Clinical trial NCT03109873: Metformin Hydrochloride in Affecting Cytokines and Exosomes in Patients With Head and Neck Cancer
Official title: Pilot Study of Metformin in Head and Neck Cancer and Its Effect on Proinflammatory Cytokines and Exosomes Implicated in Acute and Chronic Toxicity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Larynx
Lip
Oral Cavity
Pharynx
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
First posted: 2017-04-12
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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).

Eligibility criteria: 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

Primary outcomes:
measure: Cytokine/Chemokine Profile
timeFrame: Up to 1 year
Secondary outcomes:
measure: Mucositis Assessed Using WHO Classification
timeFrame: Up to 1 year
measure: Objective Response Rate
timeFrame: Up to 2 years
measure: Exosome Profile
timeFrame: Up to 1 year
measure: Incidence of Toxicities
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Sidney Kimmel Cancer Center at Thomas Jefferson University
state: Pennsylvania
Study officials:
affiliation: Sidney Kimmel Cancer Center at Thomas Jefferson University
name: Adam Luginbuhl, MD
role: PRINCIPAL_INVESTIGATOR
References: