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

NCT ID: NCT07328841

Last Updated: 2026-01-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

456 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-11-18

Study Completion Date

2032-06-30

Brief Summary

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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.

Detailed Description

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In a prospective clinical trial, under full-course immunotherapy, a platinum-based chemotherapy combined with immunotherapy regimen is used as the induction treatment protocol. Patients with stage Ⅳa (AJCC 8th,) nasopharyngeal carcinoma who achieve partial response (PR) or complete response (CR) after induction treatment, with EBV DNA reduced to zero or below the lower limit of detection, are randomized at a 1:1 ratio. One group receives reduced-dose radiotherapy combined with concurrent chemoimmunotherapy, while the other group receives conventional-dose radiotherapy combined with concurrent chemoimmunotherapy.

Through follow-up, the differences in survival prognosis, incidence of complications, and quality of life between the two groups are observed. The aim is to evaluate whether, on the premise of ensuring non-inferior 3-year progression-free survival (PFS), reduced-dose radiotherapy shows superiority or significant improvement in ≥ grade 3 radiotherapy-related toxicities (especially xerostomia, dysphagia, and hearing loss) and quality of life. Thereby, it explores whether the treatment strategy of further reduced-dose radiotherapy is suitable for patients with locally advanced nasopharyngeal carcinoma who achieve CR/PR on imaging evaluation and have EBV DNA reduced to zero after neoadjuvant therapy.

Conditions

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Nasopharyngeal Carcinoma (NPC)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Induction chemotherapy plus reduced-dose radiotherapy and concurrent chemotherapy

Group Type EXPERIMENTAL

Full course of PD-1blockades

Intervention Type 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.

Cisplatin-based induction chemotherapy

Intervention Type DRUG

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

Reduced-dose radiotherapy

Intervention Type RADIATION

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

Concurrent Chemotherapy

Intervention Type DRUG

Cisplatin 100mg/m2 every 3 weeks for 2 cycles

Induction chemotherapy plus conventional concurrent chemoradiotherapy

Group Type ACTIVE_COMPARATOR

Full course of PD-1blockades

Intervention Type 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.

Cisplatin-based induction chemotherapy

Intervention Type DRUG

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

Standard-dose radiotherapy

Intervention Type RADIATION

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

Concurrent Chemotherapy

Intervention Type DRUG

Cisplatin 100mg/m2 every 3 weeks for 2 cycles

Interventions

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Full course of PD-1blockades

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.

Intervention Type DRUG

Cisplatin-based induction chemotherapy

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

Intervention Type DRUG

Standard-dose radiotherapy

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

Intervention Type RADIATION

Reduced-dose radiotherapy

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

Intervention Type RADIATION

Concurrent Chemotherapy

Cisplatin 100mg/m2 every 3 weeks for 2 cycles

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Histologically and/or cytologically confirmed nasopharyngeal non-keratinizing carcinoma (differentiated or undifferentiated type, i.e., WHO classification Type II or Type III).
2. Clinical stage: AJCC 8th edition staging: T4N0-2M0, T1-4N3M0 (stage IVa); AJCC 9th edition staging: T4N0-2M0, T1-4N3M0 (stage III).
3. 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.
4. Age: 18-70 years old.
5. PS/ECOG score (performance status score of 0 or 1).
6. Adequate organ function:

1. Hematology: White blood cell count ≥ 4000/μL, neutrophil count ≥ 2000/μL, hemoglobin ≥ 9 g/dL, platelet count ≥ 100000/μL;
2. 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;
3. Renal function: Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min calculated by the Cockcroft-Gault formula.
4. 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.
7. 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

Exclusion Criteria

1. Patients whose laboratory test results within 7 days before enrollment do not meet the relevant standards.
2. 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.
3. 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).
4. Patients with tumors accompanied by obvious liquefaction necrosis, which are unsuitable for radiotherapy or may lead to radioresistance.
5. Patients with tumors invading the brain parenchyma.
6. Patients with a history of severe allergic reactions to any components of other monoclonal antibodies or PD-1/PD-L1 monoclonal antibodies.
7. Patients with known or suspected autoimmune diseases, including dementia and epileptic seizures.
8. Patients with recurrence, distant metastasis, or concurrent other malignant tumors.
9. Patients with severe heart disease, pulmonary dysfunction, or cardiac/pulmonary function grade 3 or lower (including grade 3).
10. 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.
11. Patients with comorbidities requiring long-term treatment with immunosuppressive drugs or systemic/local use of corticosteroids at immunosuppressive doses before enrollment.
12. 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).
13. Patients with a history of allergic reactions to the drugs used in this study (gemcitabine, docetaxel, taxanes, cisplatin).
14. Patients with active tuberculosis (TB) who are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening.
15. 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.
16. Women of childbearing age with positive pregnancy test results and lactating women.
17. Other patients deemed unsuitable for inclusion by the attending physician.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ming-Yuan Chen

OTHER

Sponsor Role lead

Responsible Party

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Ming-Yuan Chen

Professior, Chief physician

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Ming-Yuan Chen, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

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The Fifth Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Site Status RECRUITING

Cancer Center of Guangzhou Medical University

Guangzhou, Guangdong, China

Site Status RECRUITING

Sun Yat-sen University cancer center

Guangzhou, Guangdong, China

Site Status RECRUITING

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

Guangzhou, Guangdong, China

Site Status RECRUITING

Cancer Hospital of Shantou University Medical College

Shantou, Guangdong, China

Site Status RECRUITING

Zhongshan City People's Hospital

Zhongshan, Guangdong, China

Site Status RECRUITING

The People's Hospital of Guangxi Zhuang Autonomous Region

Nanning, Guangxi, China

Site Status RECRUITING

Wuzhou Red Cross Hospital

Wuzhou, Guangxi, China

Site Status RECRUITING

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

Wuhan, Hubei, China

Site Status RECRUITING

Central South University Cancer Hospital

Changsha, Hunan, China

Site Status RECRUITING

Xiangya Hospital of Central South University

Changsha, Hunan, China

Site Status RECRUITING

The Fifth Affiliated Hospital of Sun Yat-sen University

Guangdong, Zhuhai, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Ming-Yuan Chen, MD,PhD

Role: CONTACT

+86-20-87343361

Rui You, MD,PhD

Role: CONTACT

+86-13580439820

Facility Contacts

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Mingyuan Chen, PhD.

Role: primary

+86-13878480806

Bin Qi

Role: primary

+86-13580580985

Peiyu Huang

Role: primary

+86-13632396200

Yimin Liu

Role: primary

+86-13802501812

Kai Chen

Role: primary

+86-13005222990

Feng Lei

Role: primary

+86-13528227676

Shen-Hong Qu, MD, PhD

Role: primary

+86-15807813816

Jinhui Liang

Role: primary

+86-13878480806

Guangyuan Hu

Role: primary

+86-13886000095

Yaqian Han

Role: primary

+86-18673176667

Yuxiang He

Role: primary

+86-13786112914

Ming-Yuan Chen, MD,PhD

Role: primary

+86-13903052650

Other Identifiers

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ZDWY.BYAFZZX.043

Identifier Type: -

Identifier Source: org_study_id

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