Induction Chemotherapy in Young Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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1. To see the effect if a combination of induction chemotherapy followed by chemoradiotherapy works in treating children with advanced nasopharyngeal carcinoma(NPC).

Detailed Description
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This phase II trial is studying how well radiation therapy and chemotherapy work in treating young patients with newly diagnosed nasopharyngeal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin and fluorouracil and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Official Title
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Phase II Study of TPF Induction Chemotherapy Followed by Concurrent Chemoradiotherapy in Young Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

Conditions
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Children, Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Paclitaxel liposome
* Drug: Cisplatin
* Drug: 5-fu
* Radiation: Radical radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with newly histologically confirmed non-keratinizing (according to World Health Organization (WHO) histologically type). Original clinical staged as T4N0-3 M0 or any T、N3M0（according to the American Joint Committee on Cancer(AJCC) 7th edition） No evidence of distant metastasis (M0). Age ≤ 18 years old. Satisfactory performance status: Karnofsky scale (KPS) > 70. Adequate marrow: leucocyte count ≥4000/μL, hemoglobin ≥90g/L 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: WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma. Age >18 years. Treatment with palliative intent. Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer. Pregnancy or lactation. History of previous radiotherapy (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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Maximum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paclitaxel liposome, Cisplatin, 5-Fu,<br>Patients receive paclitaxel liposome(135mg/m2 on day 1), cisplatin (75mg/m2 on day 1,Separate injection on day 1 to 3) and fluorouracil (3750mg/m2 CIV 120h) every three weeks for three cycles before the radiotherapy, and then receive radical radiotherapy(Intensive modulate radiotherapy,IMRT)and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapy. | Drug: Paclitaxel liposome<br>* Patients receive paclitaxel liposome(135mg/m2 on day 1),cisplatin (75mg/m2 Separate injection on day 1 to 3) and 5-fluorouracil (3750mg/m2 CIV 120h ) every three weeks for three cycl es before the radiotherapy. Patients receive radical radiotherapy and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapy. Radical radiotherapy:Intensive modulate radiotherapy (IMRT),total dose for nasopharynx and nodule of neck:60Gy/30F,2.0Gy/daily.<br>* Other names: Paclitaxel liposome,cisplatin,fluorouracil(TPF) chemotherapy;Drug: Cisplatin<br>* Cisplatin (75mg/m2 Separate injection on day 1 to 3) with Paclitaxel liposome and 5-fu every three weeks for three cycles before the radiotherapy.Cisplatin(100mg/m2) every three weeks for three cycles during radiotherapy.<br>* Other names: Concurrent cisplatin;Drug: 5-fu<br>* Fluorouracil (3750mg/m2 CIV 120h)with Paclitaxel liposomeand cisplatin every three weeks for three cycles before the radiotherapy.<br>* Other names: TPF induction chemotherapy;Radiation: Radical radiotherapy<br>* Intensive modulate radiotherapy (IMRT) will be implement,total dose for nasopharynx and nodule of neck:60Gy(Gray)/30F(Fraction),2.0Gy/daily,5 days/week.<br>* Other names: Concurrent radiotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response (CR) | CR assessed by independent reviewers, according to the Modified Response Evaluation Criteria in Solid Tumors (RECIST) from the National Cancer Institute (NCI). Disease response evaluated after the completion of the chemoradiotherapy treatment. Complete response defined as the complete disappearance of the target and non-target lesion(s) identified at baseline after radiological evaluation by Magnetic Resonance Imaging (MRI) only | After the completion of the chemoradiotherapy treatment (up to 9 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival(OS) | The OS was defined as the duration from the date of random assignment to the date of death from any cause or censored at the date of the last follow-up. | 3-year | 
| Progress-free survival(PFS) | Progress-free survival is calculated from the date of randomization to the date of the first progress at any site or death from any cause or censored at the date of the last follow-up | 3-year | 
| Locoregional failure-free survival(LRFS) | The LRFS is evaluated and calculated from the date of random assignment until the day of first locoregional relapse or until the date of the last follow-up visit | 3-year | 
| Distant metastasis-free survival(DMFS) | The DMFS is evaluated and calculated from the date of random assignment until the day of first distant metastases or until the date of the last follow-up visit | 3-year | 
| Short-term toxic effects assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) | The shortterm toxic effects were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) | 3 months | 
| Long-term toxicities | QoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30) | Through study completion, an average of half year | 
| Long-term toxicities | EORTC quality of life questionnaire(QLQ) Head and Neck | Through study completion, an average of half year | 
| Growth | Patients will be monitored for height(in metre) | Through study completion, an average of half year | 
| Growth | Patients will be monitored for weight(in kilogram) | Through study completion, an average of half year | 
| Growth | Patients will be monitored for BMI(in kg/m^2) | Through study completion, an average of half year | 
| Sex Development | Sex hormone(estrogen,testosterone) levels(in nmol/L) | Through study completion, an average of half year | 
| Sex Development | Secondary sex characteristic survey | Through study completion, an average of half year | 
| Intelligence Development | Intelligence quotient by Stanford-Binet test | Through study completion, an average of half year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Induction Chemotherapy, Nasopharyngeal carcinoma, Chemoradiotherapy