A Phase 2 Feasibility Study Combining Pembrolizumab and Metformin to Harness the Natural Killer Cytotoxic Response in Metastatic Head and Neck Cancer Patients
Trial Snapshot
- Phase
- Phase 2
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 21
- Locations
- 2
- Primary Endpoint
- Overall Response by RECIST 1.1 and iRECIST
Study Overview
Brief 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.
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
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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.
Intervention: Pembrolizumab (Drug)
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.
Intervention: Pembrolizumab (Drug)
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.
Intervention: Metformin Extended Release Oral Tablet (Drug)
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.
Intervention: Metformin Extended Release Oral Tablet (Drug)
Outcomes
Primary Outcomes
Overall Response by RECIST 1.1 and iRECIST
Time Frame: 2 years
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.
Secondary Outcomes
- Number of patients with adverse events measured by CTCAE v5.0(2 years)
- Progression Free Survival (PFS)(1 year)
- Overall Survival (OS)(1 year)
Investigators
Trisha Wise-Draper
Principal Investigator
University of Cincinnati