Metformin as a Chemoprevention Agent in Non-small Cell Lung Cancer

• Number of Participants Screened [ Designated as safety issue: No ]
  To evaluate the feasibility of patient randomization and accrual in a pilot study of metformin versus observation following resection of stage IB-IIIA lung squamous cell cancer for patients with coincident bronchial dysplasia by collecting data on the number of participants screened.
• The Number of Participants Enrolled [ Designated as safety issue: No ]
  To evaluate the feasibility of patient randomization and accrual in a pilot study of metformin versus observation following resection of stage IB-IIIA lung squamous cell cancer for patients with coincident bronchial dysplasia by collecting data on the number of participants screened.
• The Amount of Tissue Collected [ Designated as safety issue: No ]
  To evaluate the feasibility of tissue collection in a pilot study of metformin versus observation following resection of stage IB-IIIA lung squamous cell cancer for patients with coincident bronchial dysplasia by collecting data on the amount of tissue collected.

• Frequency of Bronchial Dysplasia [ Designated as safety issue: No ]
  To identify and evaluate the frequency of bronchial dysplasia in patients undergoing resection of non-small cell lung cancer.
• Effects of Metformin on Ki67 [ Designated as safety issue: No ]
  To evaluate the effects of metformin on Ki67 staining in normal bronchial epithelium and in the progression of squamous dysplasia in patients with resected non-small cell lung cancer.
• Genomic Alterations [ Designated as safety issue: No ]
  To evaluate genomic alterations associated with the progression of squamous dysplasia, and the resulting effects of metformin administration.

The purpose of this study is to learn whether it is better to receive the drug Metformin with standard of care for lung cancer or just standard of care.

Patients will be identified and enrolled from Thoracic Surgical Clinics. A preoperative bronchoscopy will be performed to obtain systematic bronchial biopsies from defined proximal airway sites. Patients will then undergo surgical resection and tumor tissue and normal lung specimens collected. For patients with bronchial dysplasia postoperatively, starting less than 90 days from the time of surgery, patients will be randomized to receive either 850 mg po BID of metformin or observation. Metformin dosing will include a 4 week ramp up of 850 mg po daily prior to starting the BID dose. Adjuvant platinum-based chemotherapy will be applied at the discretion of treating physicians. Patients found to have bronchial dysplasia at the time of bronchoscopy will undergo follow up bronchoscopy and tissue sampling at 6 months follow up.

• Lung Neoplasms
• Carcinoma, Non-Small-Cell Lung

• Drug: Metformin
  Other Name: Glucophage
• Other: Placebo Comparator
  Standard of Care Observation

• Active Comparator: Metformin
  Metformin 850mg BID
  Intervention: Drug: Metformin
• Placebo Comparator: Observation
  Standard of Care Observation
  Intervention: Other: Placebo Comparator

Inclusion Criteria

• Suspected or biopsy proven Stage IB-IIIA NSCLC
• Coincident bronchial dysplasia and/or carcinoma in situ from at least 1 non-resected location
• Medically fit for surgical resection (based on surgeon assessment)
• Current or prior smoker
• Age > 18 years old
• Both Male and Female
• Willing and able to consent to study, undergo study interventions, and take study drug
• ECOG performance status 0, 1, 2

Exclusion Criteria

• Prior neoadjuvant therapy
• Existing untreated or prior cancer <5 years from diagnosis
• Diabetic
• Currently taking metformin or other diabetic drugs
• Current or previous congestive heart failure, renal failure or liver failure
• Creatinine in Women of 1.4 or greater and Creatinine in Men of 1.5 or greater