Concurrent Chemotherapy for the Intermediate Risk Nasopharyngeal Carcinoma In Intensity-modulated Radiotherapy Era

Study Overview
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Brief Summary
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Currently, concurrent chemoradiotherapy with/without sequential chemotherapy is the standard treatment modality for intermediate risk NPC (stage II and T3N0M0) according to the National Comprehensive Cancer Network guideline. However these recommendations were based on the evidence in the two-dimensional conventional radiotherapy (2DCRT) era. The introduction of intensity-modulated radiotherapy (IMRT) in NPC treatment has brought substantial better treatment outcomes than 2DCRT. It has been questioned whether additional concurrent chemotherapy is still necessary for intermediate risk NPC within the excellent framework of IMRT. Thus, the investigators jointly conduct the first non-inferior randomized trial to determine the value of concurrent chemotherapy with cisplatin for intermediate risk NPC patients treated with IMRT. Given the results of clinical studies mentioned above,the investigators decide to adopt the concurrent regimen to be cisplatin 100 mg/m2 on day 1, 22, 43

Detailed Description
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Currently, concurrent chemoradiotherapy with/without sequential chemotherapy is the standard treatment modality for intermediate risk NPC (stage II and T3N0M0) according to the National Comprehensive Cancer Network guideline. However these recommendations were based on the evidence in the two-dimensional conventional radiotherapy (2DCRT) era. The introduction of intensity-modulated radiotherapy (IMRT) in NPC treatment has brought substantial better treatment outcomes than 2DCRT. It has been questioned whether additional concurrent chemotherapy is still necessary for intermediate risk NPC within the excellent framework of IMRT. Thus, the investigators jointly conduct the first non-inferior randomized trial to determine the value of concurrent chemotherapy with cisplatin for intermediate risk NPC patients treated with IMRT. Given the results of clinical studies mentioned above, the investigators decide to adopt the concurrent regimen to be cisplatin 100 mg/m2 on day 1, 22, 43

Official Title
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Prospective Non-inferior Clinical Trial Comparing Concurrent Chemoradiotherapy or Radiotherapy Alone in Patients With Intermediate Risk Nasopharyngeal Carcinoma in Intensity-modulated Radiotherapy Era

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Radiation: IMRT
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with newly histologically confirmed non-keratinizing (according to WHO histologically type. Tumor staged as T1-2N1/T2-3N0(according to the 7th AJCC edition). No evidence of distant metastasis (M0). Satisfactory performance status: Karnofsky scale (KPS) ≥ 70. Adequate marrow: leucocyte count ≥ 4000/μL, hemoglobin ≥ 120g/L for male, ≥ 120g/L for female , and platelet count ≥ 100000/μL. Normal liver function test: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) < 1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) ≤ 2.5×ULN, and bilirubin ≤ ULN. Adequate renal function: creatinine clearance ≥ 60 ml/min. Patients must be informed of the investigational nature of this study and give written informed consent. Exclusion Criteria: Neck lymph node with extracapsular spread. Maximal axial diameter of neck lymph node ≥30mm, positive neck lymph node at level IV and/or Vb. Pretreatment plasma EBV DNA level ≥4000 copy/ml. WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma. Age > 65 or < 18. Treatment with palliative intent. Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer. Pregnancy or lactation (consider pregnancy test in women of child-bearing age and emphasize effective contraception during the treatment period). History of previous RT (except for non-melanomatous skin cancers outside intended RT treatment volume). Prior chemotherapy or surgery (except diagnostic) to primary tumor or nodes. Any severe intercurrent disease, which may bring unacceptable risk or affect the compliance of the trial, for example, unstable cardiac disease requiring treatment, renal disease, chronic hepatitis, diabetes with poor control (fasting plasma glucose > 1.5×ULN), and emotional disturbance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: RT group<br>intensity modulated-radiotherapy (IMRT) alone: Patients receive intensity modulated-radiotherapy (IMRT) alone | Radiation: IMRT<br>* Intensity modulated-radiotherapy (IMRT) is given as 2.0-2.30 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumor<br>* Other names: Intensity-modulated radiation therapy;|
| Active Comparator: CCRT group<br>IMRT and concurrent cisplatin Patients receive intensity modulated-radiotherapy (IMRT), concurrently with cisplatin 100 mg/m² every 3 weeks for 3 cycles | Radiation: IMRT<br>* Intensity modulated-radiotherapy (IMRT) is given as 2.0-2.30 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumor<br>* Other names: Intensity-modulated radiation therapy;Drug: Cisplatin<br>* concurrently with cisplatin 100 mg/m² every 3 weeks for 3 cycles during IMRT<br>* Other names: Concurrent cisplatin regimen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure-free survival | The failure-free survival rate will be estimated using the Kaplan-Meier method for each arm from the date of randomization to the date of treatment failure or death from any cause, whichever is first. Their differences will be compared between treatment arms using the log-rank test. | 3 Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | The overall survival rate will be estimated using the Kaplan-Meier method for each arm from randomization to death from any cause. Their differences will be compared between treatment arms using the log-rank test. | 3 Year | 
| Locoregional failure-free survival | The locoregional failure-free survival will be estimated using the Kaplan-Meier method for each arm from randomization to the first locoregional failure. Their differences will be compared between treatment arms using the log-rank test. | 3 Year | 
| Distant failure-free survival | The distant failure-free survival will be estimated using the Kaplan-Meier method for each arm from randomization to the first remote failure. Their differences will be compared between treatment arms using the log-rank test. | 3 Year | 
| Rates of participants with adverse events | Acute and late toxicities will be documented according to the Common Terminology Criteria for Adverse Events version 3.0 and/or the Radiation Morbidity Scoring Criteria of the Radiation Therapy Oncology Group. Rates of the toxicities will be estimated using a binomial distribution along and will be compared using Fisher's exact test between the 2 treatment arms. | 3 Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasopharyngeal carcinoma, Concurrent chemoradiotherapy, intermediate risk, intensity-modulated radiotherapy