Trial results for a Phase 2 study investigating metformin hydrochloride and doxycycline in patients with head and neck squamous cell carcinoma were posted on ClinicalTrials.gov on 2026-01-29. The trial, NCT03076281, was terminated early and enrolled 7 participants.
Background
This study aimed to evaluate 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 was hypothesized to reduce the metabolic activity of cancer cells and surrounding supportive tissue. Doxycycline was intended to minimize toxic side effects of anti-cancer therapy.
Trial design
The study (NCT03076281) was a Phase 2, randomized trial that enrolled 7 participants before being terminated. It investigated metformin hydrochloride and doxycycline, alone and in combination, for patients with head and neck squamous cell carcinoma affecting the Larynx, LIP, Oral Cavity, or Pharynx. The interventions included metformin hydrochloride (Arm A), doxycycline (Arm B), and a combination of metformin + doxycycline (Arm C).
Key results
The trial measured several outcomes, including changes in cellular markers and the incidence of adverse events:
- Change in Percentage of CFS Expressing Caveolin-1 at an Intensity of 1+ or Greater Assessed in Tumor-associated Stroma Cells by Immunohistochemistry:
- Arm A (Metformin Hydrochloride): Mean 32.5 percentage of cells
- Arm B (Doxycycline): Mean 30 percentage of cells
- Arm C (Metformin Hydrochloride, Doxycycline): Mean 32.5 percentage of cells
- Incidence of Adverse Events as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0:
- Arm A (Metformin Hydrochloride): 5 adverse events
- Arm B (Doxycycline): 6 adverse events
- Arm C (Metformin Hydrochloride, Doxycycline): 3 adverse events
- Change in Percent of Tumor Cells Expressing MCT4, That Are TUNEL Positive and That Express BGAL:
- Arm A (Metformin Hydrochloride): Mean 0 Percentage of tumor cells
- Arm B (Doxycycline): Mean 12.5 Percentage of tumor cells
- Arm C (Metformin Hydrochloride, Doxycycline): Mean 12.5 Percentage of tumor cells
- Change in Percent of Tumor Cells Expressing MCT4, That Are TUNEL Positive and That Express MCT1:
- Arm A (Metformin Hydrochloride): Mean 7.5 Percentage of tumor cells
- Arm B (Doxycycline): Mean 7.5 Percentage of tumor cells
- Arm C (Metformin Hydrochloride, Doxycycline): Mean 2.5 Percentage of tumor cells
What this means
The early termination of this Phase 2 trial and the very small enrollment of 7 participants significantly limit the interpretability and generalizability of these results. While the combination arm (Arm C) reported the lowest number of adverse events (3) compared to monotherapy arms (5 and 6), no definitive conclusions about efficacy or safety can be drawn from such a limited dataset. The observed changes in various tumor cell markers provide preliminary data but require further investigation in larger, completed studies.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03076281, titled "Metformin Hydrochloride and Doxycycline in Treating Patients With Head and Neck Squamous Cell Carcinoma," were posted on 2026-01-29 on clinicaltrials.gov.