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)
3 other identifiers
interventional
180
1 country
35
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Oct 2026
Longer than P75 for phase_2
35 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 26, 2025
CompletedFirst Posted
Study publicly available on registry
September 29, 2025
CompletedStudy Start
First participant enrolled
October 9, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2033
Study Completion
Last participant's last visit for all outcomes
February 1, 2033
April 13, 2026
April 1, 2026
6.3 years
September 26, 2025
April 10, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Event free survival (EFS)
Will be summarized by treatment arm using standard Kaplan-Meier methods, reporting the estimated 2-year EFS rate with corresponding 95% confidence intervals.
From randomization to disease progression or treatment-related toxicities that precludes surgery, disease progression in the absence of surgery, disease recurrence after surgery, or death due to any cause, up to 7 years
Secondary Outcomes (8)
Disease free survival (DFS)
From randomization until disease recurrence, death due to any cause, up to 7 years
Overall survival (OS)
From randomization until death due to any cause, up to 7 years
Time to distant metastasis
From randomization until detection of distant metastases or death, up to 7 years
Surgical complications
Up to 7 years
Incidence of acute adverse events
Up to 30 days from the last treatment
- +3 more secondary outcomes
Study Arms (3)
Arm 1 (Salvage surgery)
ACTIVE COMPARATORPatients undergo standard of care salvage surgery. Starting within 8 weeks of surgery, patients with high risk features also undergo radiation therapy daily for 5 treatments per week for 6 weeks and receive cisplatin IV once per week for 6 weeks during radiation treatment, in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, PET scan and optionally undergo blood sample collection throughout the study.
Arm 2 (Chemotherapy, salvage surgery)
EXPERIMENTALPatients receive paclitaxel IV and carboplatin IV on day 1 of each cycle. Cycles repeat every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. 6-10 weeks after cycle 1 day 1 patients undergo standard of care salvage surgery. Starting within 8 weeks of surgery, patients with high risk features also undergo radiation therapy daily for 5 treatments per week for 6 weeks and receive cisplatin IV once per week for 6 weeks during radiation treatment, in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, PET scan and optionally undergo blood sample collection throughout the study.
Arm 3 (Chemo-immunotherapy, salvage surgery)
EXPERIMENTALPatients receive paclitaxel IV, carboplatin IV and cemiplimab IV, over 30 minutes, on day 1 of each cycle. Cycles repeat every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. 6-10 weeks after cycle 1 day 1 patients undergo standard of care salvage surgery. Starting within 8 weeks of surgery, patients with high risk features also undergo radiation therapy daily for 5 treatments per week for 6 weeks and receive cisplatin IV once per week for 6 weeks during radiation treatment, in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, PET scan and optionally undergo blood sample collection throughout the study.
Interventions
Undergo blood sample collection
Given IV
Given IV
Given IV
Undergo CT scan
Given IV
Undergo PET scan
Undergo radiation therapy
Undergo standard of care salvage surgery
Eligibility Criteria
You may qualify if:
- 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)
- +18 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (35)
Sutter Medical Center Sacramento
Sacramento, California, 95816, United States
Emory Proton Therapy Center
Atlanta, Georgia, 30308, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023, United States
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325, United States
Methodist Jennie Edmundson Hospital
Council Bluffs, Iowa, 51503, United States
Iowa Methodist Medical Center
Des Moines, Iowa, 50309, United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309, United States
Broadlawns Medical Center
Des Moines, Iowa, 50314, United States
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314, United States
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314, United States
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa, 50263, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
LSU Health Baton Rouge-North Clinic
Baton Rouge, Louisiana, 70805, United States
Our Lady of the Lake Physician Group
Baton Rouge, Louisiana, 70808, United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109, United States
University of Michigan - Brighton Center for Specialty Care
Brighton, Michigan, 48116, United States
University of Kansas Cancer Center - Briarcliff
Kansas City, Missouri, 64116, United States
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
Omaha, Nebraska, 68114, United States
Nebraska Methodist Hospital
Omaha, Nebraska, 68114, United States
Clackamas Radiation Oncology Center
Clackamas, Oregon, 97015, United States
Providence Newberg Medical Center
Newberg, Oregon, 97132, United States
Providence Willamette Falls Medical Center
Oregon City, Oregon, 97045, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
Providence Saint Vincent Medical Center
Portland, Oregon, 97225, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
Froedtert Menomonee Falls Hospital
Menomonee Falls, Wisconsin, 53051, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Froedtert and MCW Moorland Reserve Health Center
New Berlin, Wisconsin, 53151, United States
Drexel Town Square Health Center
Oak Creek, Wisconsin, 53154, United States
Froedtert West Bend Hospital/Kraemer Cancer Center
West Bend, Wisconsin, 53095, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Nabil F Saba
NRG Oncology
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 26, 2025
First Posted
September 29, 2025
Study Start (Estimated)
October 9, 2026
Primary Completion (Estimated)
February 1, 2033
Study Completion (Estimated)
February 1, 2033
Last Updated
April 13, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.