Memory Phenotype and PD-1 Inhibition Response in Oral Cancer

August 9, 2022 updated by: Medical University of South Carolina

The Role of the Central Memory Phenotype in Predicting Response to PD-1 Inhibition in Pre-clinical Models of Oral Cancer

The purpose of this research study is collect tissue and blood samples from patients who are having surgery and use those samples in lab studies to see if there are any markers in blood and tissue that can help predict how cancer will react to different treatment. Participants in this study will have a blood sample and tissue samples collected for research. The blood and tissue collected will be tested in the laboratory. The tissue collected will be left over tissue from the standard of care surgery.

Study Overview

Detailed Description

Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most common neoplasm in the world and despite advances in treatment, the 5-year survival remains approximately 50%. Because of the need for new therapies, the possibility of immunotherapeutic approaches for HNSCC patients has gained interest. Interest in this has continued as more than half of the subjects enrolled to an ongoing clinical trial in patients with with oral squamous cell carcinoma (OCSCC) have responded to neoadjuvant presurgical Nivolumab therapy. Additionally, unlike other solid tumors it appears responders have higher proportions of CD4+ tumor-infiltrating lymphocytes (TILs) whereas non-responders have an increase in CD8+ TILs population. Furthermore, the investigator's data suggests that response to PD-1 blockade is associated with an increase in CD45RA- CD62L+ population or central memory phenotype within TIL whereas progression of disease correlates with an increase in the CD45RA- CD62L- population or effector memory phenotype.

As previously demonstrated in several other tumor types the magnitude of response to immunotherapy directly correlates to presence of antigen specific T cells within the tumor and tumor microenvironment. Therefore, the long-term objective of this project is to identify predictive biomarkers of immune response from either TILs or tumor cells from patients with head and neck squamous carcinoma. To achieve this goal the overall objective of the current study is to develop a pre-clinical murine models in an effort to more completely evaluate the memory phenotype of TILs before and after PD-1 inhibition and to subsequently to determine the efficacy of TIL therapy in this mouse model of oral cancer. This project will test a central hypothesis that TILs derived from responders to neoadjuvant pre-surgical PD-1 inhibition in both a patient derived xenograft mouse model of oral cancer.

Study Type

Observational

Enrollment (Actual)

2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Hollings Cancer Center at Medical University of South Carolina

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Participants will be selected from cancer patients being seen at MUSC.

Description

Inclusion Criteria:

  • Newly diagnosed histologically proven locoregional oral squamous cell carcinoma (OSCC) without evidence of distant metastases. OSCC includes the subsites of oral tongue, floor of mouth, gingiva, retromolar trigone and buccal mucosa OR

Recurrent or persistent histologically proven locoregional OSCC that was initially treated with surgery alone.

  • must be eligible for surgical resection
  • greater than 18 years of age

Exclusion Criteria:

  • prior immunotherapy or treatment with another anti PD-1 agent besides nivolumab
  • prior chemotherapy including cetuximab or radiation therapy
  • concomitant malignancies except cutaneous squamous cell carcinoma or basal cell carcinoma
  • unresectable primary tumor or regional disease or distant metastases

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Received Nivolumab
5 milliliters (mL) of blood will be collected at the time of surgery
Left over tissue will be collected at the time of surgery
Nivolumab Naive
5 milliliters (mL) of blood will be collected at the time of surgery
Left over tissue will be collected at the time of surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Count of PDX models that are developed from patient samples
Time Frame: 6 months
It is anticipated that there will be 12 successful PDX models developed as part of this study.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in tumor growth in PDX models
Time Frame: 6 months
Tumors will be measured with calipers bi-weekly and measurements will be plotted overtime.
6 months
Change in tumor volume in PDX models
Time Frame: 6 months
Tumor volume with be calculated based on the two greatest dimensions of the tumor and will be plotted overtime.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: David Neskey, MD, Medical University of South Carolina

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 8, 2019

Primary Completion (Actual)

June 30, 2021

Study Completion (Actual)

November 22, 2021

Study Registration Dates

First Submitted

March 1, 2019

First Submitted That Met QC Criteria

March 1, 2019

First Posted (Actual)

March 5, 2019

Study Record Updates

Last Update Posted (Actual)

August 11, 2022

Last Update Submitted That Met QC Criteria

August 9, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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