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Metformin Hydrochloride and Doxycycline, Alone or Together in Treating Patients with Head and Neck Squamous Cell Carcinoma That Can Be Removed by Surgery

Trial Status: Complete

This randomized phase II trial studies how well metformin hydrochloride and doxycycline alone or together 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.

Inclusion Criteria

  • 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 Thomas Jefferson University Hospital (TJUH) are eligible to participate
  • 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
  • All subjects must be able to comprehend and sign a written informed consent document
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1

Exclusion Criteria

  • 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 head and neck squamous cell carcinoma (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 computed tomography (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 of study drug administration
  • Aspartate aminotransferase (AST) greater than 2.5 times the upper limit of normal
  • Alanine aminotransferase (ALT) greater than 2.5 times the upper limit of normal
  • Alkaline phosphatase (Alk Phos) greater than 2.5 times the upper limit of normal
  • 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 Center for Disease Control and Prevention (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 Food and Drug Administration (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 contrast agents ** Somatropin

Pennsylvania

Philadelphia
Thomas Jefferson University Hospital
Status: COMPLETED
Contact: Jennifer Maria Johnson
Phone: 212-955-8875

PRIMARY OBJECTIVES:

I. 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:

I. 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.

EXPLORATORY OBJECTIVES:

I. 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.

OUTLINE: This is a dose-escalation study of metformin hydrochloride. Patients are randomized to 1 of 3 arms.

ARM A: Patients receive metformin hydrochloride orally (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: 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.

ARM C: 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 day 1 to the day prior to surgery in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and every 3 months for 12 months.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Thomas Jefferson University Hospital

Principal Investigator
Jennifer Maria Johnson

  • Primary ID 16D.703
  • Secondary IDs NCI-2017-00136
  • Clinicaltrials.gov ID NCT03076281