AVAPERL1 Study: A Study of Avastin (Bevacizumab) With or Without Pemetrexed as Maintenance Therapy After Avastin in First Line in Patients With Non-Squamous Non-Small Cell Lung Cancer

• Response rate, disease control rate,duration of response, overall survival [ Time Frame: tumour assessment before cycle 3, at 2nd cycle of maintenance therapy and every 9 weeks thereafter ] [ Designated as safety issue: No ]
• Safety and tolerability: AEs, laboratory parameters [ Time Frame: throughout study, laboratory assessments every 3 weeks ] [ Designated as safety issue: No ]
• Quality of life [ Time Frame: EORTC-QLQ assessments every 2 cycles ] [ Designated as safety issue: No ]

This open-label study will assess the efficacy and safety of Avastin with or without pemetrexed as maintenance therapy in patients with advanced, metastatic or recurrent non-small cell lung cancer. In Part 1, patients will receive 4 cycles of treatment with Avastin (7.5mg/kg iv) plus cisplatin (75mg/m2 iv) plus pemetrexed (500mg/m2 iv) on day 1 of each 3-week cycle. In Part 2, patients responding to treatment will be randomized to receive further treament cycles of Avastin (7.5mg/kg iv every 3 weeks) with or without pemetrexed (500mg/m2 iv every 3 weeks). Anticipated time on study treatment is until disease progression. Target sample size is <500 individuals.

• Drug: bevacizumab [Avastin]
  7.5mg/kg iv on day 1 of each 3-week cycle
• Drug: pemetrexed
  500mg/m2 iv on day 1 of each 3-week cycle
• Drug: cisplatin
  75mg/kg iv on day 1 of each 3-week cycle

• Experimental: Part 1
  Interventions:

  • Drug: bevacizumab [Avastin]
  • Drug: pemetrexed
  • Drug: cisplatin
• Experimental: Part 2A
  Intervention: Drug: bevacizumab [Avastin]
• Active Comparator: Part 2B
  Interventions:

  • Drug: bevacizumab [Avastin]
  • Drug: pemetrexed

Inclusion Criteria:

• adults >/=18 years of age
• inoperable, locally advanced, metastatic or recurrent non-squamous NSCLC
• at least 1 measurable lesion meeting RECIST criteria
• ECOG performance status 0-2
• adequate hematological, liver and renal function

Exclusion Criteria:

• prior chemotherapy or treatment with another systemic anti-cancer agent
• malignancies other than NSCLC within 5 years prior to randomization, except for adequately treated cracinoma in situ of the cervix, basal or squameous cell skin cancer, localized prostate cancer or DCIS
• evidence of tumour invading major blood vessels
• current or recent use of aspirin (>325mg/day) or full-dose anticoagulants or thrombolytic agents for therapeutic purposes
• history of haemoptysis >/=grade 2
• clinically significant cardiovascular disease