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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.

Tracking Information
First Submitted Date  ICMJE April 7, 2006
First Posted Date  ICMJE April 11, 2006
Results First Submitted Date  ICMJE March 18, 2011
Results First Posted Date  ICMJE June 22, 2011
Last Update Posted Date August 8, 2011
Study Start Date  ICMJE March 2006
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 3, 2011)
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 [ Time Frame: From the first administration of bevacizumab until 60 days after discontinuation of bevacizumab treatment was reported (up to 2 years) ]
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
Original Primary Outcome Measures  ICMJE
 (submitted: April 7, 2006)
To assess the rate of symptomatic NCI CTCAE v3.0 Grade >=2 CNS hemorrhage during bevacizumab therapy with first- or second-line systemic therapy in subjects with non-squamous NSCLC with previously treated brain metastases.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 3, 2011)
  • Overall Survival (OS) in First-line Setting [ Time Frame: Time from enrollment to death from any cause (up to 2 years) ]
    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] [ Time Frame: Time from enrollment to death from any cause (up to 2 years) ]
    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 [ Time Frame: Time from enrollment to death from any cause (up to 2 years) ]
    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] [ Time Frame: Time from enrollment to death from any cause (up to 2 years) ]
    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 [ Time Frame: From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years) ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 7, 2006)
  • 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
  • to describe the incidence of selected NCI CTCAE adverse events in all subjects.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non-Small Cell Lung Cancer
  • Brain Neoplasms
Intervention  ICMJE
  • Drug: bevacizumab
    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.
    Other Name: Avastin
  • Drug: First-Line Chemotherapy Agents

    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.

  • Drug: Second-Line Chemotherapy Agents

    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.

Study Arms  ICMJE Experimental: bevacizumab
Interventions:
  • Drug: bevacizumab
  • Drug: First-Line Chemotherapy Agents
  • Drug: Second-Line Chemotherapy Agents
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 26, 2009)
115
Original Enrollment  ICMJE
 (submitted: April 7, 2006)
110
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT00312728
Other Study ID Numbers  ICMJE AVF3752g
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jane Huang, M.D., Study Director, Genentech, Inc.
Study Sponsor  ICMJE Genentech, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: David Karlin, M.D. Genentech, Inc.
PRS Account Genentech, Inc.
Verification Date August 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP