GP Combined with Toripalimab Versus GP Induction Chemotherapy for Advanced Childhood Nasopharyngeal Carcinoma

Официальное название

Gemcitabine and Cisplatin in Combination with Toripalimab or Not As First-line Treatment in Advanced Childhood Nasopharyngeal Carcinoma: an Open, Randomised Phase II Trial

Обзор

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.

Вмешательства

• Препарат GP+Toripalimab+CCRT
  1\. Induction Chemotherapy (GP Regimen combined with Toripalimab): 1. 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. Toripalimab: For patients weighing ≥ 40 kg: 240 mg on Day 1; For patients weighing less than 40 kg: 3 mg/kg; 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
• Препарат GP+CCRT
  1. 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

Первичные конечные точки

• Complete Response (CR) Rate After Induction Chemotherapy [Срок оценки: when the induction chemotherapy complete]

Вторичные конечные точки (10)

• Overall survival [Срок оценки: 3 years]
• Progression-free survival [Срок оценки: 3 years]
• Locoregional failure-free survival(LRRFS) [Срок оценки: 3 years]
• Distant metastasis-free survival(DMFS) [Срок оценки: 3 years]
• Incidence of acute and late toxicity [Срок оценки: 3 years]
• Hormone levels [Срок оценки: 3 years]
• Growth condition of Height [Срок оценки: 3 years]
• Growth condition of Weight [Срок оценки: 3 years]
• Growth condition of BMI [Срок оценки: 3 years]
• Quality of life [Срок оценки: 3 years]

Критерии участия

Критерии включения

• 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 0-1.
• 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.

Критерии исключения

• 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.

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

• Sun Yat-sen University Cancer Center — Гуанчжоу

Идентификаторы

NCT: NCT06605131 · 2023-FXY-317

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗