Combining Pembrolizumab and Metformin in Metastatic Head and Neck Cancer Patients
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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
Arms and Interventions
| 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:
Drug: Pembrolizumab
Pembrolizumab q 3 weeks
Other Names:
|
| 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:
Drug: Pembrolizumab
Pembrolizumab q 3 weeks
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Response by RECIST 1.1 and iRECIST [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 Outcome Measures
- Number of patients with adverse events measured by CTCAE v5.0 [2 years]
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.
- Progression Free Survival (PFS) [1 year]
To observe and record progression free survival in recurrent and/or metastatic HNSCC patients receiving the combination of metformin and pembrolizumab.
- Overall Survival (OS) [1 year]
To observe and record overall survival in recurrent and/or metastatic HNSCC patients receiving the combination of metformin and pembrolizumab.
Other Outcome Measures
- Percentage of peripheral blood immune cell populations determined by flow cytometry [4 weeks]
Peripheral blood will be collected from each treatment group
- Percent tumor infiltrating NK cells determined by immunofluorescence [4 weeks]
FFPE will be stained with NK cell antibodies to determine infiltrating NK cells
- Cytokine levels including IL-2, IL-4, IL-6, IL-8, IL-10, INFgamma, TNFalpha in Plasma via ELISA based technology. [4 weeks]
Plasma will be separated from peripheral blood from both treatment groups
- Percentage of NK cell cytotoxicity via Natural Killer Cell Cytotoxicity Flow Based Assays. [4 weeks]
Peripheral Blood separated for NK cells will be used from both treatment groups.
- Stat-3 RNA levels in NK cells via RNA in situ [4 weeks]
FFPE will be used from both treatment groups.
- Percent secretion of NKG2D soluble ligands via ELISA. [4 weeks]
Peripheral Blood will be used from both treatment groups
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Cincinnati Medical Center | Cincinnati | Ohio | United States | 45219 |
Sponsors and Collaborators
- Trisha Wise-Draper
- American Cancer Society, Inc.
Investigators
- Principal Investigator: Trisha Wise-Draper, MD, PhD, University of Cincinnati
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- UCCC-HN-19-01