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Completed

NCT Number: NCT00312728

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

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.

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Key information

Conditions

Non-small Cell Lung Cancer Brain Diseases Brain Neoplasms Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Central Nervous System Diseases Central Nervous System Neoplasms Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Nervous System Diseases Nervous System Neoplasms Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Bevacizumab

Drug

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 names: Avastin

First-Line Chemotherapy Agents

Drug

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.

Second-Line Chemotherapy Agents

Drug

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 outcomes

  1. 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

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

Sponsors and collaborators

Lead sponsor

Genentech, Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2006
Primary completion
2009
Study completion
2009
First posted
Apr 11, 2006
Registry last updated
Jan 6, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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