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)

Plain English Summary

Testing the Addition of Chemotherapy or Chemo-Immunotherapy to the Usual Surgery for Advanced Head and Neck Cancer is a Phase 2 clinical trial sponsored by National Cancer Institute (NCI) studying 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. Tests adding chemotherapy or chemo-immunotherapy to standard surgery for advanced head and neck cancer. For patients with PD-L1 positive locally recurrent or persistent head and neck squamous cell carcinoma. Participation involves blood tests, IV treatments, and CT scans before and after surgery. Alternatives include standard surgery alone or other systemic therapies. The trial aims to enroll 180 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if diagnosed with locally recurrent or persistent head and neck cancer, PD-L1 positive, and deemed surgically resectable. Not eligible if have distant metastatic disease, major vascular involvement, or active infection. Age ≥ 18, ECOG performance status 0-2, and no history of allergic reactions to study agents. Must have completed prior radiation or systemic therapy as required. This trial is studying 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, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

Measures event-free survival, disease-free survival, overall survival, and surgical complications, impacting patient quality of life. The specific primary outcome measures are: Event free survival (EFS) (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). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to improve outcomes for high-risk patients with locally recurrent or persistent head and neck cancer. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets 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, where improved treatment options are needed.

Investor Insight

Addresses a significant unmet need in treating advanced head and neck cancer, with a large market and competitive landscape. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about your PD-L1 status and eligibility for the trial. Undergo blood tests, IV treatments, and CT scans before and after surgery. This trial is currently recruiting participants. The trial is being conducted at 19 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 180 participants

Interventions

• PROCEDURE: Biospecimen Collection — Undergo blood sample collection
• DRUG: Carboplatin — Given IV
• BIOLOGICAL: Cemiplimab — Given IV
• DRUG: Cisplatin — Given IV
• PROCEDURE: Computed Tomography — Undergo CT scan

Primary Outcomes

• Event free survival (EFS) (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

• 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)

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 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)

Trial Locations

• Sutter Medical Center Sacramento, Sacramento, California, United States
• Methodist Jennie Edmundson Hospital, Council Bluffs, Iowa, United States
• University of Kansas Cancer Center, Kansas City, Kansas, United States
• University of Kansas Cancer Center-Overland Park, Overland Park, Kansas, United States
• University of Kansas Hospital-Westwood Cancer Center, Westwood, Kansas, United States
• LSU Health Baton Rouge-North Clinic, Baton Rouge, Louisiana, United States
• Our Lady of the Lake Physician Group, Baton Rouge, Louisiana, United States
• University of Kansas Cancer Center - Briarcliff, Kansas City, Missouri, United States
• University of Kansas Cancer Center - North, Kansas City, Missouri, United States
• University of Kansas Cancer Center - Lee's Summit, Lee's Summit, Missouri, United States
• ...and 9 more locations

Frequently Asked Questions

Related Conditions

• Oropharyngeal cancer, laryngeal cancer, hypopharyngeal cancer, and other head and neck squamous cell carcinomas.

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