Gemcitabine and Cisplatin in Combination with Toripalimab or Not As First-line Treatment in Advanced Childhood Nasopharyngeal Carcinoma: an Open, Randomised Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Complete Response (CR) Rate After Induction Chemotherapy
研究概览
简要总结
Nasopharyngeal carcinoma (NPC) has a low incidence rate in children, accounting for only 1-2% of pediatric tumors. However, it is prone to metastasis, and most patients are already in advanced stages at the time of diagnosis. Chemoradiotherapy has been shown to effectively improve prognosis. Induction chemotherapy combined with concurrent chemoradiotherapy with adjusted radiation doses has demonstrated good efficacy in children and adolescents with locally advanced NPC. Nevertheless, 10-15% of patients still experience treatment failure, and 15-20% of patients respond poorly to induction chemotherapy, necessitating higher doses of radiation, which in turn increases the incidence of treatment-related sequelae. Therefore, it is crucial to explore further treatment strategies that can enhance response rates, reduce acute and long-term treatment toxicities, and improve overall efficacy on the basis of induction chemotherapy followed by adjusted concurrent chemoradiotherapy.
The combination of gemcitabine and cisplatin (GP regimen) has been identified as the highest level of evidence-based induction chemotherapy regimen (Class 1A). However, the complete response rate of only 10% after three cycles of GP regimen induction chemotherapy in adults with locoregionally advanced NPC indicates the need for intensified induction treatment. PD-1 inhibitors combined with chemotherapy have demonstrated synergistic tumor-killing effects, providing additional curative opportunities for patients with locally advanced disease. Toripalimab, with its dual-blocking mechanism, is an ideal PD-1 monoclonal antibody model that can fully relieve T-cell-mediated antitumor immune suppression. Previous clinical trials have confirmed the efficacy and safety of toripalimab in treating nasopharyngeal carcinoma.
This study aims to conduct the first single-center, phase II randomized controlled clinical trial in children and adolescents with nasopharyngeal carcinoma, comparing the GP regimen combined with toripalimab induction chemotherapy versus the GP regimen alone. The goal is to optimize the treatment model for pediatric and adolescent NPC, enhance therapeutic efficacy, and provide high-level evidence-based medical support for the international treatment guidelines for pediatric NPC.
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
- 6 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be informed of the investigational nature of this study and give written informed consent.
- •Age between 6 and 18 years, regardless of gender.
- •Pathologically confirmed non-keratinizing nasopharyngeal carcinoma (differentiated or undifferentiated type, i.e., WHO Type II or III).
- •Clinical stage II-III (according to AJCC 9th edition), excluding T3N0 and T3N1 (only with retropharyngeal lymph node metastasis); patients must be newly diagnosed with nasopharyngeal carcinoma.
- •ECOG performance status of 0-
- •Females of childbearing potential must agree to use contraception during the study period.
- •Hemoglobin (HGB) ≥ 90 g/L, white blood cell count (WBC) ≥ 4×10^9/L, platelet count (PLT) ≥ 100×10^9/L.
- •Normal liver function test: ALT and AST < 2.5 x upper limit of normal (ULN), total bilirubin < 2.0×ULN.
- •Adequate renal function: Serum creatinine < 1.5×ULN.
排除标准
- •Older than 18 years.
- •Presence of recurrence or distant metastasis.
- •Pathologically diagnosed as keratinizing squamous cell carcinoma (WHO Type I).
- •History of previous anti-tumor treatment.
- •Pregnant or lactating women, and women of childbearing potential not using effective contraception.
- •HIV positive.
- •History of malignancy within the past 5 years, except for patients with carcinoma in situ, adequately treated non-melanoma skin cancer, or papillary thyroid carcinoma.
- •Patients with other immunodeficiency diseases or a history of organ transplantation.
- •Patients with active autoimmune diseases, except for type I diabetes, hypothyroidism under replacement therapy, and skin conditions not requiring systemic treatment (e.g., vitiligo, psoriasis, or alopecia).
- •Conditions requiring systemic corticosteroids (equivalent to prednisone greater than 10mg/d) or other immunosuppressive therapy within 28 days prior to signing informed consent. Patients on systemic corticosteroids equivalent to prednisone ≤10 mg/day or using inhaled or topical corticosteroids are permitted.
- •Received a live vaccine within 30 days before signing informed consent or planning to receive a live vaccine in the near future.
- •Patients with significant impairment in heart, liver, lung, kidney, or bone marrow function.
- •Severe, uncontrolled medical diseases or infections.
- •Concurrent use of other investigational drugs or participation in other clinical trials.
- •Refusal or inability to sign the informed consent form to participate in the trial.
- •Known allergies to large molecule protein products or any PD-1 antibody compounds, or those with other contraindications to the treatment.
- •Individuals with personality or mental disorders, those without legal capacity or with limited legal capacity.
研究组 & 干预措施
GP combined with Toripalimab + CCRT
- Induction Chemotherapy (GP Regimen combined with Toripalimab)
- GP Regimen: Gemcitabine: 1000 mg/m² on Day 1 and Day 8; Cisplatin (DDP): 80 mg/m² on Day 1-3; every 3 weeks for 3 cycles
- Toripalimab: For patients weighing ≥ 40 kg: 240 mg on Day 1; For patients weighing < 40 kg: 3 mg/kg; every 3 weeks for 3 cycles
- Concurrent Chemoradiotherapy (CCRT):
Cisplatin (DDP): 100 mg/m², starting on the first day of radiotherapy; every 3 weeks for 3 cycles
干预措施: GP+Toripalimab+CCRT (Drug)
GP regimen + CCRT
- Induction Chemotherapy (GP Regimen):
Gemcitabine: 1000 mg/m² on Day 1 and Day 8; Cisplatin (DDP): 80 mg/m² on Day 1-3, every 3 weeks for 3 cycles. 2. Concurrent Chemoradiotherapy (CCRT):
Cisplatin (DDP): 100 mg/m², starting on the first day of radiotherapy, every 3 weeks for 3 cycles.
干预措施: GP+CCRT (Drug)
结局指标
主要结局
Complete Response (CR) Rate After Induction Chemotherapy
时间窗: when the induction chemotherapy complete
CR is assessed after induction chemotherapy by independent reviewers, according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete response defined as the complete disappearance of the target and non-target lesion(s) identified at baseline after radiological evaluation by enhanced MRI (or enhanced CT if indicated).
次要结局
- Overall survival(3 years)
- Progression-free survival(3 years)
- Locoregional failure-free survival(LRRFS)(3 years)
- Distant metastasis-free survival(DMFS)(3 years)
- Incidence of acute and late toxicity(3 years)
- Hormone levels(3 years)
- Growth condition of Height(3 years)
- Growth condition of Weight(3 years)
- Growth condition of BMI(3 years)
- Quality of life(3 years)
研究者
Hai-Qiang Mai,MD,PhD
Prof.
Sun Yat-sen University