Induction Gemcitabine and Cisplatin in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

Phase 3

• Conditions: Nasopharyngeal Carcinoma
• Interventions: Drug: gemcitabine and cisplatin (Induction chemotherapy); Radiation: IMRT and concurrent cisplatin

• Registration Number: NCT01872962
• Lead Sponsor: Sun Yat-sen University

Brief Summary

The purpose of this study is to compare induction chemotherapy (gemcitabine+cisplatin) plus concurrent chemoradiotherapy (CCRT) with CCRT alone in patients with locoregionally advanced nasopharyngeal carcinoma(NPC), in order to confirm the value of induction chemotherapy in NPC patients.

Detailed Description

Patients Patients with non-keratinizing NPC T3-4N1M0/TxN2-3M0 (UICC/AJCC 7th edition) are randomly assigned to receive induction chemotherapy plus CCRT or CCRT alone. Patients in both groups receive cisplatin 100 mg/m² every 3 weeks for 3 cycles, concurrently with intensity-modulated radiotherapy (IMRT). IMRT is given as 2.0-2.30 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. The induction chemotherapy plus CCRT group receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for three cycles before CCRT. Our primary endpoint is failure-free survival(FFS). Secondary end points include overall survival (OS), locoregional failure-free survival (LR-FFS), distant failure-free survival (D-FFS) rates and toxic effects. All efficacy analyses are conducted in the intention-to-treat population, and the safety population include only patients who receive their randomly assigned treatment.

Study Timeline

• Study First Submitted: 2013-05-31
• Study First Submitted QC: 2013-06-06
• Study First Posted: 2013-06-07
• Study Start: 2013-11
• Status Verified: 2018-04
• Last Update Submitted: 2018-04-20
• Last Update Posted: 2018-04-24
• Primary Completion: 2018-11
• Study Completion: 2020-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 480

Inclusion Criteria

• Patients with newly histologically confirmed non-keratinizing (according to WHO histologically type).
• Tumor staged as T3-4N1/N2-3 (according to the 7th AJCC edition).
• No evidence of distant metastasis (M0).
• Satisfactory performance status: Karnofsky scale (KPS) ≥ 70.
• 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 > 65 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Induction chemotherapy+IMRT and concurrent cisplatin	gemcitabine and cisplatin (Induction chemotherapy)	Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 3 cycles before radiotherapy, and then receive intensity modulated-radiotherapy (IMRT), concurrently with cisplatin 100 mg/m² every 3 weeks for 3 cycles.
IMRT and concurrent cisplatin	IMRT and concurrent cisplatin	Patients receive intensity modulated-radiotherapy (IMRT), concurrently with cisplatin 100 mg/m² every 3 weeks for 3 cycles.
Induction chemotherapy+IMRT and concurrent cisplatin	IMRT and concurrent cisplatin	Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 3 cycles before radiotherapy, and then receive intensity modulated-radiotherapy (IMRT), concurrently with cisplatin 100 mg/m² every 3 weeks for 3 cycles.

Primary Outcome Measures

Name	Time	Method
Failure-free survival	3-year	Failure-free survival rate is calculated from the date of randomization to the date of treatment failure or death from any cause, whichever is first.

Secondary Outcome Measures

Name	Time	Method
Overall survival	3-year	Overall survival is calculated from randomization to death from any cause.
Locoregional failure-free survival	3-year	Locoregional failure-free survival is calculated from randomization to the first locoregional failure.
Distant failure-free survival	3-year	Distant failure-free survival is calculated from randomization to the first remote failure.
Number of participants with adverse events	up to 3 years	Incidence of acute and late toxicity

Trial Locations

Locations (1)

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China