Modulation therapy for advanced nasopharyngeal cancer based on EBV DNA levels

Response-adapted Modulation Therapy for Locally Advanced Nasopharyngeal Carcinoma Based on Circulating Epstein-Barr Virus DNA Level Post Induction Chemotherapy

This study is testing if a personalized treatment plan based on blood tests for a virus can help people with advanced nasopharyngeal cancer live longer without their cancer getting worse after chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 198 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, prednisone, toripalimab
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT05628922 on ClinicalTrials.gov

What this trial studies

This study investigates a response-adapted treatment strategy for patients with locally advanced nasopharyngeal carcinoma (NPC) following induction chemotherapy. Patients will undergo plasma Epstein-Barr Virus (EBV) DNA testing and imaging after one cycle of chemotherapy to assess their response. Based on their response, patients will either proceed with standard concurrent chemoradiation or be randomized to receive additional immunotherapy. The primary goal is to determine if this tailored approach improves progression-free survival over standard treatment methods.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-70 with newly diagnosed, pathologically confirmed locally advanced nasopharyngeal carcinoma and detectable EBV DNA.

Not a fit: Patients with early-stage nasopharyngeal carcinoma or those who have received prior treatment for their cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly enhance survival rates for patients with locally advanced nasopharyngeal carcinoma by personalizing treatment based on individual response.

How similar studies have performed: Previous studies have shown promising results with response-adapted strategies in cancer treatment, particularly in relation to EBV DNA levels, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Subjects must sign the informed consent form, and must be willing and able to comply with the visits, treatment regimen, laboratory tests and other requirements specified in the study protocol;
2. Age at diagnosis: 18-70 years old;
3. Firstly diagnosed, pathologically confirmed primary nasopharyngeal carcinoma with "non-keratinizing carcinoma (WHO criteria)";
4. Locally advanced nasopharyngeal carcinoma (T3-4N0-1M0, TanyN2-3M0), staged according to the American Joint Committee on Cancer (AJCC) 8th edition clinical staging system;
5. Pretreatment EBV DNA \>0;
6. ECOG score: 0-1 points;
7. Does not receive any treatment after the diagnosis of nasopharyngeal carcinoma;
8. Normal bone marrow function: white blood cell \>4\*109/L, neutrophil count \>1.5\*109/L, hemoglobin concentration \> 90g/L, platelet count \>100\*109/L;
9. Normal liver and kidney function: total bilirubin ≤1.5 times the upper limit of normal; aspartate aminotransferase and/or alanine aminotransferase ≤ 2.5 times the upper limit of normal; creatinine clearance ≥ 60mL/min;
10. For those with hepatitis B infection, the HBV DNA load must be \< 2500 copies/ml at the time of screening; For those with anti-hepatitis C virus antibody, HCV RNA must be negative at the time of screening;
11. Female subjects of childbearing potential and male subjects with partners of childbearing potential must agree to use reliable contraception (e.g. condoms, regular contraceptives as directed) from screening through 1 year after treatment.

Exclusion Criteria:

1. Pathologically confirmed primary nasopharyngeal carcinoma with "keratinizing carcinoma or basaloid squamous cell carcinoma";
2. Previous or current other malignancy other than adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, and papillary thyroid carcinoma;
3. Pretreatment plasma EBV DNA undetectable;
4. History of radiation therapy prior to standard therapy (except for non-melanoma skin cancer, and the previous radiation field did not overlap with the current treatment for nasopharyngeal carcinoma);
5. Patients who received surgical treatment (except for diagnostic biopsy), biological therapy, chemotherapy or immunotherapy before enrollment;
6. Conditions mentioned below: 1) Currently enrolled in other interventional clinical trial; 2) Systemic hormonal or other immunosuppressive therapy with an equivalent dose of \> 10mg prednisone/day within 28 days prior to informed consent; 3) Receipt of live vaccines within 30 days prior to enrollment; 4) Surgery or trauma within 30 days prior to enrollment;
7. Uncontrolled heart disease, such as :1) heart failure, NYHA ≥ 2; 2) unstable angina; 3) history of myocardial infarction within 1 year; 4) supraventricular or ventricular arrhythmia requiring treatment or intervention;
8. History of stroke within 6 months;
9. Patients with severe active infection within 30 days prior to enrollment, that must be treated with systemic antibacterial, antifungal or antiviral therapy;
10. Active autoimmune disease (including but not limited to uveitis, enteritis, hepatitis, pituitary disease, nephritis, vasculitis, hyperthyroidism, etc.). Except for type I diabetes, hypothyroidism requiring hormone replacement therapy, and vitiligo not requiring systemic treatment, inactive childhood asthma that does not require treatment as an adult;
11. Positive anti-HIV antibody or diagnosis of other innate or acquired immunodeficient, immunosuppressive disease, history of organ transplantation;
12. Interstitial lung disease or pneumonia requiring oral or intravenous steroid therapy within 1 year;
13. Active tuberculosis infection, or previous lung tuberculosis infection within 1 year, or previous lung tuberculosis infection more than 1 year prior to enrollment but did not receive standard anti-tuberculosis treatment;
14. Positive hepatitis B surface antigen and hepatitis B virus DNA ≥ 2500 copies/ml or Positive hepatitis C RNA;
15. Pregnant or lactating women (pregnancy test should be considered for sexually active women of childbearing age);
16. Other conditions that may jeopardize patient safety or compliance as assessed by investigator, such as serious illness (including psychiatric disorders) requiring prompt treatment, severely abnormal test results, and other family or social risk factors.

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan Universtiy Shanghai Cancer Centre — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Chao-su Hu, M.D. — Fudan University
• Study coordinator: Chao-su Hu, M.D.

Conditions Nasopharyngeal Cancer; Epstein-Barr virus DNA; Immunotherapy; Programmed Cell Death 1 antibody; Induction chemotherapy