Elective Level Ib Irradiation in Nasopharyngeal Carcinoma Patients Based on the International Guidelines

Elective Level Ib Irradiation in Nasopharyngeal Carcinoma Patients Based on the International Guidelines: an Open-label, Non-inferiority, Multicentre, Randomised Phase 3 Trial

Currently, nasopharyngeal carcinoma (NPC) patients who had level II involvement with extracapsular extension (ECE), and/or had a maximum nodal axial diameter (MAD) of greater than 2cm in level II will be recommended to receive level Ib-covering IMRT according to the International Guidelines. Our previous study, which retrospectively analyzed a cohort of 390 patients, indicated that it should be safe and feasible for patients who only had at least one of the above two radiological features. Thus, the investigators conduct this non-inferior phase 3, randomized trial to further determine the feasibility of sparing level Ib in patients who had level II involvement with ECE, and/or had a MAD of greater than 2cm in level II.

Study Overview

• Status: Not yet recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Radiation: level Ib-covering IMRT; Radiation: level Ib-sparing IMRT

Detailed Description

Currently, nasopharyngeal carcinoma (NPC) patients who had level II involvement with extracapsular extension (ECE), and/or had a maximum nodal axial diameter (MAD) of greater than 2cm in level II will be recommended to receive level Ib-covering IMRT according to the International Guidelines. Our previous study, which retrospectively analyzed a cohort of 390 patients, indicated that it should be safe and feasible for patients who only had at least one of the above two radiological features. Thus, the investigators conduct this non-inferior phase 3, randomized trial to further determine the feasibility of sparing level Ib in patients who had level II involvement with extracapsular extension (ECE), and/or had a maximum nodal axial diameter (MAD) of greater than 2cm in level II.

• Study Type: Interventional
• Enrollment (Anticipated): 398
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. newly diagnosed, non-metastatic nasopharyngeal carcinoma histologically confirmed by biopsy;
2. the following conditions: ① involvement of level II LNs with extracapsular extension(ECE); ② level II LNs involvement with maximum nodal axial diameter (MAD) greater than 2 cm;
3. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.

Exclusion Criteria:

1. level Ib involvement with positive pathological results;
2. submandibular glands (SMGs) involvement;
3. involvement of structures that drain to level Ib as the first echelon site (the oral cavity, anterior half of nasal cavity involvement);
4. previous malignancy or other concomitant malignant disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: level Ib-covering IMRT; Patients who had level II involvement with extracapsular extension (ECE), and/or had a maximum nodal axial diameter (MAD) of greater than 2cm in level II.	Radiation: level Ib-covering IMRT; Patients who had level II involvement with extracapsular extension (ECE), and/or had a maximum nodal axial diameter (MAD) of greater than 2cm in level II.
EXPERIMENTAL: level Ib-sparing IMRT; Patients who had level II involvement with extracapsular extension (ECE), and/or had a maximum nodal axial diameter (MAD) of greater than 2cm in level II	Radiation: level Ib-sparing IMRT; Patients who had level II involvement with extracapsular extension (ECE), and/or had a maximum nodal axial diameter (MAD) of greater than 2cm in level II.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regional relapse-free survival	The regional relapse-free survival rate will be estimated using Kaplan-Meier method for each arm from the date of randomization to the date of nodal relapse or death from any cause, whichever occurred first. Their differences will be compared between treatment arms using the log-rank test.	3 year
level Ib recurrence rate	The level Ib recurrent rate will be calculated by the ratio of mumbers of patients relapsed in level Ib and the numbers of cases in the whole group.	3 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The overall survival rate will be estimated using Kaplan-Meier method for each arm from the date of randomization to death from any cause. Their differences will be compared between treatment arms using the log-rank test.	3 year
Local relapse-free survival	The local relapse-free survival rate will be estimated using Kaplan-Meier method for each arm from the date of randomization to documented local relapse or death from any cause. Their differences will be compared between treatment arms using the log-rank test.	3 year
Distant metastasis-free survival	The distant metastasis-free survival rate will be estimated using Kaplan-Meier method for each arm from the date of randomization to documented distant metastasis or death from any cause. Their differences will be compared between treatment arms using the log-rank test.	3 year
Patient's quality-of-life: dry mouth	European Organization for Research and Treatment of Cancer Quality-of-Life Head and Neck 35 items (QLQ-H&N35) version 1.0 questionnaires will be used to assess quality-of-life. All items pointing to this domain are averaged and then transformed to a scale of 0-100 according to the EORTC scoring manual. Higher scores on the symptom scales indicate more severe symptoms.	3 year
Patient's quality-of-life: sticky saliva	European Organization for Research and Treatment of Cancer Quality-of-Life Head and Neck 35 items (QLQ-H&N35) version 1.0 questionnaires will be used to assess quality-of-life. All items pointing to this domain are averaged and then transformed to a scale of 0-100 according to the EORTC scoring manual. Higher scores on the symptom scales indicate more severe symptoms.	3 year

Collaborators and Investigators

• Sponsor: Fujian Cancer Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 16, 2022
• Primary Completion (ANTICIPATED): September 1, 2025
• Study Completion (ANTICIPATED): September 30, 2025

Study Registration Dates

• First Submitted: August 26, 2022
• First Submitted That Met QC Criteria: August 26, 2022
• First Posted (ACTUAL): August 29, 2022

Study Record Updates

• Last Update Posted (ACTUAL): September 19, 2022
• Last Update Submitted That Met QC Criteria: September 16, 2022
• Last Verified: August 1, 2022

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: NPC008.1

Drug and device information, study documents

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