Primary Objectives~To determine the 1 year progression-free survival (PFS) of the combination of metformin and standard chemotherapy in patients 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 standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma.~B. To determine whether LKB1 gene status in tumors is a significant determinant of response when metformin is added to the therapy C. To acquire preliminary data regarding the effects of metformin on uptake of fluorodeoxyglucose in tumor and normal tissues.~Treatment will be administered on an outpatient basis.~Induction Therapy (Step 1, Cycles 1-4)~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 chemotherapy, if possible, but chemotherapy will not be delayed for metformin loading.~Paclitaxel 200 mg/m2 IV over 3 hours. For Paclitaxel pre-medication information~Carboplatin AUC = 6 mg/ml IV over 15 - 30 minutes, immediately following paclitaxel infusion~Bevacizumab 15 mg/kg IV infusion over 30 - 90 minutes~Metformin will be administered continuously, beginning one week before beginning chemotherapy, if possible, but chemotherapy will not be delayed for metformin loading. The other three drugs (paclitaxel, carboplatin, and bevacizumab) will be administered on day 1 of each 21 day cycle.~Maintenance Therapy~Patients responding to this therapy will be maintained with metformin (1000 mg twice daily) and bevacizumab (15 mg/kg IV over 30-90 minutes on day 1 of each 21-day cycle).~Duration of Therapy~In the absence of treatment delays due to adverse events, treatment may continue until one of the following criteria applies:~Disease progression,~Intercurrent illness that prevents further administration of treatment,~Unacceptable adverse events(s),~Patient decides to withdraw from the study, or~General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator.
To determine the 1 year progression-free survival (PFS) of the combination of metformin and standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma.