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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Nasopharyngeal Cancinoma (NPC)
• Intervention / Treatment: Drug: GP+Toripalimab+CCRT; Drug: GP+CCRT

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dong Hua Luo; Phone Number: 86-020-87343643; Email: luodh@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-Sen University Cancer Center
      • Contact: Dong Hua Luo; Phone Number: 86-13560358839; Email: luodh@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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 cyclesToripalimab: 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	Drug: GP+Toripalimab+CCRT; 1. 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 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
Active Comparator: 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.; Concurrent Chemoradiotherapy (CCRT): Cisplatin (DDP): 100 mg/m², starting on the first day of radiotherapy, every 3 weeks for 3 cycles.	Drug: GP+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.; Concurrent Chemoradiotherapy (CCRT): Cisplatin (DDP): 100 mg/m², starting on the first day of radiotherapy; every 3 weeks for 3 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response (CR) Rate After Induction Chemotherapy	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).	when the induction chemotherapy complete

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Locoregional failure-free survival(LRRFS)	defined as the time from random assignment to local or regional relapse, or death from any cause.	3 years
Overall survival	defined as the time from random assignment to death from any cause or censored at the date of last follow-up.	3 years
Progression-free survival	defined as the time from random assignment to documented local or regional relapse, distant metastasis, or death from any cause, whichever occurred first	3 years
Distant metastasis-free survival(DMFS)	defined as the time from random assignment to distant metastasis, or death from any cause	3 years
Incidence of acute and late toxicity	Incidence of acute toxicity is evaluated on basis of Common Terminology Criteria for Adverse Events (CTCAE) 5.0 criteria. Late radiation toxicities were assessed using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme. Acute adverse events, occurring during study treatment, and radiation-related late adverse events, occurring from 3 months after completion of radiotherapy, and chemotherapy-induced late adverse events, occurring from 3 months after completion of chemotherapy until end of follow up.	3 years
Hormone levels	Changes in levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), and growth hormone (GH), will be monitored.	3 years
Growth condition of Height	Patients will be monitored for height (in metres) before treatment, after treatment, and during follow-up.	3 years
Growth condition of Weight	Patients will be monitored for Weight(in kilograms) before treatment, after treatment, and during follow-up.	3 years
Growth condition of BMI	Patients will be monitored for BMI (in kg/m²) before treatment, after treatment, and during follow-up.	3 years
Quality of life	The quality of life will be evaluated using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30, Version 3.0) and the EORTC Quality of Life Questionnaire Head and Neck Cancer Module (QLQ-H and N35, Version 1.0). For the EORTC QLQ-C30, scores range from 0 to 100. In the Functioning and General Health domains, higher scores reflect better functional status and quality of life, while in the Symptoms domain, higher scores indicate more symptoms or problems, signifying poorer quality of life. For the QLQ-H and N35, scores also range from 0 to 100, with higher scores consistently indicating poorer quality of life. We will calculate the scores for patients in each domain according to the scoring criteria of the respective questionnaires and explore the correlation of these scores with treatment plans, etc. Each domain and questionnaire will be treated as a separate outcome measure.	3 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): April 17, 2025
• Primary Completion (Estimated): February 25, 2026
• Study Completion (Estimated): February 25, 2029

Study Registration Dates

• First Submitted: September 11, 2024
• First Submitted That Met QC Criteria: September 17, 2024
• First Posted (Actual): September 20, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 17, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Toripalimab; nasopharyngeal carcinoma; GP; adolescent and childhood
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Carcinoma
• Other Study ID Numbers: 2023-FXY-317

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No