Back to resultsCombining Pembrolizumab and Metformin in Metastatic Head and Neck Cancer Patients
Primary Purpose
Head and Neck Squamous Cell Carcinoma
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Metformin Extended Release Oral Tablet
Pembrolizumab
Sponsored by
About this trial
This is an interventional treatment trial for Head and Neck Squamous Cell Carcinoma
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
Sites / Locations
- University of Cincinnati Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm 1: Metformin before Pembrolizumab
Arm 2: Metformin after Pembrolizumab
Arm Description
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.
D-21 Begin Pembrolizumab 200mg. D-7 begin Metformin ER 1000mg daily. D1 begin Metformin ER 2000mg daily. Continue Pembrolizumab 200mg every 3 weeks.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Overall Survival (OS)
To observe and record overall survival in recurrent and/or metastatic HNSCC patients receiving the combination of metformin and pembrolizumab.
Full Information
NCT ID
NCT04414540
First Posted
May 11, 2020
Last Updated
October 3, 2022
Sponsor
Trisha Wise-Draper
Collaborators
American Cancer Society, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04414540
Brief Title
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
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 31, 2020 (Actual)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
July 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Trisha Wise-Draper
Collaborators
American Cancer Society, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Squamous Cell Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Patients will be on one of two arms that will be studied in parallel.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm 1: Metformin before Pembrolizumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm 2: Metformin after Pembrolizumab
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Metformin Extended Release Oral Tablet
Other Intervention Name(s)
Glucophage XR
Intervention Description
Metformin ER starting dose 1000mg daily Metformin ER escalation dose 2000mg daily
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention Description
Pembrolizumab q 3 weeks
Primary Outcome Measure Information:
Title
Overall Response by RECIST 1.1 and iRECIST
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Number of patients with adverse events measured by CTCAE v5.0
Description
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.
Time Frame
2 years
Title
Progression Free Survival (PFS)
Description
To observe and record progression free survival in recurrent and/or metastatic HNSCC patients receiving the combination of metformin and pembrolizumab.
Time Frame
1 year
Title
Overall Survival (OS)
Description
To observe and record overall survival in recurrent and/or metastatic HNSCC patients receiving the combination of metformin and pembrolizumab.
Time Frame
1 year
Other Pre-specified Outcome Measures:
Title
Percentage of peripheral blood immune cell populations determined by flow cytometry
Description
Peripheral blood will be collected from each treatment group
Time Frame
4 weeks
Title
Percent tumor infiltrating NK cells determined by immunofluorescence
Description
FFPE will be stained with NK cell antibodies to determine infiltrating NK cells
Time Frame
4 weeks
Title
Cytokine levels including IL-2, IL-4, IL-6, IL-8, IL-10, INFgamma, TNFalpha in Plasma via ELISA based technology.
Description
Plasma will be separated from peripheral blood from both treatment groups
Time Frame
4 weeks
Title
Percentage of NK cell cytotoxicity via Natural Killer Cell Cytotoxicity Flow Based Assays.
Description
Peripheral Blood separated for NK cells will be used from both treatment groups.
Time Frame
4 weeks
Title
Stat-3 RNA levels in NK cells via RNA in situ
Description
FFPE will be used from both treatment groups.
Time Frame
4 weeks
Title
Percent secretion of NKG2D soluble ligands via ELISA.
Description
Peripheral Blood will be used from both treatment groups
Time Frame
4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
UCCC Clinical Trials Office
Phone
513-584-7698
Email
cancer@uchealth.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Trisha Wise-Draper, MD, PhD
Organizational Affiliation
University of Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Cincinnati Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
UCCC CTO
Phone
513-584-7698
Email
cancer@uchealth.com
First Name & Middle Initial & Last Name & Degree
Trisha Wise-Draper, MD,PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Combining Pembrolizumab and Metformin in Metastatic Head and Neck Cancer Patients
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