Two Cycles Versus Three Cyclle of CCRT for Low Risk Locoregionally Advanced Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

Official title:

A Randomized Phase II Non-inferiority Study of Two Cycles Versus Three Cycles of Cisplatin Based Concurrent Chemoradiotherapy for Low Risk Locoregionally Advanced Nasopharyngeal Carcinoma Based on Pretreatment Plasma EBV DNA Level

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02871518
• Other study ID #: cycle of CCRT and NPC
• Status: Recruiting
• Phase: Phase 2
• First received: July 17, 2016
• Last updated: November 8, 2016
• Start date: August 2016
• Est. completion date: July 2021

Study information

• Verified date: November 2016
• Source: Sun Yat-sen University
• Contact: Lin-Quan Tang, MD,PHD
• Phone: 8602087343643
• Email: tanglq[@]sysucc.org.cn
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

This is a Phase II trial to study the effectiveness of two cycles versus three cycles of Concurrent Chemoradiotherapy in treating patients with Low Risk Locoregionally Advanced Nasopharyngeal Carcinoma based on pretreatment plasma EBV DNA.

Description:

Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. Several prospective randomized trials have demonstrated that concurrent chemoradiotherapy was superior to radiotherapy alone in the treatment of locoregionally advanced NPC. Concurrently, although cisplatin-based concurrent chemoradiotherapy was considered as the standard regimen for locoregionally advanced nasopharyngeal carcinoma, several prospective randomized trials have demonstrated that only 52-63% patients can finished three cycles cisplatin-based concurrent chemoradiotherapy( DDP, 100mg/m2,D1,D22 and D43), due to chemoradiotherapy induced toxicity. Combined analyses of NPC-9901 and NPC-9902 Trials indicated that the 5-year locoregional failure free survival was insignificant between the patients received between two and three cycles cisplatin-based concurrent chemoradiotherapy. Our previous studies have also demonstrated that the five years overall survival, distant metastasis free survival and 5-year locoregional failure free survival was not observed significant difference between the patients received between two and three cycles cisplatin-based concurrent chemotherapy. It indicated that one pressing questions remain to be resolved: can we define the optimal dose so that we can reduce toxicity by avoiding unnecessary overdose or an ineffective phase of treatment? Recently, the quantification of pretreatment plasma Epstein-Barr virus (EBV) DNA, which was considered the most potential biomarker to compliment TNM stage, was demonstrated a useful biomarker for the risk stratification, monitoring and prediction of the prognosis of NPC. The investigators previous study demonstrated that for local and regionally advanced NPC patients with EBV DNA <4,000copies/mL, the 3-year's PFS and DMFS was approximate to 90%. Pretreatment plasma EBV DNA levels might be applied to guide concurrent chemotherapy regimen for local and regionally advanced NPC patients. Therefore, the investigators make a hypothesis that the low risk locoregionally advanced NPC patients received two cycles of chemotherapy may gain similar long-term survival as those received three cycles of chemotherapy, leading to less chemotherapy induced toxicity. Therefore, this phase II non-inferiority, randomised controlled clinical trial was designed to assess efficacy for low-risk patients, identified with pretreatment plasma EBV DNA <4,000 copies/mL, received two cycle cisplatin-based chemotherapy compared with three cycle cisplatin-based chemotherapy

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 236
• Est. completion date: July 2021
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma, including WHO II or III

• Original clinical staged as T3-4N0-3 M0 or any T?N2-3M0(according to the 7th AJCC edition)

• No evidence of distant metastasis (M0)

• Pretreatment Plasm EB Virus DNA<4000copies/ml

• Male and no pregnant female

• Satisfactory performance status: ECOG (Eastern Cooperative OncologyGroup) scale 0-1

• WBC = 4×109 /L and PLT =4×109 /L and HGB =90 g/L

• With normal liver function test (ALT?AST = 2.5×ULN, TBIL= 2.0×ULN)

• With normal renal function test (Creatinine = 1.5×ULN)

Exclusion Criteria:

• Patients have evidence of relapse or distant metastasis

• Histologically confirmed keratinizing squamous cell carcinoma (WHO I)

• Receiving radiotherapy or chemotherapy previously

• The presence of uncontrolled life-threatening illness

• Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.

• Receiving other ways of anti-cancer therapy.

• Suffered from other malignant tumors (except the cure of basal cell carcinoma or uterine cervical carcinoma in situ) previously.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms

Intervention

Drug:
• Cisplatin combine with IMRT
Concurrent cisplatin (100mg/m2,D1,D22) combine with IMRT
• Cisplatin combine with IMRT
Concurrent cisplatin (100mg/m2,D1,D22 and D43) combine with IMRT

Locations

Country	Name	City	State
China	Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progress-free survival	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	No
Secondary	The shor-term toxic effects	The shorterm toxic effects were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0)	3 months	Yes
Secondary	Complete Response (CR)	CR assessed by independent reviewers, according to the Modified Response Evaluation Criteria in Solid Tumors (RECIST) from the National Cancer Institute (NCI). Disease response evaluated after the completion of the chemoradiotherapy treatment. Complete response defined as the complete disappearance of the target and non-target lesion(s) identified at baseline after radiological evaluation by Magnetic Resonance Imaging (MRI) only	after the completion of the chemoradiotherapy treatment (up to 9 weeks)	No
Secondary	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	No
Secondary	Locoregional Relapse-Free Survival(LRRFS)	The LRRFS 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	No
Secondary	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	No
Secondary	Cost-effectiveness analysis	The cost (including direct cost drug fees, inspection fees, expenses and nursing cost) and incremental cost-effectiveness ratio was calculated between two arms	3 years	No
Secondary	The monitoring of plasma EBV DNA	The plasma EBV DNA will be detected before treatment ,during treatment (weekly) and during follow up( every 3-6 months)	3 years	No
Secondary	Long-term toxicities	Patients will be monitored for long-term toxicity by standard NIH criteria. QoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30) and EORTC QLQ Head and Neck	3 years	Yes