This phase III randomized trial evaluates PD-1 inhibitor plus chemotherapy followed by immediate versus salvage locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma. The study aims to evaluate whether salvage locoregional radiotherapy is non-inferior to immediate radiotherapy following PD-1 inhibitor plus GP in de novo metastatic NPC, with potential for reduced toxicity.
Nasopharyngeal carcinoma (NPC) is highly prevalent in Southern China, with approximately 15% of patients presenting with distant metastases at diagnosis. A PD-1 inhibitor combined with gemcitabine and cisplatin (GP) has become the standard first-line therapy for metastatic NPC. However, the survival benefit of adding immediate locoregional radiotherapy to PD-1 inhibitor plus GP in de novo metastatic NPC remains uncertain. This phase III randomized trial is designed to compare immediate versus salvage locoregional radiotherapy following PD-1 inhibitor plus GP in de novo metastatic NPC, with the objective of determining whether salvage radiotherapy is non-inferior to immediate radiotherapy while offering reduced toxicity.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
260
Immediate locoregional radiotherapy (LRRT) with concurrent chemotherapy + PD-1 inhibitor Maintenance. Concurrent chemotherapy: Cisplatin (DDP) 80mg/m², starting on day 1 of radiotherapy, administered every 3 weeks during radiotherapy for a total of 3 cycles. PD-1 inhibitor maintenance therapy: Toripalimab 240 mg IV on day 1 every 3 weeks, or Tislelizumab 200 mg IV on day 1 every 3 weeks, or Camrelizumab 200 mg IV on day 1 every 3 weeks, continued until disease progression (per RECIST v1.1), unacceptable toxicity, patient withdrawal, or a maximum treatment duration of 2 years.
PD-1 inhibitor maintenance + Salvage locoregional radiotherapy PD-1 inhibitor maintenance therapy:Toripalimab 240 mg IV on day 1 every 3 weeks, or Tislelizumab 200 mg IV on day 1 every 3 weeks, or Camrelizumab 200 mg IV on day 1 every 3 weeks, continued until disease progression (per RECIST v1.1; if progression occurs in the nasopharynx or neck while metastatic lesions remain controlled, salvage locoregional radiotherapy\* will be administered and PD-1 maintenance will continue until subsequent progression), unacceptable toxicity, patient withdrawal, or a maximum treatment duration of 2 years. \*Concurrent chemotherapy: Cisplatin (DDP) 80 mg/m², starting on day 1 of radiotherapy, administered every 3 weeks during radiotherapy for a total of 3 cycles.
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China
RECRUITINGHunan Cancer Hospital
Changsha, China
NOT_YET_RECRUITINGFujian Cancer Hospital
Fuzhou, China
NOT_YET_RECRUITINGZhejiang Cancer Hospital
Hangzhou, China
NOT_YET_RECRUITINGGuangxi Medical University Cancer Hospital
Nanning, China
NOT_YET_RECRUITINGOverall survival
Defined as the time from random assignment to death from any cause.
Time frame: 2 year
Locoregional progression-free survival
Defined as the time from random assignment to the occurrence of a locoregional progression.
Time frame: 2 year
Distant progression-free survival
Defined as the time from random assignment to the occurrence of a distant progression.
Time frame: 2 year
Progression free-survival
Defined as the time from random assignment to locoregional or distant progression, or death from any cause.
Time frame: 2 year
Incidence of Acute and Late Toxicity
Incidence of acute toxicity is calculated for each adverse event respectively and severity 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.
Time frame: 2 year
Quality of life (QoL)
The change of QoL from randomization to 1month, 3 months, 6 months and 1 year randomization. Assessed using the EORTC QoL questionnaire-C30 (EORTC QLQ-C30) version 3.0. This questionnaire comprises 30 questions, 24 aggregated into nine multi-question scales: five functioning scales (e.g., physical), three symptom scales (e.g., fatigue), and one global health status scale. The remaining six single-question (e.g., dyspnoea) scales assess symptoms. These 15 scales will be scored according to the official Scoring Manual of EORTC QLQ-C30.
Time frame: 1 year
Quality of life (QoL)
The change of QoL from randomization to 1month, 3 months, 6 months and 1 year randomization.QoL scores were assessed by using EORTC quality of life questionnaire(QLQ) Head and Neck. The QLQ-H\&N35 is composed of seven multi-item symptom scales (pain, swallowing, sensation, speech, eating from a social,perspective, social interactions, and sexuality) and 11 single-item symptom scales (teeth, opening mouth,dry mouth, sticky saliva,coughing, felt ill, pain medication use, nutritional supplementation, feeding tube requirement, weight loss, and weight gain). All of the scales and items ranged in score from 0 to 100. A high score for a functional or global QoL scale represents a relatively high/healthy level of functional or global QoL, whereas a high score for a symptom scale or item represents a high number of symptoms or problems.
Time frame: 1 year
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