Combining Pembrolizumab and Metformin in Metastatic Head and Neck Cancer Patients

Head and Neck Squamous Cell Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04414540
• Other study ID #: UCCC-HN-19-01
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 31, 2020
• Est. completion date: July 2025

Study information

• Verified date: February 2024
• Source: University of Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: July 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Metformin Extended Release Oral Tablet
Metformin ER starting dose 1000mg daily Metformin ER escalation dose 2000mg daily
• Pembrolizumab
Pembrolizumab q 3 weeks

Locations

Country	Name	City	State
United States	University of Cincinnati Medical Center	Cincinnati	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Trisha Wise-Draper	American Cancer Society, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of peripheral blood immune cell populations determined by flow cytometry	Peripheral blood will be collected from each treatment group	4 weeks
Other	Percent tumor infiltrating NK cells determined by immunofluorescence	FFPE will be stained with NK cell antibodies to determine infiltrating NK cells	4 weeks
Other	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
Other	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
Other	Stat-3 RNA levels in NK cells via RNA in situ	FFPE will be used from both treatment groups.	4 weeks
Other	Percent secretion of NKG2D soluble ligands via ELISA.	Peripheral Blood will be used from both treatment groups	4 weeks
Primary	Overall Response by RECIST 1.1 and iRECIST	To determine anti-tumor activity by measuring overall response rate by RECIST 1.1 and iRECIST in recurrent and/or metastatic HNSCC patients receiving the combination of metformin and pembrolizumab.	2 years
Secondary	Number of patients with adverse events measured by CTCAE v5.0	To observe and record safety of combination in metastatic HNSCC patients receiving the combination of metformin and pembrolizumab. AEs will be graded and recorded according to NCI CTCAE Version 5.0.	2 years
Secondary	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
Secondary	Overall Survival (OS)	To observe and record overall survival in recurrent and/or metastatic HNSCC patients receiving the combination of metformin and pembrolizumab.	1 year