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)

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.

Detailed description

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. 6-10 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: 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. 6-10 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. 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.

Arms & interventions

• ProcedureBiospecimen Collection

  Undergo blood sample collection

• DrugCarboplatin

  Given IV

• BiologicalCemiplimab

  Given IV

• DrugCisplatin

  Given IV

• ProcedureComputed Tomography

  Undergo CT scan

• DrugPaclitaxel

  Given IV

• ProcedurePositron Emission Tomography

  Undergo PET scan

• RadiationRadiation Therapy

  Undergo radiation therapy

• ProcedureSalvage Surgery

  Undergo standard of care salvage surgery

Outcome measures

Eligibility criteria