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)
- 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
At a glance
- Phase
- Phase 2
- Study type
- Interventional
- Sponsor
- National Cancer Institute (NCI)
- Enrolment target
- 180
- Started
- 24 April 2026
- Main results due
- 1 February 2033
- Study sites
- 113
- Registry updated
- 29 September 2026
Can you take part?
- Aged 18 years and over.
- Open to any sex.
- You need the condition being studied — healthy volunteers are not accepted.
These are the headline rules only. Every study has a longer list, and whether you are eligible is decided by the research team at the site — never by this page.
Read the full eligibility criteria
Inclusion Criteria:
* Pathologically (histologically or cytologically) proven diagnosis of locally recurrent or persistent squamous cell carcinoma of head and neck (SCCHN) arising within the oral cavity, oropharynx, larynx, or hypopharynx
* PD-L1 combined positive score (CPS) ≥ 1 using a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory
* Verify insurance (or other payment) coverage for neoadjuvant chemotherapy
* Measurable disease as defined by RECIST 1.1
* Patients must have locally recurrent or persistent SCCHN arising within the oral cavity, oropharynx, larynx, or hypopharynx (American Joint Committee on Cancer \[AJCC\] Cancer Staging Manual, 8th Edition) AND are deemed candidates for salvage surgery:
* P16 positive oropharynx patients with T2, T3, T4, N0, N1, N2 and all other patients with T2, T3, T4a, N0, N1, N2a, N2b, N2c, N3a are eligible.
* Patients must be deemed surgically resectable without gross residual disease.
* For patients with oral cavity SCCHN, only those with recurrent or persistent disease after prior surgery are eligible.
* Patients who are candidates for salvage laryngectomy to treat recurrent laryngeal cancer and who are having salvage surgery for curative intent are eligible.
* Patients with resectable lymph node-only recurrence are eligible.
* No major vascular involvement (\> 180° involvement of the common carotid or internal carotid artery), jugular foramen involvement, or prevertebral, paraspinous muscle involvement precluding a curative resection
* No evidence of distant metastatic disease
* The following minimum diagnostic workup is required:
* General history and physical examination.
* Diagnostic-quality neck CT and PET/CT of neck (PET with attenuation-correction CT of neck, chest, and abdomen)
* Age ≥ 18
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Negative urine or serum pregnancy test (in persons of childbearing potential) within 30 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
* Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3
* Platelets ≥ 100,000 cells/mm\^3
* Hemoglobin ≥ 8.0 g/dL (Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] ≥ 8.0 g/dL is acceptable)
* Adequate renal function defined as creatinine clearance (CrCL) \> 50 mL/min by the Cockcroft-Gault formula
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (Not applicable to patients with known Gilbert's syndrome)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN
* Only patients who received prior radiation therapy in the definitive or post-operative setting (limited to one course) are eligible.
* Prior radiation therapy must have been completed at least 6 months prior to registration with the majority of the index persistent/recurrent cancer volume (\> 50%) irradiated to ≥ 40 Gy at the time
* Prior systemic therapy including immunotherapy with anti-PD1 or anti-PDL1 within the definitive setting (neo-adjuvant, or adjuvant) is permitted and must have been completed at least 4 months prior to registration
* Prior systemic therapy including immunotherapy for treatment of recurrent or metastatic SCCHN is not permitted
* No investigational anti-cancer agents received within 4 weeks prior to registration
* No New York Heart Association Functional Classification III or IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)
* No active infection requiring IV antibiotics, IV antiviral, or IV antifungal treatments
* No peripheral neuropathy grade 3 or 4
* No history of interstitial lung disease
* No active, noninfectious pneumonitis requiring immunosuppressive therapy
* No history of a solid organ transplant (other than corneal transplant)
* No active autoimmune disease that has required systemic treatment in the past 2 years (i.e., use of disease-modifying agents, corticosteroids \[\> 10 mg prednisone/day or equivalent\] or immunosuppressive drugs)
* NOTE: Patients meeting the following criteria are not considered immunosuppressed and are eligible to enroll:
* Patients who require a brief course of steroids (e.g., prophylaxis for imaging assessments due to hypersensitivity to contrast agents) are not excluded
* Patients with type I diabetes mellitus, and endocrinopathies (including hypothyroidism due to autoimmune thyroiditis) only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
* Physiologic replacement doses ≤ 10 mg prednisone/day or equivalent are allowed. Inhaled or topical steroids are permitted
* No history of allergic reaction to the study agent, compounds of similar chemical or biologic composition to the study agent, and immune checkpoint inhibitors (or any of its excipients)What this study is about
In the sponsor’s own words, from the registry.
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.
Study sites(113)
Banner University Medical Center - Tucson
Tucson, Arizona, United States
Recruiting
University of Arizona Cancer Center-North Campus
Tucson, Arizona, United States
Recruiting
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Recruiting
Stanford Cancer Institute Palo Alto
Palo Alto, California, United States
Recruiting
Sutter Medical Center Sacramento
Sacramento, California, United States
Recruiting
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
Recruiting
Emory Proton Therapy Center
Atlanta, Georgia, United States
Recruiting
Emory University Hospital Midtown
Atlanta, Georgia, United States
Recruiting
Northwestern University
Chicago, Illinois, United States
Suspended
Rush MD Anderson Cancer Center
Chicago, Illinois, United States
Recruiting
Carle at The Riverfront
Danville, Illinois, United States
Recruiting
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, United States
Suspended
Carle Physician Group-Effingham
Effingham, Illinois, United States
Recruiting
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, United States
Suspended
Northwestern Medicine Glenview Outpatient Center
Glenview, Illinois, United States
Suspended
Northwestern Medicine Grayslake Outpatient Center
Grayslake, Illinois, United States
Suspended
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, United States
Suspended
Rush MD Anderson Cancer Center at Rush Lisle
Lisle, Illinois, United States
Recruiting
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, United States
Recruiting
Northwestern Medicine Oak Brook
Oak Brook, Illinois, United States
Suspended
Northwestern Medicine Orland Park
Orland Park, Illinois, United States
Suspended
Memorial Hospital East
Shiloh, Illinois, United States
Recruiting
Carle Cancer Center
Urbana, Illinois, United States
Recruiting
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, United States
Suspended
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, United States
Recruiting
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, United States
Recruiting
Methodist Jennie Edmundson Hospital
Council Bluffs, Iowa, United States
Suspended
Iowa Methodist Medical Center
Des Moines, Iowa, United States
Recruiting
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, United States
Recruiting
Broadlawns Medical Center
Des Moines, Iowa, United States
Recruiting
Mercy Medical Center - Des Moines
Des Moines, Iowa, United States
Recruiting
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, United States
Recruiting
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa, United States
Recruiting
University of Kansas Cancer Center
Kansas City, Kansas, United States
Recruiting
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, United States
Recruiting
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, United States
Recruiting
LSU Health Baton Rouge-North Clinic
Baton Rouge, Louisiana, United States
Recruiting
Our Lady of the Lake Physician Group
Baton Rouge, Louisiana, United States
Recruiting
Our Lady of The Lake
Baton Rouge, Louisiana, United States
Recruiting
Lafayette Family Cancer Center-EMMC
Brewer, Maine, United States
Recruiting
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, United States
Recruiting
University of Michigan - Brighton Center for Specialty Care
Brighton, Michigan, United States
Recruiting
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States
Recruiting
Henry Ford Hospital
Detroit, Michigan, United States
Recruiting
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, United States
Recruiting
University of Mississippi Medical Center
Jackson, Mississippi, United States
Recruiting
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, United States
Recruiting
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, United States
Recruiting
University of Kansas Cancer Center - Briarcliff
Kansas City, Missouri, United States
Recruiting
University of Kansas Cancer Center - North
Kansas City, Missouri, United States
Recruiting
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, United States
Recruiting
Washington University School of Medicine
St Louis, Missouri, United States
Recruiting
Siteman Cancer Center-South County
St Louis, Missouri, United States
Recruiting
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, United States
Recruiting
Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
Omaha, Nebraska, United States
Recruiting
Nebraska Methodist Hospital
Omaha, Nebraska, United States
Recruiting
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, United States
Recruiting
Cooper Hospital University Medical Center
Camden, New Jersey, United States
Recruiting
Jersey City Medical Center
Jersey City, New Jersey, United States
Recruiting
Cooperman Barnabas Medical Center
Livingston, New Jersey, United States
Recruiting
Showing 60 of 113 sites — filter to narrow it down. 100 of the 113 sites on this study are recruiting right now — a site can stop enrolling while the study as a whole is still open.
Source: ClinicalTrials.gov record NCT07195734. Trialion does not run this study, is not paid to refer anyone to it, and cannot enrol you. Eligibility is always decided by the research team at the site.
Not the right study?
Answer three questions and see the studies recruiting near you, in plain language.
Find a study for me