Combination of Metformin With Gefitinib to Treat NSCLC
Condition: NSCLC; EGFR Gene Amplification; Advanced Cancer; Stage IIIB NSCLC; Stage IV NSCLC
MeSH terms: Carcinoma, Non-Small-Cell Lung
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine whether metformin in combination with gefitinib are
      effective in patients with previously untreated advanced or metastatic Non-Small-Cell Lung
      cancer with epidermal growth factor receptor (EGFR) mutations
    

Detailed description: 
      Primary Objectives: To determine the 1 year progression-free survival (PFS) of the
      combination of metformin and gefitinib in patients who harbors EGFR-mutant with previously
      untreated advanced or metastatic pulmonary adenocarcinoma.

      Secondary Objectives:

      A. To evaluate the response to therapy and overall survival of the combination of metformin
      with gefitinib in patients who harbors EGFR-mutant with previously untreated advanced or
      metastatic pulmonary adenocarcinoma.

      B. To acquire preliminary data regarding the effects of metformin on interleukin-6 (IL-6)
      levels in tumor and serum.

      Treatment will be administered on an outpatient basis. Metformin starting at a dose of 500 mg
      twice a day, orally with meals. After one week, increase the dose of metformin to 1000 mg as
      the first dose of the day and 500 mg as the second dose. After another week, increase to 1000
      mg of metformin two times a day. Metformin treatment will be initiated one week before
      beginning gefitinib, if possible, but gefitinib administration will not be delayed for
      metformin loading.

      Gefitinib will be administered 250mg QD continuously. Metformin will be administered
      continuously, beginning one week before beginning gefitinib, if possible, but tyrosine kinase
      inhibitors (TKI) will not be delayed for metformin loading.

      Maintenance Therapy Patients responding to this therapy will be maintained with metformin
      (1000 mg twice daily) and gefitinib.

      Duration of Therapy

      In the absence of treatment delays due to adverse events, treatment may continue until one of
      the following criteria applies:

        1. Disease progression,

        2. Intercurrent illness that prevents further administration of treatment,

        3. Unacceptable adverse events(s),

        4. Patient decides to withdraw from the study, or

        5. General or specific changes in the patient's condition render the patient unacceptable
           for further treatment in the judgment of the investigator.
    

Intervention name(s): Gefitinib and Metformin; Gefitinib and placebo
Intervention type(s): Drug; Drug
Intervention description(s): Gefitinib will be administered once every day. If subject has complete response, partial response, stable disease, or unacceptable toxicity.; Gefitinib will be administered once every day. If subject has complete response, partial response, stable disease, or unacceptable toxicity.
Intervention MeSH terms: Metformin; Gefitinib
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: NSCLC; TKIs; Metformin; PFS; overall survival; IL-6