Weekly Plasma EBV DNA for Non-metastatic Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is an endemic malignancy in Southern China, Hong Kong, Taiwan, Singapore and Malaysia. It is highly associated with Epstein-Barr virus (EBV). Radiation therapy alone is indicated for early stage I to II diseases while concurrent chemoradiation is required for more advanced stage III to IVB diseases. Intensity-modulated radiation therapy (IMRT) is the standard radiation technique for NPC, in virtue of its superior target coverage and dose sparing to adjacent critical organs-at-risks.

Plasma EBV DNA and other novel plasma biomarkers have been extensively investigated in NPC. Previous studies have proven their predictive and prognostic values in NPC diagnosis, surveillance and survival outcomes.

Investigators would like to investigate the roles of plasma biomarkers including plasma EBV DNA on treatment response evaluation, survival and prognosis on NPC, in the modern era of precision radiation therapy. This will help provide important information on refining on the current edition of AJCC/UICC staging classification.

Study Overview

• Status: Unknown
• Conditions: Nasopharyngeal Carcinoma

Detailed Description

Patients with histologically confirmed previously untreated NPC are be recruited to join tis study. The study has obtained approval from local institutional review board.

After written informed consent, baseline investigations including blood tests for routine hematology, biochemistry and plasma EBV DNA will be taken. Only 3ml of EDTA blood will be taken for plasma EBV DNA and other potential biomarkers. Patients will also undergo baseline imaging investigations including positron-emission tomography with integrated computed tomography (PET-CT) and magnetic resonance imaging (MRI) of the head and neck regions. An routine nasoendoscopy and nasopharyngeal biopsies will be obtained to confirm and delineate the mucosal extent of the disease.

If confirmed non-metastatic, patients will be treated with IMRT using 7-9 radiation beams. A total dose of 70Gy in 33-35 fractions over 6.5 to 7 weeks will be given. For advanced stage III to IVB diseases, concurrent chemoradiation using cisplatin 100mg/m2 on Day 1, 22 and 43 of IMRT followed by 3 cycles of adjuvant chemotherapy with cisplatin 80mg/m2 on Day 1 and 5-FU 1000mg/m2 from Day 1 to Day 4 every 4 weeks for 3 more cycles starting 4 weeks after completion of IMRT will also be given. Some patients will also receive induction chemotherapy with cisplatin100mg/m2 on Day 1 and 5-FU 1000mg/m2 on Day 1 to 5, administered every 3 weeks for 3 cycles before commencement of chemoradiation, at the discretion of treating oncologists if the primary tumours are close to critical organs e.g. brainstem, optic chiasm or optic nerves.

After treatment patients will undergo nasopharyngeal biopsies, patients will undergo nasopharyngeal biopsies again at 8 weeks after completion of IMRT to confirm histological complete local remission. Blood will be taken again on the same day for plasma EBV DNA and other potential biomarkers. Additional biopsies and salvage local treatment e.g. brachytherapy, stereotactic or IMRT boost will be offered to patients who have persistent local disease at 12 weeks after completion of IMRT. If complete local remission is confirmed, patient will have regular follow up every 3 to 4 months for surveillance and survival outcomes. Regular imaging with MRI and CT scans every 3 to 4 months will also be arranged as well. Plasma EBV DNA will be measured at weekly intervals until EBV DNA is undetectable.

For those with metastatic diseases, systemic chemotherapy (platinum-based chemotherapy) will be offered. Blood taking for plasma EBV DNA and other potential biomarkers at baseline before chemotherapy commencement and then after every 3 cycles will be arranged. Imaging examinations with CT and MRI scans will be arranged at baseline and then after 3-4 cycles of chemotherapy for tumour response evaluation.

The trend of baseline and serial plasma EBV DNA will be monitored prospectively.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Victor Lee, MD; Phone Number: 852-22554352; Email: vhflee@hku.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Department of Clinical Oncology, Queen Mary Hospital
    • Contact: Victor Lee, FRCR; Phone Number: 852-2255-4352; Email: vhflee@hku.hk

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with histologically confirmed previously untreated nasopharyngeal carcinoma (NPC) will be invited to join this study.

Description

Inclusion Criteria:

• Patients with histologically confirmed previously untreated nasopharyngeal carcinoma

Exclusion Criteria:

• Patients who are pregnant or lactating
• Patients who are not mentally capable of giving written informed consent
• Patients with performance status ECOG=3 or above or patients who are expected not able to tolerate radiation therapy and/or chemotherapy
• Patients who refuse active treatment for their nasopharyngeal carcinoma
• Patients who cannot comply with radiation therapy and/or chemotherapy for their nasopharyngeal carcinoma

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Progression-free survival is calculated from the date of diagnosis of NPC to the date of progression of NPC or the date of death from any cause, whichever comes earlier.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distant metastasis-free survival	Distant metastasis-free survival is calculated from the date of diagnosis of NPC to the date of distant metastasis or date of death from any cause, whichever comes earlier.	3 years
Overall survival	Overall survival is calculated from the date of diagnosis of NPC to the date of death from any cause	3 years

Collaborators and Investigators

• Sponsor: The University of Hong Kong

Publications and helpful links

General Publications

• Chan SK, Chan SY, Choi HC, Tong CC, Lam KO, Kwong DL, Vardhanabhuti V, Leung TW, Luk MY, Lee AW, Lee VH. Prognostication of Half-Life Clearance of Plasma EBV DNA in Previously Untreated Non-metastatic Nasopharyngeal Carcinoma Treated With Radical Intensity-Modulated Radiation Therapy. Front Oncol. 2020 Aug 21;10:1417. doi: 10.3389/fonc.2020.01417. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: February 4, 2019
• First Submitted That Met QC Criteria: February 4, 2019
• First Posted (Actual): February 5, 2019

Study Record Updates

• Last Update Posted (Actual): October 1, 2019
• Last Update Submitted That Met QC Criteria: September 29, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: 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; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma
• Other Study ID Numbers: WeeklyEBV

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