Pemetrexed Disodium With or Without Sorafenib as Second-Line Therapy in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Pemetrexed disodium and sorafenib may stop the growth of tumor cells by blocking
      some of the enzymes needed for cell growth. Sorafenib may also stop the growth of tumor cells
      by blocking blood flow to the tumor. Giving pemetrexed disodium together with sorafenib may
      kill more tumor cells.

      PURPOSE: This randomized phase II trial is studying pemetrexed disodium and sorafenib to see
      how well they work compared with pemetrexed disodium alone as second-line therapy in treating
      patients with stage IIIB or stage IV non-small cell lung cancer.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Compare the progression-free survival of patients with stage IIIB or IV non-small cell
           lung cancer treated with pemetrexed disodium with or without sorafenib tosylate as
           second-line therapy.

      Secondary

        -  Compare the overall survival of patients treated with these regimens.

        -  Compare the tumor response rate and duration of response in patients treated with these
           regimens.

        -  Compare the toxicity profile of these regimens in these patients.

      Tertiary

        -  Assess polymorphisms and gene expression in circulating peripheral mononuclear cells and
           circulating tumor cells of pemetrexed disodium target genes and genes encoding enzymes
           involved in the transport, activation, and inactivation of pemetrexed disodium.

        -  Correlate haplotype-tagged single nucleotide polymorphisms or gene expression levels
           with intracellular levels of pemetrexed disodium polyglutamates, toxicity, and/or
           efficacy of pemetrexed disodium.

        -  Assess the expression and polymorphisms in the target genes (i.e., TS, DHFR, GARFT) and
           methylthioadenosine phosphorylase (as antibodies become available) in paraffin-embedded
           tissue and compare results to those obtained in circulating tumor tissue, correlating
           results with response.

        -  Correlate predictive markers of hypertension (e.g. pharmacogenetics, vascular
           endothelial growth factor [VEGF]-A, sVEGF receptor-1, and ADMA) with clinical toxicity
           and outcomes.

      OUTLINE: This is a randomized, multicenter study. Patients are stratified according to ECOG
      performance status (0 vs 1) and North Central Cancer Treatment Group membership. Patients are
      randomized to 1 of 2 treatment arms.

        -  Arm I: Patients receive oral sorafenib tosylate twice daily on days 1-21 and pemetrexed
           disodium IV over 10 minutes on day 1.

        -  Arm II: Patients receive pemetrexed disodium IV over 10 minutes on day 1. In both arms,
           courses repeat every 21 days in the absence of disease progression or unacceptable
           toxicity.

      Blood and tissue samples are collected for pharmacokinetic analysis and research studies.
      Gene expression assays and polymorphism studies (e.g., using polymerase chain reaction) of
      circulating peripheral blood mononuclear cells are conducted for reduced folate carrier,
      multidrug resistance-associated protein, folate receptor, BCRP, folylpolyglutamate synthase,
      MTHFR, methionine synthase, methylthioadenosine phosphorylase, TS, dihydrofolate reductase,
      GARFT, endothelial nitric oxide synthase, angiotensinogen, dimethylarginine
      dimethylaminohydrolase, vascular endothelial growth factor (VEGF), and VEGF receptor.
      Enzyme-linked immunosorbent assays and immunohistochemistry are also conducted.

      After completion of study treatment, patients are followed periodically for up to 5 years.
    

Intervention name(s): pemetrexed disodium; sorafenib tosylate
Intervention type(s): Drug; Drug
Intervention description(s): given IV; given orally
Intervention MeSH terms: Pemetrexed; Sorafenib
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; adenosquamous cell lung cancer; adenocarcinoma of the lung