Testing the Addition of Chemotherapy or Chemo-Immunotherapy to the Usual Surgery for Advanced Head and Neck Cancer
Testing the Addition of Chemotherapy or Chemo-Immunotherapy to the Usual Surgery for Advanced Head and Neck Cancer
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.
Head/Neck
Phase II
Adults
Chemotherapy - cytotoxic,
Mol. targeted/Immunotherapy/Biologics,
Radiotherapy,
Surgery
Carboplatin,
Cemiplimab,
Cisplatin,
Paclitaxel
Gibson, Mike
National
Vanderbilt University
05-26-2026
Eligibility
18 Years and older
ALL
false
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 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)
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 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)
