Intensity-modulated Radiotherapy With or Without Concurrent Chemotherapy for Stage II Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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A prior phase III randomized trial showed considerable survival benefit from the combined treatment of cisplatin-based concurrent chemotherapy and two-dimensional conventional radiotherapy (2DCRT) for patients with stage II (the Chinese 1992 staging system) nasopharyngeal carcinoma. However, since intensity-modulated radiotherapy (IMRT) was known to be superior to 2DCRT in local control, progression free survival and even overall survival, it is a pivotal question whether stage II [T1N1M0 and T2N0-1M0, based on the 2010 International Union against Cancer/American Joint Committee on Cancer (UICC/AJCC) staging system] patients can still obtain significant benefit from the additional concurrent chemotherapy in the IMRT era. The investigators' retrospective study (PMID:26528755 ) indicated that low risk nasopharyngeal carcinoma (T1N1M0, T2N0-1M0 or T3N0M0, the 2010 UICC/AJCC staging system) patients who underwent IMRT could not benefit from cisplatin-based concurrent chemotherapy. Therefore, the investigators perform this randomized controlled trial to address this question, on a prudent assumption that IMRT alone was not inferior to IMRT plus concurrent chemotherapy in stage II patients.

Detailed Description
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Eligible patients are randomly assigned to receive intensity-modulated radiotherapy (IMRT) alone or IMRT plus concurrent chemotherapy. 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. Concurrent chemotherapy consisted of cisplatin 100 mg/m² every 3 weeks for 3 cycles. The primary endpoint is overall survival (OS). Secondary end points include failure-free survival(FFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), toxic effects and quality of life. All efficacy analyses are conducted in the intention-to-treat population, and the safety population include only patients who receive their randomly assigned treatment.

Official Title
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Intensity-modulated Radiotherapy With or Without Concurrent Chemotherapy for Stage II Nasopharyngeal Carcinoma: a Phase 3 Non-inferior Multicenter Randomized Controlled Trial

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Cisplatin
* Radiation: Intensity-modulated radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly histologically confirmed non-keratinizing (WHO 1991) nasopharyngeal carcinoma. Tumor staged as T1N1M0 or T2N0-1M0 (the 2010 UICC/AJCC staging system). Karnofsky scale (KPS) ≥ 70. Adequate marrow: leucocyte count ≥ 4×10E9/L, hemoglobin ≥ 110g/L and platelet count ≥ 100×10E9/L. Normal liver function test: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and bilirubin ≤ 1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) ≤ 2.5×ULN. Adequate renal function: creatinine clearance ≥ 60 ml/min or creatinine ≤ 1.5×ULN. Patients must give written informed consent. Exclusion Criteria: 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 radiotherapy (except for non-melanomatous skin cancers outside intended radiotherapy volume). Prior radiotherapy, 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: IMRT alone<br>Intensity-modulated radiotherapy without cisplatin-based concurrent chemotherapy | Radiation: Intensity-modulated radiotherapy<br>* Intensity-modulated radiotherapy<br>|
| Active Comparator: IMRT plus concurrent chemotherapy<br>Intensity-modulated radiotherapy with cisplatin-based concurrent chemotherapy | Drug: Cisplatin<br>* Cisplatin 100 mg/m² every 3 weeks for 3 cycles during radiotherapy.<br>* Other names: DDP;Radiation: Intensity-modulated radiotherapy<br>* Intensity-modulated radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | Two year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| failure-free survival |  | two year | 
| distant metastasis-free survival |  | two year | 
| locoregional relapse-free survival |  | two year | 
| Number of participants with treatment-related acute adverse events as assessed by CTCAE v4.0 |  | two months | 
| quality of life assessing by questionnaires |  | through study completion, an average of 5 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NPC, concurrent chemotherapy, IMRT, stage II