Head and Neck CancerPhase 1NCT02325401
Dose-finding Study of Metformin With Chemoradiation in Locally Advanced Head and Neck Squamous Cell Carcinoma
A Phase 1 study testing Metformin, Cisplatin and Radiation Therapy in people with Head and Neck Cancer, run by University of Cincinnati at 1 site in United States.
Trial summary
The purpose of this research study is to test the safety of adding metformin to standard of care. The standard of care treatment will be cisplatin once every 3 weeks for 3 treatments and radiation for 7 weeks. Metformin is a medication that is currently used to treat diabetes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- Metformin, Cisplatin and Radiation Therapy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 11 May 2015to 21 Feb 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Locally advanced squamous cell cancer of the head and neck, stage III or IV disease (T1-2, N2a-3 or T3-4).
- Measurable disease
- No prior chemotherapy or radiation for head and neck squamous cell cancer
- Life expectancy of greater than 3 months.
- Adequate labs
Who cannot join
- Known metastatic disease.
- Nasopharyngeal carcinoma
- History of allergic reactions attributed to metformin or other agents used in study.
- Known diagnosis of diabetes requiring insulin for control.
- Administration of metformin within last 4 weeks.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Cincinnati Cancer Institute
Cincinnati, Ohio, 45267
About this study
Official title: A Phase I Dose-finding Study of Metformin in Combination With Concurrent Cisplatin and Radiation in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma
The purpose of this research study is to test the safety of adding metformin to standard of care. The standard of care treatment will be cisplatin once every 3 weeks for 3 treatments and radiation for 7 weeks.
Metformin is a medication that is currently used to treat diabetes. Increasing amounts of metformin will be given to groups of patients already receiving normal treatment for their cancer to see if metformin causes any good effects by killing your cancer or bad effects (side effects).
Read the detailed description
Patients were registered by contacting the University of Cincinnati Clinical Trials Office. Patients must be registered and consent obtained prior to initiation of any protocol therapy.
Treatment was administered on an outpatient basis. Adverse events and potential risks for metformin and cisplatin and radiation were reported.
Patients must have screening labs performed within 2 weeks of start of treatment including a complete blood count, liver function tests, metabolic renal panel including magnesium, vitamin B12 level, lactate, and C-peptide. Renal panel must be verified within 24 hours of cisplatin administration. They must fulfill inclusion criteria.
The recommended starting dose of metformin in diabetic patients is 500mg orally twice a day which can be escalated by 500mg increments weekly as tolerated with the maximum recommended daily dose of 2550mg.
Cisplatin was given either before or after the radiation therapy fraction that is given on the same day. If radiation is held for more than 2 days (for any reason), cisplatin may be held as well until radiation resumes.
The prescribed radiotherapy dose was be 70 Gy in 2 Gy once-daily fraction size (total of 35 fractions).
- Conditions
- Head and Neck Cancer
- Medical subject headings
- Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Fortamet, Glucophage, Glucophage XR, Glumetza
Escalating doses of 2000mg, 2550 mg and 3000mg. Starting 1 week prior to the initiation of chemoradiation and ending the final day of chemo or radiation.
CisplatinDrug
Also called Platinol, Platinol-AQ
Dosed at 100mg/m2 on days 1, 22, and 43
Radiation TherapyRadiation
70 Gy in 2 Gy once daily fractions of 35 fractions
| Study group | Role | What they receive |
|---|---|---|
| Metformin with Chemoradiation | Experimental | Metformin administered orally daily to start one week prior to Cisplatin and Radiation Therapy. Metformin dose is escalating. Receives: Drug: Metformin; Drug: Cisplatin; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Metformin in Combination With Concurrent Cisplatin and Radiation
Cohorts of patients received escalating doses of metformin (2000 mg, 2550 mg, or 3000 mg divided into daily doses) with a 7-day to 14-day lead-in prior to CRT based on the modified toxicity probability interval design to allow for possible re-escalation after previous de-escalation and to maximize the ability to identify the maximum tolerated dose (MTD). Patients continued to receive metformin for the duration of CRT as tolerated.
Measured: 24 months
Secondary outcomes (4)
Number of Participants Experiencing No-Reoccurrence at 36 Months
Patients were evaulated at 36 months to determine if there was recurrence of disease.
Measured: 36 months
Number of Participants With Adverse Events
Adverse event means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Adverse event means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.Any participants with any adverse event at any grade was included. Adverse events were collected during the on study period of 21 weeks up to three months after the study for a total of 34 weeks.
Measured: 36 months
Progression Free Survival
2-year progression free survival
Measured: 24 months
Overall Survival
2 year overall survival
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Dec 2014 (estimated)
- Study start11 May 2015
- Primary completion26 Dec 2017
- Study completion21 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Trisha Wise-Draper, University of Cincinnati
- Investigators
- Trisha Wise-Draper, MD, Principal investigator, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02325401
- Sponsor's protocol ID
- UCCI-HN-14-01
- Status last verified
- May 2020
- First submitted
- 16 Dec 2014
- Last updated
- 11 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Crist M, Yaniv B, Palackdharry S, Lehn MA, Medvedovic M, Stone T, Gulati S, Karivedu V, Borchers M, Fuhrman B, Crago A, Curry J, Martinez-Outschoorn U, Takiar V, Wise-Draper TM. Metformin increases natural killer cell functions in head and neck squamous cell carcinoma through CXCL1 inhibition. J Immunother Cancer. 2022 Nov;10(11):e005632. doi: 10.1136/jitc-2022-005632.
PubMed 36328378
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose-finding Study of Metformin in Combination With Concurrent Cisplatin and Radiation in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT02325401
- Acronym / sponsor ID
- UCCI-HN-14-01
- Conditions
- Head and Neck Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Study start
- 11 May 2015 (actual)
- Primary completion
- 26 Dec 2017 (actual)
- Study completion
- 21 Feb 2020 (actual)
- First posted
- 25 Dec 2014 (estimated)
- Results
- Posted 11 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to test the safety of adding metformin to standard of care. The standard of care treatment will be cisplatin once every 3 weeks for 3 treatments and radiation for 7 weeks.
Metformin is a medication that is currently used to treat diabetes. Increasing amounts of metformin will be given to groups of patients already receiving normal treatment for their cancer to see if metformin causes any good effects by killing your cancer or bad effects (side effects).
Detailed description
Patients were registered by contacting the University of Cincinnati Clinical Trials Office. Patients must be registered and consent obtained prior to initiation of any protocol therapy.
Treatment was administered on an outpatient basis. Adverse events and potential risks for metformin and cisplatin and radiation were reported.
Patients must have screening labs performed within 2 weeks of start of treatment including a complete blood count, liver function tests, metabolic renal panel including magnesium, vitamin B12 level, lactate, and C-peptide. Renal panel must be verified within 24 hours of cisplatin administration. They must fulfill inclusion criteria.
The recommended starting dose of metformin in diabetic patients is 500mg orally twice a day which can be escalated by 500mg increments weekly as tolerated with the maximum recommended daily dose of 2550mg.
Cisplatin was given either before or after the radiation therapy fraction that is given on the same day. If radiation is held for more than 2 days (for any reason), cisplatin may be held as well until radiation resumes.
The prescribed radiotherapy dose was be 70 Gy in 2 Gy once-daily fraction size (total of 35 fractions).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Metformin with Chemoradiation | Experimental | Drug: Metformin, Drug: Cisplatin, Radiation: Radiation TherapyMetformin administered orally daily to start one week prior to Cisplatin and Radiation Therapy. Metformin dose is escalating. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Locally advanced squamous cell cancer of the head and neck, stage III or IV disease (T1-2, N2a-3 or T3-4).
- Measurable disease
- No prior chemotherapy or radiation for head and neck squamous cell cancer
- Life expectancy of greater than 3 months.
- Adequate labs
Key exclusion criteria (5 listed)
- Known metastatic disease.
- Nasopharyngeal carcinoma
- History of allergic reactions attributed to metformin or other agents used in study.
- Known diagnosis of diabetes requiring insulin for control.
- Administration of metformin within last 4 weeks.
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 |
|---|---|---|
| MetforminAlso: Fortamet, Glucophage, Glucophage XR, GlumetzaEscalating doses of 2000mg, 2550 mg and 3000mg. Starting 1 week prior to the initiation of chemoradiation and ending the final day of chemo or radiation. | Drug | Metformin with Chemoradiation |
| CisplatinAlso: Platinol, Platinol-AQDosed at 100mg/m2 on days 1, 22, and 43 | Drug | Metformin with Chemoradiation |
| Radiation Therapy70 Gy in 2 Gy once daily fractions of 35 fractions | Radiation | Metformin with Chemoradiation |
Primary outcome
Maximum Tolerated Dose (MTD) of Metformin in Combination With Concurrent Cisplatin and Radiation
Time frame: 24 months
Cohorts of patients received escalating doses of metformin (2000 mg, 2550 mg, or 3000 mg divided into daily doses) with a 7-day to 14-day lead-in prior to CRT based on the modified toxicity probability interval design to allow for possible re-escalation after previous de-escalation and to maximize the ability to identify the maximum tolerated dose (MTD). Patients continued to receive metformin for the duration of CRT as tolerated.
4 secondary outcomes
Number of Participants Experiencing No-Reoccurrence at 36 Months
Time frame: 36 months
Number of Participants With Adverse Events
Time frame: 36 months
Progression Free Survival
Time frame: 24 months
Overall Survival
Time frame: 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36328378Crist M, Yaniv B, Palackdharry S, Lehn MA, Medvedovic M, Stone T, Gulati S, Karivedu V, Borchers M, Fuhrman B, Crago A, Curry J, Martinez-Outschoorn U, Takiar V, Wise-Draper TM. Metformin increases natural killer cell functions in head and neck squamous cell carcinoma through CXCL1 inhibition. J Immunother Cancer. 2022 Nov;10(11):e005632. doi: 10.1136/jitc-2022-005632.
Related trials for Head and Neck Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
Proton Re-irradiation in Patients With Recurrent or Second Primary Head and Neck Cancer , a Multicentre Phase II Single Arm Trial
Head & Neck Cancer
RecruitingPhase 2/3
Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types
Oesophageal Cancer, Gastric Cancer
RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
RecruitingPhase 4
Lidocaine Infiltration and Neuroimmunomodulation in Head and Neck Cancer Surgery
Head and Neck Cancer (H&N)
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.
Trisha Wise-Draper, MD principal investigator
University of Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Metformin, Cisplatin and Radiation Therapy in people with Head and Neck Cancer, run by University of Cincinnati at 1 site in United States.
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 5 inclusion and 5 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 11 Jun 2020. 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 United States. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Maximum Tolerated Dose (MTD) of Metformin in Combination With Concurrent Cisplatin and Radiation (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02325401, which also lists 1 linked publication.
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 11 Jun 2020.