Pemetrexed, Carboplatin, and Bevacizumab as First-Line Therapy in Treating Older Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
Condition: Lung Cancer
MeSH terms: Lung Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as carboplatin, work in different ways to stop
      the growth of tumor cells, either by killing the cells or by stopping them from dividing.
      Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways.
      Some block the ability of tumor cells to grow and spread. Others find tumor cells and help
      kill them or carry tumor-killing substances to them. Giving pemetrexed together with
      carboplatin and bevacizumab may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving pemetrexed together with carboplatin
      and bevacizumab works as first-line therapy in treating older patients with stage IIIB or
      stage IV non-small cell lung cancer.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To estimate the progression-free survival at 6 months in elderly patients with advanced
           nonsquamous cell non-small cell lung cancer treated with pemetrexed disodium,
           carboplatin, and bevacizumab as first-line therapy.

      Secondary

        -  To assess the adverse events profile and safety of this regimen in these patients.

        -  To estimate the confirmed antitumor response rate, as defined by RECIST criteria, and
           the overall survival of these patients.

        -  To compare the quality of life (QOL) of patients treated with this regimen vs the QOL of
           younger patients.

        -  To correlate QOL with toxicities, as defined by NCI CTCAE v3.0 criteria.

      Tertiary

        -  To evaluate polymorphisms in the genes that encode proteins involved in the cellular
           transport, activation, and cytotoxic activity of pemetrexed disodium and evaluate their
           relationship with treatment toxicity/efficacy and patient QOL.

        -  To evaluate polymorphisms in the genes involved in blood pressure regulation and their
           relationship with susceptibility to hypertension induced by anti-VEGF therapy.

      OUTLINE: This is a multicenter study.

      Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and
      bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6
      courses in the absence of disease progression or unacceptable toxicity. Patients with stable
      disease or partial or complete response after 6 courses may continue to receive pemetrexed
      disodium and bevacizumab every 21 days in the absence of disease progression or unacceptable
      toxicity.

      Tissue and blood samples are collected at baseline for pharmacogenetic analysis. Blood
      samples are used to evaluate functionally relevant polymorphisms in the genes that encode
      proteins involved in the transport and activation of pemetrexed disodium and in the genes
      that encode proteins involved in susceptibility to hypertension induced by bevacizumab.
      Tissue samples are used to evaluate expression and polymorphisms in pemetrexed disodium
      target genes (TS, DHFR, and GARFT).

      Quality of life is assessed at baseline and periodically during study.

      After completion of study therapy, patients are followed periodically for up to 5 years.
    

Intervention name(s): bevacizumab; carboplatin; pemetrexed disodium
Intervention type(s): Biological; Drug; Drug
Intervention MeSH terms: Bevacizumab; Carboplatin; Pemetrexed
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; recurrent non-small cell lung cancer; adenocarcinoma of the lung; adenosquamous cell lung cancer