LarynxEarly Phase 1NCT03109873
Metformin Hydrochloride in Affecting Cytokines and Exosomes in Patients With Head and Neck Cancer
A Early Phase 1 study testing External Beam Radiation Therapy and Metformin Hydrochloride in people with Larynx and Lip, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Larynx, Lip, Oral Cavity
- What is being tested?
- External Beam Radiation Therapy and Metformin Hydrochloride
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Jan 2017to 31 Jul 2020
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- To determine the effect of metformin treatment on symptoms of fatigue as assess by the Multidimensional Fatigue Inventory (MFI).
- Conditions
- Larynx, Lip, Oral Cavity, Pharynx
- Being tested
- External Beam Radiation Therapy, Metformin Hydrochloride, Placebo
- Medical subject headings
- Laryngeal Diseases, Lymphoid Interstitial Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
External Beam Radiation TherapyRadiation
Also called Definitive Radiation Therapy, EBRT, External Beam RT
Undergo External Beam Radiation Therapy
Metformin HydrochlorideDrug
Also called 1,1-Dimethylbiguanide Hydrochloride, 1115-70-4, 91485, Cidophage
Given orally
PlaceboOther
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Arm I (EBRT, metformin hydrochloride) | Experimental | 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. Receives: Radiation: External Beam Radiation Therapy; Drug: Metformin Hydrochloride |
| Arm II (EBRT, placebo) | Placebo comparator | 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. Receives: Radiation: External Beam Radiation Therapy; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cytokine/Chemokine Profile
Mixed effects linear regression will be used to model longitudinal measurements of each cytokine.
Measured: Up to 1 year
Secondary outcomes (4)
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.
Measured: Up to 1 year
Objective Response Rate
The objective response rate will be estimated by arm along with an exact 95% binomial confidence interval
Measured: Up to 2 years
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.
Measured: Up to 1 year
Incidence of Toxicities
Evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2017
- Study start5 Jan 2017
- Primary completion31 Jul 2020
- Study completion31 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LarynxStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Adam Luginbuhl, MD, Principal investigator, Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03109873
- Sponsor's protocol ID
- 16D.639
- Other IDs
- JT 9410
- Status last verified
- Apr 2025
- First submitted
- 6 Mar 2017
- Last updated
- 30 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03109873
- Acronym / sponsor ID
- 16D.639
- Conditions
- Larynx, Lip, Oral Cavity, Pharynx
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson UniversityUniversity, hospital or other
- Study start
- 5 Jan 2017 (actual)
- Primary completion
- 31 Jul 2020 (actual)
- Study completion
- 31 Jul 2020 (actual)
- First posted
- 12 Apr 2017 (actual)
- Results
- Posted 20 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
- To determine the effect of metformin treatment on symptoms of fatigue as assess by the Multidimensional Fatigue Inventory (MFI).
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (EBRT, metformin hydrochloride) | Experimental | Radiation: External Beam Radiation Therapy, Drug: Metformin HydrochloridePatients 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. |
| Arm II (EBRT, placebo) | Placebo comparator | Radiation: External Beam Radiation Therapy, Other: PlaceboPatients 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. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| External Beam Radiation TherapyAlso: Definitive Radiation Therapy, EBRT, External Beam RTUndergo External Beam Radiation Therapy | Radiation | Arm I (EBRT, metformin hydrochloride), Arm II (EBRT, placebo) |
| Metformin HydrochlorideAlso: 1,1-Dimethylbiguanide Hydrochloride, 1115-70-4, 91485, CidophageGiven orally | Drug | Arm I (EBRT, metformin hydrochloride) |
| PlaceboGiven orally | Other | Arm II (EBRT, placebo) |
Primary outcome
Cytokine/Chemokine Profile
Time frame: Up to 1 year
Mixed effects linear regression will be used to model longitudinal measurements of each cytokine.
4 secondary outcomes
Mucositis Assessed Using WHO Classification
Time frame: Up to 1 year
Objective Response Rate
Time frame: Up to 2 years
Exosome Profile
Time frame: Up to 1 year
Incidence of Toxicities
Time frame: Up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Sidney Kimmel Cancer CenterLink provided by the sponsor.
- Thomas Jefferson University HospitalLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adam Luginbuhl, MD principal investigator
Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing External Beam Radiation Therapy and Metformin Hydrochloride in people with Larynx and Lip, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cytokine/Chemokine Profile (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2025.