Phase Ⅲ Trial of Adjuvant Chemotherapy in Patients With N2-3 Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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To see the effect if a combination of concurrent chemoradiotherapy followed by different adjuvant chemotherapy in treating patients with N2-3 nasopharyngeal carcinoma(NPC).

Detailed Description
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This phase Ⅲ trial is studying how well radiation therapy and chemotherapy work in treating patients with newly diagnosed N2-3 nasopharyngeal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin and fluorouracil or cisplatin and gemcitabine, work in different ways (concurrent chemoradiotherapy followed by different adjuvant chemotherapy) to stop the growth of tumor cells.

Official Title
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Phase Ⅲ Trial of Concurrent Chemoradiotherapy Followed by Adjuvant Chemotherapy (GP Versus PF) in Patients With N2-3 Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: CCRT+GP
* Drug: CCRT+PF


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 any T、N2-3M0（according to the American Joint Committee on Cancer(AJCC) 7th edition） No evidence of distant metastasis (M0). Age 18-65 years old. ECOG Performance status less or equal to 1. 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 or >65 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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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
Interventional Model Description: Cancer Center of Guangzhou Medical University The Affiliated Hospital of Guizhou Medical University, Guizhou Cancer Hospital The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CCRT+GP<br>Patients receive concurrent cisplatin 100mg/m2 every 21 days for three cycles during radiotherapy followed by adjuvant gemcitabine (1000mg/m2 on day 1 and day 8) and cisplatin (80mg/m2 on day 1) every 21days for three cycles | Drug: CCRT+GP<br>* Patients receive concurrent cisplatin 100mg/m2 every 21days for three cycles during Intensity modulated-radiotherapy (IMRT) followed by adjuvant gemcitabine (1000mg/m2 on day 1 and day 8) and cisplatin (80mg/m2 on day 1) every 21 days for three cycles 4 weeks after radiotherapy.<br>* Other names: Adjuvant GP;|
| Active Comparator: CCRT+PF<br>Patients receive concurrent cisplatin 100mg/m2 every 21 days for three cycles during radiotherapy followed by adjuvant cisplatin (80mg/m2 on day 1) and 5-fluorouracil (1000mg/m2 civ 96h) every 28 days for three cycles | Drug: CCRT+PF<br>* Patients receive concurrent cisplatin 100mg/m2 every 21 days for three cycles during Intensity modulated-radiotherapy (IMRT) followed by adjuvant cisplatin (80mg/m2 on day 1) and 5-fluorouracil (1000mg/m2 civ 96h) every 28 days for three cycles 4 weeks after radiotherapy.<br>* Other names: Adjuvant PF;|

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 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 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 failure-free survival(LRRFS) | 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 years | 
| 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 years | 
| Overall response rate | Tumour response was classified according to RECIST, version 1.1 | 16 weeks after completion of concurrent chemoradiotherapy | 
| Incidence of acute and late toxicity | Incidence of acute toxicity is calculated for each adverse event respectively and severity is evaluated on basis of Common Terminology Criteria for Adverse Events (CTCAE) 4.0 criteria. Late radiation toxicities were assessed using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasopharyngeal carcinoma;adjuvant chemotherapy