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

RecruitingPhase 2

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)

Who can join

Ages 18 and older · All sexes

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)

About the study

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.

What is being tested

Sponsor: National Cancer Institute (NCI) · Participants: 180 · Started: Apr 24, 2026

Contact the study team

Official record on ClinicalTrials.gov — NCT07195734

Locations in the U.S.

ArizonaBanner University Medical Center - Tucson, Tucson
University of Arizona Cancer Center-North Campus, Tucson
CaliforniaUSC / Norris Comprehensive Cancer Center, Los Angeles
Stanford Cancer Institute Palo Alto, Palo Alto
Sutter Medical Center Sacramento, Sacramento
University of California Davis Comprehensive Cancer Center, Sacramento
GeorgiaEmory Proton Therapy Center, Atlanta
Emory University Hospital Midtown, Atlanta
IllinoisRush MD Anderson Cancer Center, Chicago
Carle at The Riverfront, Danville
Carle Physician Group-Effingham, Effingham
Rush MD Anderson Cancer Center at Rush Lisle, Lisle
Carle Physician Group-Mattoon/Charleston, Mattoon
Memorial Hospital East, Shiloh
Carle Cancer Center, Urbana
IowaUI Health Care Mission Cancer and Blood - Ankeny Clinic, Ankeny
UI Health Care Mission Cancer and Blood - West Des Moines Clinic, Clive
Broadlawns Medical Center, Des Moines
Iowa Methodist Medical Center, Des Moines
Mercy Medical Center - Des Moines, Des Moines
UI Health Care Mission Cancer and Blood - Des Moines Clinic, Des Moines
UI Health Care Mission Cancer and Blood - Laurel Clinic, Des Moines
UI Health Care Mission Cancer and Blood - Waukee Clinic, Waukee
KansasUniversity of Kansas Cancer Center, Kansas City
University of Kansas Cancer Center-Overland Park, Overland Park
University of Kansas Hospital-Westwood Cancer Center, Westwood
LouisianaLSU Health Baton Rouge-North Clinic, Baton Rouge
Our Lady of The Lake, Baton Rouge
Our Lady of the Lake Physician Group, Baton Rouge
MaineLafayette Family Cancer Center-EMMC, Brewer
MichiganUniversity of Michigan Rogel Cancer Center, Ann Arbor
University of Michigan - Brighton Center for Specialty Care, Brighton
Henry Ford Hospital, Detroit
Wayne State University/Karmanos Cancer Institute, Detroit
Weisberg Cancer Treatment Center, Farmington Hills
MississippiUniversity of Mississippi Medical Center, Jackson
MissouriSiteman Cancer Center at Saint Peters Hospital, City of Saint Peters
Siteman Cancer Center at West County Hospital, Creve Coeur
University of Kansas Cancer Center - Briarcliff, Kansas City
University of Kansas Cancer Center - North, Kansas City
University of Kansas Cancer Center - Lee's Summit, Lee's Summit
Siteman Cancer Center at Christian Hospital, St Louis
Siteman Cancer Center-South County, St Louis
Washington University School of Medicine, St Louis
NebraskaNebraska Cancer Specialists/Oncology Hematology West PC - MECC, Omaha
Nebraska Methodist Hospital, Omaha
New JerseyCooper Hospital University Medical Center, Camden
Jersey City Medical Center, Jersey City
Cooperman Barnabas Medical Center, Livingston
Monmouth Medical Center, Long Branch
Rutgers Cancer Institute of New Jersey, New Brunswick
Rutgers New Jersey Medical School, Newark
Community Medical Center, Toms River
New YorkUniversity of Rochester, Rochester
Stony Brook University Medical Center, Stony Brook
Wilmot Cancer Institute at Webster, Webster
North CarolinaUNC Lineberger Comprehensive Cancer Center, Chapel Hill
Carolinas Medical Center/Levine Cancer Institute, Charlotte
Atrium Health Cabarrus/LCI-Concord, Concord
OhioProMedica Flower Hospital, Sylvania
OklahomaUniversity of Oklahoma Health Sciences Center, Oklahoma City
OregonLegacy Mount Hood Medical Center, Gresham
Legacy Good Samaritan Hospital and Medical Center, Portland
Providence Portland Medical Center, Portland
Providence Saint Vincent Medical Center, Portland
Legacy Meridian Park Hospital, Tualatin
PennsylvaniaSaint Vincent Hospital, Erie
UPMC Hillman Cancer Center Erie, Erie
UPMC Cancer Center at UPMC Horizon, Farrell
IRMC Cancer Center, Indiana
Jefferson Hospital, Jefferson Hills
UPMC-Johnstown/John P. Murtha Regional Cancer Center, Johnstown
Forbes Hospital, Monroeville
UPMC Cancer Center - Monroeville, Monroeville
UPMC Hillman Cancer Center - Monroeville, Monroeville
Thomas Jefferson University Hospital, Philadelphia
Allegheny General Hospital, Pittsburgh
UPMC Hillman Cancer Center, Pittsburgh
UPMC-Saint Clair Hospital Cancer Center, Pittsburgh
UPMC-Saint Margaret, Pittsburgh
UPMC-Shadyside Hospital, Pittsburgh
UPMC Cancer Center at UPMC Northwest, Seneca
UPMC Cancer Center-Washington, Washington
UPMC Washington Hospital Radiation Oncology, Washington
Wexford Health and Wellness Pavilion, Wexford
Asplundh Cancer Pavilion, Willow Grove
South CarolinaMedical University of South Carolina, Charleston
TennesseeVanderbilt University/Ingram Cancer Center, Nashville
WashingtonLegacy Cancer Institute Medical Oncology and Day Treatment, Vancouver
Legacy Salmon Creek Hospital, Vancouver
WisconsinUniversity of Wisconsin Carbone Cancer Center - Johnson Creek, Johnson Creek
Gundersen Lutheran Medical Center, La Crosse
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center, Madison
University of Wisconsin Carbone Cancer Center - University Hospital, Madison
Froedtert Menomonee Falls Hospital, Menomonee Falls
Medical College of Wisconsin, Milwaukee
Froedtert and MCW Moorland Reserve Health Center, New Berlin
Drexel Town Square Health Center, Oak Creek
Froedtert West Bend Hospital/Kraemer Cancer Center, West Bend

Conditions

From ClinicalTrials.gov, data retrieved Sep 29, 2026. Each study sets its own eligibility; the study team decides who can join.