Nedaplatin Versus Cisplatin and Capecitabine Versus Fluorouracil in IC + CCRT for Locoregionally Advanced NPC

Study Overview
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Brief Summary
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This is a phase 3, multicentre, non-inferiority, randomised factorial trial. The purpose of this study is to study the efficacy and safety of nedaplatin versus cisplatin, and capecitabine versus fluorouracil in induction docetaxel, cisplatin, and fluorouracil (TPF) plus concurrent chemoradiotherapy with cisplatin (P-RT) in locoregionally advanced nasopharyngeal carcinoma (NPC).

Detailed Description
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In this study, patients with non-keratinizing NPC and staged III-IVA (except T3-4N0) are randomly assigned to one of the four groups: Group A: TPF+P-RT; Group B: TNF+N-RT; Group C: TPX+P-RT; Group D: TNX+N-RT. In induction chemotherapy, patients will receive docetaxel(60 mg/m2 on day 1), cisplatin or nedaplatin (60 mg/m2 on day 1) and fluorouracil (600 mg/m2 on Days 1 to 5) or capecitabine (625 mg/m2 bid, on Days 1 to 14) every three weeks for three cycles before the radical radiotherapy. Concurrent cisplatin or nedaplatin (100mg/m2 on day 1) was given every three weeks for two cycles during radiotherapy. Patients are stratified according to the treatment centers and stage. The primary endpoint is progression-free survival (PFS). Secondary end points include overall survival (OS), distant failure-free survival (D-FFS), locoregional failure-free survival (LR-FFS), toxic effects, and quality of life (QOL). 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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Nedaplatin Versus Cisplatin and Capecitabine Versus Fluorouracil in Induction Chemotherapy Plus Concurrent Chemoradiotherapy for Locoregionally Advanced NPC： a Phase 3, Multicentre, Non-inferiority, Randomised Factorial Trial

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: docetaxel, nedaplatin, and capecitabine
* Drug: nedaplatin
* Drug: docetaxel, cisplatin, and fluorouracil
* Drug: cisplatin
* Drug: docetaxel, cisplatin, and capecitabine
* Drug: docetaxel, nedaplatin, and fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-60 Patients with newly histologically confirmed non-keratinizing (according to World Health Organization (WHO) histologically type) Performance status of Eastern Cooperative Oncology Group (ECOG) grade 0 or 1 Tumor staged as American Joint Committee on Cance (AJCC) III-IVA (except T3-4N0) Adequate marrow: leucocyte count ≥ 4×10^9/L, hemoglobin ≥ 90g/L and platelet count ≥ 100×10^9/L. Normal liver and renal 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; 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. 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. Patients who could not tolerate or allergic to capecitabine. Illness that would interfere with oral medication, including dysphagia, chronic diarrhea, or ileus.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A (TPF+P-RT)<br>Induction docetaxel, cisplatin, and fluorouracil plus concurrent chemoradiotherapy with cisplatin | Drug: docetaxel, cisplatin, and fluorouracil<br>* Patients receive docetaxel (60mg/m2 on day 1), cisplatin (60mg/m2 on day 1) and fluorouracil (600mg/m2 on Days 1 to 5) every three weeks for three cycles before the radiotherapy.<br>* Other names: TPF induction chemotherapy;Drug: cisplatin<br>* Patients receive concurrent cisplatin (100mg/m2) every three weeks for two cycles during radiotherapy.<br>* Other names: P;|
| Experimental: B (TNF+N-RT)<br>Induction docetaxel, nedaplatin, and fluorouracil plus concurrent chemoradiotherapy with nedaplatin | Drug: nedaplatin<br>* Patients receive concurrent nedaplatin (100mg/m2) every three weeks for two cycles during radiotherapy.<br>* Other names: N;Drug: docetaxel, nedaplatin, and fluorouracil<br>* Patients receive docetaxel (60mg/m2 on day 1), nedaplatin (60mg/m2 on day 1) and fluorouracil (600mg/m2 on Days 1 to 5) every three weeks for three cycles before the radiotherapy.<br>* Other names: TNF induction chemotherapy;|
| Experimental: C (TPX+P-RT)<br>Induction docetaxel, cisplatin, and capecitabine plus concurrent chemoradiotherapy with cisplatin | Drug: cisplatin<br>* Patients receive concurrent cisplatin (100mg/m2) every three weeks for two cycles during radiotherapy.<br>* Other names: P;Drug: docetaxel, cisplatin, and capecitabine<br>* Patients receive docetaxel(60 mg/m2 on day 1), cisplatin (60 mg/m2 on day 1) and capecitabine (625 mg/m2 bid, on Days 1 to 14) every three weeks for three cycles before the radiotherapy.<br>* Other names: TPX induction chemotherapy;|
| Experimental: D (TNX+N-RT)<br>Induction docetaxel, nedaplatin, and capecitabine plus concurrent chemoradiotherapy with nedaplatin | Drug: docetaxel, nedaplatin, and capecitabine<br>* Patients receive docetaxel(60 mg/m2 on day 1), nedaplatin (60 mg/m2 on day 1) and capecitabine (625 mg/m2 bid, on Days 1 to 14) every three weeks for three cycles before the radiotherapy.<br>* Other names: TNX induction chemotherapy;Drug: nedaplatin<br>* Patients receive concurrent nedaplatin (100mg/m2) every three weeks for two cycles during radiotherapy.<br>* Other names: N;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Progression-free survival is calculated from the date of randomisation to the date of disease progression or death from any cause, whichever is first. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival is calculated from randomization to death from any cause. | 3 years | 
| Distant failure-free survival | Distant failure-free survival 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 years | 
| Locoregional failure-free survival | Locoregional failure-free survival 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 years | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (acute toxicity) and RTOG/EORTC (late toxicity) | Incidence of acute and late toxicity | Up to 3 years | 
| Quality of life (QOL) as assessed by EORTC quality of life questionnaire(QLQ)-C30 | QOL was assessed by EORTC QLQ-C30 during the treatment period | Up to 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nedaplatin, Nasopharyngeal Carcinoma, Induction chemotherapy, Concurrent chemoradiotherapy, Capecitabine