EP-STAREpstein-Barr Virus DNA to Systemic Therapy for Treatment Adaptation in High Risk Nasopharyngeal Carcinoma (EP-STAR Trial) A Phase II, Multi-center, Biomarker-guided, Umbrella Trial

Fecha de inicio: 1 de junio de 2020

Inclusion Criteria: 1. Newly diagnosed, pathologically proven World Health Organization (WHO) type II/III untreated LANPC; 2. LANPC (except T3N0, according to the 8th edition of the AJCC/UICC clinical staging system); 3. Age at diagnosis: 18-65 years; 4. Eastern Cooperative Oncology Group (ECOG) score: 0-1 5. Receiving recommended three cycles of induction chemotherapy (IC) (gemcitabine-cisplatin \[GP\] regimen); 6. Pre-treatment and post-IC1 cell-free Epstein-Barr virus (cfEBV) DNA \> 0 copy/mL; systemic cfEBV DNA monitoring during IC phase for risk stratification; 7. Normal hematic, liver, and kidney function: hemoglobin (HG) \> 90 g/L; neutrophil \> 1.5 × 109/L; platelet \> 100 × 109/L; total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 × ULN; alkaline phosphatase (ALP) ≤ 2.5 × ULN; creatinine clearance (Ccr) ≥ 60 mL/min; 8. Female subjects capable of becoming pregnant agree to use reliable contraceptive measures from screening to 1 year after treatment; 9. Patients will be required to sign informed consent forms and be willing and able to comply with the requirements for visits, treatment, laboratory tests, and other research requirements stipulated in the research schedule. Exclusion Criteria: 1. Receiving surgery, target therapy, and/or immunotherapy during or before induction phase; 2. Hepatitis B surface antigen-positive \[HBsAg(+)\],hepatitis B virus (HBV) DNA \> 1×103 copy/mL; hepatitis C virus (HCV) antibody(+); 3. Other previous or concurrent malignant tumors, except adequately treated non-melanoma skin cancer, cervical carcinoma in situ, and thyroid papillary cancer; 4. Pregnant or lactating women (a pregnancy test should be considered for fertile women with an active sex life); 5. Previously treated with radical radiotherapy (RT), except non-melanoma skin cancers outside intended RT treatment volume; 6. Uncontrolled heart disease, e.g.: 1) Heart failure, Hew York Heart Association (NYHA) level ≥ 2; 2) unstable angina; 3) myocardial infarction in the past 1 year; 4) supraventricular or ventricular arrhythmia requiring treatment or intervention; \*For patients recruited to Arm II, the additional exclusion criteria are: 7. Active, known, or suspected autoimmune disease (including, but not limited to, uveitis, enteritis, hepatitis, pituitary, nephritis, vasculitis, hyperthyroidism, hypothyroidism, and asthma requiring bronchiectasis). Exceptions are type I diabetes mellitus, hypothyroidism requiring hormone replacement therapy, and skin disorders requiring no systemic treatment (e.g., vitiligo, psoriasis, alopecia); 8. Received live vaccine within 1 month before treatment initiation; 9. Allergy to macromolecular protein preparations, or any component of sintilimab; 10. Human immunodeficiency virus (HIV)-positive or diagnosed with Acquired Immune Deficiency Syndrome (AIDS).