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

Study Overview
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Brief Summary
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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.

Detailed Description
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Participants will need to be scheduled to undergo a surgical resection of their lung cancer at the Mayo Clinic in Rochester, Minnesota. They will be asked to provide a blood sample prior to their surgery. Samples of tumor tissue and normal lung tissue will be taken from the samples removed during your lung surgery. The tissue will be used to evaluate DNA. A skin biopsy at the edge of the incision that has already been made will be done during your surgery. We will take the skin and grow skin fibroblasts. Then we will reprogram the skin fibroblasts into induced pluripotent cells. You will be randomized into one of the study groups to either take Metformin for 6 months with your standard of care follow up or to receive standard of care follow up.

Official Title
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A Pilot Study of Metformin as a Chemoprevention Agent in Non-small Cell Lung Cancer

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

Intervention / Treatment
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* Drug: Metformin
* Other: Placebo Comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Suspected or biopsy proven Stage IA-IIIA lung squamous cell carcinoma (SCC) (must be proven SCC at the time of surgery) 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 Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2 Subject must start Metformin within 90 days of surgery. Exclusion Criteria 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 Existing untreated or prior cancer <5 years from diagnosis Received neo-adjuvant platinum-based chemotherapy or targeted therapy Receiving adjuvant platinum-based chemotherapy or targeted therapy after surgical resection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metformin<br>Metformin 850mg twice a day | Drug: Metformin<br> <br> * Other names: Glucophage;|
| Placebo Comparator: Observation<br>Standard of Care Observation | Other: Placebo Comparator<br>* Standard of Care Observation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate Feasibility of Patient Randomization, Accrual, and Tissue Collection for Study Conduction | To evaluate the feasibility of patient randomization, accrual, and tissue collection in a pilot study of metformin versus observation following resection of stage IA-IIIA lung squamous cell cancer for patients by assessing the reasons patients decline randomization, tracking accrual numbers, and tracking collected tissue and reasons why tissue was not collected. | 2 years | 
| Number of Participants With 2-year Recurrence Free Survival | To compare the 2-year recurrence free survival (RFS) rate between metformin and observation. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure Metformin Sensitivity in Induced Pluripotent Stem Cells (iPS) | To develop the metformin sensitivity index based on iPS cell line metformin sensitivity measurements from the first 20 patients randomized to the metformin arm. We will then To apply the metformin sensitivity index on the remaining 25 patients randomized to metformin and the 45 observation patients (70 patients total) to compare the 2-year RFS rate between metformin-sensitive and metformin-not-sensitive patients. | 4 years | 
| Number of Participants With Adverse Events as a Measure of Safety | To compare participant adverse events between metformin and observation arms using CTCAE version 4. | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bronchoscopy, Metformin