Nedaplatin Versus Cisplatin in Treatment for Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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To compare the effectiveness and toxicity of nedaplatin versus cisplatin in induction chemotherapy combined with concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma.

Detailed Description
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This is a prospective, parallel, randomized, open labeled, phase III, non-inferiority clinical trial to compare the effectiveness and toxicity of nedaplatin versus cisplatin in induction chemotherapy combined with concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma patients in endemic area - nedaplatin, docetaxel and fluorouracil as induction chemotherapy regimen combined with nedaplatin as concurrent chemoradiotherapy (DNF-N) versus cisplatin, docetaxel and fluorouracil as induction chemotherapy regimen combined with cisplatin as concurrent chemoradiotherapy (DPF-P). All patients will receive radical intense modulate radiation therapy (IMRT). The primary endpoint is progress free survival (PFS).

Official Title
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Nedaplatin Versus Cisplatin in Induction Chemotherapy Combined With Concurrent Chemoradiotherapy for Locally Advanced Nasopharyngeal Carcinoma：a Prospective, Parallel, Randomized, Open Labeled, Phase III Non-Inferiority Clinical Study

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Docetaxel, nedaplatin, fluorouracil
* Drug: Docetaxel, cisplatin, fluorouracil
* Drug: Nedaplatin
* Drug: 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 nasopharyngeal carcinoma, including WHO II or III Original clinical staged as III-IVa (except T3-4N0) according to the 8th edition American Joint Committee on Cancer staging system No evidence of distant metastasis (M0) Age between 18-65 WBC≥4×10^9/ l, platelet ≥ 100×10^9/ l and hemoglobin ≥ 90g/l With normal liver function test (TBIL、ALT、AST ≤ 2.5×uln) With normal renal function test (creatinine ≤ 1.5×uln or ccr ≥ 60ml/min) Satisfactory performance status: KARNOFSKY scale (KPS) > 70 Patients must give signed informed consent Exclusion Criteria: Histologically confirmed keratinizing nasopharyngeal carcinoma (WHO I) Age >65 or < 18 years Treatment with palliative intent Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer History of previous radiotherapy, chemotherapy, or surgery (except diagnostic) to the primary tumor or nodes History of previous radiotherapy Pregnancy or lactation Any severe intercurrent disease, which may bring unacceptable risk or affect the compliance of the trial, for example, unstable cardiac disease requiring treatment, acute exacerbation of chronic obstructive pulmonary disease or other respiratory illness requiring admission to hospital, active hepatitis, and mental 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: DNF-N<br>Induction chemotherapy: three cycles of intravenous docetaxel 60 mg/m² on day 1, intravenous nedaplatin 60 mg/m² on day 1, and continuous intravenous fluorouracil 600 mg/m² per day from day 1 to day 5, every 3 weeks Concurrent chemoradiotherapy: three cycles of 100 mg/m² nedaplatin every 3 weeks, concurrently with intensity-modulated radiotherapy Radiotherapy: radical intense modulated radiation therapy | Drug: Docetaxel, nedaplatin, fluorouracil<br>* Induction chemotherapy. Docetaxel 60 mg/m2 intravenous day1. Nedaplatin 60 mg/m2 intravenous day1. Fluorouracil 3000 mg/m2 continuous intravenous infusion 120 hours from day1. Every 21 days, 3 cycles.<br>* Other names: DNF;Drug: Nedaplatin<br>* Concurrent chemotherapy. Nedaplatin 100 mg/m2 intravenous at day1, 22, 43 of radiotherapy.<br>* Other names: NDP;Radiation: Intensity modulated-radiotherapy<br>* Intensity modulated-radiotherapy (IMRT) is given as 2.0-2.33 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.<br>* Other names: IMRT;|
| Active Comparator: DPF-P<br>Induction chemotherapy: three cycles of intravenous docetaxel 60 mg/m² on day 1, intravenous cisplatin 60 mg/m² on day 1, and continuous intravenous fluorouracil 600 mg/m² per day from day 1 to day 5, every 3 weeks Concurrent chemoradiotherapy: three cycles of 100 mg/m² cisplatin every 3 weeks, concurrently with intensity-modulated radiotherapy Radiotherapy: radical intense modulated radiation therapy | Drug: Docetaxel, cisplatin, fluorouracil<br>* Induction chemotherapy. Docetaxel 60 mg/m2 intravenous day1. Cisplatin 60 mg/m2 intravenous day1. Fluorouracil 3000 mg/m2 continuous intravenous infusion 120 hours from day1. Every 21 days, 3 cycles.<br>* Other names: DPF;Drug: Cisplatin<br>* Concurrent chemotherapy. Cisplatin 100 mg/m2 intravenous at day1, 22, 43 of radiotherapy.<br>* Other names: DDP;Radiation: Intensity modulated-radiotherapy<br>* Intensity modulated-radiotherapy (IMRT) is given as 2.0-2.33 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.<br>* Other names: IMRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress-Free Survival (PFS) | Progress-free survival is calculated from the date of randomisation to the date of locoregional failure, distant failure, or death from any cause, whichever occurred first. | 3 years | 

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 years | 
| Locoregional Relapse-Free Survival(LRRFS) | Relapse-free survival was defined as the time from random assignment to local or regional relapse, or death from any cause. | 3 years | 
| Distant metastasis-Free Survival(DMFS) | Distant metastasis-free survival was defined as the time from random assignment to distant metastasis, or death from any cause. | 3 years | 
| Quality of life (QoL) | Quality of life (QoL) was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire module for head and neck (EORTC QLQ-H&N35). The EORTC QLQ-H&N35 scale employs a 4-point response format (not at all to very much). Scale scores are transformed to a scale from 0 to 100 according to the EORTC scoring algorithm. For the functioning and the global QoL scale, a higher score indicates better health. For the symptom scales, a higher score indicates a higher level of symptom burden. Either English or Chinese version will be used according to patient's language habits. | 3 years | 
| Objective Response Rate (ORR) | Objective Response Rate (ORR) were assessed with nasopharyngeal and neck MRI and flexible nasopharyngoscopy, according to the Response Evaluation Criteria in Solid tumors(version 1.1) | 12 weeks after the interventions | 
| Disease Control Rate (DCR) | Disease Control Rate (DCR) were assessed with nasopharyngeal and neck MRI and flexible nasopharyngoscopy, according to the Response Evaluation Criteria in Solid tumors(version 1.1) | 12 weeks after the interventions | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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induction chemotherapy, nedaplatin, cisplatin, concurrent chemoradiotherapy