Larynx, Lip, Oral Cavity, Pharynx
Conditions
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).
Interventions
RADIATIONExternal Beam Radiation Therapy
Undergo External Beam Radiation Therapy
DRUGMetformin Hydrochloride
Given orally
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, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cytokine/Chemokine Profile | Up to 1 year | Mixed effects linear regression will be used to model longitudinal measurements of each cytokine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mucositis Assessed Using WHO Classification | Up to 1 year | 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. |
| Objective Response Rate | Up to 2 years | The objective response rate will be estimated by arm along with an exact 95% binomial confidence interval |
| Exosome Profile | Up to 1 year | 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. |
| Incidence of Toxicities | Up to 2 years | Evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
External Beam Radiation Therapy: Undergo External Beam Radiation Therapy
Metformin Hydrochloride: Given orally | 5 |
| 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.
External Beam Radiation Therapy: Undergo External Beam Radiation Therapy
Placebo: Given orally | 4 |
| Total | 9 |
Baseline characteristics
| Characteristic | Arm I (EBRT, Metformin Hydrochloride) | Arm II (EBRT, Placebo) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 4 Participants | 8 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 | 0 Participants | 0 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 | 4 Participants | 9 Participants |
| Region of Enrollment United States | 5 participants | 4 participants | 9 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 4 |
| other Total, other adverse events | 4 / 5 | 3 / 4 |
| serious Total, serious adverse events | 0 / 5 | 0 / 4 |
Outcome results
Primary
Cytokine/Chemokine Profile
Mixed effects linear regression will be used to model longitudinal measurements of each cytokine.
Time frame: Up to 1 year
Population: Due to insufficient accrual, statistical results cannot be reported.
Secondary
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.
Time frame: Up to 1 year
Population: Due to insufficient accrual, statistical results cannot be reported.
Secondary
Incidence of Toxicities
Evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time frame: Up to 2 years
Population: Due to insufficient accrual, statistical results cannot be reported.
Secondary
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.
Time frame: Up to 1 year
Population: Due to insufficient accrual, statistical results cannot be reported.
Secondary
Objective Response Rate
The objective response rate will be estimated by arm along with an exact 95% binomial confidence interval
Time frame: Up to 2 years
Population: Due to insufficient accrual, statistical results cannot be reported.