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

Primary Purpose

Larynx, Lip, Oral Cavity

Status

Completed

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

External Beam Radiation Therapy

Metformin Hydrochloride

Placebo

About this trial

This is an interventional supportive care trial for Larynx

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Sidney Kimmel Cancer Center at Thomas Jefferson University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I (EBRT, metformin hydrochloride)

Arm II (EBRT, placebo)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Cytokine/Chemokine Profile

Mixed effects linear regression will be used to model longitudinal measurements of each cytokine.

Secondary Outcome Measures

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.

Objective Response Rate

The objective response rate will be estimated by arm along with an exact 95% binomial confidence interval

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.

Incidence of Toxicities

Evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

Full Information

NCT ID

NCT03109873

First Posted

March 6, 2017

Last Updated

December 7, 2020

Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University

1. Study Identification

Unique Protocol Identification Number

NCT03109873

Brief Title

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

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Completed

Study Start Date

January 5, 2017 (Actual)

Primary Completion Date

July 31, 2020 (Actual)

Study Completion Date

July 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Larynx, Lip, Oral Cavity, Pharynx

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantOutcomes Assessor

Allocation

Randomized

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm I (EBRT, metformin hydrochloride)

Arm Type

Experimental

Arm Description

Arm Title

Arm II (EBRT, placebo)

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Radiation

Intervention Name(s)

External Beam Radiation Therapy

Other Intervention Name(s)

Definitive Radiation Therapy, EBRT, External Beam RT

Intervention Description

Undergo External Beam Radiation Therapy

Intervention Type

Drug

Intervention Name(s)

Metformin Hydrochloride

Other Intervention Name(s)

1,1-Dimethylbiguanide Hydrochloride, 1115-70-4, 91485, Cidophage, Glucoformin, Glucophage ER, Dimefor

Intervention Description

Given orally

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Given orally

Primary Outcome Measure Information:

Title

Cytokine/Chemokine Profile

Description

Mixed effects linear regression will be used to model longitudinal measurements of each cytokine.

Time Frame

Up to 1 year

Secondary Outcome Measure Information:

Title

Mucositis Assessed Using WHO Classification

Description

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

Title

Objective Response Rate

Description

The objective response rate will be estimated by arm along with an exact 95% binomial confidence interval

Time Frame

Up to 2 years

Title

Exosome Profile

Description

Time Frame

Up to 1 year

Title

Incidence of Toxicities

Description

Evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

Time Frame

Up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Adam Luginbuhl, MD

Organizational Affiliation

Sidney Kimmel Cancer Center at Thomas Jefferson University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sidney Kimmel Cancer Center at Thomas Jefferson University

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19107

Country

United States

12. IPD Sharing Statement

Links:

URL

http://hospitals.jefferson.edu/

Description

Thomas Jefferson University Hospital

Learn more about this trial

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

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