Metformin in Head and Neck Squamous Cell Carcinoma: Effect on Tissue Oxygenation

• Status: Recruiting
• Trial end date: 2021-12-30
• Target enrollment: 0
• Participant gender: All

Summary

The study evaluates the effects of the drug Metformin on the oxygen content in cancer tissue. Low oxygen concentration in cancer tissue accelerates cancer growth. Moreover, the response to radiation therapy is worse when tissue oxygen is low, because radiation therapy depends on oxygen to unfold therapeutic effects. Metformin has been used to treat type II diabetes for over 50 years and features additional properties that could slow down cancer growth. One of these properties is the improved oxygen concentration in cancer tissue. This effect has been proven for various cancers.

This study was planned to verify this effect in head and neck cancer. Patients who suffer from cancer of the mouth and are planned for surgical removal of the cancer will be given Metformin for 9 to 14 days. The tissue removed in the subsequent surgery will be compared to a tissue sample that had been taken from the same patient prior to Metformin intake. To evaluate the oxygen content in the tissue samples, the expression of genes that react to oxygen levels will be measured and compared between the samples taken before and after treatment with Metformin.

A secondary aim is to evaluate whether changes in the oxygen content within the tumor can be visualized by means of magnetic resonance imaging (MRI). Therefore, participants undergo an MRI scan, before and after Treatment with Metformin. The changes in the MRI will be correlated to the changes measured in gene expression.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital Inselspital, Berne
• Collaborators: University of Bern; Werner und Hedy Berger-Janser - Stiftung; Werner und Hedy Berger-Janser – Stiftung
• Treatments: Metformin

Criteria

Inclusion Criteria:

• Patients with biopsy-proven oral cavity squamous cell carcinoma, planned for tumor resection upon institutional tumor board decision.

• Tumor tissue (biopsy) prior to metformin administration available for genetic testing

• Age ≥ 18 years of age.

• First diagnosis, no prior treatment.

• All subjects must be able to comprehend and sign a written informed consent document.

• Informed consent as documented by signature

Exclusion Criteria:

• Pregnancy or lactation.

• Distant metastasis.

• Hypersensitivity to metformin or any of its components.

• Metformin treatment for any reason during the preceding 3 months.

• Diabetic patients regardless of treatment.

• Patients planned for imaging using iodinated contrast dye within 16 days prior to surgery.

• Any concomitant drug contraindicated for use with metformin according to the approved product information.

• Plasma alanine aminotransferase > 50 IU/dL.

• Plasma aspartate aminotransferase > 50 IU/dL.

• Estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2.

• Plasma alkaline phosphatase greater than 190 IU/dL.

• History of lactic or any other metabolic acidosis.

• History of diseases potentially causing tissue hypoxia and/or increased risk of lactic acidosis:

• Congestive heart failure.

• Myocardial ischemia within the last 6 months

• Sepsis or severe infection.

• History of lung disease currently requiring any pharmacologic or supplemental oxygen treatment.

• History of hepatic dysfunction or hepatic disease.

• Chronic alcoholism which poses a risk for acute alcohol intoxication at the discretion of the treating physician.

• Scheduled definitive surgical resection less than 10 days from enrollment.

• Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment, affect patient compliance or place the patient at high risk from treatment-related complication

• Known or suspected non-compliance.

• Participation in another study with investigational drug within the 30 days preceding and during the present study.