Head and Neck CancerHEAD-METNCT03510390
Metformin in Head and Neck Squamous Cell Carcinoma: Effect on Tissue Oxygenation
A study testing Metformin in people with Head and Neck Cancer and Oral Cavity Squamous Cell Carcinoma, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer, Oral Cavity Squamous Cell Carcinoma
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteSwitzerland
- Study dates
- 13 Jun 2018to 15 Nov 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 23Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Metformin in Head and Neck Squamous Cell Carcinoma: A Window of Opportunity Study to Assess the Effect on Tissue Oxygenation
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.
Read the detailed description
The main objective of this trial is to prove the hypothesis that Metformin reduces tissue hypoxia in oral cavity squamous cell carcinoma after a course of treatment of 9-14 days.
The primary endpoint of the trial is the change in hypoxia-regulated gene expression upon Treatment with Metformin. Secondary endpoint are changes in MRI imaging correlating with the changes in gene expression.
Study design: This is a single-arm, open-label interventional window of opportunity study for proof of principle. Oral cavity squamous cell carcinoma is primarily treated by surgical tumor resection. This offers the possibility to study the effect of metformin on the tumor tissue.
Baseline tissue from potential participants before the intervention will be acquired by biopsy during diagnostic panendoscopy. Provided surgery is recommended by tumor board decision, 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, depending on the date of the planned surgery. The resected tumor tissue as well as the biopsy taken prior to metformin treatment will be subjected to massive parallel sequencing and immunohistochemistry.
To assess whether changes in hypoxia regulated gene expression can be correlated to changes in MRI scans, each participants will undergo a MRI scan before metformin treatment and a second MRI scan within 48 hours prior to the surgical resection of the tumor.
- Being tested
- Metformin
- Keywords
- head and neck cancer, tissue hypoxia, metformin
- Medical subject headings
- Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
850 mg, oral, twice daily, 9-14 days
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline and two weeks
Secondary outcomes (1)
Hypoxia dependent changes in MRI
Diffusion-weighted MRI and blood oxygen level dependent imaging (BOLD) will be obtained before and after the Intervention and compared. Alterations will be correlated to changes in gene Expression.
Measured: baseline and two weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2018
- Study start13 Jun 2018
- Primary completion15 Sep 2021
- Study completion15 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Window-of-opportunity
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Collaborators
- University of Bern, Werner und Hedy Berger-Janser - Stiftung
- Responsible party
- Sponsor
- Investigators
- Olgun Elicin, MD, Principal investigator, University Hospital Inselspital, Bern, SwitzerlandSimon Mueller, MD, Principal investigator, University Hospital Inselspital, Bern, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03510390
- Sponsor's protocol ID
- 3598
- Acronym
- HEAD-MET
- Status last verified
- Nov 2021
- First submitted
- 20 Apr 2018
- Last updated
- 18 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformin in Head and Neck Squamous Cell Carcinoma: A Window of Opportunity Study to Assess the Effect on Tissue Oxygenation
- ClinicalTrials.gov ID
- NCT03510390
- Acronym / sponsor ID
- HEAD-MET / 3598
- Keywords
- head and neck cancer, tissue hypoxia, metformin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Collaborators
- University of Bern, Werner und Hedy Berger-Janser - Stiftung
- Study start
- 13 Jun 2018 (actual)
- Primary completion
- 15 Sep 2021 (actual)
- Study completion
- 15 Nov 2021 (actual)
- First posted
- 27 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The main objective of this trial is to prove the hypothesis that Metformin reduces tissue hypoxia in oral cavity squamous cell carcinoma after a course of treatment of 9-14 days.
The primary endpoint of the trial is the change in hypoxia-regulated gene expression upon Treatment with Metformin. Secondary endpoint are changes in MRI imaging correlating with the changes in gene expression.
Study design: This is a single-arm, open-label interventional window of opportunity study for proof of principle. Oral cavity squamous cell carcinoma is primarily treated by surgical tumor resection. This offers the possibility to study the effect of metformin on the tumor tissue.
Baseline tissue from potential participants before the intervention will be acquired by biopsy during diagnostic panendoscopy. Provided surgery is recommended by tumor board decision, 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, depending on the date of the planned surgery. The resected tumor tissue as well as the biopsy taken prior to metformin treatment will be subjected to massive parallel sequencing and immunohistochemistry.
To assess whether changes in hypoxia regulated gene expression can be correlated to changes in MRI scans, each participants will undergo a MRI scan before metformin treatment and a second MRI scan within 48 hours prior to the surgical resection of the tumor.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Window-of-opportunity
| Arm | Type | Receives |
|---|---|---|
| Metformin | Experimental | Drug: MetforminParticipants 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin850 mg, oral, twice daily, 9-14 days | Drug | Metformin |
Primary outcome
Metformin dependent changes in gene expression
Time frame: Baseline and two weeks
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
1 secondary outcome
Hypoxia dependent changes in MRI
Time frame: baseline and two weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olgun Elicin, MD principal investigator
University Hospital Inselspital, Bern, Switzerland
Simon Mueller, MD principal investigator
University Hospital Inselspital, Bern, Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Metformin in people with Head and Neck Cancer and Oral Cavity Squamous Cell Carcinoma, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Metformin dependent changes in gene expression (time frame: Baseline and two weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2021.