Proton Versus Photon Radiotherapy for Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to compare the toxicity and therapeutic efficacy of proton or photon combined with carbon ion radiotherapy for newly diagnosed nasopharyngeal carcinoma.Participants will be randomized to 2 arms. Arm 1, participants received photon combined with carbon ion radiotherapy group, Arm 2, participants received proton combined with carbon ion radiotherapy.

Detailed Description
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The purpose of this study is to compare the toxicity and therapeutic efficacy of photon or proton combined with carbon ion radiotherapy for newly diagnosed nasopharyngeal carcinoma.Participants will be randomized to 2 arms. Arm 1 participants received photon combined with carbon ion radiotherapy (photon: 56 Gy/28 Fx, plus carbon: 15-17.5 gray equivalent [GyE]/5 Fx for boost). Arm 2, participants received proton combined with carbon ion radiotherapy (proton: 56 GyE/28 Fx, plus carbon: 15-17.5 GyE/5 Fx for boost). Adverse events will be documented according to CTCAE v4.03.The response of treatment will be evaluated according to RECIST criteria.

Official Title
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A Randomized Phase II Trial Evaluating Toxicity and Efficacy Between Proton and Photon for Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Radiation: Photon
* Radiation: Proton
* Radiation: Carbon ion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed Nasopharyngeal carcinoma(WHO II/III type). Age ≥ 18 and ≤ 70 years of age. 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. Received radiotherapy for head and neck before. Received surgery(except for biopsy) for primary lesion or cervical lymph node. Previous history of malignant tumor (within 5 years) or simultaneous existence of multiple primary tumors. Presence of diseases (such as Sjögren syndrome) that may interfere evaluation of xerostomia. 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 |
| --- | --- |
| Experimental: Photon combined with Carbon ion<br>The participants received photon: 56 Gy/28 Fx for high-risk area(CTVhigh), 50.4 Gy/28 Fx for lower neck low-risk area(CTVlow), plus carbon ion: 15-17.5 GyE/5 Fx for boost for visible tumors. | Radiation: Photon<br>* Photon combined with Carbon ion in Arm 1<br>Radiation: Carbon ion<br>* Same dose and fractionation will be used in both arms.<br>|
| Experimental: Proton combined with Carbon ion<br>The participants received proton: 56 GyE/28 Fx for high-risk area(CTVhigh), 50.4 GyE/28 Fx for lower neck low-risk area(CTVlow), plus carbon ion: 15-17.5 GyE/5 Fx for boost for visible tumors. | Radiation: Proton<br>* Proton combined with Carbon ion in Arm 2<br>Radiation: Carbon ion<br>* Same dose and fractionation will be used in both arms.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related Xerostomia (≥Grade 2) as assessed by NCI CTCAE v4.03 | CTCAE refers to Common Terminology Criteria for Adverse Events, which is one of the most frequently used criteria for toxicity grading after anti-cancer treatment. | Xerostomia (≥Grade 2) occurred at 6 months after completion of radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival of all patients |  | From randomization to death, a median of 3 years. | 
| Progression-free survival of all patients |  | From randomization to death or disease progression, a median of 3 years. | 
| Local control |  | From randomization to local failure, a median of 3 years. | 
| Regional control |  | From randomization to regional failure, a median of 3 years. | 
| Distant control |  | From randomization to distant failure, a median of 3 year. | 
| Treatment-related adverse events as assessed by NCI CTCAE v4.03 | Acute and late toxicities induced by radiation therapy other than xerostomia. | Time interval from start to 3 months after completion of radiotherapy. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasopharyngeal carcinoma, Intensity-modulated radiation therapy, Proton beam therapy, Carbon-ion radiotherapy, Toxicity, Survival, Disease control