Toripalimab Combined With Different Platinum-Based Induction Chemotherapy Regimens for Locally Advanced Nasopharyngeal Carcinoma: A Randomized, Open-label, Controlled, Multicenter Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 243
- 试验地点
- 4
- 主要终点
- Progression-free survival
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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).
排除标准
- •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.
研究组 & 干预措施
GP plus Toripalimab Induction chemotherapy
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.
干预措施: GP plus Toripalimab Induction chemotherapy+CCRT (Drug)
TP plus Toripalimab Induction chemotherapy
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.
干预措施: TP plus Toripalimab Induction chemotherapy+CCRT (Drug)
TPC plus Toripalimab Induction chemotherapy
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.
干预措施: TPC plus Toripalimab Induction chemotherapy+CCRT (Drug)
结局指标
主要结局
Progression-free survival
时间窗: 2 years
The time from randomization to any documented local or regional relapse, distant metastasis, or death from any cause, whichever occur first.
次要结局
- Overall survival(2 years)
- Local-Regional failure free survial(2 years)
- Distant metastasis-free survival(2 years)
- Complete Response Rate(9 weeks)
- Incidence of Acute and Late Toxicity(2 years)
研究者
Hai-Qiang Mai,MD,PhD
Director of the Department of Nasopharyngeal Carcinoma
Sun Yat-sen University