The Role of Concurrent Chemotherapy for Lower Risk Locally Advanced Nasopharyngeal Carcinoma(NPC) in the Era of IMRT

Study Overview
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Brief Summary
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The purpose of this study is to verify that simultaneous integrated boost IMRT (SIB-IMRT) alone is non-inferior to SIB-IMRT combined with concurrent chemotherapy for low-risk locally advanced nasopharyngeal carcinoma.

Detailed Description
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There were several randomized clinical trials confirmed that concurrent chemoradiotherapy (CCRT) is superior to radiotherapy (RT)alone for locally advanced NPC, most of the patients in the trials were treated with conventional radiotherapy technique. As the new technique of IMRT used more and more in the clinical practice, the role of concurrent chemoradiotherapy (CCRT) seems blurred, in two of Hongkong phaseIII studies(NPC9901/9902), half of the patients were treated by 3-dimensional conformal radiotherapy (3DCRT)/IMRT,the results showed that there were no significant different in terms of overall survival between RT alone and CCRT groups. Furthermore, several large sample size retrospective studies from China, showed that there were no advantage of CCRT over RT alone when treated by SIB-IMRT. In an analysis of who will benefit from CCRT,( Lin, et.al, IJROBP,2004; 60:156-164), the author divided the locally advanced NPC patients into two groups, with the high-risk group defined as patients met at least one of following criteria: nodal size >6 cm, (2) supraclavicular node metastasesN3, T4N2 and multiple neck node metastases with 1 node >4cm. Based on these information, we hypothesize that, for low-risk locally advanced NPC patients, there may no need CCRT under SIB-IMRT treatment.

Official Title
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Multicenter Phase III Study of Intensity-modulated Radiotherapy Alone Compared to Intensity-modulated Radiotherapy Combined Chemotherapy for Lower Risk Locally Advanced Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Radiation: SIB-IMRT
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathological proven non-keratin nasopharyngeal carcinoma AJCC 7th edition stage III/IVM0, without any one of following factors: node size >6cm;supraclavicular metastasis node; T4N2; multiple neck node metastases with 1 node >4 cm Life expectancy≥6 months Adequate renal function, defined as follows: Serum creatinine < 2 x institutional upper limit of normal(ULN) within 2 weeks prior to registration or creatinine clearance rate (CCr) ≥ 50 ml/min within 2 weeks prior to registration determined by 24- hour collection or estimated by Cockcroft-Gault formula: CCr male = [(140 - age) x (wt in kg)] [(Serum Cr mg/dl) x (72)] CCr female = 0.85 x (CCrmale) The following assessments are required within 2 weeks prior to the start of registration: Na, K, Cl, glucose, Ca, Mg, and albumin Exclusion Criteria: Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; noninvasive cancers (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible) are permitted even if diagnosed and treated < 3 years ago Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields Severe, active co-morbidity Treatment planning does not meet the requirement of prescription dose.

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RT alone<br>SIB-IMRT was given to the patients with a regimen of 69.96Gy-73.92Gy to the gross target volume, 60Gy to the high risk clinical target volume, 50Gy to the low risk clinical target volume | Radiation: SIB-IMRT<br>* SIB-IMRT was given to the patients with regimen of 69.96Gy-73.92Gy to the gross target volume, 60Gy to the high risk clinical target volume, 50Gy to the low risk clinical target volume<br>|
| Active Comparator: CCRT group<br>SIB-IMRT was given to the patients with regimen of 69.96Gy-73.92Gy to the gross target volume, 60Gy to the high risk clinical target volume, 50Gy to the low risk clinical target volume and cisplatin 100mg/m2 was given at d1, d22,d43 during radiotherapy. | Radiation: SIB-IMRT<br>* SIB-IMRT was given to the patients with regimen of 69.96Gy-73.92Gy to the gross target volume, 60Gy to the high risk clinical target volume, 50Gy to the low risk clinical target volume<br>Drug: Cisplatin<br>* Cisplatin 100mg/m2 was delivered at d1,d22 and d43 to the CCRT group patients during radiotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | according to the recruitment, a interrim analysis will done in July, 2019, if there is inferior finding of RT alone group, the study will premature terminate | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute and late toxicities | compare the acute radiation and chemotherapy-related toxicities during treatment course compare late toxicities after treatment | 5years | 
| 3 year Progression-free survival (PFS) | to compare the 3years PFS between the IMRT alone and IMRT with concurrent chemoradiotherapy | 5year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasopharyngeal carcinoma, current chemotherapy, intensity-modulated radiotherapy, low-risk