title: A multicenter, open-label phase II study of metformin with erlotinib in second-line therapy of stage IV non-small-cell lung cancer patients: treatment rationale and protocol dynamics of the METAL trial.
abstract: We present the rationale and study design of the METAL (METformin in Advanced Lung cancer) trial (EudraCT number: 2014-000349-59), a multicenter, open label phase II study, designed to evaluate the safety and activity of metformin combined with erlotinib as second-line therapy in patients with stage IV non-small-cell lung cancer. This is a 2-part trial, consisting of a safety run-in part followed by a phase II part. The primary end point for the first part is the maximum tolerated dose and the identification of the recommended phase II dose of metformin in combination with erlotinib. Secondary end points are the study of pharmacokinetics and the antitumor activity evaluation of the experimental combination. The primary end point of part II is the time to disease progression with the combination, and antitumor activity as a secondary end point. Based on the statistical design, we plan to enroll approximately 60 patients.
authors.affiliation: Division of Medical Oncology, Department of Clinical and Experimental Medicine and Surgery "F. Magrassi A. Lanzara", Second University of Naples, Naples, Italy.
authors.forename: Morena
authors.initials: M
authors.lastname: Fasano
authors.affiliation: Division of Medical Oncology, Department of Clinical and Experimental Medicine and Surgery "F. Magrassi A. Lanzara", Second University of Naples, Naples, Italy.
authors.forename: Carminia Maria
authors.initials: CM
authors.lastname: Della Corte
authors.affiliation: Regional Centre of Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine "L. Donatelli", Second University of Naples, Naples, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Capuano
authors.affiliation: Division of Internal Medicine, Department of Internal and Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Ferdinando Carlo
authors.initials: FC
authors.lastname: Sasso
authors.affiliation: Division of Medical Oncology, Department of Clinical and Experimental Medicine and Surgery "F. Magrassi A. Lanzara", Second University of Naples, Naples, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Papaccio
authors.affiliation: Regional Centre of Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine "L. Donatelli", Second University of Naples, Naples, Italy.
authors.forename: Liberato
authors.initials: L
authors.lastname: Berrino
authors.affiliation: Division of Medical Oncology, Department of Clinical and Experimental Medicine and Surgery "F. Magrassi A. Lanzara", Second University of Naples, Naples, Italy.
authors.forename: Fortunato
authors.initials: F
authors.lastname: Ciardiello
authors.affiliation: Division of Medical Oncology, Department of Clinical and Experimental Medicine and Surgery "F. Magrassi A. Lanzara", Second University of Naples, Naples, Italy. Electronic address: florianamorgillo@yahoo.com.
authors.forename: Floriana
authors.initials: F
authors.lastname: Morgillo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000401:mortality; D018572:Disease-Free Survival; D054796:Drug Dosage Calculations; D000069347:Erlotinib Hydrochloride; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects; D009367:Neoplasm Staging; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D000069347:Erlotinib Hydrochloride; D008687:Metformin; D011799:Quinazolines
keywords: 2-Part trial; EGFR tyrosine kinase inhibitors; Erlotinib; Metformin; Recurrent NSCLC