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

NCT ID: NCT07195734

Last Updated: 2025-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

180 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-02-12

Study Completion Date

2033-02-01

Brief Summary

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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.

Detailed Description

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PRIMARY OBJECTIVE:

I. To assess and compare investigator-assessed event-free survival (EFS) of patients treated with chemotherapy (carboplatin + paclitaxel) or chemo-immunotherapy (carboplatin + paclitaxel + cemiplimab \[REGN2810\]) prior to salvage surgery (SS) versus patients undergoing standard of care SS.

SECONDARY OBJECTIVES:

I. To assess and compare disease-free survival (DFS). II. To assess and compare overall survival (OS). III. To assess and compare distant metastasis (DM). IV. To assess and compare acute and late toxicity (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0), and surgical complications.

V. To assess radiographic response (Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1) to neoadjuvant therapy in the experimental arms.

VI. To assess pathologic response in the experimental arms.

EXPLORATORY OBJECTIVES:

I. To assess and compare clinical outcomes (EFS, DFS, OS, DM, and response) within the PD-L1 subgroups (combined positive score \< 20 versus ≥ 20).

II. To determine the impact of surgical quality benchmarks (margin assessment, cervical lymph node harvest collected per central surgery review) and oncologic outcomes.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM 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 intravenously (IV) once per week for 6 weeks during radiation treatment, in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan, positron emission tomography (PET) scan and optionally undergo blood sample collection throughout the study.

ARM 2: Patients 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. 6-8 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: Patients 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. 6-8 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.

After completion of study treatment, patients are followed up at 12 weeks or at the end of post operative radiation, then every 3 months for 2 years, every 6 months for years 3 and 4 and annually thereafter.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1 (Salvage surgery)

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.

Group Type ACTIVE_COMPARATOR

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Cisplatin

Intervention Type DRUG

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo CT scan

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET scan

Radiation Therapy

Intervention Type RADIATION

Undergo radiation therapy

Salvage Surgery

Intervention Type PROCEDURE

Undergo standard of care salvage surgery

Arm 2 (Chemotherapy, salvage surgery)

Patients 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. 6-8 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.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Carboplatin

Intervention Type DRUG

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo CT scan

Paclitaxel

Intervention Type DRUG

Given IV

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET scan

Radiation Therapy

Intervention Type RADIATION

Undergo radiation therapy

Salvage Surgery

Intervention Type PROCEDURE

Undergo standard of care salvage surgery

Arm 3 (Chemo-immunotherapy, salvage surgery)

Patients 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. 6-8 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.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Carboplatin

Intervention Type DRUG

Given IV

Cemiplimab

Intervention Type BIOLOGICAL

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo CT scan

Paclitaxel

Intervention Type DRUG

Given IV

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET scan

Radiation Therapy

Intervention Type RADIATION

Undergo radiation therapy

Salvage Surgery

Intervention Type PROCEDURE

Undergo standard of care salvage surgery

Interventions

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Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Carboplatin

Given IV

Intervention Type DRUG

Cemiplimab

Given IV

Intervention Type BIOLOGICAL

Cisplatin

Given IV

Intervention Type DRUG

Computed Tomography

Undergo CT scan

Intervention Type PROCEDURE

Paclitaxel

Given IV

Intervention Type DRUG

Positron Emission Tomography

Undergo PET scan

Intervention Type PROCEDURE

Radiation Therapy

Undergo radiation therapy

Intervention Type RADIATION

Salvage Surgery

Undergo standard of care salvage surgery

Intervention Type PROCEDURE

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 JM8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo Cemiplimab RWLC Cemiplimab-rwlc Libtayo REGN 2810 REGN-2810 REGN2810 Abiplatin Blastolem Briplatin CDDP Cis-diammine-dichloroplatinum Cis-diamminedichloridoplatinum Cis-diamminedichloro Platinum (II) Cis-diamminedichloroplatinum Cis-dichloroammine Platinum (II) Cis-platinous Diamine Dichloride Cis-platinum Cis-platinum II Cis-platinum II Diamine Dichloride Cismaplat Cisplatina Cisplatinum Cisplatyl Citoplatino Citosin Cysplatyna DDP Lederplatin Metaplatin Neoplatin Peyrone's Chloride Peyrone's Salt Placis Plastistil Platamine Platiblastin Platiblastin-S Platinex Platinol Platinol- AQ Platinol-AQ Platinol-AQ VHA Plus Platinoxan Platinum Platinum Diamminodichloride Platiran Platistin Platosin CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type tomography Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography PT Cancer Radiotherapy Energy Type ENERGY_TYPE Irradiate Irradiated Irradiation Radiation Radiation Therapy, NOS Radiotherapeutics Radiotherapy RT Therapy, Radiation Rescue Surgery Salvage Resection Salvage Surgical Resection Surgical Salvage

Eligibility Criteria

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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
* No prior systemic therapy or immunotherapy for treatment of recurrent or metastatic SCCHN.

* Note: Patients who have completed immunotherapy within the definitive setting (neo-adjuvant, or adjuvant) at least 4 months prior to registration are eligible
* 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 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nabil F Saba

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Other Identifiers

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NCI-2025-06920

Identifier Type: REGISTRY

Identifier Source: secondary_id

NRG-HN015

Identifier Type: OTHER

Identifier Source: secondary_id

NRG-HN015

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180868

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2025-06920

Identifier Type: -

Identifier Source: org_study_id