Non-metastatic Nasopharyngeal Carcinoma
Conditions
Keywords
Radiotherapy, Target Delineation, Primary Clinical Target Volume, Margin
Brief summary
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.
Detailed description
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.
Interventions
PROCEDUREComprehensive Therapy Based on Tumor Stage
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).
RADIATIONIMRT with Primary Clinical Target Volume Based on Margin Expansion
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.
RADIATIONIMRT with Consensus Primary Clinical Target Volume
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.
Sponsors
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age: 18 Years to 65 Years. 2. Eastern Cooperative Oncology Group performance status ≤1. 3. Patients with newly diagnosed, histologically confirmed nasopharyngeal carcinoma (non-keratinizing subtype). 4. Tumor staged as T1-4N0-3M0 (AJCC 9th). 5. Patients must sign informed consent and be willing and able to comply with the requirements of visits, treatment, laboratory tests and other research requirements stipulated in the research schedule. 6. Women of childbearing potential and male subjects with female partners of childbearing potential must agree to use reliable contraceptive measures from screening to 1 year after treatment. 7. For subjects requiring chemotherapy, the following are additionally required: 1. normal bone marrow function (white blood cell count \> 4 × 10\^9/L, hemoglobin \> 90 g/L, platelet count \> 100 × 10\^9/L); 2. normal liver and kidney function (total bilirubin ≤ 1.5 × upper limit of normal, alanine transaminase and aspartate transaminase ≤ 2.5 × upper limit of normal, alkaline phosphatase ≤ 2.5 × upper limit of normal, creatinine clearance rate ≥ 60 mL/min).
Exclusion criteria
1. Active tuberculosis: active tuberculosis within the past 1 year should be excluded regardless of treatment; a history of active tuberculosis \> 1 year ago is exclusionary unless prior adequate anti-tuberculosis treatment is documented. 2. Active infection requiring systemic treatment. 3. Previous or concurrent with other malignant tumors, except for adequately treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary cancer. 4. History of radiotherapy, except for non-melanoma skin cancer located outside the target volume of radiotherapy for nasophayngeal carcinoma. 5. Prior or concurrent treatment for local or regional disease other than that specified in the research plan. 6. Pregnant or lactating women (a pregnancy test is required for women of childbearing potential). 7. Contraindications to MRI examination, for example: claustrophobia, allergy to MRI contrast. 8. History of psychiatric disorders, alcoholism or drug abuse, and other situations assessed by the investigators that may compromise the safety or compliance of patients, such as serious disease requiring timely treatment (including mental illness), severe laboratory abnormalities, or family-social risk factors. 9. For participants requiring chemotherapy, the following must also be excluded: 1. anti-human immunodeficiency virus positive or diagnosed with acquired immune deficiency syndrome; 2. uncontrolled heart disease (heart failure \[NYHA Class ≥ 2\], unstable angina, myocardial infarction in past 1 year, supraventricular or ventricular arrhythmia requiring treatment or intervention). 10. For participants requiring immunotherapy, the following must also be excluded: 1. hepatitis B virus surface antigen positive and Hepatitis B virus DNA \> 1000 copies/mL; 2. anti-hepatitis C virus positive; 3. active, known or suspected autoimmune disease (including but not limited to uveitis, enteritis, hepatitis, pituitary disease, nephritis, vasculitis, hyperthyroidism, hypothyroidism and asthma requiring bronchodilators, exceptions are type I diabetes mellitus, hypothyroidism not requiring hormone replacement therapy, skin disorders not requiring systemic treatment \[such as vitiligo, psoriasis or alopecia\]); 4. previous interstitial lung disease or pneumonia requiring oral or intravenous steroid therapy; 5. chronic treatment with systemic glucocorticoid (dose equivalent to or over 10 mg prednisone per day, subjects who use inhaled or topical corticosteroids are eligible) or any other form of immunosuppressive therapy; 6. allergy to macromolecular protein preparations, or any component of PD-1 monoclonal antibody; 7. receiving live vaccine within 30 days prior to the first dose of PD-1 monoclonal antibody.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Local relapse-free survival (LRFS) | 3 years | Local relapse-free survival is estimated from randomisation to documented local relapse or death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | 3 years | Overall survival is measured from the date of randomisation until death from any cause. |
| Failure-free survival (FFS) | 3 years | 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. |
| Distant metastasis-free survival (DMFS) | 3 years | Distant metastasis-free survival is calculated from randomisation to documented distant metastasis or death. |
| Locoregional relapse-free survival (LRFFS) | 3 years | Locoregional relapse-free survival is measured from the date of randomisation until local or regional recurrence or death. |
| Regional relapse-free survival (RRFS) | 3 years | Regional relapse-free survival is defined as the time from randomisation to documented nodal relapse or death. |
| Incidence rate of investigator-reported radiotherapy-related complications | Within (acute complication) / since (late complication) 90 days after the radiotherapy onset. | — |
| Incidence rate of patient-reported adverse events | Periprocedural. | — |
| Quality of life (QoL): questionnaire | Up to 5 years. | — |
Countries
China
Contacts
CONTACTJun Ma, Prof.
CONTACTCheng-Long Huang, Dr.
PRINCIPAL_INVESTIGATORJun Ma, Prof.
Sun Yat-sen University
Outcome results
None listed