Combining Pembrolizumab and Metformin in Metastatic Head and Neck Cancer Patients

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Metformin Extended Release Oral Tablet; Drug: 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 Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Metformin before Pembrolizumab; 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.	Drug: Metformin Extended Release Oral Tablet; Metformin ER starting dose 1000mg daily Metformin ER escalation dose 2000mg daily; Other Names: Glucophage XR; Drug: Pembrolizumab; Pembrolizumab q 3 weeks; Other Names: Keytruda
Experimental: Arm 2: Metformin after Pembrolizumab; D-21 Begin Pembrolizumab 200mg. D-7 begin Metformin ER 1000mg daily. D1 begin Metformin ER 2000mg daily. Continue Pembrolizumab 200mg every 3 weeks.	Drug: Metformin Extended Release Oral Tablet; Metformin ER starting dose 1000mg daily Metformin ER escalation dose 2000mg daily; Other Names: Glucophage XR; Drug: Pembrolizumab; Pembrolizumab q 3 weeks; Other Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 2 years after completion of study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1 year
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.	2 years
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.	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of peripheral blood immune cell populations determined by flow cytometry	Peripheral blood will be collected from each treatment group	4 weeks
Percent tumor infiltrating NK cells determined by immunofluorescence	FFPE will be stained with NK cell antibodies to determine infiltrating NK cells	4 weeks
Cytokine levels including IL-2, IL-4, IL-6, IL-8, IL-10, INFgamma, TNFalpha in Plasma via ELISA based technology.	Plasma will be separated from peripheral blood from both treatment groups	4 weeks
Percentage of NK cell cytotoxicity via Natural Killer Cell Cytotoxicity Flow Based Assays.	Peripheral Blood separated for NK cells will be used from both treatment groups.	4 weeks
Stat-3 RNA levels in NK cells via RNA in situ	FFPE will be used from both treatment groups.	4 weeks
Percent secretion of NKG2D soluble ligands via ELISA.	Peripheral Blood will be used from both treatment groups	4 weeks

Collaborators and Investigators

• Sponsor: Trisha Wise-Draper
• Collaborators: American Cancer Society, Inc.
• Investigators: Principal Investigator: Trisha Wise-Draper, MD, PhD, University of Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2020
• Primary Completion (Actual): February 2, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: May 11, 2020
• First Submitted That Met QC Criteria: May 29, 2020
• First Posted (Actual): June 4, 2020

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Organic Chemicals; Biguanides; Guanidines; Amidines; Metformin; pembrolizumab
• Other Study ID Numbers: UCCC-HN-19-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No