A Study Comparing Bevacizumab Therapy With or Without Erlotinib for First-Line Treatment of Non-Small Cell Lung Cancer (ATLAS)

• All adverse events [ Time Frame: Post-chemo phase ] [ Designated as safety issue: No ]
• Serious and selected adverse events [ Time Frame: Length of study ] [ Designated as safety issue: No ]
• Study treatment discontinuation for reasons other than disease progression [ Time Frame: Length of study ] [ Designated as safety issue: No ]
• Overall survival [ Time Frame: Until death or loss to follow-up ] [ Designated as safety issue: No ]

This is a Phase IIIb, multicenter, randomized, placebo-controlled trial to evaluate the safety and efficacy of chemotherapy+bevacizumab followed by bevacizumab+erlotinib versus bevacizumab+erlotinib placebo in subjects with locally advanced or metastatic NSCLC.

• Drug: bevacizumab
  Intravenous repeating dose
• Drug: placebo
  Oral repeating dose
• Drug: erlotinib HCl
  Oral repeating dose

• Experimental: 1
  Interventions:

  • Drug: bevacizumab
  • Drug: erlotinib HCl
• Placebo Comparator: 2
  Interventions:

  • Drug: bevacizumab
  • Drug: placebo

Inclusion Criteria:

• Signed Informed Consent Form
• Histologically or cytologically confirmed NSCLC
• Advanced NSCLC or recurrent disease
• INR no greater than 1.3 and aPTT no greater than upper limits of normal (ULN) within 28 days prior to enrollment for subjects not on low molecular weight heparin or fondaparinux. Subjects on low molecular weight heparin or fondaparinux are not required to meet INR or aPTT limits. Chronic full-dose anticoagulation with warfarin is not permitted.
• 18 years of age or older
• For women of childbearing potential and sexually active men, use of an accepted and effective method of contraception (hormonal or barrier methods, abstinence) prior to enrollment and for the duration of the study

Exclusion Criteria:

• Prior systemic chemotherapy in the metastatic setting
• Treatment with an investigational or marketed agent that acts by either EGFR inhibition or anti-angiogenesis mechanisms
• Pregnancy or lactation
• Any other medical condition, including mental illness or substance abuse, deemed by the clinician to be likely to interfere with a subject's ability to provide informed consent, cooperate, and participate in the study, or to interfere with the interpretation of the results
• Active infection or a fever within 3 days of enrollment
• Active malignancy other than lung cancer
• Radiation therapy to sites other than whole brain within 14 days prior to enrollment
• History of gross hemoptysis within 3 months prior to enrollment
• Known hypersensitivity to any of the components of cytotoxic chemotherapy combinations, bevacizumab, or tyrosine kinase inhibitors
• Inadequately controlled hypertension
• Unstable angina or New York Heart Association Grade II or greater CHF
• Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to enrollment
• History of myocardial infarction within 6 months prior to enrollment
• History of stroke within 6 months prior to enrollment
• Symptomatic peripheral vascular disease within 6 months prior to enrollment
• Evidence of bleeding diathesis or coagulopathy
• Serious, non-healing wound, ulcer, or bone fracture
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment; anticipation of need for major surgical procedure during the course of the study
• Current, recent, or planned participation in an experimental drug study other than this Genentech-sponsored bevacizumab/erlotinib study
• Progressive neurologic symptoms in subjects with a history of brain metastases
• History of significant vascular disease (e.g., aortic aneurysm)