A Phase II, Randomized, Placebo Controlled Study to Evaluate the Efficacy of the Combination of Gefitinib and Metformin in Patients With Locally Advanced and Metastatic Non-Small-Cell-Lung-Cancer
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.
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
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.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
One year progression-free survival (PFS) of the patients.
Yong He, MD
Daping Hospital, Third Military Medical University
China: Third Military Medical University