Personalized treatment for nasopharyngeal carcinoma based on EBV DNA levels

tReatment Individualisation By EBV stratificatiON in Nasopharyngeal Carcinoma: an Umbrella Platform Study (RIBBON-Umbrella)

This study is testing if tailoring chemotherapy for people with advanced nasopharyngeal carcinoma based on their EBV DNA levels can improve their chances of staying cancer-free.

Quick facts

• Study type: Observational
• Enrollment: 1000 (estimated)
• Ages: 21 Years to 99 Years
• Sex: All
• Sponsor: National Cancer Centre, Singapore (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Singapore)
• Trial ID: NCT05517135 on ClinicalTrials.gov

What this trial studies

This observational study aims to evaluate the outcomes of patients with locoregionally-advanced or recurrent-metastatic nasopharyngeal carcinoma by assigning them to different chemotherapy treatment arms based on their plasma EBV DNA levels before and during treatment. The study will validate the prognostic potential of an EBV DNA-based risk-stratification strategy and assess whether individualized treatment approaches can enhance survival outcomes. Patients will be monitored for disease-free survival over a two-year period.

Who should consider this trial

Good fit: Ideal candidates include adults aged 21 and older with suspected or confirmed nasopharyngeal carcinoma associated with EBV infection.

Not a fit: Patients with nasopharyngeal carcinoma not associated with EBV infection or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to more effective and personalized treatment strategies for patients with nasopharyngeal carcinoma.

How similar studies have performed: Other studies have shown promise in using biomarker-guided treatment strategies for cancer, suggesting potential success for this approach.

Eligibility criteria

Inclusion Criteria:

Each patient eligible to participate in this study must meet all the following criteria:

1. Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments.
2. Age ≥21 years on the day of signing the ICF
3. Fulfil one of the following three scenarios:

   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

   All confirmed NPC patients must meet these additional criteria before they can continue participation in the study:
4. NPC associated with EBV infection, determined as:

   1. The presence of EBV has been confirmed in the tumour by immunohistochemistry for EBV antigens or in situ hybridization for EBV early RNA (EBER), or
   2. NPC occurred in association with a raised serum titre of IgA to EBV viral capsid antigen (VCA) or early antigen (EA) in a patient living in endemic area of high incidence of EBV+ undifferentiated NPC, or
   3. NPC in the context of an elevated circulating EBV genome level
5. AJCC 8th edition stage 2-4A or RM NPC based on the following diagnostic workup:

   1. Evaluation of tumour extent with magnetic resonance imaging (MRI) of the nasopharynx and neck. If MRI is medically contraindicated, computed tomography (CT) scan with ≤3 mm and intravenous contrast is acceptable.
   2. Distant metastasis staging:

      * CT scan with contrast of the chest, abdomen, and pelvis or a total body 18F-Fluorodeoxygenase positron emission tomography CT (18F-FDG-PET-CT) scan;
      * Bone scan, if a 18F-FDG-PET-CT scan is not performed.
6. ECOG Performance Status ≤1
7. Adequate organ function

Exclusion Criteria:

Patients who meet any of the following criteria are not eligible to enrol:

1. Age \<21 years or \>99 years old
2. Has received any prior RT or systemic anti-cancer therapy including investigational agents that are not part of the intended treatment plan for NPC
3. Any known central nervous system metastases and/or carcinomatous meningitis
4. Any active malignancy ≤2 years before start of study except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast)
5. Patients with severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc.

   a. Severe infections within 4 weeks before start of study, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
6. Patients with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers whose HBV DNA is \>500 IU/mL or patients with active hepatitis C virus (HCV) should be excluded.

   Note: Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B (HBV DNA \<500 IU/mL), and cured hepatitis C patients can be enrolled
7. Prior allogeneic stem cell transplantation or organ transplantation
8. Any of the following cardiovascular risk factors:

   1. Cardiac chest pain, defined as moderate pain or any cardiac condition e.g., arrhythmias, malignant hypertension, etc. that limits instrumental activities of daily living, ≤28 days before start of study
   2. Pulmonary embolism ≤28 days before start of study
   3. Any history of cerebrovascular accident or seizure ≤ 28 days before start of study
9. A history of severe hypersensitivity reactions to gemcitabine, cisplatin, capecitabine and/or any of its excipients
10. Has received any herbal medicine used to control cancer within 14 days of the start of study
11. Patients with toxicities (as a result of prior anticancer therapy) which have not recovered to baseline or stabilized, except for adverse events (AEs) not considered a likely safety risk (eg, alopecia, neuropathy and specific laboratory abnormalities)
12. Underlying medical conditions (including laboratory abnormalities) or alcohol or drug abuse or dependence that, will be unfavorable for the administration of treatment or affect the explanation of drug toxicity or AEs or result in insufficient or might impair compliance with study conduct
13. Concurrent participation in another therapeutic clinical study

Where this trial is running

Singapore

• National Cancer Centre Singapore — Singapore, Singapore (RECRUITING)

Study contacts

• Principal investigator: Melvin Lee Kiang Chua, MBBS, FRCR, PhD, FAMS — National Cancer Centre, Singapore
• Study coordinator: Melvin Lee Kiang Chua, MBBS, FRCR, PhD, FAMS

Conditions: Nasopharyngeal Carcinoma, EBV DNA, Biomarker-guided, Treatment Individualization, Risk Stratification