S-1 Combined With IMRT Concurrent Chemoradiotherapy in Locally Advanced Nasopharyngeal Carcinoma

Study Overview
=================
Brief Summary
-----------------
This study is a prospective phase II trial which is designed to evaluate the efficacy and safety of IMRT combined with S-1 CCRT for locally advanced NPC. Eligibility criteria include histologically confirmed locally advanced NPC according to the American Joint Committee on Cancer (AJCC) Staging System (the eighth edition); Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; at least one measurable lesion based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1; normal complete blood count, normal hepatic function and normal renal function. Prior induction chemotherapy with platinum was allowed. Exclusion criteria include previous radiotherapy, a history of any other type of malignancy; pregnancy or lactation; allergy to S-1; obvious dysfunction of liver, renal, cardiac or lung function; uncontrolled infection; systemic metastasis or distant metastasis; patients with severe gastrointestinal diseases, and patients with mental disorders affecting patient participation in trial judgement. The full-set pretreatment evaluation will be performed to every patient.All patients in this study will receive intensity-modulated radiation therapy (IMRT). During the IMRT course, S-1 will be administered orally according to body surface area.The dose modifications of S-1 will not be permitted during concurrent chemotherapy unless progression of the disease, toxicities of grade 4 or patient's refusal. The primary endpoints of this study is adverse events (AE) rate and progression-free survival (PFS).

Detailed Description
-----------------
This study is a prospective phase II trial which is designed to evaluate the efficacy and safety of IMRT combined with S-1 CCRT for locally advanced NPC. Eligibility criteria include histologically confirmed locally advanced NPC according to the American Joint Committee on Cancer (AJCC) Staging System (the eighth edition); Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; at least one measurable lesion based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1; normal complete blood count (white blood cell counts ≥4×1012/L, hemoglobin level ≥100g/L and platelet counts ≥100×1012/L), normal hepatic function (total bilirubin level ≤1.5 mg/dl, alanine aminotransferase and aspartate aminotransferase levels ≤1.5 times the upper limit of normal) and normal renal function (creatinine ≤ 1.5 times the upper limit of normal). Prior induction chemotherapy with platinum was allowed. Exclusion criteria include previous radiotherapy, a history of any other type of malignancy; pregnancy or lactation; allergy to S-1; obvious dysfunction of liver, renal, cardiac or lung function; uncontrolled infection; systemic metastasis or distant metastasis; patients with severe gastrointestinal diseases, and patients with mental disorders affecting patient participation in trial judgement. The full-set pretreatment evaluation will be performed to every patient.All patients in this study will receive intensity-modulated radiation therapy (IMRT). During the IMRT course, S-1 will be administered orally according to body surface area (BSA<1.25m2, 30mg; BSA: 1.25-1.5m2, 40mg; BSA>1.5m2, 50mg).The dose modifications of S-1 will not be permitted during concurrent chemotherapy unless progression of the disease, toxicities of grade 4 or patient's refusal. Adverse events (AEs) will be evaluated every week during CCRT based on the evaluation criteria of adverse reactions of CTCAE V4.0. Tumor response is assessed at the end of CCRT according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1. Radiation-related acute and late toxicities are graded according to the Radiation Therapy Oncology Group (RTOG). Late toxicities are evaluated beyond three months from the end of radiotherapy. After the completion of CCRT, all patients will be followed up every 3 months during the first years, every 6 months for the following 2-5 years, and annually thereafter. Local recurrence is confirmed by nasopharynx MRI or histological biopsy. Regional recurrence is confirmed by fine needle aspiration or surgical biopsy. Distant metastases is detected by imaging examinations including PET-CT, bone Emission Computed Tomography (ECT), CT, MRI or confirmed by histological confirmation of biopsy. The primary endpoints of this study is adverse events (AE) rate and progression-free survival (PFS). PFS is calculated from the date of enrollment to the date of disease progression or the date of death for any cause.

Official Title
-----------------
S-1 Combined With IMRT Concurrent Chemoradiotherapy in Locally Advanced Nasopharyngeal Carcinoma

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

Intervention / Treatment
-----------------
* Drug: S-1


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed locally advanced NPC Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Normal complete blood count Normal hepatic function Normal renal function (creatinine ≤ 1.5 times the upper limit of normal). Exclusion Criteria: Previous radiotherapy A history of any other type of malignancy Pregnancy or lactation Allergy to S-1 Obvious disfunction of liver, renal, cardiac or lung function Uncontrolled infection Systemic metastasis or distant metastasis Patients with severe gastrointestinal diseases Patients with mental disorders affecting patient participation in trial judgement.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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: S-1 arm<br>The patients in the S-1 arm will receive IMRT (66-70.4Gy to GTV, 57-60.8Gy to CTV1, 54-56Gy to CTV2, given in 30-32 fractions). During the IMRT course, S-1 will be administered orally according to body surface area (BSA<1.25m2, 30mg; BSA: 1.25-1.5m2, 40mg; BSA>1.5m2, 50mg) twice per day for 30-32 days. The dose modifications of S-1 will not be permitted during concurrent chemotherapy unless progression of the disease, toxicities of grade 4 or patient's refusal. | Drug: S-1<br>* The patients will receive IMRT combined with S-1 concurrent chemoradiotherapy. The specific treatment description is included in arm description.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | PFS is calculated from the date of the enrollment to the date of disease progression or the date of death for any cause. | 3-year PFS （2018-2021） | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nasopharyngeal Carcinoma, IMRT, S-1