Metformin in Non Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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The goal of this clinical research study is to learn if giving metformin in combination with radiation therapy is more effective than radiation therapy alone. In this study, participants will receive either metformin or a placebo. A placebo is not a drug. It looks like the study drug but is not designed to treat any disease or illness. It is designed to be compared with a study drug to learn if the study drug has any real effect. This is an investigational study. Metformin is FDA approved for the treatment of diabetes. Its use in this study to be given with radiation therapy to treat lung cancer is investigational. The study doctor can explain how the study drug is designed to work. Up to 70 participants will be enrolled in this study. All will take part at MD Anderson.

Official Title
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Tumor Mutation Status Will Predict Metabolic Response to Metformin in Non Small Cell Lung Cancer (NSCLC)

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Metformin
* Other: Placebo
* Radiation: Stereotactic body Radiotherapy (SBRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with pathologic diagnosis of lung NSCLC or squamous cell carcinoma. Patients are to be treated with hypofractionated RT. Patient is not a surgical candidate due to medical comorbidities determined by a thoracic surgeon or patient refusal Patient plans to receive treatment at MD Anderson Patients must sign informed consent Patient must have adequate renal function within 30 days prior to registration, defined as serum creatinine within normal institutional limits or creatinine clearance at least 60 ml/min Exclusion Criteria: Patient has: random glucose >200 mg/dl or is taking an oral hypoglycemic agent or insulin at the time of study entry Patient has a history of lactic acidosis, chronic kidney disease or a creatinine >/= 1.2 mg/dl Women who are pregnant or breast feeding, as treatment involves unforeseeable risks to the participant, embryo, fetus, or nursing infant Patients with history of allergic reaction to metformin

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stereotactic body Radiotherapy (SBRT) + Metformin<br>Participants randomized to Metformin treatment receive Metformin for 3 weeks prior to SBRT treatment and for 1 week during SBRT treatment. Metformin administered at a dose of 2000 mg by mouth in divided dose daily (500 mg am, 1000 mg noon, 500 mg pm). To reduce GI toxicity, participants start Metformin at 1000 mg daily in a divided dose (500mg am, 500 mg pm) for 1 week. SBRTdelivered per standard of care practice. | Drug: Metformin<br>* Metformin treatment given at a dose of 2000 mg by mouth in divided dose daily (500 mg am, 1000 mg noon, 500 mg pm). To reduce GI toxicity, participants start Metformin at 1000 mg daily in a divided dose (500mg am, 500 mg pm) for 1 week.<br>* Other names: Metformin ER;Radiation: Stereotactic body Radiotherapy (SBRT)<br>* SBRT delivered per standard of care practice as determined by participant's physician.<br>* Other names: XRT;|
| Placebo Comparator: Stereotactic Body Radiotherapy (SBRT) + Placebo<br>Participants randomized to placebo treatment 3 weeks prior to SBRT treatment and for 1 week during SBRT treatment. Placebo administered by mouth three times a day. SBRT delivered per standard of care practice. | Other: Placebo<br>* Placebo treatment given 3 weeks prior to SBRT treatment and for 1 week during SBRT treatment. Placebo administered by mouth three times a day.<br>* Other names: Sugar pill;Radiation: Stereotactic body Radiotherapy (SBRT)<br>* SBRT delivered per standard of care practice as determined by participant's physician.<br>* Other names: XRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RECIST and PERCIST Tumor Response | The primary objective is the effect of metformin on response in NSCLC patients treated with hypofractionated RT. All patients will receive FDG-PET/CT scan at baseline (prior to metformin start), prior to RT and at 6 months (+/- 30 days) following RT. PET/CT imaging using [18F]-2-fluoro-2-deoxyglucose positron emission tomography (18F-FDG), using a standard approved radiopharmaceutical dose and administration selected by the nuclear medicine physician (120 min). Response will be determined at 6 months post-treatment via relative change from pre-treatment tumor by Response Evaluation Criteria in Solid Tumor (RECIST) by complete response (CR), partial response (PR) and stable disease (SD) and PET Response Criteria in Solid Tumors (PERCIST) by stable metabolic disease (SMD), progressive metabolic disease (PMD) and complete metabolic response(CMR). | From baseline (prior to metformin start) to Post-Radiotherapy (RT) Treatment, assessed up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung Cancer, Non small cell lung cancer, Stereotactic body radiotherapy, SBRT, XRT, Radiation therapy, Metformin, Metformin ER, Placebo, Sugar pill, Lung adenocarcinoma, Genotypes, Genetic mutations