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

NCT03510390 | Completed DMC

• 1 other identifier: 3598
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Head and Neck Cancer; Oral Cavity Squamous Cell Carcinoma

Keywords

head and neck cancer; tissue hypoxia; metformin

Outcome Measures

Primary Outcomes (1)

• Metformin dependent changes in gene expression

  Metformin induced changes in gene expression between samples taken before and after the intervention, analyzed by RNAseq, with special attention to hypoxia responsive genes: * Hypoxia inducible factor 1 (HIF1) and co-transcription factors (ARNT, COPS5, HIF1A, HIFAN, HIF3a, HNF4A, NCOA1, PER1) * HIF interactors (APEX1, EGLN1, EGLN2, NFKB1, P4HA1, P4HB, TP53) * Markers of Angiogenesis (ADROA2B, ANGPTL4, ANXA2, BTG1, EGR1, EDN1, EPO, F3, GPI, HMOX1, JMJD6, LOX, MMP9, PGF, PLAU, SERPINE1, VEGFA) Additionally, metformin induced changes in HIF1A, Ki67, cleaved caspase 3, CAIX, p-mTOR and p-AKT will be assessed by immunohistochemistry

  Baseline and two weeks

Secondary Outcomes (1)

• Hypoxia dependent changes in MRI

  baseline and two weeks

Study Arms (1)

Metformin

EXPERIMENTAL

Participants will be orally administered 850 mg of metformin twice daily between the therapeutic decision of the tumor board and the surgical resection of the tumor. The duration of the treatment is 9-14 days

Drug: Metformin

Interventions

Metformin DRUG

850 mg, oral, twice daily, 9-14 days

Metformin

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• University of Bern: collaborator
• Werner und Hedy Berger-Janser - Stiftung: collaborator

Study Sites (1)

Inselspital, Bern University Hospital

Bern, 3010, Switzerland

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Metformin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Olgun Elicin, MD

  University Hospital Inselspital, Bern, Switzerland

  PRINCIPAL INVESTIGATOR

• Simon Mueller, MD

  University Hospital Inselspital, Bern, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Window-of-opportunity

Study Record Dates

• First Submitted: April 20, 2018
• First Posted: April 27, 2018
• Study Start: June 13, 2018
• Primary Completion: September 15, 2021
• Study Completion: November 15, 2021
• Last Updated: November 18, 2021

Record last verified: 2021-11

Locations

CH (1)