The Value of Single-cycle TPF Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma

• Conditions: Nasopharyngeal Carcinoma
• Interventions: Drug: One cycle TPF induction chemotherapy for NPC; Drug: Three cycles TPF induction chemotherapy for NPC

• Registration Number: NCT02096380
• Lead Sponsor: First People's Hospital of Foshan

Brief Summary

Two Phase Ⅲ trials (TAX323 and TAX324) showed induction chemotherapy adding docetaxel to cisplatin plus fluorouracil (TPF) could significant improve survival in head and neck cancer, and a Phase Ⅱ trial from Hong Kong by Hui and colleges with this strategy has also been reported in nasopharyngeal carcinoma (NPC). However, whether three cycles induction could delay the whole time of treatment and reduce the survival benefit are still unknown. A retrospective study of one cycle TPF induction chemotherapy by the investigators group (not yet published) could improve survival in NPC. It encourage us to conduct this clinical trial.

Detailed Description

Patients presented with non-keratinizing NPC and stage Ⅲ-Ⅳb T3-4N1M0/TxN2M0 are randomly assigned to receive one cycle induction chemotherapy (docetaxel+cisplatin+fluorouracil) plus concurrent chemoradiotherapy (investigational arm) or three cycles induction chemotherapy (docetaxel+cisplatin+fluorouracil) plus concurrent chemoradiotherapy (investigational arm)(control arm). Patients in both arms receive radical Intensity modulated radiation therapy (Trilogy, Varian), and cisplatin (30mg/m2) every weeks for six cycles during radiotherapy. Radiation is delivered to GTV at 70 Gy in 30 fractions, CTV1 at at 60 Gy in 30 fractions and CTV2 at 54 Gy in 30 fractions. Patients in the investigational arm receive docetaxel (60mg/m2 on day 1), cisplatin (20mg/m2 on day 1-4) and fluorouracil (800mg/m2/d,continuous infusion, day 1-4) every three weeks for one cycle or three cycles before the radiotherapy. The primary end point is response rates after radiotherapy, failure-free survival (FFS) and toxic effects and treatment compliance. Secondary end points include overall survival (OS), distant failure-free survival (D-FFS), locoregional failure-free survival (LR-FFS). All efficacy analyses are conducted in the intention-to-treat population; the safety population include only patients who receive their randomly assigned treatment.

Study Timeline

• Study First Submitted: 2011-11-13
• Status Verified: 2014-03
• Study First Submitted QC: 2014-03-22
• Last Update Submitted: 2014-03-22
• Study First Posted: 2014-03-26
• Last Update Posted: 2014-03-26
• Study Start: 2014-05
• Primary Completion: 2017-12
• Study Completion: 2018-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• Patients with newly histologically confirmed non-keratinizing (according to World Health Organization (WHO 2005) histologically type).
• Satisfactory performance status: Karnofsky scale (KPS) > 70.
• Tumor staged is according to the 7th American Joint Commission on Cancer edition as Stage III：T1-2N2M0, T3N0-2M0 Stage IVa：T4N0-2M0
• 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.

Exclusion Criteria

• Age >60 years or <18 years.
• Pregnancy or lactation.
• Treatment with palliative intent.
• Prior radiotherapy, chemotherapy or surgery (except diagnostic) to primary tumor or nodes.
• Any severe intercurrent disease including unstable cardiac disease requiring treatment, renal disease, chronic hepatitis, diabetes with poor control and emotional disturbance.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
one cycle induction chemotherapy	One cycle TPF induction chemotherapy for NPC	Drug: docetaxel, cisplatin and fluorouracil Patients receive docetaxel (60mg/m2 on day 1), cisplatin (20mg/m2 on day 1-4) and fluorouracil (800mg/m2/d, continuous infusion, d1-4) every three weeks for single one cycle before the radiotherapy, then receive radical radiotherapy with IMRT and cisplatin (30mg/m2) every week for six cycles during radiotherapy. Other Names: docetaxel, cisplatin and fluorouracil
three cycles induction chemotherapy	Three cycles TPF induction chemotherapy for NPC	Drug: docetaxel, cisplatin and fluorouracil Patients receive docetaxel (60mg/m2 on day 1), cisplatin (20mg/m2 on day 1-4) and fluorouracil (800mg/m2/d, continuous infusion, d1-4) every three weeks for three cycles before the radiotherapy, then receive radical radiotherapy with IMRT and cisplatin (30mg/m2) every week for six cycles during radiotherapy. Other Names: docetaxel, cisplatin and fluorouracil

Primary Outcome Measures

Name	Time	Method
Failure-free survival	3 year	Failure-free survival is calculated from the date of randomization to the date of the first failure at any site.

Secondary Outcome Measures

Name	Time	Method
Distant failure-free survival	3-year	the data of randomization to the first remote failure
Locoregional failure-free survival	3-year	the data of randomization to the first local failure,
Overall survival	3-year	Overall survival is calculated from randomization to death from any cause.