Treatment Individualisation by EBV Stratification in Nasopharyngeal Carcinoma: a Prospective Observational Study

Recruiting

• Conditions: Nasopharyngeal Carcinoma
• Interventions: Other: Arm 1; Other: Arm 2; Other: Arm 3; Other: Group 1; Other: Group 2

• Registration Number: NCT05517135
• Lead Sponsor: National Cancer Centre, Singapore

Brief Summary

This is a prospective platform study that will investigate the outcomes of patients with locoregionally-advanced nasopharyngeal carcinoma (LA-NPC) or recurrent-metastatic nasopharyngeal carcinoma (RM-NPC) who are assigned to treatment arms of different chemotherapy sequencing and intensity based on their pre- and on-treatment plasma EBV DNA results.

Detailed Description

The primary objectives of this platform are: (1) to prospectively validate the prognostic potential of an EBV DNA-based risk-stratification strategy of patients with LA- and RM-NPC; and (2) to test if treatment individualization strategies based on pre- and on-treatment plasma EBV DNA will improve survival outcomes. Primary study end-point is 2-year disease-free survival (DFS).

Study Timeline

• Study First Submitted: 2022-08-23
• Study First Submitted QC: 2022-08-25
• Study First Posted: 2022-08-26
• Study Start: 2022-11-17
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-03
• Last Update Posted: 2023-04-05
• Primary Completion: 2027-07-01
• Study Completion: 2027-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

Any patients ≥21 years of age with any of the following:

1. Suspected NPC cases, diagnosed clinically based on symptoms (neck swelling, unilateral epistaxis, nasal obstruction etc.)
2. Newly-diagnosed, histologically confirmed NPC patients with Stages 2-4A disease based on the AJCC/UICC 8th Edition TNM stage classification
3. Newly-diagnosed patients with RM-NPC

Exclusion Criteria

All patients <21 years or >99 years old will be excluded from participation.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Arm 1	Arm 1	Arm 1: Pre-treatment EBV DNA \<4000 copies/mL AND N0-1 or T4N0 (TNM AJCC/UICC 8th edition)
Arm 2	Arm 2	Arm 2: Pre-treatment EBV DNA ≥4000 copies/mL OR N2-N3 OR T4N+ (TNM AJCC/UICC 8th edition) AND EBV DNA UNDETECTABLE after 2-3 cycles of induction chemotherapy (IC)
Arm 3	Arm 3	Arm 3: Pre-treatment EBV DNA ≥4000 copies/mL OR N2-N3 OR T4N+ (TNM AJCC/UICC 8th edition) AND EBV DNA DETECTABLE after 2-3 cycles of IC
Group 1	Group 1	Group 1: Recurrent/metastatic NPC, EBV DNA \<4000 copies/mL
Group 2	Group 2	Group 2: Recurrent/metastatic NPC, EBV DNA ≥4000 copies/mL

Primary Outcome Measures

Name	Time	Method
Disease-Free Survival	2 years from end of treatment

Secondary Outcome Measures

Name	Time	Method
Overall survival	2 years after end of treatment
Distant metastasis-free survival	2 years after end of treatment
Loco-regional recurrence-free survival	2 years after end of treatment
Treatment-related adverse events	From start of treatment to 30 days after last treatment and up to 5 years post - treatment
Genome sequencing of biological samples	baseline, mid/post IC, mid CCRT, 1-2 weeks post-RT, 3 months post-RT/mid-adjuvant chemotherapy, at point of recurrence and post immune checkpoint blockade treatment (for recurrence, if any) up to 5 years	Blood samples will be collected at up to 7 timepoints - baseline, mid/post IC, mid CCRT, 1-2 weeks post-RT, 3 months post-RT/mid-adjuvant chemotherapy, at point of recurrence and post immune checkpoint blockade treatment (ICB) for recurrence, if any; fresh biopsy samples will be collected at baseline, mid-IC, at point of recurrence and mid-ICB, if amenable for biopsy. Saliva samples will be collected at baseline and at point of recurrence.

Trial Locations

Locations (1)

National Cancer Centre Singapore; 🇸🇬 Singapore, Singapore