Patient case: 64-year-old male with head and neck squamous cell carcinoma; genetic feature: CDKN2A

Clinical trial: Metformin Hydrochloride and Doxycycline in Treating Patients With Head and Neck Squamous Cell Carcinoma That Can Be Removed by Surgery

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.

Detailed description: 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.
  TERTIARY 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.

Eligibility: Inclusion Criteria:
  -  Subjects with a 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
  -  No prior cancer therapy is permitted for the head and neck squamous cell carcinoma (HNSCC) that is being resected
  -  Patient must be able to swallow pills
  -  All subjects must be able to comprehend and sign a written informed consent document
  Exclusion Criteria:
  -  Subjects who are pregnant or breastfeeding, or may become pregnant during metformin and doxycycline administration
  -  Subjects on metformin or doxycycline for any reason during the preceding 4 weeks
  -  Diabetic subjects are only eligible if they are not taking metformin or insulin
  -  Subjects who have received iodinated contrast dye less than 48 hours prior to screening meet a temporary exclusion criterion to receive metformin; these patients cannot start investigational metformin until 48 hours have elapsed from contrast administration; subjects who are scheduled for iodinated contrast dye administration within 48 hours of definitive surgery are excluded
  -  Patients with estimated glomerular filtration rate (eGFR) < 30 (as determined by Cockroft and Gault formula)
  -  Patients with serum bicarbonate less than 22 mEq/L or 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 enrollment or greater than 6 weeks from enrollment
  -  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 with a history of excessive alcohol intake which is defined in accordance with Center for Disease Control and Prevention (CDC) definitions as more than 1 drink per day for women and more than 2 drinks per day for men; this definition is referring to the amount consumed on any single day and is not intended as an average over several days; a standard drink is equal to 13.7 grams (0.6 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)
  -  Patients with a history of excessive alcohol intake which is defined in accordance with Center for Disease Control (CDC) definitions as more than 1 drink per day for women and more than 2 drinks per day for men
  -  Patient with prior allergic reaction to metformin, doxycycline, or any other tetracycline antibiotic in the past
  -  All medications are permitted except those 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 C (monitor therapy) and class D (consider therapy modification) when treatment with metformin or doxycycline is considered:
  -  Class C:
  -  Carbonic anhydrase inhibitors
  -  Cephalexin
  -  Corticosteroids (orally inhaled)
  -  Corticosteroids (systemic)
  -  Dalfampridine
  -  Dofetilide
  -  Glycopyrrolate
  -  Lamotrigine
  -  Luteinizing hormone-releasing hormone analogs
  -  Pegvisomant
  -  Penicillin
  -  Trospium
  -  Class D:
  -  Bismuth Subsalicylate
  -  Cimetidine
  -  Iodinated contrast agents
  -  Somatropin

Relevance to patient case: not relevant