Individualized Carbon-Ion Radiotherapy for Patients With Locally Recurrent Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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This is a randomized phase 2 trial with 2 groups (control group vs experimental group). Patients with locally recurrent nasopharyngeal carcinoma (LR-NPC) assigned to the control group will receive standardized carbon-ion radiotherapy (CIRT). For patients assigned to the experimental group, a predictive model will be used to predict the chance of developing mucosal necrosis after salvage carbon-ion radiotherapy, and individualized dose prescription will be given. The primary endpoint of the study is to compare the 2-year progression-free survival (PFS) between 2 groups.

Detailed Description
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This is a randomized phase 2 trial with 2 groups (control group vs experimental group). Patients with locally recurrent nasopharyngeal carcinoma (LR-NPC) assigned to the control group will receive standardized CIRT with a dose of 63 gray equivalent (GyE) in 21 fractions (fx). This regimen was obtained from our previous phase 1 (dose escalation) study. For patients assigned to the experimental group, a predictive model will be used to predict the chance of developing mucosal necrosis after salvage carbon-ion radiotherapy, and individualized dose prescription will be given. A dose of 60 GyE/20 fx, 63 GyE/21 fx and 66 GyE/22 fx will be given to patients with high, moderate and low risk of developing mucosal necrosis, respectively. The primary endpoint of the study is to compare the 2-year progression-free survival (PFS) between 2 groups. The secondary endpoints include 2-year overall survival (OS), local progression-free survival, regional progression-free survival, distant metastasis-free survival, toxicities and quality of life.

Official Title
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Predictive-Model Based Individualized Carbon-Ion Radiotherapy for Patients With Locally Recurrent Nasopharyngeal Carcinoma: A Phase 2 Randomized Trial

Conditions
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Locally Recurrent Nasopharyngeal Carcinoma

Intervention / Treatment
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* Radiation: Standardized CIRT
* Radiation: Individualized CIRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 17-70 years. Pathologically diagnosed as WHO type 2/3 nasopharyngeal carcinoma. Failed previous definitive radiotherapy at least 6 months ago. Only had 1 previous course of radiotherapy. Eastern Cooperative Oncology Group score: 0-1. Adequate laboratory values within 30 dyas of enrollment to study defined as follows: 1) neutrophil > 2000/mm^3; 2) platelet > 100,000/mm^3; 3) total bilirubin < 1.5mg/dl; 4) alanine aminotransferase/aspartate aminotransferase < 1.5 upper limit of normal; 5) SCr < 1.5mg/dl; creatinine clearance rate > 60ml/min. Willing to accept adequate contraception for women with childbearing potential. Willing to sign the written informed consent; Informed consent must be signed before the enrollment in the trial. Exclusion Criteria: Presence of distant metastasis. Without measurable lesion. Previous history of malignant tumor (within 5 years) or simultaneous existence of multiple primary tumors. Accompanied with severe major organ dysfunction. Presence of mental disease that may influence the understanding of informed consent.

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 |
| --- | --- |
| Active Comparator: Standardized CIRT<br>Patients will receive standardized CIRT with a dose of 63 GyE/21 fx. | Radiation: Standardized CIRT<br>* CIRT with a dose of 63 GyE/21 fx<br>|
| Experimental: Individualized CIRT<br>A previously predictive model will be used to predict the chance of developing mucosal necrosis after salvage carbon-ion radiotherapy, and individualized dose prescription will be given. A dose of 60 GyE/20 fx, 63 GyE/21 fx and 66 GyE/22 fx will be given to patients with high, moderate and low risk of developing mucosal necrosis, respectively. | Radiation: Individualized CIRT<br>* A predictive model will be used to predict the chance of developing mucosal necrosis after salvage carbon-ion radiotherapy, and individualized dose prescription will be given. A dose of 60 GyE/20 fx, 63 GyE/21 fx and 66 GyE/22 fx will be given to patients with high, moderate and low risk of developing mucosal necrosis, respectively.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | From randomization to death or disease progression, a median of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | From randomization to death, a median of 2 years | 
| Local progression-free survival |  | From randomization to local failure, a median of 2 years | 
| Regional progression-free survival |  | From randomization to regional failure, a median of 2 years | 
| Distant metastasis-free survival |  | From randomization to distant metastasis, a median of 2 years | 
| Incidence of radiation-induced acute toxicity evaluated by CTCAE 5.0 |  | Within 3 months after initiation of radiation therapy | 
| Incidence of radiation-induced late toxicity evaluated by CTCAE 5.0 |  | Three months after initiation of radiation therapy | 
| Quality of life by questionnaires evaluated using EORTC-Q30 questionnaire. |  | Throughout the study, an average of 2 years | 
| Quality of life by questionnaires evaluated using EORTC-H&N35 questionnaire. |  | Throughout the study, an average of 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally recurrent nasopharyngeal carcinoma, Individualized carbon-ion radiotherapy, Predictive model of mucosal necrosis, Survival, Toxicity