Thyroid
Conditions
Brief summary
This pilot clinical trial studies how will metformin hydrochloride works in mitigating the side effects of radioactive iodine treatment in patients with differentiated thyroid cancer. Metformin hydrochloride may reduce the metabolic activity of cancer cell and of surrounding supportive tissues.
Detailed description
PRIMARY OBJECTIVES: I. To evaluate 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 assess 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.
Interventions
DRUGMetformin Hydrochloride
Given Orally
OTHERRadioactive Iodine
Undergo radioactive iodine treatment
OTHERPlacebo
Given orally
Sponsors
Sidney Kimmel Cancer Center at Thomas Jefferson University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Red Blood Cell Count From Pre-Resection to Post-Resection | Up to 36 months of study duration, an average of 1.5 months | Change in red blood cell count measured from baseline to two weeks after completion of RAI, measured via standard CBC laboratory testing. Longitudinal measures of CBC will be modeled using mixed effects linear regression. Will use a linear contrast to test the null hypothesis that change from pre-resection to post-resection is the same in the control and metformin groups. |
| Serum and Salivary Exosome Profile | Up to 36 months of study duration | Will be modeled using mixed effects linear regression |
| Number of Adverse Events | Up to 36 months of study duration, an average of 1.5 months | Number of adverse events assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version v 4.0, from treatment initiation through 15 days post-treatment follow-up. |
Secondary
| Measure | Time frame |
|---|---|
| Xerostomia Assessed by Modified Vanderbilt Head and Neck Cancer Symposium Survey (Version 2.0) | Up to 36 months of study duration |
| Xerophthalmia Assessed by Modified Vanderbilt Head and Neck Cancer Symposium Survey (Version 2.0) | Up to 36 months of study duration |
| Dysgeusia Assessed by Modified Vanderbilt Head and Neck Cancer Symposium Survey (Version 2.0) | Up to 36 months of study duration |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Metformin Hydrochloride) Patients receive metformin hydrochloride PO daily for 3 days and then PO BID for up to 2 weeks after completing radioactive iodine treatment.
Metformin Hydrochloride: Given Orally
Radioactive Iodine: Undergo radioactive iodine treatment | 5 |
| Arm II (Placebo) Patients receive placebo PO daily for 3 days and then PO BID for up to 2 weeks after completing radioactive iodine treatment
Radioactive Iodine: Undergo radioactive iodine treatment
Placebo: Given orally | 7 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Arm I (Metformin Hydrochloride) | Arm II (Placebo) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 5 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 7 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 1 Participants | 4 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 7 |
| other Total, other adverse events | 5 / 6 | 4 / 7 |
| serious Total, serious adverse events | 0 / 6 | 0 / 7 |
Outcome results
Primary
Change in Red Blood Cell Count From Pre-Resection to Post-Resection
Change in red blood cell count measured from baseline to two weeks after completion of RAI, measured via standard CBC laboratory testing. Longitudinal measures of CBC will be modeled using mixed effects linear regression. Will use a linear contrast to test the null hypothesis that change from pre-resection to post-resection is the same in the control and metformin groups.
Time frame: Up to 36 months of study duration, an average of 1.5 months
Population: Participants with both pre- and post-treatment CBC values were included in the analysis. Due to missing laboratory data, 4 participants in Arm 1 (Metformin) and 3 participants in Arm 2 (Placebo) were analyzable for this outcome.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm I (metformin hydrochloride) | Change in Red Blood Cell Count From Pre-Resection to Post-Resection | -0.11 million cells per microliter |
| Arm II (placebo) | Change in Red Blood Cell Count From Pre-Resection to Post-Resection | -0.63 million cells per microliter |
p-value: 0.40495% CI: [-1.26, 2.29]t-test, 2 sided
Primary
Number of Adverse Events
Number of adverse events assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version v 4.0, from treatment initiation through 15 days post-treatment follow-up.
Time frame: Up to 36 months of study duration, an average of 1.5 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (metformin hydrochloride) | Number of Adverse Events | 32 Adverse Events |
| Arm II (placebo) | Number of Adverse Events | 11 Adverse Events |
Primary
Serum and Salivary Exosome Profile
Will be modeled using mixed effects linear regression
Time frame: Up to 36 months of study duration
Population: The study terminated early due to poor accrual; no samples collected for exosome profiling. Therefore, no participants were analyzed for this outcome. Data were not collected and the outcome cannot be reported.
Secondary
Dysgeusia Assessed by Modified Vanderbilt Head and Neck Cancer Symposium Survey (Version 2.0)
Time frame: Up to 36 months of study duration
Population: The study terminated early due to poor accrual; no surveys collected for Dysgeusia. Therefore, no participants were analyzed for this outcome. Data were not collected due to study termination prior to participants' assessment at the pre-specified time points
Secondary
Xerophthalmia Assessed by Modified Vanderbilt Head and Neck Cancer Symposium Survey (Version 2.0)
Time frame: Up to 36 months of study duration
Population: The study terminated early due to poor accrual; no surveys collected for Xerophthalmia. Therefore, no participants were analyzed for this outcome. Data were not collected due to study termination prior to participants' assessment at the pre-specified time points
Secondary
Xerostomia Assessed by Modified Vanderbilt Head and Neck Cancer Symposium Survey (Version 2.0)
Time frame: Up to 36 months of study duration
Population: The study terminated early due to poor accrual; no surveys collected for Xerostomia. Therefore, no participants were analyzed for this outcome. Data were not collected due to study termination prior to participants' assessment at the pre-specified time points