Trial Outcomes & Findings for A Study of Bevacizumab in Combination With First- or Second-Line Therapy in Subjects With Treated Brain Metastases Due to Non-Squamous NSCLC (PASSPORT) (NCT NCT00312728)

Last Updated: 2023-01-06

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

115 participants

Primary outcome timeframe

From the first administration of bevacizumab until 60 days after discontinuation of bevacizumab treatment was reported (up to 2 years)

Results posted on

2023-01-06

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Bevacizumab 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 Study STARTED	115
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	110

Reasons for withdrawal

Reasons for withdrawal
Measure	Bevacizumab 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 Study Progressive disease	53
Overall Study Adverse Event	32
Overall Study Withdrawal by Subject	10
Overall Study Required non-protocol cancer treatment	2
Overall Study Protocol Violation	2
Overall Study Other	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bevacizumab n=115 Participants 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
Sex: Female, Male Male	62 Participants n=5 Participants
Age, Continuous	58 years STANDARD_DEVIATION 10.6 • n=5 Participants
Age, Customized 18-40 years	6 patients n=5 Participants
Age, Customized 41-64 years	77 patients n=5 Participants
Age, Customized >=65 years	32 patients n=5 Participants
Sex: Female, Male Female	53 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the first administration of bevacizumab until 60 days after discontinuation of bevacizumab treatment was reported (up to 2 years)

Population: The safety-evaluable population consisted of all patients who received at least one dose of bevacizumab.

Outcome measures

Outcome measures
Measure	Bevacizumab n=106 Participants 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
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	0 percentage of participants Interval 0.0 to 2.5

SECONDARY outcome

Timeframe: Time from enrollment to death from any cause (up to 2 years)

Population: The first-line efficacy-evaluable population consisted of 70 patients who received at least one dose of bevacizumab.

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.

Outcome measures

Outcome measures
Measure	Bevacizumab n=70 Participants 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 Survival (OS) in First-line Setting	11.8 Months Interval 9.6 to 13.9

SECONDARY outcome

Timeframe: Time from enrollment to death from any cause (up to 2 years)

Population: The first-line efficacy-evaluable population consisted of 70 patients who received at least one dose of bevacizumab.

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.

Outcome measures

Outcome measures
Measure	Bevacizumab n=70 Participants 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
Number of Participants With Overall Survival (OS) in First-line Setting [1-Year or More Survival]	30 participants

SECONDARY outcome

Timeframe: Time from enrollment to death from any cause (up to 2 years)

Population: The efficacy-evaluable population consisted of all patients who received at least one dose of bevacizumab.

Outcome measures

Outcome measures
Measure	Bevacizumab n=106 Participants 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
OS in First-line and Second-line Settings	12.1 Months Interval 10.3 to 14.9

SECONDARY outcome

Timeframe: Time from enrollment to death from any cause (up to 2 years)

Population: The efficacy-evaluable population consisted of all patients who received at least one dose of bevacizumab.

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.

Outcome measures

Outcome measures
Measure	Bevacizumab n=106 Participants 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
Number of Participants With OS in First-line and Second-line Settings [1-Year or More Survival]	49 participants

SECONDARY outcome

Timeframe: From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years)

Population: The safety-evaluable population consisted of all patients who received at least one dose of bevacizumab.

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.

Outcome measures

Outcome measures
Measure	Bevacizumab n=106 Participants 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
Number of Participants With Selected Adverse Events Grade ≥ 3 proteinuria	0 participants
Number of Participants With Selected Adverse Events Grade ≥ 2 left ventricular systolic dysfunction	0 participants
Number of Participants With Selected Adverse Events Reversible Posterior Leukoencephalopathy Syndrome	1 participants
Number of Participants With Selected Adverse Events Any event leading to treatment discontinuation	30 participants
Number of Participants With Selected Adverse Events Any grade CNS hemorrhage	0 participants
Number of Participants With Selected Adverse Events Any grade pulmonary hemorrhage	4 participants
Number of Participants With Selected Adverse Events Grade ≥ 2 arterial thromboembolic event	1 participants
Number of Participants With Selected Adverse Events Grade ≥ 3 non-CNS non-pulmonary hemorrhage	2 participants
Number of Participants With Selected Adverse Events Grade ≥ 3 venous thromboembolic event	7 participants
Number of Participants With Selected Adverse Events Any grade gastrointestinal perforation	0 participants
Number of Participants With Selected Adverse Events Grade ≥ 3 hypertension	3 participants

Adverse Events

Bevacizumab

Serious events: 45 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Bevacizumab n=106 participants at risk 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
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	5.7% 6/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Respiratory, thoracic and mediastinal disorders Pulmonary Hemorrhage	2.8% 3/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Respiratory, thoracic and mediastinal disorders Hemoptysis	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Respiratory, thoracic and mediastinal disorders Respiratory Distress	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Nervous system disorders Convulsion	3.8% 4/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Nervous system disorders Ataxia	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Nervous system disorders BRAIN OEDEMA	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Nervous system disorders Cerebral Arteriosclerosis	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Nervous system disorders Headache	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Nervous system disorders Leukoencephalopathy	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Nervous system disorders Syncope	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Nervous system disorders Transient Ischemic Attack	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Infections and infestations Pneumonia	2.8% 3/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Infections and infestations Urinary Tract Infection	1.9% 2/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Infections and infestations Diverticulitis	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Infections and infestations Lobar Pneumonia	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Infections and infestations Perirectal Abscess	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Infections and infestations Rectal Abscess	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Gastrointestinal disorders Gastrointestinal Hemorrhage	1.9% 2/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Gastrointestinal disorders Abdominal Pain	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Gastrointestinal disorders Constipation	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Gastrointestinal disorders Gastroesophageal Reflux Disease	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Gastrointestinal disorders Nausea	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Gastrointestinal disorders Pancreatitis	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Gastrointestinal disorders Small Intestinal Obstruction	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Gastrointestinal disorders Vomiting	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Blood and lymphatic system disorders Anemia	1.9% 2/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Blood and lymphatic system disorders Febrile Neutropenia	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Blood and lymphatic system disorders Thrombocytopenia	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
General disorders Chest Pain	1.9% 2/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
General disorders Death	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
General disorders Pyrexia	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Metabolism and nutrition disorders Dehydration	1.9% 2/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Metabolism and nutrition disorders Anorexia	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Metabolism and nutrition disorders Failure to Thrive	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Injury, poisoning and procedural complications Hip Fracture	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Injury, poisoning and procedural complications Spinal Compression Fracture	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Psychiatric disorders Mental Status Changes	1.9% 2/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Vascular disorders Hypotension	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Vascular disorders Orthostatic Hypotension	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Vascular disorders Venous Thrombosis Limb	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Endocrine disorders Hypoaldosteronism	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Musculoskeletal and connective tissue disorders Muscular Weakness	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung Neoplasm Malignant	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).
Renal and urinary disorders Renal Failure Acute	0.94% 1/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).

Other adverse events

Other adverse events
Measure	Bevacizumab n=106 participants at risk 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
Blood and lymphatic system disorders Thrombocytopenia	6.6% 7/106 • From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years).

Additional Information

Medical Communications

Hoffman-LaRoche

Phone: 800-821-8590

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER