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

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

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.

Study Overview

• Status: Completed
• Conditions: Larynx; Oral Cavity; Lip; Pharynx
• Intervention / Treatment: Other: Placebo; Drug: Metformin Hydrochloride; Radiation: External Beam Radiation Therapy

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Sidney Kimmel Cancer Center at Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (EBRT, metformin hydrochloride); 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.	Drug: Metformin Hydrochloride; Given orally; Other Names: Cidophage; Dimefor; Glucoformin; Glucophage ER; 1,1-Dimethylbiguanide Hydrochloride; 1115-70-4; 91485; Radiation: External Beam Radiation Therapy; Undergo External Beam Radiation Therapy; Other Names: EBRT; Definitive Radiation Therapy; External Beam RT
Placebo Comparator: Arm II (EBRT, placebo); 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.	Other: Placebo; Given orally; Radiation: External Beam Radiation Therapy; Undergo External Beam Radiation Therapy; Other Names: EBRT; Definitive Radiation Therapy; External Beam RT

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Investigators: Principal Investigator: Adam Luginbuhl, MD, Sidney Kimmel Cancer Center at Thomas Jefferson University

Publications and helpful links

Helpful Links

• Thomas Jefferson University Hospital
• Sidney Kimmel Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2017
• Primary Completion (Actual): July 31, 2020
• Study Completion (Actual): July 31, 2020

Study Registration Dates

• First Submitted: March 6, 2017
• First Submitted That Met QC Criteria: April 5, 2017
• First Posted (Actual): April 12, 2017

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 28, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Physiological Effects of Drugs; Hypoglycemic Agents; Metformin
• Other Study ID Numbers: 16D.639; JT 9410 (Other Identifier: JeffTrial Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes