Toripalimab Combined With Different Platinum-Based Induction Chemotherapy Regimens for Locally Advanced Nasopharyngeal Carcinoma

Официальное название

Toripalimab Combined With Different Platinum-Based Induction Chemotherapy Regimens for Locally Advanced Nasopharyngeal Carcinoma: A Randomized, Open-label, Controlled, Multicenter Phase II Trial

Обзор

This phase II randomized trial compares the efficacy and safety of Toripalimab combined with three different platinum-based induction chemotherapy regimens, sequentially followed by standard concurrent chemoradiotherapy, for the treatment of locally advanced nasopharyngeal carcinoma (NPC). The study is aimed to pick up the most effective platinum-based induction chemotherapy regimen plus Toripalimab for these patients which provides the most survival benefit.

Подробное описание

This phase II randomized trial compares the efficacy and safety of Toripalimab combined with three different platinum-based induction chemotherapy regimens, sequentially followed by standard concurrent chemoradiotherapy, for the treatment of locally advanced nasopharyngeal carcinoma (NPC). The enrolled patients will be 1:1:1 randomly assigned to receive induction chemotherapy of Gemcitabine plus Cisplatin plus Toripalimab(GP plus Toripalimab regimen), Nab-paclitaxel plus Cisplatin plus Toripalimab (TP plus Toripalimab regimen) or Nab-paclitaxel plus Cisplatin plus Capecitabine plus Toripalimab(TPC plus Toripalimab regimen).The study is aimed to pick up the most effective platinum-based induction chemotherapy regimen plus Toripalimab for these patients which provides the most survival benefit.

Вмешательства

• Препарат GP plus Toripalimab Induction chemotherapy+CCRT
  Induction Chemotherapy + Immunotherapy (3 Cycles): Gemcitabine 1000mg/m\^2 (Days 1, 8) + Cisplatin 80mg/m\^2 (Day 1) + Toripalimab 240mg (Day 1), administered every 3 weeks for a total of 3 cycles. Sequentially followed by Concurrent Chemoradiotherapy (CCRT): Cisplatin 100mg/m\^2 (Day 1), administered every 3 weeks for a total of 3 cycles during the radiotherapy period (on Days 1, 22, and 43 of radiotherapy).
• Препарат TP plus Toripalimab Induction chemotherapy+CCRT
  Induction Chemotherapy + Immunotherapy (3 Cycles): Nab-paclitaxel 260mg/m\^2 (Days 1) + Cisplatin 75mg/m\^2 (Day 1) + Toripalimab 240mg (Day 1), administered every 3 weeks for a total of 3 cycles. Sequentially followed by Concurrent Chemoradiotherapy (CCRT): Cisplatin 100mg/m\^2 (Day 1), administered every 3 weeks for a total of 3 cycles during the radiotherapy period (on Days 1, 22, and 43 of radiotherapy).
• Препарат TPC plus Toripalimab Induction chemotherapy+CCRT
  Induction Chemotherapy + Immunotherapy (3 Cycles): Nab-paclitaxel 200mg/m\^2 (Days 1) + Cisplatin 75mg/m\^2 (Day 1) + Capecitabine 1000mg/m\^2 BID (Day 1-Day14) + Toripalimab 240mg (Day 1), administered every 3 weeks for a total of 3 cycles. Sequentially followed by Concurrent Chemoradiotherapy (CCRT): Cisplatin 100mg/m\^2 (Day 1), administered every 3 weeks for a total of 3 cycles during the radiotherapy period (on Days 1, 22, and 43 of radiotherapy).

Первичные конечные точки

• Progression-free survival [Срок оценки: 2 years]

Вторичные конечные точки (5)

• Overall survival [Срок оценки: 2 years]
• Local-Regional failure free survial [Срок оценки: 2 years]
• Distant metastasis-free survival [Срок оценки: 2 years]
• Complete Response Rate [Срок оценки: 9 weeks]
• Incidence of Acute and Late Toxicity [Срок оценки: 2 years]

Критерии участия

Критерии включения

• Age between 18 and 70 years, male or non-pregnant female.
• Pathologically confirmed nasopharyngeal non-keratinizing carcinoma (differentiated or undifferentiated type, i.e., WHO type II or type III).
• Stage Any T, N2-3 or T4, N1 (AJCC 9th edition staging), with no distant metastasis (M0).
• ECOG performance status score of 0 or 1.
• Adequate hematological function: Hemoglobin (HGB)≥90g/L, Absolute Neutrophil Count (ANC) ≥ 1.5\*10\^9/L, and Platele (PLT) ≥100\*10\^9/L.
• Adequate hepatic function: ALT and AST≤2.5\*Upper Limit of Normal (ULN), total bilirubin ≤2.0\*ULN, and serum albumin≥30g/L.
• Adequate renal function: Serum creatinine ≤ 1.5\*ULN or calculated creatinine clearance (CrCl) ≥ 60 mL/min (using the Cockcroft-Gault formula).
• International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 \*ULN (unless the subject is receiving anticoagulant therapy and the coagulation parameters (PT/INR and APTT) are within the expected therapeutic range for the anticoagulant at the time of screening).

Критерии исключения

• Patients with nasopharyngeal carcinoma presenting with recurrence or distant metastasis.
• Pathologically confirmed diagnosis of keratinizing squamous cell carcinoma (WHO Type I).
• Prior history of radiotherapy or systemic chemotherapy.
• Women who are pregnant, lactating, or of childbearing potential not employing effective contraception.
• HIV-positive status.
• History of other malignancies (except for cured basal cell carcinoma or carcinoma in situ of the cervix).
• Patients previously treated with immune checkpoint inhibitors (e.g., CTLA-4, PD-1, PD-L1 inhibitors).
• Patients with immunodeficiency diseases or a history of organ transplantation.
• Patients who have received high-dose glucocorticoids, anticancer monoclonal antibodies, or other immunosuppressive therapy within 4 weeks prior.
• Patients with significantly impaired cardiac, hepatic, pulmonary, renal, or bone marrow function.
• Concurrent use of other investigational drugs or current participation in another clinical trial.
• Patients who refuse or are unable to provide signed informed consent for trial participation.
• Patients with personality or psychiatric disorders, or those lacking legal capacity or with limited legal capacity.
• Hepatitis B surface antigen (HBsAg) positive with peripheral blood Hepatitis B virus deoxyribonucleic acid (HBV DNA) ≥ 1000 copies/ml.
• Patients with positive Hepatitis C virus (HCV) antibody test results are eligible only if the HCV ribonucleic acid (RNA) polymerase chain reaction test result is negative.
• Arterial or venous thrombotic events within 6 months prior to screening initiation, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism.
• Known history of active tuberculosis (TB). Subjects suspected of having active TB must be evaluated and ruled out via chest X-ray, sputum examination, and clinical signs and symptoms.

21.Any other severe, uncontrolled medical condition, infection, or treatment contraindication, or any other condition that, in the investigator's judgment, may pose a risk for receiving the investigational drug, or may interfere with the assessment of the investigational drug, subject safety, or interpretation of the study results.

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 · 4 центра

• Dongguan People's Hospital — Дунгуань
• Sun Yat-sen University Cancer Center — Гуанчжоу
• Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen — Шэньчжэнь
• Affiliated Hospital of Guangdong Medical University — Zhanjiang

Идентификаторы

NCT: NCT07362979 · 2025-FXY-446

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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