Trial Evaluating Carbon Ion Radiotherapy With Concurrent Chemotherapy for Locally Recurrent Nasopharyngeal Carcinoma

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the maximal tolerated dose (MTD) of re-irradiation using carbon ion radiotherapy (CIRT) along with concurrent chemotherapy 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 along with concurrent chemotherapy (40 mg/m^2, weekly) to evaluate the maximal tolerated dose (MTD) in terms of acute and subacute toxicity observed during and within 4 months after the completion of concurrent chemoradiotherapy. 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
-----------------
The purpose of this study is to determine the maximal tolerated dose (MTD) of re-irradiation using carbon ion radiotherapy (CIRT) along with concurrent chemotherapy in the treatment of locally recurrent nasopharyngeal cancer (NPC) and to evaluate the efficacy of such treatment at the MTD in the setting of concurrent chemoradiotherapy. Participants will be treated with CIRT with escalating dose starting from 52.5GyE (2.5GyE/daily fraction) to potentially 62.5GyE (2.5GyE/daily fraction) along with concurrent chemotherapy (40 mg/m^2, weekly) to evaluate the maximal tolerated dose (MTD) in terms of acute and subacute toxicity observed during and within 4 months after the completion of concurrent chemoradiotherapy. Time-to-event continual reassessment method (TITE-CRM) is used for the phase I dose escalating part of the trial and approximately 25 patients will be accrued. Once the MTD in the setting of concurrent chemoradiotherapy 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
-----------------
Phase I/II Trial Evaluating Carbon Ion Radiotherapy With Concurrent Chemotherapy for Salvaging Treatment of Locally Recurrent Nasopharyngeal Carcinoma

Conditions
-----------------
Nasopharyngeal Carcinoma

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: -Pathologically confirmed NPC 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 CIS of the cervix, BCC and SCC of the skin within the past 5 years Refusal of the patient to participate into the study

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CIRT with concurrent chemo arm<br>Treated with carcon ion radiotherapy along with concurrent chemotherapy (Cisplatin 40mg/m^2, weekly). | Radiation: Carbon ion radiotherapy (CIRT)<br>* Five dose levels (52.5GyE, 55GyE, 57.5GyE, 60GyE, 62.5GyE) are planned within the Phase I part. Daily fraction of 2.5 GyE will be delivered for all dose levels. After the recommended dose (RD), i.e., MTD, is determined or if the treatments to 62.5 GyE are safely delivered, the recommended dose (or 62.5 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 GTV+3 5mm.<br>Drug: Cisplatin<br>* Cisplatin (40mg/m^2) monotherapy will be given weekly along with radiotherapy.<br>|

What is the study measuring?
-----------------
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 to 4 months after the completion of concurrent chemoradiotherapy | 

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 |  | Time Frame: From the completion of CIRT, a median of 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Carbon Ion Therapy, Concurrent Chemoradiotherapy