Cluster Randomized Controlled Screening Trial for NPC (CRCSTNPC)

A Cluster Randomized Controlled Screening Trial for Nasopharyngeal Carcinoma in Southern China (CRCSTNPC Study)

This study is aimed to estimate the effectiveness of an Epstein-Barr virus (EBV) serology-based screening program to reduce nasopharyngeal carcinoma (NPC) mortality in a cluster randomized controlled trial in an NPC high-risk population. Sixteen towns in Sihui and Zhongshan Cities, China will be selected, with eight allocated to the screening group and eight to the control group. Cantonese residents aged 30-69 years with no history of NPC will be included. Residents in the screening towns will be invited to undergo serum EBV VCA/EBNA1 IgA antibody tests.

Study Overview

• Status: Active, not recruiting
• Conditions: Nasopharyngeal Cancer; Morality; Screening
• Intervention / Treatment: Diagnostic test: Experimental: Screening with EBV VCA/EBNA1-IgA testing

Detailed Description

Nasopharyngeal carcinoma (NPC) has a high prevalence in southern China. Sihui and Zhongshan cities are located along the Pearl River in Guangdong Province, China, and are well known for a high incidence of NPC worldwide. During the last 20 years, Screening for NPC has been demonstrated to increase the early detection rate of NPC in endemic regions. It is well shown that the effect of Epstein-Barr virus (EBV) serological antibodies is elevated several years before NPC diagnosis; therefore, EBV antibodies have been considered screening markers for NPC. However, none of the studies have reported the impact of screening on NPC-specific mortality.

This study aims to launch a cluster-randomized screening trial with combined VCA/IgA and EBNA1/IgA measurement by ELISA as the primary screening method in these 2 cities to examine the impact of EBV serological screening on NPC-specific mortality. Residents aged 30-69 years in eight screening towns in the intervention group will be invited to EBV antibody tests-IgA antibodies to EBV VCA/IgA and EBV nuclear antigen-1 (EBNA1/IgA) by ELISA. The primary objective of this trial is to assess an estimate of the EBV serological antibody-based screening for NPC on NPC-specific in the populations with a high incidence of NPC

• Study Type: Interventional
• Enrollment (Anticipated): 87600
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Sihui, Guangdong, China
      • Sihui Cancer Institute
    • Zhongshan, Guangdong, China
      • Cancer Research Institute of Zhongshan City

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Clusters

1. Inclusion criteria 1) the town located in Sihui or Zhongshan city; 2) the town established a tertiary cancer prevention network; 3) the medical staff in the town hospitals agreed to take part in.
2. Exclusion criteria 1) having conducted NPC screening program.

Individuals

1. Inclusion criteria 1) being aged 30-69 years; 2) being Cantonese; 3) having signed the informed consent; 4) having an Eastern Cooperative Oncology Group score of 0-2; and 5) having a good physical or psychological condition and consciousness.
2. Exclusion criteria 1) having prevalent NPC.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: intervention; Residents aged 30-69 years in eight screening towns in the intervention group are invited to screening marker tests - IgA antibodies to EBV VCA/IgA and EBV nuclear antigen-1 (EBNA1/IgA) by ELISA. The trial will use two minimally acceptable false-positive rates (i.e., 10% and 3%) as the cutoffs to define "medium-risk" (seropositive, 0.65 ≤ score < 0.98) and "high-risk" participants (seropositive, score ≥ 0.98). After a blood test, participants whose EBV-based risk exceeds the predefined "high-risk" threshold (score ≥ 0.98) will be referred to endoscopy for clinical evaluation. Participants who are defined as "medium-risk" or "high-risk" (score ≥ 0.65) will be followed annually through blood testing and linkage to registers. The remaining participants (seronegative, score < 0.65) will be asked to return for a follow-up visit after five years.	Diagnostic test: Experimental: Screening with EBV VCA/EBNA1-IgA testing; Participants in the screening towns will be offered screening tests. Those with high-risk scores will be referred to a diagnostic workup examination using fiberoptic endoscopy examination and nasopharyngeal biopsies if suspicious lesions is observed.; Other Names: Diagnostic work-up using fiberoptic endoscopy examination and/or nasopharyngeal biopsies
No Intervention: Control; The individuals aged 30-69 in the other eight towns will be included as controls, which is a comparable population that will not be screened for NPC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality rate of NPC at 12 years by intervention group	NPC mortality rate will be compared between screening group and control group at 12-year follow-up.	December, 2019

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality at 12 years by intervention group	All-cause mortality rate will be compared between screening group and control group at 12-year follow-up.	December, 2019
NPC incidence at 12 years by intervention group	NPC incidence rate will be compared between screening group and control group at 12-year follow-up.	December, 2019
Stage distribution at diagnosis for NPC patients by intervention group	Stage distribution will be compared between screening group and control group at 12-year follow-up.	December, 2019
NPC overall survival by cases from the two intervention groups	Survival rate will be compared between screening group and control group at 12-year follow-up.	December, 2019
Cost-effectiveness	Cost-effectiveness of this screening program will be calculated at 12-year follow-up.	December, 2019

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Cancer Research Institute of Zhongshan City; Sihui Cancer Institute
• Investigators: Principal Investigator: Minghuang Hong, M.D, Sun Yat-sen University

Publications and helpful links

General Publications

• Ji MF, Sheng W, Cheng WM, Ng MH, Wu BH, Yu X, Wei KR, Li FG, Lian SF, Wang PP, Quan W, Deng L, Li XH, Liu XD, Xie YL, Huang SJ, Ge SX, Huang SL, Liang XJ, He SM, Huang HW, Xia SL, Ng PS, Chen HL, Xie SH, Liu Q, Hong MH, Ma J, Yuan Y, Xia NS, Zhang J, Cao SM. Incidence and mortality of nasopharyngeal carcinoma: interim analysis of a cluster randomized controlled screening trial (PRO-NPC-001) in southern China. Ann Oncol. 2019 Oct 1;30(10):1630-1637. doi: 10.1093/annonc/mdz231.
• Liu Z, Ji MF, Huang QH, Fang F, Liu Q, Jia WH, Guo X, Xie SH, Chen F, Liu Y, Mo HY, Liu WL, Yu YL, Cheng WM, Yang YY, Wu BH, Wei KR, Ling W, Lin X, Lin EH, Ye W, Hong MH, Zeng YX, Cao SM. Two Epstein-Barr virus-related serologic antibody tests in nasopharyngeal carcinoma screening: results from the initial phase of a cluster randomized controlled trial in Southern China. Am J Epidemiol. 2013 Feb 1;177(3):242-50. doi: 10.1093/aje/kws404. Epub 2012 Dec 19.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2008
• Primary Completion (Actual): December 1, 2019
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: July 16, 2009
• First Submitted That Met QC Criteria: July 16, 2009
• First Posted (Estimate): July 17, 2009

Study Record Updates

• Last Update Posted (Estimate): February 28, 2023
• Last Update Submitted That Met QC Criteria: February 26, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: early detection; mortality; screening; randomized control trial; nasopharyngeal cancer; Epstain-Barr Virus
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms
• Other Study ID Numbers: CRCSTNPC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No