Trail Evaluating Carbon Ion Radiotherapy (3 GyE Per Fraction) for Locally Recurrent Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to determine the maximal tolerated dose (MTD) of re-irradiation using carbon ion radiotherapy (CIRT) with the fraction size of 3 gray equivalent (GyE) in the treatment of locally recurrent nasopharyngeal cancer (NPC) and to evaluate the efficacy of such treatment at the MTD. Participants will be treated with CIRT with escalating dose regimens to evaluate the MTD in terms of acute and subacute toxicity observed during and within 4 months after the completion of CIRT. Once the MTD for locally recurrent NPC is determined, the MTD will be used as the recommended dose to patients fulfilling the inclusion criteria in the Phase II part of the trial.

Detailed Description
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The purpose of this study is to determine the maximal tolerated dose (MTD) of re-irradiation using carbon ion radiotherapy (CIRT) with the fraction size of 3 GyE in the treatment of locally recurrent nasopharyngeal cancer (NPC) and to evaluate the efficacy of such treatment at the MTD. Participants will be treated with CIRT with escalating dose starting from 54GyE (3GyE/daily fraction) to potentially 63GyE (3GyE/daily fraction) to evaluate the maximal tolerated dose (MTD) in terms of acute and subacute toxicity observed during and within 4 months after the completion of CIRT. The classic 3+3 method is used for the phase I dose escalating part of the trial and approximately 4-18 patients will be accrued. Once the MTD for locally recurrent NPC is determined, the MTD will be used as the recommended dose to patients fulfilling the inclusion criteria in the Phase II part of the trial. The Phase II part of the trial will be a single phase single arm study.

Official Title
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Phase I/II Trail Evaluating Carbon Ion Radiotherapy (3 GyE Per Fraction) for Salvaging Treatment of Locally Recurrent Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Radiation: Carbon ion radiotherapy (CIRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed a definitive course of intensity-modulated photon radiation therapy (IMXT) to a total dose of ≥ 66 Gy Recurrence diagnosed more than 12 months after the initial course of IMXT Age ≥ 18 and < 70 years of age Karnofsky Performance Score ≥70 Willing to accept adequate contraception for women with childbearing potential Ability to understand character and individual consequences of the clinical trial Willing to sign the written informed consent; Informed consent must be signed before the enrollment in the trial Exclusion Criteria: Local recurrence of NPC diagnosed within 12 months from the completion of previous course of radiation therapy Presence of distant metastasis Technology used other than IMXT (including brachytherapy following IMXT) for the treatment of initial diagnosis of NPC Pregnant or lactating women Patients who have not yet recovered from acute toxicities of prior therapies A diagnosis of malignancy other than carcinoma in situ of the cervix, basal cell carcinoma and squamous cell carcinoma of the skin within the past 5 years Refusal of the patient to participate into the study

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CIRT Arm (3GyE per fraction)<br>Patients included in this arm were treated with carbon ion radiotherapy with a fraction size of 3GyE. | Radiation: Carbon ion radiotherapy (CIRT)<br>* Four dose levels (54GyE, 57GyE, 60GyE, 63GyE) are planned within the Phase I part. Daily fraction of 3 GyE will be delivered for all dose levels. After the recommended dose (RD), i.e., maximal tolerated dose, is determined or if the treatments to 63 GyE are safely delivered, the recommended dose (or 63 GyE) will be the prescribed dose in the Phase II part of the study. Ninety-five percent (95%) of the isodose line should cover the gross tumor volume plus 3 5mm.<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 adverse events as assessed by CTCAE v4.0 |  | Time interval from the start of CIRT to 4 months after the completion of CIRT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival of all patients |  | From the diagnosis of local recurrence of NPC, a median of 2 years | 
| Progression-free survival of all patients |  | From the completion of CIRT, a median of 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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re-irradiation, carbon ion therapy