Reduced-dose Versus Conventional-dose Intensity-modulated Radiation Therapy for Locally Advanced Nasopharyngeal Carcinoma With Remission After Induction Chemotherapy and Immunotherapy

NCT07328841 | Recruiting Phase 3 DMC

• 1 other identifier: ZDWY.BYAFZZX.043
• Study Type: interventional
• Target: 456
• Locations: 1 country
• Sites: 12

Brief Summary

To explore the efficacy and safety of reduced-dose radiotherapy combined with concurrent chemotherapy and immunotherapy in stage Ⅳa (AJCC 8th,) locally advanced nasopharyngeal carcinoma patients who are sensitive to induction chemoimmunotherapy (assessed as complete response \[CR\]/partial response \[PR\] by imaging, with EBV DNA copy number reduced to zero or below the lower limit of detection), so as to provide a new treatment option for these patients.

Conditions

Nasopharyngeal Carcinoma (NPC)

Keywords

Nasopharyngeal Carcinoma; Locally Advanced; Epstein-Barr Virus DNA; EBV DNA clearance; undetectable EBV DNA; reduced-dose radiotherapy; Randomized non-inferiority trial; Concurrent chemoradiotherapy; complete response; partial response; PD-1inhibitor

Outcome Measures

Primary Outcomes (1)

• Progress-Free Survival (PFS)

  Defined as time from randomization to locoregional or distant metastasis relapse or death from any cause, whichever occurred first.

  3 years

Secondary Outcomes (8)

• Overall Survival (OS)

  3 years

• Locoregional Relapse-Free Survival (LRRFS)

  3 years

• Distant Metastasis-Free Survival (DMFS)

  3 years

• Objective Response Rate (ORR)

  assessed at 3 months after the end of concurrent chemoradiotherapy

• The proportion of patients with treatment related acute complications

  1 year

Study Arms (2)

Induction chemotherapy plus reduced-dose radiotherapy and concurrent chemotherapy

EXPERIMENTAL

Drug: Full course of PD-1blockades; Drug: Cisplatin-based induction chemotherapy; Radiation: Reduced-dose radiotherapy; Drug: Concurrent Chemotherapy

Induction chemotherapy plus conventional concurrent chemoradiotherapy

ACTIVE COMPARATOR

Drug: Full course of PD-1blockades; Drug: Cisplatin-based induction chemotherapy; Radiation: Standard-dose radiotherapy; Drug: Concurrent Chemotherapy

Interventions

Full course of PD-1blockades DRUG

Toripalimab 240 mg, once every 3 weeks (Q3W), intravenous infusion (iv). A total of 12 courses of treatment will be administered, including 3 courses during the induction chemotherapy phase, 3 courses during the radiotherapy phase, and 6 courses during the post-radiotherapy maintenance phase. Administration will start on Day 1 of induction chemotherapy and continue after the end of radiotherapy until the occurrence of intolerable toxicities, disease progression, withdrawal of consent, determination by the investigator that the patient needs to withdraw from treatment, or the completion of 12 courses, whichever comes first.

Induction chemotherapy plus conventional concurrent chemoradiotherapy; Induction chemotherapy plus reduced-dose radiotherapy and concurrent chemotherapy

Cisplatin-based induction chemotherapy DRUG

Cisplatin-based induction chemotherapy will be given every 3 weeks for 3 cycles before radiotherapy.

Induction chemotherapy plus conventional concurrent chemoradiotherapy; Induction chemotherapy plus reduced-dose radiotherapy and concurrent chemotherapy

Standard-dose radiotherapy RADIATION

GTVnx/nd:69.96Gy/33Fr/2.12Gy CTV1: 59.4Gy/33Fr/1.8Gy CTV2: 54.12Gy/33Fr/1.64Gy

Induction chemotherapy plus conventional concurrent chemoradiotherapy

Reduced-dose radiotherapy RADIATION

GTVnx/nd:63.6Gy/30Fr/2.12Gy CTV1: 54Gy/30Fr/1.8Gy CTV2: 49.2Gy/30Fr/1.64Gy

Induction chemotherapy plus reduced-dose radiotherapy and concurrent chemotherapy

Concurrent Chemotherapy DRUG

Cisplatin 100mg/m2 every 3 weeks for 2 cycles

Induction chemotherapy plus conventional concurrent chemoradiotherapy; Induction chemotherapy plus reduced-dose radiotherapy and concurrent chemotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically and/or cytologically confirmed nasopharyngeal non-keratinizing carcinoma (differentiated or undifferentiated type, i.e., WHO classification Type II or Type III).
• Clinical stage: AJCC 8th edition staging: T4N0-2M0, T1-4N3M0 (stage IVa); AJCC 9th edition staging: T4N0-2M0, T1-4N3M0 (stage III).
• After 3 courses of platinum-based chemotherapy combined with immunotherapy as induction treatment, the efficacy is assessed as PR or CR by nasopharyngoscopy and enhanced MRI of nasopharynx + neck, with EBV DNA reduced to zero or below the lower limit of detection.
• Age: 18-70 years old.
• PS/ECOG score (performance status score of 0 or 1).
• Adequate organ function:
• Hematology: White blood cell count ≥ 4000/μL, neutrophil count ≥ 2000/μL, hemoglobin ≥ 9 g/dL, platelet count ≥ 100000/μL;
• Liver function: Bilirubin ≤ 1.5 × upper limit of normal (ULN) (patients with known Gilbert's disease and serum bilirubin level ≤ 3 × ULN are eligible), AST and ALT ≤ 1.5 × ULN, and alkaline phosphatase ≤ 1.5 × ULN; albumin ≥ 3 g/dL;
• Renal function: Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min calculated by the Cockcroft-Gault formula.
• Proteinuria: Urine protein/creatinine ratio (UPC ratio) \< 1.0. For those with UPC ratio ≤ 0.5, no further examination is required; for those with UPC ratio \> 0.5, further testing showing 24-hour urine protein \< 1000 mg is eligible.
• Note: The UPC ratio of random urine is an estimate of 24-hour urine protein quantification, and the two have a good correlation. The UPC ratio can be calculated using the following formulas:
• i. Urine protein/urine creatinine (if both protein and creatinine are in mg/dL); ii. (Urine protein) × 0.088/urine creatinine (if urine creatinine is in mmol/L).
• e) Coagulation function: International normalized ratio (INR) ≤ 1.5, activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
• Patients have signed the informed consent form and are willing and able to comply with the study's scheduled visits, treatment plans, laboratory tests, and other study procedures

You may not qualify if:

• Patients whose laboratory test results within 7 days before enrollment do not meet the relevant standards.
• Patients with efficacy evaluation of stable disease (SD) or progressive disease (PD) after 3 courses of platinum-based chemotherapy combined with immunotherapy as induction treatment, or whose EBV DNA has not been reduced to zero or below the lower limit of detection.
• Patients who have received any of the following for primary lesions and/or cervical metastatic lesions: chemotherapy, immunotherapy, targeted therapy, or surgical treatment (excluding diagnostic treatment).
• Patients with tumors accompanied by obvious liquefaction necrosis, which are unsuitable for radiotherapy or may lead to radioresistance.
• Patients with tumors invading the brain parenchyma.
• Patients with a history of severe allergic reactions to any components of other monoclonal antibodies or PD-1/PD-L1 monoclonal antibodies.
• Patients with known or suspected autoimmune diseases, including dementia and epileptic seizures.
• Patients with recurrence, distant metastasis, or concurrent other malignant tumors.
• Patients with severe heart disease, pulmonary dysfunction, or cardiac/pulmonary function grade 3 or lower (including grade 3).
• Patients with previous use of anti-PD-1/PD-L1 antibodies, anti-CTLA-4 antibodies, or any other antibodies acting on T-cell costimulatory or checkpoint pathways.
• Patients with comorbidities requiring long-term treatment with immunosuppressive drugs or systemic/local use of corticosteroids at immunosuppressive doses before enrollment.
• Patients with HIV positivity; HBsAg positivity with positive HBV DNA copy number (quantitative detection ≥ 1000 cps/ml); positive screening for chronic hepatitis C (HCV antibody positivity).
• Patients with a history of allergic reactions to the drugs used in this study (gemcitabine, docetaxel, taxanes, cisplatin).
• Patients with active tuberculosis (TB) who are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening.
• Patients who, within 4 weeks before enrollment: have received systemic or local glucocorticoid treatment, been vaccinated with any anti-infective vaccines (such as influenza vaccine, varicella vaccine, etc.), or used traditional Chinese herbal medicines with anti-tumor effects.

Sponsors & Collaborators

• Ming-Yuan Chen: lead

Study Sites (12)

The Fifth Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 516000, China

RECRUITING

Cancer Center of Guangzhou Medical University

Guangzhou, Guangdong, China

RECRUITING

Sun Yat-sen University cancer center

Guangzhou, Guangdong, China

RECRUITING

The Second Affiliated Hospital of Sun Yat-sen University (SYSU)

Guangzhou, Guangdong, China

RECRUITING

Cancer Hospital of Shantou University Medical College

Shantou, Guangdong, China

RECRUITING

Zhongshan City People's Hospital

Zhongshan, Guangdong, China

RECRUITING

The People's Hospital of Guangxi Zhuang Autonomous Region

Nanning, Guangxi, 530021, China

RECRUITING

Wuzhou Red Cross Hospital

Wuzhou, Guangxi, China

RECRUITING

Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, China

RECRUITING

Central South University Cancer Hospital

Changsha, Hunan, China

RECRUITING

Xiangya Hospital of Central South University

Changsha, Hunan, China

RECRUITING

The Fifth Affiliated Hospital of Sun Yat-sen University

Guangdong, Zhuhai, 519000, China

RECRUITING

MeSH Terms

Conditions

Nasopharyngeal Carcinoma; Pathologic Complete Response

Interventions

Radiotherapy

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; Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Ming-Yuan Chen, MD,PhD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ming-Yuan Chen, MD,PhD

CONTACT

+86-20-87343361; chenmy@sysucc.org.cn

Rui You, MD,PhD

CONTACT

+86-13580439820; your5@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professior, Chief physician

Study Record Dates

• First Submitted: December 27, 2025
• First Posted: January 9, 2026
• Study Start: November 18, 2025
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2032
• Last Updated: January 9, 2026

Record last verified: 2025-12

Locations

CN (12)