLC or superficial basal/squamous cell carcinoma within the previous 5 years

• Prior systemic therapy, radiation therapy, or surgery for SCLC

• Inadequate bone marrow function, renal function, or hepatic function

• Serum sodium of < 120 mg/dL

• Inadequately controlled hypertension

• History of hypertensive crisis or hypertensive encephalopathy

• New York Heart Association Class II or greater congestive heart failure

• History of myocardial infarction or unstable angina within 6 months prior to study enrollment

• History of stroke or transient ischemic attack within 6 months prior to study enrollment

• Known central nervous system disease, except for brain metastases treated with whole-brain radiotherapy

• Significant vascular disease or recent peripheral arterial thrombosis within 6 months prior to study enrollment

• History of hemoptysis within 4 weeks prior to study enrollment

• Evidence of bleeding diathesis or coagulopathy in the absence of therapeutic anticoagulation

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of a need for a major surgical procedure during the course of the study

• Core biopsy or other minor surgical procedure, including placement of a vascular access device, within 7 days prior to Day 1

• History of abdominal fistula or gastrointestinal perforation within 6 months prior to study enrollment

• Serious, non-healing wound, active ulcer, or untreated bone fracture

• Known hypersensitivity to any component of bevacizumab

• Pregnant (positive pregnancy test) or lactating

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Genentech, Inc.

Investigators

• Study Director: David Karlin, M.D., Genentech, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00403403
• Other Study ID Numbers: AVF3995g
• First Posted: Nov 23, 2006
• Last Update Posted: Apr 29, 2011
• Last Verified: Apr 1, 2011

• Keywords provided by , ,: SCLC; SALUTE; Lung Cancer; Avastin
• Additional relevant MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma; Bevacizumab

Study Results

Participant Flow

Arm/Group Title	Placebo+Chemotherapy	Bevacizumab+Chemotherapy
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

Baseline Characteristics

Arm/Group Title	Placebo+Chemotherapy	Bevacizumab+Chemotherapy	Total
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 Participants	50	52	102
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.0 (10.0)	61.3 (8.5)	62.7 (9.3)
Sex: Female, Male (Count of Participants)
Female	20 40%	26 50%	46 45.1%
Male	30 60%	26 50%	56 54.9%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS)
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)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Placebo+Chemotherapy	Bevacizumab+Chemotherapy
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.
Measure Participants	50	52
Median (95% Confidence Interval) [Months]	4.4	5.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Chemotherapy, Bevacizumab+Chemotherapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0097
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.528
	Confidence Interval	() 95%; 0.323 to 0.862
	Parameter Dispersion	Type: Value:
	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
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)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Placebo+Chemotherapy	Bevacizumab+Chemotherapy
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.
Measure Participants	50	52
Median (95% Confidence Interval) [Months]	10.9	9.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Chemotherapy, Bevacizumab+Chemotherapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6054
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.160
	Confidence Interval	(2-Sided) 95%; 0.660 to 2.039
	Parameter Dispersion	Type: Value:
	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
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)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Placebo+Chemotherapy	Bevacizumab+Chemotherapy
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.
Measure Participants	50	52
Number [Percentage of participants]	48.0 96%	57.7 111%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Chemotherapy, Bevacizumab+Chemotherapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3269
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	9.7
	Confidence Interval	() 95%; -9.6 to 29.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Number of Participants With an Objective Response
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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo+Chemotherapy	Bevacizumab+Chemotherapy
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.
Measure Participants	50	52
Number [number of participants]	24 48%	30 57.7%

5. Secondary Outcome

Title	Duration of Objective Response
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)

Outcome Measure Data

Analysis Population Description

Randomized patients with measurable disease at baseline.

Arm/Group Title	Placebo+Chemotherapy	Bevacizumab+Chemotherapy
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.
Measure Participants	24	30
Median (95% Confidence Interval) [Months]	3.2	4.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Chemotherapy, Bevacizumab+Chemotherapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.305
	Confidence Interval	(2-Sided) 95%; 0.144 to 0.644
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR estimated from a stratified Cox regression model, stratified for ECOG performance (0-1 vs. 2) and chemotherapy type (cisplatin vs. carboplatin)

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo+Chemotherapy		Bevacizumab+Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/47 (23.4%)		20/51 (39.2%)
Blood and lymphatic system disorders
Pancytopenia	2/47 (4.3%)		0/51 (0%)
Febrile Neutropenia	0/47 (0%)		1/51 (2%)
Cardiac disorders
Cardiac Failure Congestive	0/47 (0%)		1/51 (2%)
Myocardial Infarction	1/47 (2.1%)		0/51 (0%)
Pericardial Effusion	0/47 (0%)		1/51 (2%)
Tachycardia	0/47 (0%)		1/51 (2%)
Atrial Fibrillation	0/47 (0%)		1/51 (2%)
Cardiac Arrest	0/47 (0%)		1/51 (2%)
Gastrointestinal disorders
Diarrhea	0/47 (0%)		2/51 (3.9%)
Gastrointestinal Perforation	0/47 (0%)		2/51 (3.9%)
Nausea	1/47 (2.1%)		0/51 (0%)
Vomiting	0/47 (0%)		1/51 (2%)
Gastrointestinal Hemorrhage	0/47 (0%)		2/51 (3.9%)
Abdominal Pain	0/47 (0%)		1/51 (2%)
Constipation	1/47 (2.1%)		0/51 (0%)
Ileus	1/47 (2.1%)		0/51 (0%)
General disorders
Death	0/47 (0%)		1/51 (2%)
Infections and infestations
Pneumonia	2/47 (4.3%)		3/51 (5.9%)
Lobar Pneumonia	1/47 (2.1%)		0/51 (0%)
Injury, poisoning and procedural complications
Road Traffic Accident	1/47 (2.1%)		0/51 (0%)
Investigations
Hemoglobin Decreased	1/47 (2.1%)		0/51 (0%)
Metabolism and nutrition disorders
Dehydration	2/47 (4.3%)		0/51 (0%)
Electrolyte Imbalance	1/47 (2.1%)		0/51 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	0/47 (0%)		1/51 (2%)
Nervous system disorders
Depressed Level of Consciousness	0/47 (0%)		1/51 (2%)
Reversible Posterior Leukoencephalopathy Syndrome	0/47 (0%)		1/51 (2%)
Psychiatric disorders
Mental Status Changes	0/47 (0%)		1/51 (2%)
Renal and urinary disorders
Renal Failure	1/47 (2.1%)		1/51 (2%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/47 (4.3%)		2/51 (3.9%)
Pulmonary Embolism	2/47 (4.3%)		0/51 (0%)
Chronic Obstructive Pulmonary Disease	0/47 (0%)		1/51 (2%)
Hemoptysis	0/47 (0%)		1/51 (2%)
Stridor	1/47 (2.1%)		0/51 (0%)
Hydropneumothorax	0/47 (0%)		1/51 (2%)
Pneumothorax	0/47 (0%)		1/51 (2%)
Respiratory Failure	0/47 (0%)		1/51 (2%)
Vascular disorders
Deep Vein Thrombosis	1/47 (2.1%)		0/51 (0%)
Other (Not Including Serious) Adverse Events
	Placebo+Chemotherapy		Bevacizumab+Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/47 (66%)		35/51 (68.6%)
Blood and lymphatic system disorders
Neutropenia	20/47 (42.6%)		20/51 (39.2%)
Thrombocytopenia	2/47 (4.3%)		4/51 (7.8%)
Vascular disorders
Hypertension	12/47 (25.5%)		15/51 (29.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.