Metformin Hydrochloride in Mitigating Side Effects of Radioactive Iodine Treatment in Patients With Differentiated Thyroid Cancer

PRIMARY OBJECTIVES:

I. To determine if treatment with metformin hydrochloride (metformin) inhibits radioactive
iodine (RAI)-induced myelosuppression and induces faster recovery of white blood cell count
to baseline values, the blood counts will be compared in the pre- and post-treatment samples.

SECONDARY OBJECTIVES:

I. Assess safety and tolerability of metformin treatment in subjects undergoing RAI treatment
for differentiated thyroid cancer.

II. To determine the effect of metformin treatment on symptoms of xerostomia, xerophthalmia
and dysgeusia as assessed by the Xerostomia Questionnaire (XQ), the modified Vanderbilt Head
and Neck Cancer Symposium Survey (version 2.0), University of Washington Quality of Life
Questionnaire, and European Organization for Research and Treatment of Cancer Quality of Life
Questionnaire (EORTCQLQ)-Head and Neck (H&N)35.

Inclusion Criteria:

- Subjects with a diagnosis of differentiated thyroid cancer who have undergone total or
near-total thyroidectomy and are candidates for iodine I-131 (I-131) treatment at
Thomas Jefferson University Hospital (TJUH) are eligible to participate

- Subjects must be diagnosed with differentiated thyroid cancer

- Patients must have previously undergone or plan to undergo thyroidectomy; for those
patients who have previously undergone surgery, pre-operative labs, including complete
blood cell count with differential must be available

- Patients who have a negative urine pregnancy test prior to enrollment. This should be
done as part of pre-admission testing prior to surgery (within 14 days of study
enrollment).

- 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 in
accordance with radioactive iodine treatment guidelines

- Subjects on metformin for any reason during the preceding 4 weeks

- Diabetic subjects are eligible if they are not taking metformin, insulin or
sulfonylureas

- Subjects who have received iodinated contrast dye. Metformin treatment can be started
the day after subjects complete iodinated contrast treatment. If a CT scan with
contrast is scheduled after screening and consent, the metformin treatment should be
stopped the day before iodinated contrast administration. Metformin can be resumed on
the day after last iodinated contrast was administered to the subject.

- Patients with history of hepatic dysfunction or hepatic disease and abnormal liver
function tests (previously documented alanine aminotransferase greater than 40 IU/dL
and/or plasma aspartate aminotransferase greater than 45 IU/d); patients who have a
history of hepatic dysfunction or hepatic disease but whose most recent liver function
tests have been documented as normal will be eligible to participate

- Patients with plasma creatinine level greater than 1.3 mg/dL

- Patients with plasma alkaline phosphatase greater than 190 IU/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 pharmacologic or
supplemental oxygen treatment

- Patients with a current history (in the past 30 days) of heavy 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.

- Patients with a systemic disease that could affect their bone marrow or peripheral
blood cells (e.g. systemic lupus erythematosus, human immunodeficiency virus
infection, rheumatoid arthritis)

- Patients who have received or will receive medication that could affect their
hematologic state (tyrosine kinase inhibitors, cytotoxic chemotherapy)

- Patients who are Non-English speaking *Note: This is due to the nature of the study
and the process for full translations of the study documents.