Head and Neck Squamous Cell CarcinomaPhase 2NCT04414540
Combining Pembrolizumab and Metformin in Metastatic Head and Neck Cancer Patients
A Phase 2 study testing Metformin Extended Release Oral Tablet and Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma, run by Trisha Wise-Draper at 1 site in United States.
Trial summary
The purpose of this study is to determine anti-tumor activity by measuring overall response rate in recurrent and/or metastatic HNSCC patients receiving the combination of metformin and pembrolizumab. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma
- What is being tested?
- Metformin Extended Release Oral Tablet and Pembrolizumab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Aug 2020to 30 Sep 2026
- Phase
- Phase 2
- 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
- Histologically or cytologically confirmed recurrent or metastatic non-cutaneous HNSCC for which there are no surgical or radiation curative options.
- Patients may have received up to 3 prior lines of therapy for metastatic or recurrent disease.
- ECOG performance status ≤2
Who cannot join
- Patients with nasopharyngeal HNSCC will be excluded
- Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study.
- Patients who have not recovered from adverse events due to prior anti-cancer therapy
- Patients who have previously received PD-1 or PD-L1 inhibitors for metastatic/recurrent disease
- Patients currently receiving metformin or who have received metformin in the last 6 months
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219
About this study
Official title: A Phase 2 Feasibility Study Combining Pembrolizumab and Metformin to Harness the Natural Killer Cytotoxic Response in Metastatic Head and Neck Cancer Patients
The purpose of this study is to determine anti-tumor activity by measuring overall response rate in recurrent and/or metastatic HNSCC patients receiving the combination of metformin and pembrolizumab.
Read the detailed description
Recurrent and/or metastatic HNSCC patients will be treated with combination of metformin and pembrolizumab. Patients will be randomized into arms 1 and 2, to either receive Metformin prior to pembrolizumab or to begin Metformin after pembrolizumab treatment begins. The patients are randomized for the exploratory endpoints in order to better understand the difference of effects of metformin versus pembrolizumab on the immune system although efficacy is based on combination.
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Being tested
- Metformin Extended Release Oral Tablet, Pembrolizumab
- Medical subject headings
- 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.
Metformin Extended Release Oral TabletDrug
Also called Glucophage XR
Metformin ER starting dose 1000mg daily Metformin ER escalation dose 2000mg daily
PembrolizumabDrug
Also called Keytruda
Pembrolizumab q 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Metformin before Pembrolizumab | Experimental | Metformin ER 1000mg daily D-14 to D-7. Metformin ER 2000mg daily D-7 to D1. D1 Begin Pembrolizumab 200mg every 3 weeks, while continuing Metformin ER 2000mg daily. Receives: Drug: Metformin Extended Release Oral Tablet; Drug: Pembrolizumab |
| Arm 2: Metformin after Pembrolizumab | Experimental | D-21 Begin Pembrolizumab 200mg. D-7 begin Metformin ER 1000mg daily. D1 begin Metformin ER 2000mg daily. Continue Pembrolizumab 200mg every 3 weeks. Receives: Drug: Metformin Extended Release Oral Tablet; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate by RECIST 1.1 and iRECIST
A complete response is defined as the disappearance of all target lesions, with any affected lymph nodes reduced to less than 10 mm. A partial response occurs when there is at least a 30% reduction in the total size of target lesions compared with baseline. Progressive disease is indicated by at least a 20% increase in lesion size (with a minimum absolute increase of 5 mm) or the appearance of new lesions. Stable disease describes cases where tumor size changes do not meet criteria for partial response or progressive disease.
Measured: Up to 2 years after completion of study treatment
Secondary outcomes (3)
Number of Patients With Adverse Events Measured by CTCAE v5.0
To observe and record safety of combination in metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) patients receiving the combination of metformin and pembrolizumab. AEs will be graded and recorded according to NCI CTCAE Version 5.0.
Measured: 2 years
Progression Free Survival (PFS)
To observe and record progression free survival in recurrent and/or metastatic HNSCC patients receiving the combination of metformin and pembrolizumab.
Measured: 1 year
Overall Survival (OS)
Overall survival was analyzed using the Kaplan-Meier method. The reported 1-year overall survival percentages represent Kaplan-Meier-estimated probabilities of survival at 1 year and do not correspond to the observed proportion of participants alive or deceased due to censoring. Observed all-cause mortality is reported separately as the number of participants who died due to any cause in each arm.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2020
- Study start31 Aug 2020
- Primary completion2 Feb 2026
- Study completion30 Sep 2026 (estimated)
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.
- Other trials for Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be on one of two arms that will be studied in parallel.
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Trisha Wise-Draper
- Sponsor type
- University, hospital or other
- Collaborators
- American Cancer Society, Inc.
- Responsible party
- Sponsor-investigator, Trisha Wise-Draper, University of Cincinnati
- Investigators
- Trisha Wise-Draper, MD, PhD, Principal investigator, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04414540
- Sponsor's protocol ID
- UCCC-HN-19-01
- Status last verified
- May 2026
- First submitted
- 11 May 2020
- Last updated
- 8 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Feasibility Study Combining Pembrolizumab and Metformin to Harness the Natural Killer Cytotoxic Response in Metastatic Head and Neck Cancer Patients
- ClinicalTrials.gov ID
- NCT04414540
- Acronym / sponsor ID
- UCCC-HN-19-01
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Trisha Wise-DraperUniversity, hospital or other
- Collaborators
- American Cancer Society, Inc.
- Study start
- 31 Aug 2020 (actual)
- Primary completion
- 2 Feb 2026 (actual)
- Study completion
- 30 Sep 2026 (estimated)
- First posted
- 4 Jun 2020 (actual)
- Results
- Posted 8 May 2026
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 study is to determine anti-tumor activity by measuring overall response rate in recurrent and/or metastatic HNSCC patients receiving the combination of metformin and pembrolizumab.
Detailed description
Recurrent and/or metastatic HNSCC patients will be treated with combination of metformin and pembrolizumab. Patients will be randomized into arms 1 and 2, to either receive Metformin prior to pembrolizumab or to begin Metformin after pembrolizumab treatment begins. The patients are randomized for the exploratory endpoints in order to better understand the difference of effects of metformin versus pembrolizumab on the immune system although efficacy is based on combination.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients will be on one of two arms that will be studied in parallel.
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Metformin before Pembrolizumab | Experimental | Drug: Metformin Extended Release Oral Tablet, Drug: PembrolizumabMetformin ER 1000mg daily D-14 to D-7. Metformin ER 2000mg daily D-7 to D1. D1 Begin Pembrolizumab 200mg every 3 weeks, while continuing Metformin ER 2000mg daily. |
| Arm 2: Metformin after Pembrolizumab | Experimental | Drug: Metformin Extended Release Oral Tablet, Drug: PembrolizumabD-21 Begin Pembrolizumab 200mg. D-7 begin Metformin ER 1000mg daily. D1 begin Metformin ER 2000mg daily. Continue Pembrolizumab 200mg every 3 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Histologically or cytologically confirmed recurrent or metastatic non-cutaneous HNSCC for which there are no surgical or radiation curative options.
- Patients may have received up to 3 prior lines of therapy for metastatic or recurrent disease.
- ECOG performance status ≤2
Key exclusion criteria (5 listed)
- Patients with nasopharyngeal HNSCC will be excluded
- Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study.
- Patients who have not recovered from adverse events due to prior anti-cancer therapy
- Patients who have previously received PD-1 or PD-L1 inhibitors for metastatic/recurrent disease
- Patients currently receiving metformin or who have received metformin in the last 6 months
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 |
|---|---|---|
| Metformin Extended Release Oral TabletAlso: Glucophage XRMetformin ER starting dose 1000mg daily Metformin ER escalation dose 2000mg daily | Drug | Arm 1: Metformin before Pembrolizumab, Arm 2: Metformin after Pembrolizumab |
| PembrolizumabAlso: KeytrudaPembrolizumab q 3 weeks | Drug | Arm 1: Metformin before Pembrolizumab, Arm 2: Metformin after Pembrolizumab |
Primary outcome
Overall Response Rate by RECIST 1.1 and iRECIST
Time frame: Up to 2 years after completion of study treatment
A complete response is defined as the disappearance of all target lesions, with any affected lymph nodes reduced to less than 10 mm. A partial response occurs when there is at least a 30% reduction in the total size of target lesions compared with baseline. Progressive disease is indicated by at least a 20% increase in lesion size (with a minimum absolute increase of 5 mm) or the appearance of new lesions. Stable disease describes cases where tumor size changes do not meet criteria for partial response or progressive disease.
3 secondary outcomes
Number of Patients With Adverse Events Measured by CTCAE v5.0
Time frame: 2 years
Progression Free Survival (PFS)
Time frame: 1 year
Overall Survival (OS)
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Head and Neck Squamous Cell Carcinoma
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
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
RecruitingObservational study
Multicenter Prospective Cohort on Esophageal Endoscopic Submucosal Dissection
Superficial Esophageal Cancer, Oesophageal Adenocarcinoma
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
Not yet recruiting
Tumoral Versus Luminal Microbiome in Head and Neck Squamous Cell Carcinoma
Squamous Cell Cancer of Head and Neck (SCCHN)
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, PhD 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 2 study testing Metformin Extended Release Oral Tablet and Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma, run by Trisha Wise-Draper 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 3 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: under way, not looking for participants, as of the sponsor's last update on 8 May 2026. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 8 May 2026). 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?
Overall Response Rate by RECIST 1.1 and iRECIST (time frame: Up to 2 years after completion of study treatment). 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 8 May 2026.