Induction Chemotherapy With GP Versus TPF in the Treatment of Advanced Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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The present study is a randomized, control, phase II study of locally advanced nasopharyngeal carcinoma (NPC) treated with Gemcitabine plus cisplatin regimen (GP) or Docetaxel，cisplatin regimen plus 5-Fluorouracil (TPF) induction chemotherapy followed by concurrent chemoradiotherapy.

Detailed Description
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Nasopharyngeal carcinoma (NPC) prevalence is reported to be highest in southern China, where an average of 80 cases per 100,000 population are reported each year. Nasopharyngeal carcinoma is both radiosensitive and chemosensitive. The National Comprehensive Cancer Network (NCCN) guidelines (version 1, 2013), have recommended use of concurrent chemoradiotherapy (CCRT) with or without adjuvant chemotherapy (AC) and induction chemotherapy (IC) followed by CCRT plus AC as standard treatment for NPC. However, it was unclear whether patients with NPC could benefit from IC. Recently, many new drugs including docetaxel and gemcitabine have been incorporated in the induction chemotherapy phase of NPC. The investigators designed the present study with induction chemotherapy follow by CCRT for locoregionally advanced NPC, comparing induction chemotherapy regime of gemcitabine plus cisplatin (GP) and docetaxel, cisplatin, and fluorouracil (TPF).

Official Title
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Phase II Study Comparing Gemcitabine Plus Cisplatin to Docetaxel, Cisplatin, and Fluorouracil Induction Chemotherapy Followed by Chemoradiotherapy in Locally Advanced Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: A combination of Gemcitabine and cisplatin
* Drug: A combination of Docetaxel, cisplatin and 5-Fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with newly histologically confirmed non-keratinizing (according to WHO histologically type). 18 years to 70 years; Tumor staged as T3-4N1/N2-3M0 (according to the 7th AJCC edition), Performance status: Karnofsky scale (KPS) > 70 (Appendix I ). Adequate marrow: leucocyte count > 4×109/L, neutrophil count > 2×109/L, hemoglobin > 90g/L and platelet count > 100×109/L. 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 > 70 or < 18. Treatment with palliative intent. 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.

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: A combination of Gemcitabine and cisplatin<br>The GP regimen consists of gemcitabine at a dose of 1,000 mg/m2 by intravenous (i.v.) infusion over 30 min on day 1 and day 8, and cisplatin 80 mg/m2 by i.v. infusion for 4 h on day 1-3, The regime will be repeated every 3 weeks up to a total of 2-3 courses. Concurrent chemoradiotherapy is administrated with 3 cycles of weekly Cisplatin 100 mg/m2 starting on the first day of IMRT. | Drug: A combination of Gemcitabine and cisplatin<br>* The GP regimen consists of gemcitabine at a dose of 1,000 mg/m2 by intravenous (i.v.) infusion over 30 min on day 1 and day 8, and cisplatin 80 mg/m2 by i.v. infusion for 4 h on day 1-3, The regime will be repeated every 3 weeks up to a total of 2-3 courses. Concurrent chemoradiotherapy is administrated with 3 cycles of weekly Cisplatin 100 mg/m2 starting on the first day of IMRT.<br>* Other names: GP;|
| Active Comparator: A combination of Docetaxel, cisplatin and 5-Fluorouracil<br>The TPF regimen consists of docetaxel at a dose of 60 mg/m2/day on day 1, cisplatin 60 mg/m2 by i.v. infusion for 4 h on day 1-3, plus 5-Fluorouracil 600 mg/m2 CIV over 120 hours. The regime will be repeated every 3 weeks up to a total of 2-3 courses. Concurrent chemoradiotherapy is administrated with 3 cycles of weekly Cisplatin 100 mg/m2 starting on the first day of IMRT. | Drug: A combination of Docetaxel, cisplatin and 5-Fluorouracil<br>* The TPF regimen consists of docetaxel at a dose of 60 mg/m2/day on day 1, cisplatin 60 mg/m2 by i.v. infusion for 4 h on day 1-3, plus 5-Fluorouracil 600 mg/m2 CIV over 120 hours. The regime will be repeated every 3 weeks up to a total of 2-3 courses. Concurrent chemoradiotherapy is administrated with 3 cycles of weekly Cisplatin 100 mg/m2 starting on the first day of IMRT.<br>* Other names: TPF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure-free survival (FFS) | From the date of registration to the date of either locally, regionally or distant failure or last follow-up | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Survival from the date of registration to the date of death or last follow-up | One year | 
| Loco-regional failure-free survival (LFFS) | Survival from the date of registration to the date of either locally, regional recurrence or last follow-up | One year | 
| Distant metastasis failure-free survival (DMFS) | Survival from the date of registration to the date of either distant metastasis or last follow-up | One year | 
| Acute induction chemotherapy toxicity | The side effects will be evaluated according to NCI-CTC AE V 3.0. | Two months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasopharyngeal carcinoma, Induction chemotherapy, Concurrent chemoradiotherapy, Gemcitabine, Docetaxel