A Study of Avastin (Bevacizumab) Versus Placebo in Combination With Carboplatin/Paclitaxel) in Patients With Advanced or Recurrent Non-Squamous Non-Small Cell Lung Cancer Who Have Not Received Previous Chemotherapy

• Overall survival (OS) [ Time Frame: approximately 48 months ] [ Designated as safety issue: No ]
• 1-year survival rate [ Time Frame: approximately 30 months ] [ Designated as safety issue: No ]
• Overall response rate (ORR): complete response + partial response [ Time Frame: approximately 24 months ] [ Designated as safety issue: No ]
• Duration of response [ Time Frame: approximately 24 months ] [ Designated as safety issue: No ]
• Safety: Incidence of adverse events [ Time Frame: approximately 48 months ] [ Designated as safety issue: No ]
• Correlation of baseline vascular endothelial growth factor (VEGF) plasma levels with clinical outcome (PFS/OS/ORR) [ Time Frame: approximately 48 months ] [ Designated as safety issue: No ]

This randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of Avastin (bevacizumab) versus placebo in combination with carboplatin/paclitaxel in patients with advanced or recurrent non-squamous non-small cell lung cancer who have not received prior chemotherapy for advanced disease. Patients will be randomized to receive either Avastin 15 mg/kg intravenously or placebo on Day 1 of each 3-week cycle, plus up to 6 cycles of carboplatin/paclitaxel. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs. After progression, patients in the Avastin-arm may continue to receive Avastin in combination with approved second- and third-line treatment at the discretion of the investigator, up to the third progression.

• Drug: bevacizumab [Avastin]
  15 mg/kg intravenously (iv) on Day 1 of each 3-week cycle
• Drug: placebo
  15 mg iv on Day 1 of each 3-week cycle
• Drug: carboplatin
  AUC 6.0 iv on Day 1 of each 3-week cycle, up to 6 cycles
• Drug: paclitaxel
  175 mg/m2 iv on Day 1 of each 3-week cycle, up to 6 cycles

• Experimental: A
  Interventions:

  • Drug: bevacizumab [Avastin]
  • Drug: carboplatin
  • Drug: paclitaxel
• Active Comparator: B
  Interventions:

  • Drug: placebo
  • Drug: carboplatin
  • Drug: paclitaxel

Inclusion Criteria:

• Adult patients, >/= 18 years of age
• Locally advanced (Stage IIIb not amenable for combined modality treatment), metastatic (Stage IV) or recurrent non-squamous non-small cell lung cancer (NSCLC)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Adequate haematological, renal and liver function

Exclusion Criteria:

• Prior chemotherapy or treatment with another systemic anti-cancer agent for the current stage of the disease (IIIb, IV or recurrent)
• Mixed non-small cell and small cell tumours or mixed adenosquamous carcinomas with a predominant squamous component
• Evidence of tumour invading major blood vessels on imaging
• CNS metastases, even if previously treated
• History of haemoptysis in the 3 months prior to enrollment
• History or evidence of inherited bleeding diathesis or coagulopathy
• Uncontrolled hypertension and/or history of hypertensive crisis or hypertensive encephalopathy
• Clinically significant cardiovascular or vascular disease
• Malignancies other than NSCLC within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or localized prostate cancer or ductal carcinoma in situ treated surgically with curative intent