LarynxPhase 2NCT03076281
Metformin Hydrochloride and Doxycycline in Treating Patients With Head and Neck Squamous Cell Carcinoma
A Phase 2 study testing Metformin Hydrochloride, Doxycycline and Metformin +Doxycycline 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 randomized phase II trial studies how well metformin hydrochloride and doxycycline work in treating patients with head and neck squamous cell carcinoma that can be removed by surgery. Metformin hydrochloride may reduce the metabolic activity of cancer cells and of surrounding supportive tissue. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Larynx, LIP, Oral Cavity
- What is being tested?
- Metformin Hydrochloride, Doxycycline and Metformin +Doxycycline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Apr 2017to 3 Dec 2018
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of head and neck squamous cell carcinoma that is either biopsy proven or suspected based on history, physical, and or radiographic findings, and who are planned for definitive resection of the tumor without the use of neoadjuvant chemotherapy or radiation therapy at TJUH are eligible to participate.
- Subjects must be ≥ 18 years of age at time of consent.
- Patient must be able to swallow pills.
- Patients with serum creatinine levels less than 1.5 mg/dL
- Women of childbearing potential must have a negative urine or blood pregnancy test within 14 days of study enrollment.
- Informed Consent: All subjects must be able to comprehend and sign a written informed consent document.
- ECOG Performance status ≤1
Who cannot join
- Subjects that do not have a baseline tumor specimen/biopsy prior to starting study medications.
- Tumor specimens do not need to be at Jefferson at time of eligibility determination. Tumor specimens held at outside institutions should be requested for analysis of pre-treatment tumor vs post-treatment tumor.
- Subjects who are pregnant or breastfeeding, or may become pregnant during metformin and doxycycline administration.
- Received prior cancer therapy for the HNSCC that is being resected.
- Subjects on metformin or doxycycline for any reason during the preceding 4 weeks.
- Diabetic subjects that are managed by taking metformin or insulin
Show all 19Show fewer
- 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 serum creatine ≥1.5 mg/dL
- Patients with history of lactic or any other metabolic acidosis.
- Patients with history of congestive heart failure stage III or greater.
- Patients scheduled for definitive cancer surgical resection less than 7 days from beginning of study drug administration or greater than 6 weeks from beginning study drug administration.
- Patients with history of hepatic dysfunction or hepatic disease and abnormal liver function tests defined as AST, ALT, Alk Phos, and or total bilirubin greater than 2.5 times the upper limit of normal. 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 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.
- Patient with prior allergic reaction to metformin, doxycycline, or any other tetracycline antibiotic in the past.
- Patient is on medications that are contraindicated with metformin or doxycycline under current FDA recommendations. The following is a list of medications identified as class D (consider therapy modification) when treatment with metformin or doxycycline is considered:
- Class D:
- Bismuth Subsalicylate
- Cimetidine
- Iodinated cont
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: A Phase II Study of Metformin, Doxycycline, or a Combination of Both Agents in Head and Neck Squamous Cell Carcinoma
This randomized phase II trial studies how well metformin hydrochloride and doxycycline work in treating patients with head and neck squamous cell carcinoma that can be removed by surgery. Metformin hydrochloride may reduce the metabolic activity of cancer cells and of surrounding supportive tissue. Doxycycline may minimize toxic side effects of anti-cancer therapy. Giving metformin hydrochloride and doxycycline may work better in treating patients with head and neck squamous cell carcinoma.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine if treatment with metformin hydrochloride (metformin), doxycycline, or a combination of metformin and doxycycline can increase the percentage of stromal cells that express CAV1 in patients with squamous cell carcinoma of the head and neck.
SECONDARY OBJECTIVES:
- To determine the effect of metformin, doxycycline, or metformin and doxycycline treatment on the percentage of tumor cells that are apoptotic as determined by the TdT-Mediated dUTP Nick End Labeling Assay (TUNEL) assay, and express MCT4, MCT1, BGAL, and TOMM20 in squamous carcinoma of head and neck region tumor cells.
II. To assess safety and tolerability of metformin, doxycycline, or metformin and doxycycline treatment in subjects with squamous cell carcinoma of the head and neck.
TERTIARY OBJECTIVES:
- To assess the effect of metformin, doxycycline, or metformin and doxycycline therapy on the metabolic profile of cancer cells and stroma using mass spectroscopy imaging (MSI) on paired samples, comparing metabolite profiles in the pre-treatment and post-treatment tumor samples.
II. To assess the effect of metformin, doxycycline, or metformin and doxycycline therapy on the metabolic state of the patient as characterized serologically by: erythrocyte sedimentation rate, exosome evaluation, metabolomics profile, and micro ribonucleic acid (RNA) expression profiles and physiologically by performing a nutritional assessment via a nutritionist-mediated 3-day dietary recall and comparing a patient's estimated dietary intake against their estimated caloric needs.
- Conditions
- Larynx, LIP, Oral Cavity, Pharynx
- Being tested
- Metformin Hydrochloride, Doxycycline, Metformin +Doxycycline
- Medical subject headings
- Laryngeal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin HydrochlorideDrug
Also called 1,1-Dimethylbiguanide Hydrochloride, 1115-70-4, 91485, Cidophage
Given orally
DoxycyclineDrug
Also called 17086-28-1, Doxycycline Monohydrate
Given orally
Metformin +DoxycyclineDrug
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Arm A (metformin hydrochloride) | Experimental | Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery in the absence of disease progression or unacceptable toxicity Receives: Drug: Metformin Hydrochloride |
| Arm B (doxycycline) | Experimental | Patients receive doxycycline PO every 12 hours on days 1 to the day prior to surgery in the absence of disease progression or unacceptable toxicity. Receives: Drug: Doxycycline |
| Arm C (metformin hydrochloride, doxycycline) | Experimental | Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery and doxycycline PO every 12 hours on days 1to the day prior to surgery in the absence of disease progression or unacceptable toxicity. Receives: Drug: Metformin +Doxycycline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Percentage of CFS Expressing Caveolin-1 at an Intensity of 1+ or Greater Assessed in Tumor-associated Stroma Cells by Immunohistochemistry
Within-patient change in IHC scores will be analyzed using the Wilcoxon signed-rank test. Comparisons will be made between pretreatment and post-treatment within each of the cohorts. Caveolin-1 (CAV1) immunohistochemistry (IHC) will be performed on pre- and post-treatment tumor specimens. The mean percentage of fibroblasts expressing CAV1 will be compared before and after treatment.
Measured: Baseline to 30 days after last drug dose
Secondary outcomes (5)
Incidence of Adverse Events as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Safety will be provided in descriptive tables as Incidence of adverse events as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
Measured: Up to 30 days after last drug dose: approximately1 year
Change in Percent of Tumor Cells Expressing MCT4, That Are TUNEL Positive and That Express BGAL
Immunohistochemistry will be performed for Caveolin-1, TUNEL, BGAL, MCT1, MCT4, and TOMM20 on the pre- and post- treatment specimens and evaluated for staining distribution and intensity by two blinded pathologists.
Measured: Baseline to 30 days after last drug dose
Change in Percent of Tumor Cells Expressing MCT4, That Are TUNEL Positive and That Express MCT1
Immunohistochemistry will be performed for Caveolin-1, TUNEL, BGAL, MCT1, MCT4, and TOMM20 on the pre- and post- treatment specimens and evaluated for staining distribution and intensity by two blinded pathologists.
Measured: Baseline to 30 days after last drug dose
Change in Percent of Tumor Cells Expressing MCT4, That Are TUNEL Positive and That Express MCT4
Immunohistochemistry will be performed for Caveolin-1, TUNEL, BGAL, MCT1, MCT4, and TOMM20 on the pre- and post- treatment specimens and evaluated for staining distribution and intensity by two blinded pathologists.
Measured: Baseline to 30 days after last drug dose
Change in Percent of Tumor Cells Expressing MCT4, That Are TUNEL Positive and That Express TOMM20
Immunohistochemistry will be performed for Caveolin-1, TUNEL, BGAL, MCT1, MCT4, and TOMM20 on the pre- and post- treatment specimens and evaluated for staining distribution and intensity by two blinded pathologists.
Measured: Baseline to 30 days after last drug dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2017
- Study start3 Apr 2017
- Primary completion3 Dec 2018
- Study completion3 Dec 2018
Why it stopped: Insufficient staff to conduct the trial
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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 7 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
- Jennifer Johnson, MD, PhD, Principal investigator, Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03076281
- Sponsor's protocol ID
- 16D.703
- Other IDs
- JT 9611
- Status last verified
- Jan 2026
- First submitted
- 6 Mar 2017
- Last updated
- 29 Jan 2026
- 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 29 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Metformin, Doxycycline, or a Combination of Both Agents in Head and Neck Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT03076281
- Acronym / sponsor ID
- 16D.703
- Conditions
- Larynx, LIP, Oral Cavity, Pharynx
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient staff to conduct the trial
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson UniversityUniversity, hospital or other
- Study start
- 3 Apr 2017 (actual)
- Primary completion
- 3 Dec 2018 (actual)
- Study completion
- 3 Dec 2018 (actual)
- First posted
- 10 Mar 2017 (actual)
- Results
- Posted 29 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase II trial studies how well metformin hydrochloride and doxycycline work in treating patients with head and neck squamous cell carcinoma that can be removed by surgery. Metformin hydrochloride may reduce the metabolic activity of cancer cells and of surrounding supportive tissue. Doxycycline may minimize toxic side effects of anti-cancer therapy. Giving metformin hydrochloride and doxycycline may work better in treating patients with head and neck squamous cell carcinoma.
Detailed description
PRIMARY OBJECTIVES:
- To determine if treatment with metformin hydrochloride (metformin), doxycycline, or a combination of metformin and doxycycline can increase the percentage of stromal cells that express CAV1 in patients with squamous cell carcinoma of the head and neck.
SECONDARY OBJECTIVES:
- To determine the effect of metformin, doxycycline, or metformin and doxycycline treatment on the percentage of tumor cells that are apoptotic as determined by the TdT-Mediated dUTP Nick End Labeling Assay (TUNEL) assay, and express MCT4, MCT1, BGAL, and TOMM20 in squamous carcinoma of head and neck region tumor cells.
II. To assess safety and tolerability of metformin, doxycycline, or metformin and doxycycline treatment in subjects with squamous cell carcinoma of the head and neck.
TERTIARY OBJECTIVES:
- To assess the effect of metformin, doxycycline, or metformin and doxycycline therapy on the metabolic profile of cancer cells and stroma using mass spectroscopy imaging (MSI) on paired samples, comparing metabolite profiles in the pre-treatment and post-treatment tumor samples.
II. To assess the effect of metformin, doxycycline, or metformin and doxycycline therapy on the metabolic state of the patient as characterized serologically by: erythrocyte sedimentation rate, exosome evaluation, metabolomics profile, and micro ribonucleic acid (RNA) expression profiles and physiologically by performing a nutritional assessment via a nutritionist-mediated 3-day dietary recall and comparing a patient's estimated dietary intake against their estimated caloric needs.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A (metformin hydrochloride) | Experimental | Drug: Metformin HydrochloridePatients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery in the absence of disease progression or unacceptable toxicity |
| Arm B (doxycycline) | Experimental | Drug: DoxycyclinePatients receive doxycycline PO every 12 hours on days 1 to the day prior to surgery in the absence of disease progression or unacceptable toxicity. |
| Arm C (metformin hydrochloride, doxycycline) | Experimental | Drug: Metformin +DoxycyclinePatients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery and doxycycline PO every 12 hours on days 1to the day prior to surgery in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Diagnosis of head and neck squamous cell carcinoma that is either biopsy proven or suspected based on history, physical, and or radiographic findings, and who are planned for definitive resection of the tumor without the use of neoadjuvant chemotherapy or radiation therapy at TJUH are eligible to participate.
- Subjects must be ≥ 18 years of age at time of consent.
- Patient must be able to swallow pills.
- Patients with serum creatinine levels less than 1.5 mg/dL
- Women of childbearing potential must have a negative urine or blood pregnancy test within 14 days of study enrollment.
Key exclusion criteria (19 listed)
- Subjects that do not have a baseline tumor specimen/biopsy prior to starting study medications.
- Subjects who are pregnant or breastfeeding, or may become pregnant during metformin and doxycycline administration.
- Received prior cancer therapy for the HNSCC that is being resected.
- Subjects on metformin or doxycycline for any reason during the preceding 4 weeks.
- Diabetic subjects that are managed by taking metformin or insulin
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 |
|---|---|---|
| Metformin HydrochlorideAlso: 1,1-Dimethylbiguanide Hydrochloride, 1115-70-4, 91485, CidophageGiven orally | Drug | Arm A (metformin hydrochloride) |
| DoxycyclineAlso: 17086-28-1, Doxycycline MonohydrateGiven orally | Drug | Arm B (doxycycline) |
| Metformin +DoxycyclineGiven orally | Drug | Arm C (metformin hydrochloride, doxycycline) |
Primary outcome
Change in Percentage of CFS Expressing Caveolin-1 at an Intensity of 1+ or Greater Assessed in Tumor-associated Stroma Cells by Immunohistochemistry
Time frame: Baseline to 30 days after last drug dose
Within-patient change in IHC scores will be analyzed using the Wilcoxon signed-rank test. Comparisons will be made between pretreatment and post-treatment within each of the cohorts. Caveolin-1 (CAV1) immunohistochemistry (IHC) will be performed on pre- and post-treatment tumor specimens. The mean percentage of fibroblasts expressing CAV1 will be compared before and after treatment.
5 secondary outcomes
Incidence of Adverse Events as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Time frame: Up to 30 days after last drug dose: approximately1 year
Change in Percent of Tumor Cells Expressing MCT4, That Are TUNEL Positive and That Express BGAL
Time frame: Baseline to 30 days after last drug dose
Change in Percent of Tumor Cells Expressing MCT4, That Are TUNEL Positive and That Express MCT1
Time frame: Baseline to 30 days after last drug dose
Change in Percent of Tumor Cells Expressing MCT4, That Are TUNEL Positive and That Express MCT4
Time frame: Baseline to 30 days after last drug dose
Change in Percent of Tumor Cells Expressing MCT4, That Are TUNEL Positive and That Express TOMM20
Time frame: Baseline to 30 days after last drug dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Jennifer Johnson, MD, PhD 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 Phase 2 study testing Metformin Hydrochloride, Doxycycline and Metformin +Doxycycline 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 7 inclusion and 19 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: stopped early, as of the sponsor's last update on 29 Jan 2026. 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. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 29 Jan 2026). 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?
Change in Percentage of CFS Expressing Caveolin-1 at an Intensity of 1+ or Greater Assessed in Tumor-associated Stroma Cells by Immunohistochemistry (time frame: Baseline to 30 days after last drug dose). 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 29 Jan 2026.