Tislelizumab Combined With Chemotherapy for Different Cycles of Neoadjuvant Therapy for Locally Advanced Resectable Squamous Cell Carcinoma of the Head and Neck (NeoTempo)

Официальное название

A Prospective, Randomized Controlled, Phase II Clinical Study on the Neoadjuvant Treatment of Locally Advanced Resectable Head and Neck Squamous Cell Carcinoma With Tislelizumab Combined With Chemotherapy for Different Cycles (NeoTempo)

Обзор

This study aims to explore the optimal course of neoadjuvant immunotherapy for HNSCC by comparing the efficacy and safety of 4 cycles and 2 cycles of neoadjuvant tislelizumab combined with chemotherapy.

Вмешательства

• Препарат Tislelizumab Combined With Chemotherapy for 4 cycles
  Tislelizumab: 200mg, day 1, every 3 weeks for 4 cycles Cisplatin: 75mg/m\^2, day 1, every 3 weeks for 4 cycles Nab-paclitaxel: 260mg/m\^2, day 1, every 3 weeks for 4 cycles
• Препарат Tislelizumab Combined With Chemotherapy for 2 cycles
  Tislelizumab: 200mg, day 1, every 3 weeks for 2 cycles Cisplatin: 75mg/m\^2, day 1, every 3 weeks for 2 cycles Nab-paclitaxel: 260mg/m\^2, day 1, every 3 weeks for 2 cycles

Первичные конечные точки

• Pathological Complete Response (pCR) [Срок оценки: 6 months]

Вторичные конечные точки (9)

• Major Pathological Response (mPR) [Срок оценки: 6 months]
• Organ perservation rate [Срок оценки: 6 months]
• Operation delay rate [Срок оценки: 6 months]
• Objective resopnse rate (ORR) [Срок оценки: 6 months]
• Event-free Survival (EFS) [Срок оценки: 3 years]
• Overall Survival (OS) [Срок оценки: 3 years]
• Percentage of adverse events graded by CTCAE v5.0 [Срок оценки: 3 years]
• Change From Baseline in Quality of Life Scale (QoL) (EORTC QLQ-C30) items 30 [Срок оценки: 3 years]
• Change From Baseline in Quality of Life Scale (QoL) EOTRC QLQ -H&N 35 [Срок оценки: 3 years]

Критерии участия

Критерии включения

• Histological or pathological diagnosis of head and neck squamous cell carcinoma;
• Initially resectable stage III-IVB oral cancer/laryngeal cancer/hypopharyngeal cancer/P16-oropharyngeal cancer, or stage III p16+ oropharyngeal cancer (AJCC 8th), and evaluated by the researcher to achieve R0 resection;
• Plan to perform neoadjuvant therapy;
• No previous anti-tumor treatment for HNSCC;
• There is at least one measurable lesion;
• Eastern Cooperative Oncology Group Performance Status (ECOG) score 0-2;
• The expected survival period is ≥3 months
• The functions of vital organs meet the following requirements (excluding any blood components and cell growth factors used within 7 days) :

i. Normal bone marrow reserve function, white blood cell (WBC) ≥3.0×109/L; Neutrophil count (NEUT) ≥ 1.5×109/L, platelet count (PLT) ≥100×109/L, hemoglobin (Hb) ≥90 g/L; ii. Normal renal function or serum creatinine (SCr) ≤ 1.5 times the upper limit of normal value (ULN) or creatinine clearance rate ≥50 ml/min (Cockcroft-Gault formula); iii. Normal liver function or total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (ULN); The level of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) is ≤ 2.5 times the upper limit of the normal value (ULN).

• Be able to and willing to abide by the research and follow-up procedures;
• Men and women of gestational age must agree to take adequate contraceptive measures throughout the study period and within 6 months after the end of treatment.
• The patient voluntarily joined this clinical study, signed the informed consent form, had good compliance and was able to cooperate with the follow-up.

Критерии исключения

• Previously received anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody or anti-CTLA-4 antibody (or any other antibody acting on T-cell co-stimulation or checkpoint pathways);
• There is a clear history of allergies, and there may be potential allergies or intolerances to the research drug and its similar biological agents;
• Participated in clinical trials of other anti-tumor drugs within 4 weeks before the first administration; Or within 4 weeks before the first administration or planning to receive a live attenuated vaccine during the study period;
• Other malignant tumors have occurred within the past five years (except for well-treated squamous cell carcinoma of the skin or controlled basal cell carcinoma of the skin);
• Immunosuppressive drugs have been used within 14 days prior to the first use of tislelizumab, excluding nasal and inhaled corticosteroids or physiological doses of systemic steroid hormones (i.e., no more than 10 mg/ day of prednisolone or equivalent physiological doses of other corticosteroids).
• Advanced patients with symptoms, who have spread to internal organs and are at risk of life-threatening complications in the short term (including those with uncontrollable large amounts of exudate \[thoracic, pericardial, abdominal\], pulmonary lymphangitis and more than 30% liver involvement)
• Any active autoimmune diseases or a history of autoimmune diseases (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; subjects with vitiligo or those whose asthma has completely relieved in childhood and do not require any intervention in adulthood can be included; Asthma subjects who require bronchodilators for medical intervention cannot be included.
• Suffering from grade II or above myocardial ischemia or myocardial infarction, and poorly controlled arrhythmias (including QTc interval ≥450ms in men and ≥470ms in women). According to the NYHA standard, patients with grade Ⅲ to Ⅳ cardiac failure, or those whose left ventricular ejection fraction (LVEF) is less than 50% as indicated by echocardiography; Myocardial infarction occurred within 6 months before enrollment, New York Heart Association Class II or above heart failure, uncontrolled angina pectoris, uncontrolled severe ventricular arrhythmia, clinically significant pericardial disease, or electrocardiogram indicating acute ischemia or abnormal active conduction system
• Concurrent severe infection within 4 weeks before the first administration (e.g., requiring intravenous infusion of antibiotics, antifungal or antiviral drugs), or unexplained fever >38.5°C during the screening period/before the first administration;
• Those with a history of abuse of psychotropic drugs and unable to quit, or those with mental disorders;
• Major surgical operations have been performed within 4 weeks prior to the first administration. Or have an open wound or fracture;
• Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), active hepatitis B (HBV DNA ≥ 500 IU/ml), hepatitis C (positive hepatitis C antibody and HCV-RNA higher than the detection limit of the analytical method), or co-infection with hepatitis B and hepatitis C;
• There is central nervous system metastasis;
• Those with a history of hereditary or acquired bleeding or coagulation disorders (the specific inclusion is determined by the researcher);
• Other circumstances where the researcher determines that one is not suitable to participate in this study.

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

Китай · 1 центр

• Tianjin Medical University Cancer Institute and Hospital, Tianjin, Tianjin 300000 — Тяньцзинь

Идентификаторы

NCT: NCT07147426 · E20250855

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗