A Multicenter, Prospective, Phase III Randomized Controlled Clinical Study for the Treatment of N2-3 Nasopharyngeal Carcinoma Patients

Study Overview
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Brief Summary
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At the initial diagnosis of locally advanced nasopharyngeal carcinoma, a considerable proportion of patients have developed distant metastasis, forming subclinical lesions. Nowadays, with the advent of intensity modulated radiotherapy, the local-regional area is under well controlled. However, distant metastasis is still the main cause of failure in treatment of stage N2-3 nasopharyngeal carcinoma.The severe toxicity of synchronous chemotherapy and the dose intensity of single drug is not enough to effectively control existing subclinical lesions. Neoadjuvant chemotherapy with sufficient intensity (four cycles) can possible effectively kill subclinical lesions prior to the initiation of concurrent chemoradiotherapy, thereby reducing distant metastasis of stage N2-3 nasopharyngeal carcinoma. Meanwhile, four cycles of chemotherapy have been shown to be well tolerated in other tumors. In conclusion, 4-cycle neoadjuvant chemotherapy in combination with radiotherapy is expected to further control the distant metastasis rate of N2-3 nasopharyngeal carcinoma and improve the survival rate.

Official Title
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A Multicenter, Prospective, Phase III Randomized Controlled Clinical Study Comparing 4 Cycles of Neoadjuvant Chemotherapy Combined With Radiotherapy Versus 3cycles of Neoadjuvant Chemotherapy Combined With Concurrent Chemoradiotherapy for the Treatment of N2-3 Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma, Neoadjuvant Chemotherapy

Intervention / Treatment
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* Drug: 4 cycles of Neoadjuvant Chemotherapy With Definitive Radiotherapy
* Drug: 3 cycles of Neoadjuvant Chemotherapy With concurrent chemoradiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-keratinizing nasopharyngeal carcinoma diagnosed by pathology; According to the UICC/AJCC eighth edition staging criteria, clinical staging was T1-4N2 -3M0 (stage N2-3 nasopharyngeal carcinoma); Patients who have not received disease-related anti-tumor system therapy; Age 18 70 years; Perfect liver and kidney function: total bilirubin ≤1.5 times the upper limit of normal value (ULN); AST and ALT≤2.5 ULN; Alkaline phosphatase ≤2.5 ULN; Creatinine clearance rate ≥80 mL/min; Complete blood system function: neutrophil count (ANC) ≥2×109/L, platelet count ≥100×109/L and hemoglobin ≥9 g/dL; Cartesian score ≥70; or ECOG PS 0 or 1 Prior to enrollment, the patients must undergo nasopharynx + neck MRI, chest + upper abdomen CT, ECT and other examinations of the whole body bone. Sign the informed consent. Exclusion Criteria: Patients with distant metastases were identified at the time of diagnosis; Patients with severe medical complications, severe organ (heart, lung) dysfunction, or neuropsychiatric disorders at the time of diagnosis; Previous cases of other malignancies;Complicated with other malignant tumors;Except for cured basal cell carcinoma of the skin or squamous cell carcinoma of the skin or carcinoma in situ of any other site; Use any other investigational drug or participate in another clinical trial with therapeutic intent within 3 months prior to enrollment; A woman who is pregnant or lactating; Known active HIV or HBV, HCV infection; Known to be allergic to drugs that may be used; The researchers did not consider participants to be eligible for this study.

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: 4 Cycles of Neoadjuvant Chemotherapy With Radiotherapy<br>Four cycles of neoadjuvant chemotherapy combined with radical radiotherapy | Drug: 4 cycles of Neoadjuvant Chemotherapy With Definitive Radiotherapy<br>* 4 Cycles of Neoadjuvant Chemotherapy With Definitive Radiotherapy, instead of Concurrent Chemoradiotherapy<br>|
| Active Comparator: 3cycles of Neoadjuvant Chemotherapy With chemoradiotherapy<br>3 cycles of Neoadjuvant Chemotherapy Combined With Concurrent Chemoradiotherapy | Drug: 3 cycles of Neoadjuvant Chemotherapy With concurrent chemoradiotherapy<br>* 3 cycles of Neoadjuvant Chemotherapy With concurrent chemoradiotherapy, instead of definitive radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5-year overall survival | the duration between the date of diagnosed and date of patient death | 5 years | 
| 5-year metastatic free survival | the duration between the date of diagnosed and date of metastasis | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5-year disease-free survival | the duration between the date of diagnosed and date of related disease | 5 years | 
| 5-year recurrence-free survival | the duration between the date of diagnosed and date of recurrence | 5 years | 
| Safety (incidence of grade 3/4 adverse reactions) | treatment related toxic effects | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasopharyngeal Carcinoma, Neoadjuvant Chemotherapy, Concurrent Chemoradiotherapy