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A Study of Bevacizumab in Combination With First- or Second-Line Therapy in Subjects With Treated Brain Metastases Due to Non-Squamous NSCLC (PASSPORT)

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ClinicalTrials.gov Identifier: NCT00312728
Recruitment Status : Completed
First Posted : April 11, 2006
Results First Posted : June 22, 2011
Last Update Posted : August 8, 2011
Sponsor:
Information provided by:
Genentech, Inc.

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Non-Small Cell Lung Cancer
Brain Neoplasms
Interventions Drug: bevacizumab
Drug: First-Line Chemotherapy Agents
Drug: Second-Line Chemotherapy Agents
Enrollment 115
Recruitment Details Approximately 110 subjects were to be enrolled at approximately 40 sites to obtain 100 bevacizumab-treated evaluable subjects. Study started 28 NOV 2005 and completed 5 JUN 2009.
Pre-assignment Details This was an open-label, multicenter, single-arm, Phase II trial of bevacizumab combined with first- or second-line therapy in subjects with metastatic non-squamous non-small cell lung cancer (NSCLC) with previously treated CNS metastases.
Arm/Group Title Bevacizumab
Hide Arm/Group Description 15 mg/kg IV on the first day of each 21- to 28-day cycle (+/-4 days) in combination with first or second-line therapy
Period Title: Overall Study
Started 115
Completed 5
Not Completed 110
Reason Not Completed
Progressive disease             53
Adverse Event             32
Withdrawal by Subject             10
Required non-protocol cancer treatment             2
Protocol Violation             2
Other             10
Other             1
Arm/Group Title Bevacizumab
Hide Arm/Group Description 15 mg/kg IV on the first day of each 21- to 28-day cycle (+/-4 days) in combination with first or second-line therapy
Overall Number of Baseline Participants 115
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 115 participants
58  (10.6)
Age, Customized  
Measure Type: Number
Unit of measure:  Patients
Number Analyzed 115 participants
18-40 years 6
41-64 years 77
>=65 years 32
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants
Female
53
  46.1%
Male
62
  53.9%
1.Primary Outcome
Title Percentage of Participants With Symptomatic National Cancer Institute's Common Terminology Criteria for Adverse Events v3.0 (NCI CTCAE) Grade ≥2 Central Nervous System (CNS) Hemorrhage
Hide Description

The percentage of participants with symptomatic NCI CTCAE Grade ≥ 2 CNS hemorrhage, defined as the presence of clinical symptoms determined by the investigator to be directly referable to a Grade ≥ 2 CNS hemorrhage.

Grade 1: Asymptomatic, radiographic findings only Grade 2: Medical intervention indicated Grade 3: Ventriculostomy, intracranial pressure (ICP) monitoring, intraventricular thrombolysis, or operative intervention indicated Grade 4: Life-threatening consequences; neurologic deficit or disability Grade 5: Death

Time Frame From the first administration of bevacizumab until 60 days after discontinuation of bevacizumab treatment was reported (up to 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety-evaluable population consisted of all patients who received at least one dose of bevacizumab.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
15 mg/kg IV on the first day of each 21- to 28-day cycle (+/-4 days) in combination with first or second-line therapy
Overall Number of Participants Analyzed 106
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
0
(0 to 2.5)
2.Secondary Outcome
Title Overall Survival (OS) in First-line Setting
Hide Description To assess overall survival in the subset of subjects treated in the first-line setting with bevacizumab plus either chemotherapy or erlotinib for non-squamous NSCLC with previously treated brain metastases.
Time Frame Time from enrollment to death from any cause (up to 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The first-line efficacy-evaluable population consisted of 70 patients who received at least one dose of bevacizumab.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
15 mg/kg IV on the first day of each 21- to 28-day cycle (+/-4 days) in combination with first or second-line therapy
Overall Number of Participants Analyzed 70
Median (95% Confidence Interval)
Unit of Measure: Months
11.8
(9.6 to 13.9)
3.Secondary Outcome
Title Number of Participants With Overall Survival (OS) in First-line Setting [1-Year or More Survival]
Hide Description Number of Participants with overall survival in the subset of subjects treated in the first-line setting with bevacizumab plus either chemotherapy or erlotinib for non-squamous NSCLC with previously treated brain metastases.
Time Frame Time from enrollment to death from any cause (up to 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The first-line efficacy-evaluable population consisted of 70 patients who received at least one dose of bevacizumab.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
15 mg/kg IV on the first day of each 21- to 28-day cycle (+/-4 days) in combination with first or second-line therapy
Overall Number of Participants Analyzed 70
Measure Type: Number
Unit of Measure: participants
30
4.Secondary Outcome
Title OS in First-line and Second-line Settings
Hide Description To assess overall survival in the subset of subjects treated in the first-line setting with bevacizumab plus either chemotherapy or erlotinib for non-squamous NSCLC with previously treated brain metastases.
Time Frame Time from enrollment to death from any cause (up to 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy-evaluable population consisted of all patients who received at least one dose of bevacizumab.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
15 mg/kg IV on the first day of each 21- to 28-day cycle (+/-4 days) in combination with first or second-line therapy
Overall Number of Participants Analyzed 106
Median (95% Confidence Interval)
Unit of Measure: Months
12.1
(10.3 to 14.9)
5.Secondary Outcome
Title Number of Participants With OS in First-line and Second-line Settings [1-Year or More Survival]
Hide Description To assess the number of participants with overall survival in the subset of subjects treated in the first-line setting with bevacizumab plus either chemotherapy or erlotinib for non-squamous NSCLC with previously treated brain metastases.
Time Frame Time from enrollment to death from any cause (up to 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy-evaluable population consisted of all patients who received at least one dose of bevacizumab.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
15 mg/kg IV on the first day of each 21- to 28-day cycle (+/-4 days) in combination with first or second-line therapy
Overall Number of Participants Analyzed 106
Measure Type: Number
Unit of Measure: participants
49
6.Secondary Outcome
Title Number of Participants With Selected Adverse Events
Hide Description

Number of participants with selected adverse events (all grades based on NCI CTCAE) included any grade CNS hemorrhage, any grade pulmonary hemorrhage, any grade gastrointestinal (GI) perforation, Grade ≥ 2 arterial thromboembolic event, Grade ≥ 2 left ventricular systolic dysfunction, Grade ≥ 3 non-CNS non-pulmonary hemorrhage, Grade ≥ 3 proteinuria, Grade ≥ 3 proteinuria, Grade ≥ 3 hypertension, any serious adverse event*, and any adverse event leading to study treatment discontinuation.

*For serious adverse events, please see Adverse Event Reporting Section.

Time Frame From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety-evaluable population consisted of all patients who received at least one dose of bevacizumab.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
15 mg/kg IV on the first day of each 21- to 28-day cycle (+/-4 days) in combination with first or second-line therapy
Overall Number of Participants Analyzed 106
Measure Type: Number
Unit of Measure: participants
Any grade CNS hemorrhage 0
Any grade pulmonary hemorrhage 4
Grade ≥ 2 arterial thromboembolic event 1
Grade ≥ 3 non-CNS non-pulmonary hemorrhage 2
Grade ≥ 3 venous thromboembolic event 7
Any grade gastrointestinal perforation 0
Grade ≥ 3 hypertension 3
Grade ≥ 3 proteinuria 0
Grade ≥ 2 left ventricular systolic dysfunction 0
Reversible Posterior Leukoencephalopathy Syndrome 1
Any event leading to treatment discontinuation 30
Time Frame From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Bevacizumab
Hide Arm/Group Description 15 mg/kg IV on the first day of each 21- to 28-day cycle (+/-4 days) in combination with first or second-line therapy
All-Cause Mortality
Bevacizumab
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Bevacizumab
Affected / at Risk (%)
Total   45/106 (42.45%) 
Blood and lymphatic system disorders   
Anemia  1  2/106 (1.89%) 
Febrile Neutropenia  1  1/106 (0.94%) 
Thrombocytopenia  1  1/106 (0.94%) 
Endocrine disorders   
Hypoaldosteronism  1  1/106 (0.94%) 
Gastrointestinal disorders   
Gastrointestinal Hemorrhage  1  2/106 (1.89%) 
Abdominal Pain  1  1/106 (0.94%) 
Constipation  1  1/106 (0.94%) 
Gastroesophageal Reflux Disease  1  1/106 (0.94%) 
Nausea  1  1/106 (0.94%) 
Pancreatitis  1  1/106 (0.94%) 
Small Intestinal Obstruction  1  1/106 (0.94%) 
Vomiting  1  1/106 (0.94%) 
General disorders   
Chest Pain  1  2/106 (1.89%) 
Death  1  1/106 (0.94%) 
Pyrexia  1  1/106 (0.94%) 
Infections and infestations   
Pneumonia  1  3/106 (2.83%) 
Urinary Tract Infection  1  2/106 (1.89%) 
Diverticulitis  1  1/106 (0.94%) 
Lobar Pneumonia  1  1/106 (0.94%) 
Perirectal Abscess  1  1/106 (0.94%) 
Rectal Abscess  1  1/106 (0.94%) 
Injury, poisoning and procedural complications   
Hip Fracture  1  1/106 (0.94%) 
Spinal Compression Fracture  1  1/106 (0.94%) 
Metabolism and nutrition disorders   
Dehydration  1  2/106 (1.89%) 
Anorexia  1  1/106 (0.94%) 
Failure to Thrive  1  1/106 (0.94%) 
Musculoskeletal and connective tissue disorders   
Muscular Weakness  1  1/106 (0.94%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Lung Neoplasm Malignant  1  1/106 (0.94%) 
Nervous system disorders   
Convulsion  1  4/106 (3.77%) 
Ataxia  1  1/106 (0.94%) 
BRAIN OEDEMA  1  1/106 (0.94%) 
Cerebral Arteriosclerosis  1  1/106 (0.94%) 
Headache  1  1/106 (0.94%) 
Leukoencephalopathy  1  1/106 (0.94%) 
Syncope  1  1/106 (0.94%) 
Transient Ischemic Attack  1  1/106 (0.94%) 
Psychiatric disorders   
Mental Status Changes  1  2/106 (1.89%) 
Renal and urinary disorders   
Renal Failure Acute  1  1/106 (0.94%) 
Respiratory, thoracic and mediastinal disorders   
Pulmonary Embolism  1  6/106 (5.66%) 
Pulmonary Hemorrhage  1  3/106 (2.83%) 
Chronic Obstructive Pulmonary Disease  1  1/106 (0.94%) 
Hemoptysis  1  1/106 (0.94%) 
Respiratory Distress  1  1/106 (0.94%) 
Respiratory Failure  1  1/106 (0.94%) 
Vascular disorders   
Hypotension  1  1/106 (0.94%) 
Orthostatic Hypotension  1  1/106 (0.94%) 
Venous Thrombosis Limb  1  1/106 (0.94%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bevacizumab
Affected / at Risk (%)
Total   7/106 (6.60%) 
Blood and lymphatic system disorders   
Thrombocytopenia  1  7/106 (6.60%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
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: Hoffman-LaRoche
Phone: 800-821-8590
Layout table for additonal information
Responsible Party: Jane Huang, M.D., Study Director, Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00312728    
Other Study ID Numbers: AVF3752g
First Submitted: April 7, 2006
First Posted: April 11, 2006
Results First Submitted: March 18, 2011
Results First Posted: June 22, 2011
Last Update Posted: August 8, 2011