The Role of Adding Concurrent Chemotherapy to IMRT in the Treatment of Stage II Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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The study is designed to compare Intensity Modulated Radiotherapy (IMRT) in combination with concurrent chemotherapy and IMRT alone in treatment of stage II nasopharyngeal carcinoma.

Detailed Description
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Nasopharyngeal carcinoma (NPC) is endemic in Southern China, Southeast Asia, the Arctic, and mid-East/North Africa. NPC prevalence is reported to be highest in southern China, where an average of 80 cases per 100,000 population are reported each year. It is both radiosensitive and chemosensitive. The National Comprehensive Cancer Network (NCCN) guidelines (version 1, 2013), have recommended use of concurrent chemoradiotherapy (CCRT) with or without adjuvant chemotherapy (AC) as standard treatment for NPC. Recently, the technique of IMRT has become widely used in the treatment of nasopharyngeal carcinoma. The preliminary results showed that IMRT might improve the rate of local control and the quality of life in NPC. In a retrospective study (Ivan,2010), the result showed that IMRT without concurrent chemotherapy provides good outcome for patients with stage IIB NPC with acceptable toxicity. Another study showed that Comparing with IMRT alone, IMRT in combination with chemotherapy provided no significant benefit to locoregionally advanced NPC (Su,2011). With IMRT, it was unclear whether the additional of concurrent chemotherapy was essential for stage II nasopharyngeal carcinoma. The investigators designed the present study to research the role of adding concurrent chemotherapy to intensity modulated radiotherapy in the treatment of stage II NPC. The primary endpoint is failure-free survival (FFS).The second endpoints were overall survival (OS),loco-regional failure-free survival (LFFS), distant metastasis failure-free survival (DMFS), and acute and late adverse events.

Official Title
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Phase II Study Comparing Intensity Modulated Radiotherapy (IMRT) in Combination With Concurrent Chemotherapy and IMRT Alone for Stage II Nasopharyngeal Carcinoma

Conditions
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Effects of Chemotherapy

Intervention / Treatment
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* Drug: Concurrent chemotherapy with cisplatin
* Radiation: Intensity modulated radiotherapy


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). 18 Years to 70 Years Tumor staged as T1-2N1/ T2N0 (according to the 7th AJCC edition),No evidence of distant metastasis (M0) Satisfactory performance status: Karnofsky scale (KPS) > 70 (Appendix I ). Adequate marrow: leucocyte count > 4×109/L, neutrophil count > 2×109/L, hemoglobin > 90g/L and platelet count > 100×109/L 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: WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma. Age > 60 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: 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Concurrent chemoradiotherapy<br>Concurrent chemoradiotherapy: IMRT was given to the patients with regimen of 66Gy-76Gy to the gross target volume of nasopharynx,66-70Gy to the gross target volume of positive nodes, 60-62Gy the high risk clinical target volume, 50-56Gy to the low risk clinical target volume. Concurrent chemotherapy is administrated with cisplatin 100mg/m2 at d1, d22, d43 during radiotherapy. | Drug: Concurrent chemotherapy with cisplatin<br>* Three cycles of weekly Cisplatin 100 mg/m2 starting on the first day of IMRT<br>Radiation: Intensity modulated radiotherapy<br>* Intensity modulated radiotherapy is a technique of radiotherapy.<br>|
| Active Comparator: IMRT alone<br>IMRT is given to the patients with regimen of 66Gy-76Gy to the gross target volume of nasopharynx,66-70Gy to the gross target volume of positive nodes, 60-62Gy the high risk clinical target volume, 50-56Gy to the low risk clinical target volume. | Radiation: Intensity modulated radiotherapy<br>* Intensity modulated radiotherapy is a technique of radiotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure-free survival (FFS) | The time is calculated from the date of diagnosis to the date of occurrence of relapse or distant metastasis. | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | The time is calculated from the date of diagnosis to the date of patient death. | One year | 
| Loco-regional failure-free survival (LFFS) | The time is calculated from the date of diagnosis to the date of a relapse of local or nodal tumors. | One year | 
| Distant metastasis failure-free survival (DMFS) | The time is calculated from the date of diagnosis to the date of occurrence of relapse or distant metastasis. | One year | 
| Acute and late adverse events | The side effects will be evaluated according to CTCAE V 3.0. | Four months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasopharyngeal neoplasm;IMRT; Concurrent chemotherapy