Head and Neck Squamous Cell Carcinoma
Conditions
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.
Interventions
Metformin ER starting dose 1000mg daily Metformin ER escalation dose 2000mg daily
DRUGPembrolizumab
Pembrolizumab q 3 weeks
Sponsors
American Cancer Society, Inc.
Trisha Wise-Draper
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients will be on one of two arms that will be studied in parallel.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Stat-3 RNA levels in NK cells via RNA in situ | 4 weeks | FFPE will be used from both treatment groups. |
| Percentage of peripheral blood immune cell populations determined by flow cytometry | 4 weeks | Peripheral blood will be collected from each treatment group |
| Percent secretion of NKG2D soluble ligands via ELISA. | 4 weeks | Peripheral Blood will be used from both treatment groups |
| 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. |
Countries
United States
Outcome results
None listed