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Metformin Hydrochloride and Doxycycline in Treating Patients with Localized Breast, Uterine, or Cervical Cancer

Trial Status: Closed to Accrual

This phase II trial studies how well metformin hydrochloride works together with doxycycline in treating patients with localized breast, uterine, or cervical cancer. Metformin hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Doxycycline may stop the growth of bacteria by keeping them from making proteins and minimized the toxic side effects of anti-cancer therapy. It is not yet known whether giving metformin hydrochloride together with doxycycline may be a better way in treating patients with localized breast, uterine, or cervical cancer.

Inclusion Criteria

  • Diagnosis of localized breast, uterine or cervical cancer 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
  • Subjects must be newly diagnosed or suspected to have breast, uterine (endometrial cancer with histologies including endometrioid, serous, clear cell, and carcinosarcoma) or cervical cancer
  • Patient must be able to swallow pills
  • Patients with serum creatinine levels less than 1.5 mg/dL
  • Women of child bearing 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

  • Received any prior cancer therapy for the breast, uterine, or cervical cancer that is being resected, including progesterone therapy for endometrial cancer patients * Patients may have had prior therapy for other contra-lateral breast cancer
  • 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 eligible if they are not 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 creatinine level greater than 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 5 weeks from beginning study drug administration
  • Patients with history of hepatic dysfunction or hepatic disease and abnormal liver function tests defined aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline (Alk) phosphatase (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 Centers 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; patients who feel they cannot comply with this recommendation are not eligible
  • 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: CLOSED_TO_ACCRUAL
Contact: Jennifer Maria Johnson
Phone: 215-955-8875

PRIMARY OBJECTIVES:

I. To determine if treatment with a combination of metformin hydrochloride (metformin) and doxycycline can increase the percentage of cells that express caveolin-1 in the cancer associated fibroblasts of patients with breast, uterine, or cervical cancers.

SECONDARY OBJECTIVES:

I. To determine the effect of metformin and doxycycline treatment on the percentage of cells that express monocarboxylate transporter (MCT)4 in cancer associated fibroblasts and MCT1 and transporter of outer mitochondrial membrane (TOMM)20 in the cancer cells of breast, uterine and cervical cancer patients.

II. To assess safety and tolerability of metformin and doxycycline treatment in subjects with breast, uterine and cervical cancer.

III. To determine the relationship of the percentage of stromal cells expressing caveolin (CAV)1 or MCT4 and tumor cells that express MCT1 and TOMM20 at baseline and after treatment with metformin and doxycycline with the percentage of cells expressing estrogen receptor (ER) and progesterone receptor (PR) for breast, uterine and cervical samples and human epidermal growth factor (HER)2 in breast cancer samples.

CORRELATIVE OBJECTIVES:

I. To assess the effect of combined 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-metformin and post-metformin tumor sample.

II. To assess, when possible, the impact of a patient’s nutritional status, estimated using 3-day dietary recall versus caloric needs as calculated by the Harris-Benedict equation on the baseline and net change in CAV1.

III. To assess the effect of combined metformin and doxycycline therapy on oncomiR micro ribonucleic acid (RNA) (miR-21) after intervention.

IV. To assess the effect of combined metformin and doxycycline therapy on adipokines and the insulin-like growth factor (IGF)-1/insulin signaling pathways through assessment of serum triglycerides, IGF-1, IGF-binding protein (BP)3, erythrocyte sedimentation rate (ESR), adiponectin, leptin, IGF-1 receptor (R), exosome evaluation, metabolomics profile, and microRNA expression profile.

OUTLINE:

Patients receive metformin hydrochloride orally (PO) once daily (QD) on days 1-3 and twice daily (BID) starting on day 4. Patients also receive doxycycline PO every 12 hours starting on day 1. Treatment repeats every 7 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

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

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Thomas Jefferson University Hospital

Principal Investigator
Jennifer Maria Johnson

  • Primary ID 16D.317
  • Secondary IDs NCI-2016-00977
  • Clinicaltrials.gov ID NCT02874430