Back to resultsA Study of Bevacizumab in Combination With First- or Second-Line Therapy in Subjects With Treated Brain Metastases Due to Non-Squamous NSCLC (PASSPORT)
Primary Purpose
Non-Small Cell Lung Cancer, Brain Neoplasms
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
bevacizumab
First-Line Chemotherapy Agents
Second-Line Chemotherapy Agents
Sponsored by
About this trial
This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring Brain Cancer, Brain Metastases, Avastin, NSCLC, Lung Cancer, PASSPORT
Eligibility Criteria
Inclusion Criteria: Signed informed consent Histologically or cytologically confirmed NSCLC except for squamous cell carcinoma Treated brain metastases without evidence of progression or hemorrhage after treatment, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period Appropriateness for first- or second-line systemic therapy for advanced NSCLC Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Age ≥ 18 years For women of childbearing potential and sexually active males, use of an accepted and effective method of contraception (e.g., hormonal or barrier methods, abstinence) prior to study entry and for the duration of the study Exclusion Criteria: Brain biopsy/neurosurgical procedure performed within 3 months prior to Day 1 Progressive neurologic symptoms Active malignancy other than lung cancer Current, recent, or planned participation in an experimental drug study Prior treatment with an investigational or marketed agent that acts by anti-angiogenesis mechanisms Gross hemoptysis within 3 months prior to Day 1 Inadequately controlled hypertension Unstable angina or New York Heart Association Grade II or greater congestive heart failure (CHF) Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1 Myocardial infarction within 6 months prior to Day 1 Stroke within 6 months prior to Day 1 Active symptomatic peripheral vascular disease within 6 months prior to Day 1 History of significant vascular disease Evidence of bleeding diathesis or coagulopathy Known hypersensitivity to any components of bevacizumab Inadequate organ function Serious non-healing wound, ulcer, or bone fracture Urine protein/creatinine (UPC) ratio of ≥ 1.0 Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, or anticipation of need for major surgical procedure during the course of the study Pregnancy or lactation Known evidence of disseminated intravascular coagulation (DIC) Active infection or fever > 38.5°C within 3 days prior to Day 1 Any other medical condition (including mental illness or substance abuse) deemed by the clinician to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
bevacizumab
Arm Description
Outcomes
Primary Outcome Measures
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
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
Secondary Outcome Measures
Overall Survival (OS) in First-line Setting
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.
Number of Participants With Overall Survival (OS) in First-line Setting [1-Year or More Survival]
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.
OS in First-line and Second-line Settings
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.
Number of Participants With OS in First-line and Second-line Settings [1-Year or More Survival]
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.
Number of Participants With Selected Adverse Events
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00312728
Brief Title
A Study of Bevacizumab in Combination With First- or Second-Line Therapy in Subjects With Treated Brain Metastases Due to Non-Squamous NSCLC (PASSPORT)
Official Title
A Phase II Trial of Bevacizumab in Combination With First- or Second-Line Therapy in Subjects With Treated Brain Metastases Due to Non-Squamous Non-Small Cell Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
March 2006 (Actual)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
June 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
5. Study Description
Brief Summary
This was an open-label, multicenter, single-arm, Phase II trial of bevacizumab combined with first- or second-line therapy in patients with metastatic non-squamous non-small cell lung cancer (NSCLC) with previously treated central nervous system (CNS) metastases. A total of 115 patients enrolled in the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer, Brain Neoplasms
Keywords
Brain Cancer, Brain Metastases, Avastin, NSCLC, Lung Cancer, PASSPORT
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
115 (Actual)
8. Arms, Groups, and Interventions
Arm Title
bevacizumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
15 mg/kg intravenously (IV) on the first day of each 21- to 28-day cycle (± 4 days); the interval between infusions could not be < 17 days, but could extend beyond 28 days if chemotherapy was delayed to allow recovery from toxicity.
Intervention Type
Drug
Intervention Name(s)
First-Line Chemotherapy Agents
Intervention Description
Carboplatin, cisplatin, paclitaxel, docetaxel, gemcitabine, vinorelbine, pemetrexed, or erlotinib administered on Day 1 of every 21-day cycle except gemcitabine, which was administered on Days 1 and 8 of every cycle. Agents were administered as a platinum doublet, or erlotinib alone, at the investigator's discretion. Chemotherapy was administered for a total of 6 planned cycles (up to 8 cycles with prior approval from the Medical Monitor), followed by single-agent bevacizumab therapy. The chemotherapy regimen was to be consistent throughout the study. Erlotinib was administered orally daily.
All agents were dosed and administered per institutional standards using the respective package insert as a guideline.
Intervention Type
Drug
Intervention Name(s)
Second-Line Chemotherapy Agents
Intervention Description
Erlotinib, pemetrexed, docetaxel, or chemotherapy at the investigator's discretion. Erlotinib was administered orally daily; pemetrexed and docetaxel were administered IV on Day 1 of every 21-day cycle. Single-agent bevacizumab therapy could be continued at the investigator's discretion if the second-line agent was discontinued.
All agents were dosed and administered per institutional standards using the respective package insert as a guideline.
Primary Outcome Measure Information:
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
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)
Secondary Outcome Measure Information:
Title
Overall Survival (OS) in First-line Setting
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)
Title
Number of Participants With Overall Survival (OS) in First-line Setting [1-Year or More Survival]
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)
Title
OS in First-line and Second-line Settings
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)
Title
Number of Participants With OS in First-line and Second-line Settings [1-Year or More Survival]
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)
Title
Number of Participants With Selected Adverse Events
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed informed consent
Histologically or cytologically confirmed NSCLC except for squamous cell carcinoma
Treated brain metastases without evidence of progression or hemorrhage after treatment, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period
Appropriateness for first- or second-line systemic therapy for advanced NSCLC
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Age ≥ 18 years
For women of childbearing potential and sexually active males, use of an accepted and effective method of contraception (e.g., hormonal or barrier methods, abstinence) prior to study entry and for the duration of the study
Exclusion Criteria:
Brain biopsy/neurosurgical procedure performed within 3 months prior to Day 1
Progressive neurologic symptoms
Active malignancy other than lung cancer
Current, recent, or planned participation in an experimental drug study
Prior treatment with an investigational or marketed agent that acts by anti-angiogenesis mechanisms
Gross hemoptysis within 3 months prior to Day 1
Inadequately controlled hypertension
Unstable angina or New York Heart Association Grade II or greater congestive heart failure (CHF)
Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1
Myocardial infarction within 6 months prior to Day 1
Stroke within 6 months prior to Day 1
Active symptomatic peripheral vascular disease within 6 months prior to Day 1
History of significant vascular disease
Evidence of bleeding diathesis or coagulopathy
Known hypersensitivity to any components of bevacizumab
Inadequate organ function
Serious non-healing wound, ulcer, or bone fracture
Urine protein/creatinine (UPC) ratio of ≥ 1.0
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, or anticipation of need for major surgical procedure during the course of the study
Pregnancy or lactation
Known evidence of disseminated intravascular coagulation (DIC)
Active infection or fever > 38.5°C within 3 days prior to Day 1
Any other medical condition (including mental illness or substance abuse) deemed by the clinician to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Karlin, M.D.
Organizational Affiliation
Genentech, Inc.
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
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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