Metformin Hydrochloride in Affecting Cytokines and Exosomes in Patients With Head and Neck Cancer

Study Overview
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Brief Summary
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This pilot clinical trial studies how well metformin hydrochloride works in affecting cytokines and exosomes in patients with head and neck cancer. Metformin hydrochloride may reduce the metabolic activity of cancer cells and of surrounding supportive tissues.

Detailed Description
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PRIMARY OBJECTIVES: I. To assess the capacity of metformin hydrochloride (metformin) to alter the cytokine and exosome profiles. II. To assess the capacity of metformin to mitigate known side effects of external beam radiation therapy including inflammation, mucositis, dysphagia, xerostomia, and fatigue. SECONDARY OBJECTIVES: I. Assess safety and tolerability of metformin treatment in subjects undergoing external beam radiation treatment for head and neck cancer. II. To determine the effect of metformin treatment on symptoms of xerostomia as assessed by the Xerostomia Questionnaire (XQ). III. To determine the effect of metformin treatment on symptoms of mucositis as assessed by World Health Organization (WHO) classification. IV. To determine the effect of metformin treatment on symptoms of dysphagia as assessed by the MD Anderson Dysphagia Inventory. V. To determine the effect of metformin treatment on symptoms of fatigue as assess by the Multidimensional Fatigue Inventory (MFI).

Official Title
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Pilot Study of Metformin in Head and Neck Cancer and Its Effect on Proinflammatory Cytokines and Exosomes Implicated in Acute and Chronic Toxicity

Conditions
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Larynx, Lip, Oral Cavity, Pharynx

Intervention / Treatment
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* Radiation: External Beam Radiation Therapy
* Drug: Metformin Hydrochloride
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with a diagnosis of head and neck cancer biopsy proven, and who are candidates for radiation therapy All subjects must be able to comprehend and sign a written informed consent document. Exclusion Criteria: Subjects who are pregnant or may become pregnant during metformin administration; pregnancy testing will be done in conjunction with preradiation protocols Subjects on metformin for any reason during the preceding 4 weeks Diabetic subjects are eligible if they are not taking metformin or insulin Subjects who have received iodinated contrast dye must wait 12 hours prior to starting Metformin. If a CT scan with contrast is scheduled after screening and consent, the metformin cannot be taken until after the CT with contrast has been completed and they have waited 12 hours. Patients with plasma creatinine level greater than 1.3 mg/dL Patients with plasma bicarbonate less than 22 mEq/L or history of lactic or any other metabolic acidosis Patients with history of congestive heart failure Patients with myocardial ischemia or peripheral muscle ischemia Patients with sepsis or severe infection Patients with history of lung disease currently requiring any supplemental oxygen treatment Patients scheduled for radiation less than 6 days from enrollment Patients with history of hepatic dysfunction or hepatic disease and abnormal liver function tests; patients who have a history of hepatic dysfunction or hepatic disease and normal liver function tests will be eligible to participate Patients with a current history (in the past 30 days) of heaving drinking which is defined in accordance with CDC definition as more than 8 drinks per week for women and more than 15 drinks per week for men. A standard drink contains .6 ounces of pure alcohol. Generally, this amount of pure alcohol is found in 12-ounces of beer, 8-ounces of malt liquor, 5-ounces of wine, 1.5-ounces or a shot of 80-proof distilled spirits or liquor (e.g., gin, rum, vodka, or whiskey). While on study, patients should limit their alcohol consumption to no more than 8 drinks per week for women and no more than 15 drinks per week for men. Patients who feel they cannot comply with this recommendation are not eligible. All medications are permitted except those that are contraindicated with metformin under current Food and Drug Administration (FDA) recommendations

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (EBRT, metformin hydrochloride)<br>Patients undergo External Beam Radiation Therapy (EBRT). Beginning 1 week prior to start of EBRT, patients receive metformin hydrochloride PO QD for 3 days and BID thereafter until 2 weeks after completion of EBRT. | Radiation: External Beam Radiation Therapy<br>* Undergo External Beam Radiation Therapy<br>* Other names: External Beam RT;Drug: Metformin Hydrochloride<br>* Given orally<br>* Other names: Dimefor;|
| Placebo Comparator: Arm II (EBRT, placebo)<br>Patients undergo External Beam Radiation Therapy (EBRT). Beginning 1 week prior to start of EBRT, patients receive placebo PO QD for 3 days and BID thereafter until 2 weeks after completion of EBRT. | Radiation: External Beam Radiation Therapy<br>* Undergo External Beam Radiation Therapy<br>* Other names: External Beam RT;Other: Placebo<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cytokine/Chemokine Profile | Mixed effects linear regression will be used to model longitudinal measurements of each cytokine. | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mucositis Assessed Using WHO Classification | Analysis will be primarily descriptive. The distribution of swallowing function and mucositis scores will be summarized by arm using means, medians, standard deviations, and ranges. | Up to 1 year | 
| Objective Response Rate | The objective response rate will be estimated by arm along with an exact 95% binomial confidence interval | Up to 2 years | 
| Exosome Profile | Longitudinal measurements of exosomes will also be modeled using mixed effects linear regression. This analysis is treated as separate from the cytokine questions and the p-value will not be adjusted. | Up to 1 year | 
| Incidence of Toxicities | Evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 | Up to 2 years |