Combining Pembrolizumab and Metformin in Metastatic Head and Neck Cancer Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 2 Feasibility Study Combining Pembrolizumab and Metformin to Harness the Natural Killer Cytotoxic Response in Metastatic Head and Neck Cancer Patients

Conditions
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Head and Neck Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Metformin Extended Release Oral Tablet
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be on one of two arms that will be studied in parallel.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Metformin before Pembrolizumab<br>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<br>* Metformin ER starting dose 1000mg daily Metformin ER escalation dose 2000mg daily<br>* Other names: Glucophage XR;Drug: Pembrolizumab<br>* Pembrolizumab q 3 weeks<br>* Other names: Keytruda;|
| Experimental: Arm 2: Metformin after Pembrolizumab<br>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<br>* Metformin ER starting dose 1000mg daily Metformin ER escalation dose 2000mg daily<br>* Other names: Glucophage XR;Drug: Pembrolizumab<br>* Pembrolizumab q 3 weeks<br>* Other names: Keytruda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 |