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

NCT06605131 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2023-FXY-317
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Nasopharyngeal Cancinoma (NPC)

Keywords

nasopharyngeal carcinoma; adolescent and childhood; Toripalimab; GP

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• 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

Study Arms (2)

GP combined with Toripalimab + CCRT

EXPERIMENTAL

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 \< 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

Drug: GP+Toripalimab+CCRT

GP regimen + CCRT

ACTIVE COMPARATOR

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.

Drug: GP+CCRT

Interventions

GP+Toripalimab+CCRT DRUG

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

GP combined with Toripalimab + CCRT

GP+CCRT DRUG

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

GP regimen + CCRT

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Central Study Contacts

Dong Hua Luo

CONTACT

86-020-87343643; luodh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: September 11, 2024
• First Posted: September 20, 2024
• Study Start: April 17, 2025
• Primary Completion: February 25, 2026
• Study Completion (Estimated): February 25, 2029
• Last Updated: March 20, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)