Sequencing-based Counting of Plasma Epstein-Barr Virus DNA in Non-metastatic Nasopharyngeal Carcinoma

The investigators aim to explore a new EBV DNA surveillance method with both high sensitivity and specificity in nasopharyngeal carcinoma (NPC) patients. the investigators aim to conduct plasma EBV DNA counting by next generation sequencing (NGS) in non-metastatic NPC patients on their diagnose, after two cycles of induction chemotherapy (IC), and 4-8 weeks after definitive radiotherapy. The investigators aim to explore whether sequencing-based counting is better than PCR analysis in plasma EBV-DNA surveillance, so as to monitoring tumor responses to treatment and for guiding individualized treatment adaptation in the future.

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Carcinoma; Herpesvirus 4, Human
• Intervention / Treatment: Diagnostic test: EBV-DNA next generation sequencing

Detailed Description

The investigators aim to explore a new EBV DNA surveillance method with both high sensitivity and specificity in nasopharyngeal carcinoma (NPC) patients. the investigators aim to conduct plasma EBV DNA counting by next generation sequencing (NGS) in non-metastatic NPC patients on their diagnose, after two cycles of induction chemotherapy (IC), and 4-8 weeks after definitive radiotherapy. The investigators aim to explore whether sequencing-based counting is better than PCR analysis in plasma EBV-DNA surveillance, so as to monitoring tumor responses to treatment and for guiding individualized treatment adaptation in the future.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Yaqian Han; Phone Number: (+86)18673176667; Email: hanyaqian@hnca.org.cn

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China
      • Recruiting
      • Hunan Cancer Hospital
      • Contact: Yaqian Han; Phone Number: +8618673176667; Email: hanyaqiancs@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Non-metastatic NPC

Description

Inclusion Criteria:

1. Newly diagnosed, pathologically proven World Health Organization (WHO) type II/III untreated NPC;
2. Non-metastatic NPC (I-IVA, according to the 8th edition of the AJCC/UICC clinical staging system);
3. Age at diagnosis: over 18 years old;
4. Eastern Cooperative Oncology Group (ECOG) score: 0-1
5. Receiving recommended curative intention treatments：definitive radiotherapy w/wo three cycles of induction chemotherapy (IC) (gemcitabine-cisplatin [GP] or paclitaxel-cisplatin [TP] regimen);
6. Pre-treatment and post-IC1 cell-free Epstein-Barr virus (cfEBV) DNA > 0 copy/mL; systemic cfEBV DNA monitoring during IC phase for risk stratification;
7. Normal hematic, liver, and kidney function: hemoglobin (HG) > 90 g/L; neutrophil > 1.5 × 109/L; platelet > 100 × 109/L; total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 × ULN; alkaline phosphatase (ALP) ≤ 2.5 × ULN; creatinine clearance (Ccr) ≥ 60 mL/min;
8. Female subjects capable of becoming pregnant agree to use reliable contraceptive measures from screening to 1 year after treatment;
9. Patients will be required to sign informed consent forms and be willing and able to comply with the requirements for visits, treatment, laboratory tests, and other research requirements stipulated in the research schedule.

Exclusion Criteria:

1. Receiving surgery, target therapy, and/or immunotherapy during or before induction phase;
2. Other previous or concurrent malignant tumors, except adequately treated non-melanoma skin cancer, cervical carcinoma in situ, and thyroid papillary cancer;
3. Pregnant or lactating women (a pregnancy test should be considered for fertile women with an active sex life);
4. Previously treated with radical radiotherapy (RT), except non-melanoma skin cancers outside intended RT treatment volume;
5. Uncontrolled heart disease, e.g.: 1) Heart failure, New York Heart Association (NYHA) level ≥ 2; 2) unstable angina; 3) myocardial infarction in the past 1 year; 4) supraventricular or ventricular arrhythmia requiring treatment or intervention.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positivity rate of plasma EpsteineBarr virus (EBV) DNA by next generation sequencing	Plasma EBV DNA analysis by NGS on enrollment, after 2 cycles of induction chemotherapy, and 4-8 weeks after definitive radiotherapy.	from diagnose to 4-8 weeks after definitive radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Measured from the day of enrollment until death due to any cause, or the last follow-upmeasured from the day of enrollment until death due to any cause, or the last follow-up visit.	2 year
Distant metastasis failure-free survival	Measured from the day of enrollment until death until distant metastasis , or the last follow-up visit.	2 year
Locoregional failure-free survival	Measured from the day of enrollment until death until local and/or regional recurrence, or the last follow-up visit.	2 year
Failure-free survival	Measured from the day of enrollment until treatment failure, death from any cause, or the last follow-up visit, whichever occurred first.	2 year
Patient reported quality-of-life score	Patient reported quality of life would be evaluated using the Quality of Life Questionnaire-Core 30 module (QLQ-C30).	up to 2 years
Biomarker analysis	Exploratory biomarker analysis that would be able to predict patient treatment benefits, for example PD-L1 expression, antigen (other than EBV, eg. human cytomegalovirus(human cytomegalovirus [HCMV], TTV) DNA counting.	from diagnose to 4-8 weeks after definitive radiotherapy

Collaborators and Investigators

• Sponsor: Hunan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: February 24, 2024
• First Submitted That Met QC Criteria: March 14, 2024
• First Posted (Actual): March 20, 2024

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; DNA Virus Infections; Tumor Virus Infections; Herpesviridae Infections; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma; Epstein-Barr Virus Infections
• Other Study ID Numbers: NPCNS 001

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