Metformin Hydrochloride and Doxycycline in Treating Patients With Head and Neck Squamous Cell Carcinoma

NCT03076281 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 16D.703JT 9611
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

LIP; Oral Cavity; Pharynx; Larynx

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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

  Baseline to 30 days after last drug dose

• Change in Percent of Tumor Cells Expressing MCT4, That Are TUNEL Positive and That Express MCT1

  Baseline to 30 days after last drug dose

• Change in Percent of Tumor Cells Expressing MCT4, That Are TUNEL Positive and That Express MCT4

  Baseline to 30 days after last drug dose

• Change in Percent of Tumor Cells Expressing MCT4, That Are TUNEL Positive and That Express TOMM20

  Baseline to 30 days after last drug dose

Study Arms (3)

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

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.

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.

Drug: Metformin +Doxycycline

Interventions

Doxycycline DRUG

Given orally

Also known as: 17086-28-1, Doxycycline Monohydrate

Arm B (doxycycline)

Metformin +Doxycycline DRUG

Given orally

Arm C (metformin hydrochloride, doxycycline)

Metformin Hydrochloride DRUG

Given orally

Also known as: 1,1-Dimethylbiguanide Hydrochloride, 1115-70-4, 91485, Cidophage, Dimefor, Glucoformin, Glucophage, Glifage

Arm A (metformin hydrochloride)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Subjects that do not have a baseline tumor specimen/biopsy prior to starting study medications.
• a. 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
• 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:

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University: lead

Study Sites (1)

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Thomas Jefferson University Hospital

MeSH Terms

Conditions

Laryngeal Diseases

Interventions

Metformin; Doxycycline

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Limitations and Caveats

The study was terminated early due to insufficient staff, which limited enrollment and overall data collection. While the outcome measures were completed for the few subjects enrolled, the small sample size and early termination prevent meaningful statistical interpretation.

Results Point of Contact

• Title: Dr. Jennifer Johnson
• Organization: Sidney Kimmel Cancer Center at Thomas Jefferson University

Jennifer.Johnson@jefferson.edu

215-955-8875

Study Officials

• Jennifer Johnson, MD, PhD

  Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2017
• First Posted: March 10, 2017
• Study Start: April 3, 2017
• Primary Completion: December 3, 2018
• Study Completion: December 3, 2018
• Last Updated: January 29, 2026
• Results First Posted: January 29, 2026

Record last verified: 2026-01

Locations

US (1)