Clinical trial NCT04414540: Combining Pembrolizumab and Metformin in Metastatic Head and Neck Cancer Patients
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
Collaborators: name: American Cancer Society, Inc.
First posted: 2020-06-04
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be on one of two arms that will be studied in parallel.
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Overall Response by RECIST 1.1 and iRECIST
timeFrame: 2 years
Secondary outcomes:
measure: Number of patients with adverse events measured by CTCAE v5.0
timeFrame: 2 years
measure: Progression Free Survival (PFS)
timeFrame: 1 year
measure: Overall Survival (OS)
timeFrame: 1 year
Other outcomes:
measure: Percentage of peripheral blood immune cell populations determined by flow cytometry
timeFrame: 4 weeks
measure: Percent tumor infiltrating NK cells determined by immunofluorescence
timeFrame: 4 weeks
measure: Cytokine levels including IL-2, IL-4, IL-6, IL-8, IL-10, INFgamma, TNFalpha in Plasma via ELISA based technology.
timeFrame: 4 weeks
measure: Percentage of NK cell cytotoxicity via Natural Killer Cell Cytotoxicity Flow Based Assays.
timeFrame: 4 weeks
measure: Stat-3 RNA levels in NK cells via RNA in situ
timeFrame: 4 weeks
measure: Percent secretion of NKG2D soluble ligands via ELISA.
timeFrame: 4 weeks
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
Study officials:
affiliation: University of Cincinnati
name: Trisha Wise-Draper, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: