Reduced Volume of Neck Prophylactic Irradiation in Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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This is a multi-center, non-inferiority, open-label, randomized controlled phase III clinical trial in primary diagnosed nasopharyngeal carcinoma (NPC) patients without distant metastasis. The purpose of this study is to evaluate the efficacy of reduced neck prophylactic radiotherapy versus conventional neck prophylactic radiotherapy, and compare the radiotherapy-related adverse events and quality of life in two groups.

Official Title
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Reduced Volume of Neck Prophylactic Irradiation in Nasopharyngeal Carcinoma: a Multi-center, Non-inferiority, Open-label, Randomized Controlled Phase III Clinical Trial

Conditions
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Nasopharyngeal Carcinoma, Radiotherapy; Complications

Intervention / Treatment
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* Radiation: Intensity Modulated Radiation Therapy
* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly histologic diagnosis of nasopharyngeal non-keratinizing carcinoma (WHO II/III); All genders, range from 18-70 years old; ECOG score 0-1; Clinical stage I-IVa (AJCC/UICC 8th); Not received radiotherapy, chemotherapy and other anti-tumor treatment (including immunotherapy); No contraindications to chemotherapy or radiotherapy; Adequate organ function: white blood cell count ≥ 4×109/L, neutrophile granulocyte count ≥ 1.5×109/L, hemoglobin ≥ 9g/L, platelet count ≥ 100×109/L; alanine aminotransferase or aspartate aminotransferase < 2.5×upper limit of normal; blood urea nitrogen or creatinine ≤ 1.5×upper limit of normal or endogenous creatinine clearance ≥ 60ml/min (Cockcroft-Gault formula); Sign the consent form. Exclusion Criteria: Neck lymph nodes exist skipping metastasis; Distant metastases; Keratinized squamous cell carcinoma or basal cell like squamous cell carcinoma; Have or are suffering from other malignant tumors; Participating in other clinical trials; Pregnancy or lactation; Have uncontrolled cardiovascular disease; Severe complication, eg, uncontrolled hypertension; Mental disorder; Drug or alcohol addition; Do not have full capacity for civil acts.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reduced CTVn2<br>Patients will receive the reduced neck prophylactic irradiation, only the level of positive lymph nodes and its next level. | Radiation: Intensity Modulated Radiation Therapy<br>* All target volumes will be outlined slice by slice on the axial contrast-enhanced CT with MR fusion images in the treatment planning system. The target volumes are defined in accordance with the International Commission on Radiation Units and Measurements Reports 83. The prescribed dose is 70-72 Gy to PTVp (Planning target volume of the primary tumor), 64-70 Gy to PTVn (Planning target volume of the lymph node),60- 64Gy to PTV1 (High-risk planning target volume), and 54-58 Gy to PTV2 (Low-risk planning target volume) in 30-32 fractions. The details of dose limits for organs at risk are based on the study 0225 from The Radiation Therapy Oncology Group (RTOG 0225).<br>* Other names: IMRT;Drug: Chemotherapy<br>* Chemotherapy will be arranged by the physician-in-charge according to the NCCN guideline, patient's stage and physical condition.<br>|
| Active Comparator: Conventional CTVn2<br>Patients will receive the conventional neck prophylactic irradiation, as suggested by the international guideline. | Radiation: Intensity Modulated Radiation Therapy<br>* All target volumes will be outlined slice by slice on the axial contrast-enhanced CT with MR fusion images in the treatment planning system. The target volumes are defined in accordance with the International Commission on Radiation Units and Measurements Reports 83. The prescribed dose is 70-72 Gy to PTVp (Planning target volume of the primary tumor), 64-70 Gy to PTVn (Planning target volume of the lymph node),60- 64Gy to PTV1 (High-risk planning target volume), and 54-58 Gy to PTV2 (Low-risk planning target volume) in 30-32 fractions. The details of dose limits for organs at risk are based on the study 0225 from The Radiation Therapy Oncology Group (RTOG 0225).<br>* Other names: IMRT;Drug: Chemotherapy<br>* Chemotherapy will be arranged by the physician-in-charge according to the NCCN guideline, patient's stage and physical condition.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regional recurrence-free survival | From the date of randomization to regional recurrence or any death | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | From the date of randomization to any death, with patients unavailable for follow-up censored at the date of last follow-up | 3 years | 
| Local recurrence-free survival | From the date of randomization to local recurrence or any death | 3 years | 
| Distant metastasis-free survival | From the date of randomization to distant metastasis or any death | 3 years | 
| Progression free survival | From the date of randomization to local or regional recurrence, distant metastasis or any death | 3 years | 
| Acute toxicities | Assessed with CTCAE v5.0 | From the start of treatment until 3 months post treatment | 
| Late toxicities | Assessed with RTOG/EORTC | 3 years post treatment | 
| Quality of life score | Assessed with EORTC-Quality of life questionnaire-C30 version 3.0 | During treatment and 3 years post treatment |