This is a non-inferiority, multicenter, randomized phase 3 trial aimed to evaluate whether primary clinical target volume (CTVp) delineation based on margin expansion provides comparable outcomes compared with the consensus CTVp approach based on margin expansion and the stepwise extension pattern in newly diagnosed non-metastatic nasopharyngeal carcinoma.
This multicenter, prospective, randomized phase 3 trial aims to evaluate a margin-expansion-based primary clinical target volume (CTVp) delineation strategy in patients with newly diagnosed non-metastatic nasopharyngeal carcinoma (NPC). The primary objective is to demonstrate non-inferiority of this CTVp approach compared with the consensus CTVp defined by the CSTRO, CACA, CSCO, HNCIG, ESTRO, and ASTRO guidelines (which incorporate both margin expansion and local stepwise extension patterns), with local relapse-free survival as the primary endpoint. Secondary objectives include comparisons of overall survival, failure-free survival, distant metastasis-free survival, locoregional relapse-free survival, and regional relapse-free survival between the two CTVp strategies, as well as assessments of radiotherapy-related complications, quality of life, and their impact on the tumor immune microenvironment, along with exploration of the underlying biological mechanisms. Eligible patients will be prospectively enrolled from multiple centers across China and randomized in a 1:1 ratio to receive either the margin-based CTVp or the consensus guideline-based CTVp. Comprehensive treatment in both arms will follow current clinical guidelines and be stratified by tumor stage. Prognosis, toxicity, and quality-of-life outcomes will be systematically compared between the two groups.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
568
1. T1N0: Radiotherapy Only. 2. T1N1, T2N0-1, T3N0: Radiotherapy with or without Concurrent Chemotherapy (Cisplatin). 3. T3N1, T4N0: Concurrent Chemoradiotherapy (Cisplatin) with or without Induction Chemotherapy (GP Regimen). 4. T1-4N2-3, T4N1: ① Induction Chemotherapy (GP Regimen) + Concurrent Chemoradiotherapy (Cisplatin); ② Induction Chemoimmunotherapy (GP Regimen + PD-1 Monoclonal Antibody) + Concurrent Chemoradiotherapy (Cisplatin) + Adjuvant Immunotherapy (PD-1 Monoclonal Antibody); ③ Induction Chemotherapy (GP Regimen) + Concurrent Chemoradiotherapy (Cisplatin) + Adjuvant Immunotherapy (PD-1 Monoclonal Antibody).
1. Target delineation: 1. CTVp\_High = GTVp + 0 mm; 2. CTVp\_Mid = CTVp\_High + 5 mm; 3. CTVp\_Low = CTVp\_Mid + 5 mm + whole nasopharynx; 4. CTVn\_High = GTVn + 0 mm; 5. CTVn\_Mid = CTVn\_High + 3-5 mm (for nodes with imaging-detected extranodal extension) or 0 mm (for nodes without imaging-detected extranodal extension) + equivocal nodes in the anticipated drainage levels, close proximity to enlarged nodes, or with suspicious PET results; 6. CTVn\_Low = CTVn\_Mid + 3 mm + elective drainage levels. 2. Dose prescription: 1. 6996 cGy/33 fx for CTVp\_High and CTVn\_High; 2. 6006 cGy/33 fx for CTVp\_Mid and CTVn\_Mid; 3. 5412 cGy/33 fx for CTVp\_Low and CTVn\_Low.
Dongguan People's Hospital
Dongguan, Guangdong, China
NOT_YET_RECRUITINGFirst People's Hospital of Foshan
Foshan, Guangdong, China
NOT_YET_RECRUITINGSun Yat-Sen University Cancer Center
Guangzhou, Guangdong, China
Local relapse-free survival (LRFS)
Local relapse-free survival is estimated from randomisation to documented local relapse or death.
Time frame: 3 years
Overall survival (OS)
Overall survival is measured from the date of randomisation until death from any cause.
Time frame: 3 years
Failure-free survival (FFS)
Failure-free survival is measured from the date of randomisation until local recurrence, regional recurrence, distant failure, or death from any cause, whichever occurs first.
Time frame: 3 years
Distant metastasis-free survival (DMFS)
Distant metastasis-free survival is calculated from randomisation to documented distant metastasis or death.
Time frame: 3 years
Locoregional relapse-free survival (LRFFS)
Locoregional relapse-free survival is measured from the date of randomisation until local or regional recurrence or death.
Time frame: 3 years
Regional relapse-free survival (RRFS)
Regional relapse-free survival is defined as the time from randomisation to documented nodal relapse or death.
Time frame: 3 years
Incidence rate of investigator-reported radiotherapy-related complications
Time frame: Within (acute complication) / since (late complication) 90 days after the radiotherapy onset.
Incidence rate of patient-reported adverse events
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
1. Target delineation: 1. CTVp\_High = GTVp + 0 mm; 2. CTVp\_Mid = CTVp\_High + 5 mm; 3. CTVp\_Low = CTVp\_Mid + 5 mm + whole nasopharynx + high-risk structures based on stepwise local extension patterns of tumor spread; 4. CTVn\_High = GTVn + 0 mm; 5. CTVn\_Mid = CTVn\_High + 3-5 mm (for nodes with imaging-detected extranodal extension) or 0 mm (for nodes without imaging-detected extranodal extension) + equivocal nodes in the anticipated drainage levels, close proximity to enlarged nodes, or with suspicious PET results; 6. CTVn\_Low = CTVn\_Mid + 3 mm + elective drainage levels; 2. Dose prescription: 1. 6996 cGy/33 fx for CTVp\_High and CTVn\_High; 2. 6006 cGy/33 fx for CTVp\_Mid and CTVn\_Mid; 3. 5412 cGy/33 fx for CTVp\_Low and CTVn\_Low.
Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen
Shenzhen, Guangdong, China
NOT_YET_RECRUITINGZhongshan City People's Hospital
Zhongshan, Guangdong, China
NOT_YET_RECRUITINGHunan Cancer Hospital
Changsha, Hunan, China
NOT_YET_RECRUITINGXiangya Hospital Central South University
Changsha, Hunan, China
NOT_YET_RECRUITINGTime frame: Periprocedural.
Quality of life (QoL): questionnaire
Time frame: Up to 5 years.