Anti-PD-1 Therapy in Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma

Официальное название

Anti-PD-1 Therapy in Locoregionally Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma: A Multicenter, Randomized Controlled Clinical Trial

Обзор

The goal of this clinical trial is to determine whether a perioperative PD-1 antibody-based treatment strategy, consisting of neoadjuvant PD-1 antibody plus chemotherapy followed by adjuvant PD-1 antibody after surgery, improves outcomes compared with the current standard treatment in patients with resectable locally recurrent head and neck squamous cell carcinoma (HNSCC). The study will also evaluate the safety of this perioperative treatment approach. The main questions it aims to answer are: Does perioperative PD-1 antibody-based therapy improve event-free survival compared with the current standard treatment? What adverse events occur during treatment with neoadjuvant PD-1 antibody plus chemotherapy and adjuvant PD-1 antibody? Researchers will compare a perioperative PD-1 antibody-based treatment strategy with the current standard treatment to determine which approach provides better clinical outcomes. Participants will: Be randomly assigned to one of two study groups. Receive either neoadjuvant PD-1 antibody plus chemotherapy followed by surgery and adjuvant PD-1 antibody, or undergo upfront surgery followed by standard postoperative treatment as indicated. Visit the clinic regularly for physical examinations, blood tests, imaging assessments, and other study procedures. Be followed after treatment to monitor disease status, treatment response, survival outcomes, and adverse events.

Вмешательства

• Препарат Neoadjuvant PD-1 antibody plus chemotherapy
  Administered once every 3 weeks for 2 to 4 cycles before surgery
• Процедура surgery
  Surgery followed by postoperative radiotherapy or chemoradiotherapy as clinically indicated.
• Препарат Adjuvant PD-1 antibody
  Administered postoperatively every 3 weeks for up to 15 cycles.

Первичные конечные точки

• Event-Free Survival (EFS) [Срок оценки: 2 years after randomization]

Вторичные конечные точки (7)

• Overall Survival (OS) [Срок оценки: 2 years after randomization]
• 5-Year Event-Free Survival (EFS) [Срок оценки: 5 years after randomization]
• 5-Year Overall Survival (OS) [Срок оценки: 5 years after randomization]
• Adverse Events and Serious Adverse Events [Срок оценки: From initiation of assigned treatment through 30 days after treatment completion or discontinuation; serious adverse events and adverse events of special interest through 90 days after treatment completion or discontinuation.]
• Pathologic Complete Response (pCR) Rate [Срок оценки: Within 2 weeks after surgery]
• Major Pathologic Response (MPR) Rate [Срок оценки: Within 2 weeks after surgery]
• Objective Response Rate (ORR) [Срок оценки: At the preoperative tumor assessment after completion of 2 to 4 cycles of neoadjuvant treatment (each cycle is 21 days; approximately 6 to 12 weeks after initiation of neoadjuvant treatment).]

Критерии участия

Критерии включения

• Age: 18 to 80 years old (inclusive).
• Primary Tumor: Histologically or cytologically confirmed head and neck squamous cell carcinoma (excluding nasopharyngeal carcinoma). Patients must have previously received surgery and/or radiotherapy.
• Diagnosis: Locally recurrent or metastatic disease confirmed by pathology and/or imaging.
• Clinical Stage: T1-4a, N0-2, M0 (AJCC TNM Staging System, 8th Edition), with no evidence of distant metastasis, and the recurrent lesion is assessed as surgically resectable.
• Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life Expectancy: Expected survival ≥ 6 months.
• Immunotherapy: No significant contraindications to immunotherapy.
• Consent to Surgery: Willing to undergo surgical treatment.
• Adequate Organ Function:

Hematology (without transfusion or hematopoietic growth factor support within 14 days): WBC ≥ 4.0 × 10⁹/L, ANC ≥ 1.5 × 10⁹/L, Platelets ≥ 100 × 10⁹/L, Hemoglobin ≥ 90 g/L.

Biochemistry: Serum albumin ≥ 3.0 g/dL (30 g/L), Total bilirubin (TBIL) ≤ 1.5 × ULN, ALT and AST ≤ 2.5 × ULN, BUN and Creatinine ≤ 1.5 × ULN, or calculated creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula).

Coagulation: Adequate coagulation function defined as International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × ULN. For participants receiving anticoagulant therapy, PT must be within the intended therapeutic range of the anticoagulant.

• Contraception: Female participants of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment and must agree to use effective contraception during the study and for 6 months after the last dose of the anti-PD-1 antibody. Male participants with female partners of childbearing potential must agree to use effective contraception during the study and for 6 months after the last dose of the anti-PD-1 antibody.
• Informed Consent: The participant must voluntarily join the study, sign the informed consent form, be compliant, and be willing to cooperate with follow-up.

Критерии исключения

• Prior treatment with anti-PD-1/PD-L1 antibodies, anti-PD-L2 antibodies, anti-CD137 antibodies, CTLA-4 antibodies, or other drugs/antibodies targeting T-cell co-stimulation or checkpoint pathways.
• Presence of active severe autoimmune disease. Participants with conditions that are stable and do not require systemic immunosuppressive therapy are eligible, such as: Type I diabetes mellitus, hypothyroidism requiring only hormone replacement therapy, and skin conditions not requiring systemic treatment (e.g., vitiligo, psoriasis, and alopecia).
• Has a congenital or acquired immunodeficiency (e.g., HIV infection), active hepatitis B (HBV-DNA ≥ 10⁴ copies/mL), or active hepatitis C (positive hepatitis C antibody and HCV-RNA above the lower limit of detection of the assay).
• Known allergy to the study drug or any of its excipients; or a history of severe allergic reactions to other monoclonal antibodies.
• Occurrence of any of the following within 6 months prior to randomization: myocardial infarction, severe/unstable angina pectoris, cardiac insufficiency of NYHA Class 2 or higher, clinically significant supraventricular or ventricular arrhythmias, or symptomatic congestive heart failure.
• Vaccination with a live vaccine within 4 weeks prior to the first dose of the study drug. Inactivated virus vaccines for seasonal influenza administered via injection are permitted; however, intranasal live attenuated influenza vaccines are not permitted.
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Known history of psychoactive substance abuse or drug addiction.
• Pregnant or breastfeeding women.
• Diagnosis of any other malignancy within 5 years prior to study entry, with the exception of locally treated and cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ, ductal carcinoma in situ of the breast, and papillary thyroid cancer.
• Presence of any other severe physical or mental illness or laboratory abnormality that may increase the risk of participating in the study, interfere with the study results, or render the participant unsuitable for participation in the study, as judged by the investigator.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07751289 · neo-Recur

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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