Testing the Addition of Chemotherapy or Chemo-Immunotherapy to the Usual Surgery for Advanced Head and Neck Cancer

This phase II trial tests the addition of chemotherapy, with carboplatin and paclitaxel, or chemo-immunotherapy, with carboplatin, paclitaxel and cemiplimab to standard salvage surgery followed by post operative radiation therapy and cisplatin for high risk patients, for the treatment of patients with PD-L1 positive head and neck squamous cell carcinoma that has come back and spread to nearby tissue or lymph nodes after a period of improvement (locally recurrent) or is persistent. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Salvage surgery is surgery that takes place to remove tumor tissue after a failure of other treatment. High risk patients also receive radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Adding chemotherapy or chemo-immunotherapy to standard salvage surgery may kill more tumor cells than salvage surgery alone in patients with PD-L1 positive locally recurrent or persistent head and neck squamous cell carcinoma.

NCT Number	NCT07195734
Lead Sponsor	National Cancer Institute (NCI)
Conditions	Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Locally Recurrent Head and Neck Squamous Cell Carcinoma, Locally Recurrent Hypopharyngeal Squamous Cell Carcinoma, Locally Recurrent Laryngeal Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oropharyngeal Squamous Cell Carcinoma, Stage II Laryngeal Cancer AJCC v8 +10 more
Enrollment	180 participants
Start Date	2026-04-24
Primary Completion	2033-02-01 (estimated)
Study Completion	2033-02-01 (estimated)
Updated on ClinicalTrials.gov	2026-08-11