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

Study Overview
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Brief Summary
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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
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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).

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

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Other: Arm 1
* Other: Arm 2
* Other: Arm 3
* Other: Group 1
* Other: Group 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any patients ≥21 years of age with any of the following: Suspected NPC cases, diagnosed clinically based on symptoms (neck swelling, unilateral epistaxis, nasal obstruction etc.) Newly-diagnosed, histologically confirmed NPC patients with Stages 2-4A disease based on the AJCC/UICC 8th Edition TNM stage classification Newly-diagnosed patients with RM-NPC Exclusion Criteria: All patients <21 years or >99 years old will be excluded from participation.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Arm 1<br>Arm 1: EBV DNA <4000 copies/mL AND T3N0-2 or T4N0 (TNM AJCC/UICC 8th edition) | Other: Arm 1<br>* Concurrent chemoradiotherapy (CCRT) using cisplatin (100 mg/m2 IV) or carboplatin (AUC 5 IV) with radiotherapy +/- adjuvant chemotherapy (AC) with capecitabine (physician's choice of 650 mg/m2 bid or 1000 mg/m2 bid oral, d1-21, q3w)<br>|
| Arm 2<br>Arm 2: EBV DNA ≥4000 copies/mL OR N3 OR T4N+ (TNM AJCC/UICC 8th edition) AND EBV DNA undetectable after 2-3 cycles of induction chemotherapy (IC) | Other: Arm 2<br>* IC using cisplatin (80 mg/m2 IV) or carboplatin (AUC 3-5 IV) in combination with gemcitabine (1000 mg/m2 d1,8) or 5-fluorouracil (1000 mg/m2 bolus IV d1-4) or docetaxel (75 mg/m2 IV), and CCRT<br>|
| Arm 3<br>Arm 3: EBV DNA ≥4000 copies/mL OR N3 OR T4N+ (TNM AJCC/UICC 8th edition) AND EBV DNA detectable after 2-3 cycles of IC | Other: Arm 3<br>* CCRT + metronomic capecitabine (650 mg/m2 bid oral, d1-21, q3w)<br>|
| Group 1<br>Group 1: Recurrent/metastatic NPC, EBV DNA <4000 copies/mL | Other: Group 1<br>* Combination chemotherapy (using cisplatin or carboplatin with gemcitabine, 5-fluorouracil or docetaxel) and consolidative RT to the nasopharynx and neck (if good response to chemotherapy) +/- metastasis-directed therapy (surgery, radiofrequency ablation or RT) +/- immune checkpoint blockade (ICB) or capecitabine<br>|
| Group 2<br>Group 2: Recurrent/metastatic NPC, EBV DNA ≥4000 copies/mL | Other: Group 2<br>* Combination chemotherapy (using cisplatin or carboplatin with gemcitabine, 5-fluorouracil or docetaxel) with or without ICB +/- maintenance ICB or capecitabine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-Free Survival |  | 2 years from end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 (for recurrence, if any); fresh biopsy samples will be collected at baseline and at point of recurrence, if amenable for biopsy. Saliva samples will be collected at baseline and at point of recurrence. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasopharyngeal Carcinoma, EBV DNA, Biomarker-guided, Treatment Individualization, Risk Stratification