A Study of Bevacizumab in Combination With First- or Second-Line Therapy in Subjects With Treated Brain Metastases Due to Non-Squamous NSCLC (PASSPORT)
Condition: Non-Small Cell Lung Cancer; Brain Neoplasms
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Brain Neoplasms
Intervention: bevacizumab; First-Line Chemotherapy Agents; Second-Line Chemotherapy Agents
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.; 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.; 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.
Intervention MeSH terms: Bevacizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 115.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Brain Cancer; Brain Metastases; Avastin; NSCLC; Lung Cancer; PASSPORT

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.
    

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