A Study of Cemiplimab With Chemotherapy and Immunotherapy in People With Head and Neck Cancer

Официальное название

A Pilot Study of Neoadjuvant Cemiplimab With Platinum-Doublet Chemotherapy, and Cetuximab in Patients With Resectable, Locally Advanced Head and Neck Squamous Cell Carcinoma

Обзор

The purpose of this study is to find out whether combining the standard chemotherapy for head and neck cancer with the immunotherapy drugs cetuximab and cemiplimab (the study drug) is a safe treatment for head and neck cancer, and whether receiving this combination treatment before surgery may allow participants to forgo the standard radiation treatment after surgery.

Вмешательства

• Препарат Cisplatin
  Cisplatin 75mg/m2 AUC 5 on weeks 2, 5, and 8
• Препарат Carboplatin
  Carboplatin AUC 5 on weeks 2, 5, and 8
• Препарат Docetaxel
  Docetaxel 75mg/m2 on weeks 2, 5, and 8
• Препарат Cetuximab
  Cetuximab 400mg/m2 on week 1, 250mg/m2 on weeks 2, 3, 4, 5, 6, 7, 8, 9, 10
• Препарат Cemiplimab
  Cemiplimab 350mg on weeks 2, 5, 8, 11; if adjuvant radiation +/- chemotherapy is omitted, Cemiplimab will be administered on weeks 16, 19, 22, 25, 28, 31, 34, 37
• Процедура Surgical Resection of Primary +/- Neck Dissection
  Twenty-eight days (+ 7 days) following the 3rd cycle of neoadjuvant therapy, patients will then undergo definitive surgical resection of the primary site +/- neck dissection(s).
• Лучевая терапия Post-operative radiation therapy
  Post-operative radiation therapy +/- radiosensitizing agent(s) will be administered per standard-of-care based on pathologic staging of the surgical specimen. If there is an excellent response to treatment with a high degree of downstaging the addition of adjuvant radiation may be omitted if NCCN guidelines are met. If the pathologic stage following induction systemic therapy and surgery is ypT1-2N0 without the presence of adverse features that include positive margins or a combination of perine
• Препарат Paclitaxel
  If participants are unable to receive Docetaxel due to lack of insurance approval or due to an allergic reaction, Docetaxel can be substituted with Paclitaxel. Paclitaxel would be dosed at 90 mg/m2 on weeks 2, 3, 5, 6, 8 and 9.

Первичные конечные точки

• Incidence of toxicities graded according to NCI CTCAE [Срок оценки: 1 year]

Критерии участия

Критерии включения

• Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma of the head and neck that has arisen from the oral cavity, oropharynx, nasal cavity, paranasal sinuses, larynx, or hypopharynx
• Clinical stage T1, N2-3; T2, N1-3, T3/T4a, Any N (AJCC, 8th ed.) without evidence of distant metastasis (M0) based on PET/CT or CT chest, abdomen, and pelvis, for which standard-of-care treatment would entail surgical resection with adjuvant radiation +/- chemotherapy.

° Patients with recurrent and multiple primary head and neck cancers that are surgically resectable are eligible if the patient did not receive prior radiation or systemic therapy.

• Disease must be amenable to surgical resection.
• The patient must be a surgical candidate.

• Hemoglobin > 9.0 g/dL
• Absolute neutrophil count (ANC) >1.5 x 10\^9/L
• Platelet count >100 x 10\^9/L
• Serum creatinine <1.5 upper limit of normal (ULN) or estimated creatinine clearance (CrCl) >30 mL/min
• Adequate hepatic function:
• Total bilirubin <1.5 x upper limit of normal ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both < 3 x ULN
• Alkaline phosphatase (ALP) <2.5 x ULN Note: For patients with Gilbert syndrome, total bilirubin <3x ULN. Upper central must be documented appropriately as past medical history.
• Men and woman >18 years old
• Eastern cooperative oncology group performance status < 1

Критерии исключения

• Prior radiation and systemic therapy for a head and neck cancer.
• Oral cavity cancer that is not amenable to surgical resection or the patient is not a surgical candidate.
• Active or prior documented autoimmune or inflammatory disorders that have been treated with steroids or immunomodulator therapy in the past 5 years.

Exceptions: Patients with vitiligo, type 1 diabetes mellitus, and endocrinopathies (including hypothyroidism due to autoimmune thyroiditis) only requiring hormone replacement, childhood asthma that is resolved, or psoriasis it does not require systemic treatment are permitted.

• Conditions requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressant medications within 14 days of treatment on study.
• Receipt of live attenuated vaccine within 30 days prior initiating treatment on study.
• Prior allogeneic stem cell transplantation, or autologous stem cell transplantation.
• Any infection requiring hospitalization and/or intravenous antibiotic therapy within 2 weeks of the start of treatment.
• Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C virus (HBV or HCV) infection; or diagnosis of immunodeficiency.

• Patients with known HIV infection who have controlled infection (undetectable viral load (HIV RNA PCR) and CD4 count above 350, either spontaneously or on a stable antiviral regimen) are permitted. For patients with controlled HIV infection monitoring will be performed per local standards
• Patients with HBV (hepatitis B surface antigen positive; HBsAg+) who have controlled infection (serum HBV DNA PCR that is below the limit of detection and receiving anti-viral therapy for HBV) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA. Patients must remain on anti-viral therapy for at least 6 months be on the last dose of Cemiplimab.
• Patients were HCV antibody positive (HCV Ab+) who have controlled infection (undetectable HCV RNA by PCR, either spontaneously or in response to successful prior course of anti-HCV therapy) are permitted.
• History of immune-related pneumonitis with the last 5 years.
• History of interstitial lung disease (e.g., idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis that required immune-suppressive doses of leuko-corticoids to assist with management.
• Known hypersensitivity or allergy to any of the excipients in the cemiplimab drug product.
• Patients with a history of solid organ transplant (exception: corneal transplant)
• Any medical comorbidity, physical examination finding, or metabolic dysfunction, or clinical laboratory abnormality that in the opinion of the investigator renders the patient unsuitable for participation in a clinical trial due to high safety risks.
• Women with a positive serum or urine beta-hCG pregnancy test at screening/baseline visit. If positive, pregnancy must be ruled out by ultrasound for patient to be eligible.
• Breast-feeding women
• Women of childbearing potential who are sexually active and aren't willing to practice highly effective contraception prior to the first dose of Cemiplimab, during the study, and for at least 180 days after the last dose. Highly effective contraceptive measures include:

• Stable use of combined estrogen and progesterone containing hormonal contraception or progesterone and-only hormonal contraception associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening
• Intrauterine device; intrauterine hormone-releasing system
• Bilateral tubal ligation
• Vasectomized partner and/or
• Sexual abstinence

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 7 центров

• Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities) — Basking Ridge
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown
• Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale
• Memorial Sloan Kettering Cancer Center @ Suffolk-Commack (Consent only) — Commack
• Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison
• Memorial Sloan Kettering Cancer Center — New York
• Memorial Sloan Kettering Nassau (Limited Protocol Activites) — Rockville Centre

Идентификаторы

NCT: NCT04722523 · 20-445

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗