Metformin Hydrochloride and Doxycycline in Treating Patients With Localized Breast or Uterine Cancer

NCT02874430 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 16D.317JT 8988
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well metformin hydrochloride works together with doxycycline in treating patients with localized breast or uterine 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 or uterine cancer.

Conditions

Breast Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Uterine Corpus Cancer; Uterine Corpus Carcinosarcoma

Outcome Measures

Primary Outcomes (1)

• Change in the Percentage of Stromal Cells Expressing Caveolin-1 (CAV1) at an Intensity of 1+ or Greater by Immunohistochemistry

  Caveolin-1 (CAV1) expression in stromal cells is assessed by immunohistochemistry using a standard intensity scale of 0 to 3+, where 0 indicates no staining and 1+, 2+, and 3+ indicate increasing levels of staining intensity. For this measure, stromal cells with CAV1 staining of 1+ or higher are considered positive. Results are reported as the percentage of positive stromal cells, ranging from 0% (no positive cells) to 100% (all cells positive). Higher percentages indicate a worse outcome, as higher CAV1 expression is associated with more aggressive tumor behavior. Within-patient changes will be analyzed using the Wilcoxon signed-rank test.

  Pre-treatment (Baseline) and Post-treatment (week 6)

Secondary Outcomes (8)

• Number of Adverse Events

  12 months

• Change in the Percent of Stromal Cells Expressing Express Monocarboxylate Transporter 4 (MCT4) in the Cancer Cells

  at 5 weeks

• Percent of Tumor Cells That Express Transporter of Outer Mitochondrial Membrane 20 (TOMM20) in the Cancer Cells

  at 5 weeks

• Percentage of Stromal Cells Expressing Caveolin-1 (CAV1) or Monocarboxylate Transporter 4 (MCT4)

  5 weeks

• Percentage of Tumor Cells That Express Monocarboxylate Transporter 1 (MCT1)

  Pre-treatment (Baseline) and Post-treatment (week 6)

Study Arms (1)

Treatment (metformin hydrochloride, doxycycline)

EXPERIMENTAL

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

Drug: Metformin Hydrochloride; Drug: Doxycycline

Interventions

Metformin Hydrochloride DRUG

Given orally

Also known as: 1,1-Dimethylbiguanide Hydrochloride, 1115-70-4, 91485, Cidophage, Dimefor, Glifage, Glucoformin, Glucophage, N,N-Dimethylimidodicarbonimidic Diamide Monohydrochloride, Riomet, Siofor

Treatment (metformin hydrochloride, doxycycline)

Doxycycline DRUG

Given orally

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

Treatment (metformin hydrochloride, doxycycline)

Eligibility Criteria

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

You may qualify if:

• In order to be eligible for participation in this trial, the subject must:
• Diagnosis of localized breast or uterine 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 TJUH are eligible to participate.
• Subjects must be ≥ 18 years of age at time of consent.
• 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.
• 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:

• The subject must be excluded from participating in the trial if the subject:
• Received any prior cancer therapy for the breast or uterine cancer that is being resected, including progesterone therapy for endometrial cancer patients.
• a. 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 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 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 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.
• a. 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. 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.

Sponsors & Collaborators

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

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Thomas Jefferson University Hospital

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Metformin; Doxycycline

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue 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 slow accrual. Although limited paper records were found, no outcome-specific data were retained in an analyzable format. The absence of a complete dataset prevents reporting of pre-specified outcomes. No further records could be obtained, as the study team is no longer at the institution.

Results Point of Contact

• Title: Jennifer Johnson, MD, PhD, FACP
• Organization: Thomas Jefferson University

Jennifer.M.Johnson@jefferson.edu

215-955-8874

Study Officials

• Jennifer Johnson, MD, PhD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2016
• First Posted: August 22, 2016
• Study Start: June 8, 2016
• Primary Completion: December 11, 2020
• Study Completion: December 11, 2020
• Last Updated: April 22, 2026
• Results First Posted: April 22, 2026

Record last verified: 2026-03

Locations

US (1)