Effect of Triple Combination of Induction, Concurrent and Adjuvant Chemotherapy in High Risk Nasopharyngeal Carcinoma

Phase 3

• Conditions: Nasopharyngeal Carcinoma
• Interventions: Drug: Cisplatin 2; Drug: Cisplatin 1; Drug: Docetaxel; Drug: Xeloda; Radiation: Intensity-modulated radiotherapy

• Registration Number: NCT02621970
• Lead Sponsor: Sun Yat-sen University

Brief Summary

The investigators aim to evaluate the survival benefit from triple combination of induction, concurrent and aduvant chemotherapy versus concurrent chemotherapy alone for high risk locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy.

Detailed Description

All eligible patients receive intensity-modulated radiotherapy (IMRT) with a total dose of 68 to 70 Gy in 33 fractions to the primary tumor. Patients in the experimental arm receive triple therapy of induction, concurrent and adjuvant chemotherapy. Induction chemotherapy consists of docetaxel 75 mg/m², D1 and cisplatin 25 mg/m², D1-3 every 3 weeks for 2 cycles. Concurrent chemotherapy in the experimental arm consists of cisplatin 25 mg/m², D1-3 every 3 weeks and Xeloda 2000mg/m², D1-14 for 3 cycles. Adjuvant chemotherapy consists of Xeloda 2500mg/m², D1-14 for 2 cycles. Concurrent chemotherapy in the control arm consists of cisplatin 100 mg/m², D1 every 3 weeks for 3 cycles.The primary endpoint is failure-free survival (FFS). Secondary end points include overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and the incidence of grade 3 or higher acute toxicities. 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

• Status Verified: 2015-12
• Study First Submitted: 2015-12-02
• Study First Submitted QC: 2015-12-02
• Last Update Submitted: 2015-12-02
• Study First Posted: 2015-12-04
• Last Update Posted: 2015-12-04
• Study Start: 2016-01
• Primary Completion: 2022-01
• Study Completion: 2024-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 534

Inclusion Criteria

• Newly histologically confirmed non-keratinizing (WHO 1991) nasopharyngeal carcinoma.
• Tumor staged as T4N0-3M0 or T1-3N3M0 (the 2010 UICC/AJCC staging system).
• Pretreatment EBV DNA ≥ 4000 copies/mL.
• Karnofsky scale (KPS) ≥ 70.
• Adequate marrow: leucocyte count ≥ 4×10E9/L, hemoglobin ≥ 110g/L and platelet count ≥ 100×10E9/L.
• Normal liver function test: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and bilirubin ≤ 1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) ≤ 2.5×ULN.
• Adequate renal function: creatinine clearance ≥ 60 ml/min or creatinine ≤ 1.5×ULN.
• Patients must give written informed consent.

Exclusion Criteria

• 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 radiotherapy (except for non-melanomatous skin cancers outside intended radiotherapy volume).
• Prior radiotherapy, 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.
• Dihydropyrimidine dehydrogenase deficiency.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IC plus CC plus IMRT plus AC	Xeloda	Induction chemotherapy: TP -- Docetaxel 75mg/m2, D1 and cisplatin 25 mg/m2, D1-3 every 3 weeks for 2 cycles; Concurrent chemotherapy: PX -- Cisplatin 25 mg/m2, D1-3 and Xeloda 2000mg/m2, D1-14, every 3 weeks for 3 cycles; Radiation: Intensity-modulated radiotherapy; Adjuvant chemotherapy: Xeloda 2500mg/m2, D1-14, every 3 weeks for 2 cycles
IC plus CC plus IMRT plus AC	Docetaxel	Induction chemotherapy: TP -- Docetaxel 75mg/m2, D1 and cisplatin 25 mg/m2, D1-3 every 3 weeks for 2 cycles; Concurrent chemotherapy: PX -- Cisplatin 25 mg/m2, D1-3 and Xeloda 2000mg/m2, D1-14, every 3 weeks for 3 cycles; Radiation: Intensity-modulated radiotherapy; Adjuvant chemotherapy: Xeloda 2500mg/m2, D1-14, every 3 weeks for 2 cycles
IC plus CC plus IMRT plus AC	Intensity-modulated radiotherapy	Induction chemotherapy: TP -- Docetaxel 75mg/m2, D1 and cisplatin 25 mg/m2, D1-3 every 3 weeks for 2 cycles; Concurrent chemotherapy: PX -- Cisplatin 25 mg/m2, D1-3 and Xeloda 2000mg/m2, D1-14, every 3 weeks for 3 cycles; Radiation: Intensity-modulated radiotherapy; Adjuvant chemotherapy: Xeloda 2500mg/m2, D1-14, every 3 weeks for 2 cycles
CC plus IMRT	Cisplatin 2	Concurrent chemotherapy: Cisplatin 100 mg/m2, D1, every 3 weeks for 3 cycles; Radiation: Intensity-modulated radiotherapy
CC plus IMRT	Intensity-modulated radiotherapy	Concurrent chemotherapy: Cisplatin 100 mg/m2, D1, every 3 weeks for 3 cycles; Radiation: Intensity-modulated radiotherapy
IC plus CC plus IMRT plus AC	Cisplatin 1	Induction chemotherapy: TP -- Docetaxel 75mg/m2, D1 and cisplatin 25 mg/m2, D1-3 every 3 weeks for 2 cycles; Concurrent chemotherapy: PX -- Cisplatin 25 mg/m2, D1-3 and Xeloda 2000mg/m2, D1-14, every 3 weeks for 3 cycles; Radiation: Intensity-modulated radiotherapy; Adjuvant chemotherapy: Xeloda 2500mg/m2, D1-14, every 3 weeks for 2 cycles

Primary Outcome Measures

Name	Time	Method
failure-free survival	Two year

Secondary Outcome Measures

Name	Time	Method
overall survival	two year
distant metastasis-free survival	two year
locoregional relapse-free survival	two year
Number of participants with treatment-related acute adverse events as assessed by CTCAE v4.0	two months

Trial Locations

Locations (1)

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