RecruitingPhase 2NCT07195734

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

A Phase II Randomized Trial of Neoadjuvant Chemotherapy or Chemo-Immunotherapy in Patients With Recurrent/Persistent PD-L1 Enriched Squamous Cell Carcinoma of the Head and Neck Undergoing Salvage Surgery (NEOPOLIS)

Sponsor

National Cancer Institute (NCI)

Enrollment

180 participants

Start Date

Apr 24, 2026

Study Type

INTERVENTIONAL

Conditions

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 III Laryngeal Cancer AJCC v8 Stage III Lip and Oral Cavity Cancer AJCC v8 Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8 Stage IVA Laryngeal Cancer AJCC v8 Stage IVA Lip and Oral Cavity Cancer AJCC v8 Stage IVB Laryngeal Cancer AJCC v8 Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Stage II Laryngeal Cancer AJCC v8 Stage II Oropharyngeal (p16-Negative) Carcinoma AJCC v8 Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8 Stage IVB Oropharyngeal (p16-Negative) Carcinoma AJCC v8 Stage II Lip and Oral Cavity Cancer AJCC v8

Summary

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.

Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This trial is testing whether adding chemotherapy or chemo-immunotherapy before surgery (called neoadjuvant treatment) to the usual surgical approach improves outcomes in people with locally recurrent or persistent head and neck squamous cell carcinoma who are candidates for salvage surgery. **You may be eligible if...** - You have a confirmed diagnosis of recurrent or persistent squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx - Your tumor tests positive for PD-L1 (a protein used to predict immunotherapy response) with a combined positive score (CPS) of 1 or higher - You have measurable disease and are considered a surgical candidate for salvage (repeat) surgery - Your insurance or payment coverage for neoadjuvant chemotherapy has been verified **You may NOT be eligible if...** - Your tumor is PD-L1 negative (CPS below 1) - You are not considered eligible for surgery - You have stage IV disease with distant metastases that would not benefit from surgery - Other eligibility criteria specific to tumor stage and prior treatment are not met Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

PROCEDUREBiospecimen Collection

Undergo blood sample collection

DRUGCarboplatin

Given IV

BIOLOGICALCemiplimab

Given IV

DRUGCisplatin

Given IV

PROCEDUREComputed Tomography

Undergo CT scan

DRUGPaclitaxel

Given IV

PROCEDUREPositron Emission Tomography

Undergo PET scan

RADIATIONRadiation Therapy

Undergo radiation therapy

PROCEDURESalvage Surgery

Undergo standard of care salvage surgery

Locations(40)

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Sutter Medical Center Sacramento

Sacramento, California, United States

Emory Proton Therapy Center

Atlanta, Georgia, United States

Emory University Hospital Midtown

Atlanta, Georgia, United States

Rush MD Anderson Cancer Center

Chicago, Illinois, United States

UI Health Care Mission Cancer and Blood - Ankeny Clinic

Ankeny, Iowa, United States

UI Health Care Mission Cancer and Blood - West Des Moines Clinic

Clive, Iowa, United States

Methodist Jennie Edmundson Hospital

Council Bluffs, Iowa, United States

Iowa Methodist Medical Center