Memory Phenotype and PD-1 Inhibition Response in Oral Cancer

NCT ID: NCT03862066

Last Updated: 2022-08-11

Basic Information

• Recruitment Status: TERMINATED
• Total Enrollment: 2 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-02-08
• Study Completion Date: 2021-11-22

Brief Summary

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.

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.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Received Nivolumab

Blood collection

Intervention Type: OTHER

5 milliliters (mL) of blood will be collected at the time of surgery

Tissue collection

Intervention Type: OTHER

Left over tissue will be collected at the time of surgery

Nivolumab Naive

Blood collection

Intervention Type: OTHER

5 milliliters (mL) of blood will be collected at the time of surgery

Tissue collection

Intervention Type: OTHER

Left over tissue will be collected at the time of surgery

Interventions

Blood collection

5 milliliters (mL) of blood will be collected at the time of surgery

Intervention Type: OTHER

Tissue collection

Left over tissue will be collected at the time of surgery

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Neskey, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States

Countries

United States

Other Identifiers

102985

Identifier Type: -

Identifier Source: org_study_id