ADjuVant Apatinib in Nasopharyngeal Carcinoma Patients With Residual Epstein-Barr Virus (EBV) DNA Following Radiotherapy (ADVANCE)

Inclusion Criteria:

1. Biopsy proven nasopharyngeal carcinoma, with detectable pretreatment plasma EBV DNA
2. Have detectable plasma EBV DNA at the end of (+/- 1 week) curative radiotherapy or chemoradiotherapy (radiation dose > 66Gy), determined by the central lab
3. No clinical evidence of persistent loco-regional disease
4. No evidence of distant metastasis, based upon skeletal scintigraphy, chest X-ray examination, and liver ultrasound or other appropriate workup (e.g., CT, MRI or positron emission tomography (PET)/CT]) within 21 days prior to registration
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
6. Anticipated survival >= 3 months
7. Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
8. Platelets > 80,000 cells/mm^3
9. Hemoglobin >= 8.0 g/dl (no transfusion within the last 14 days)
10. Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
11. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x institutional ULN
12. Creatinine clearance (CC) >= 50 ml/min estimated by Cockcroft-Gault formula

Exclusion Criteria:

1. Patients with stage III-IV disease (American Joint Committee On Cancer/Union for International Cancer Control 7th) and no contraindication to chemotherapy that didn't receive platinum based concurrent chemotherapy during radiation
2. Patients with tumor possibly invaded main vessels (e.g. encasement of the internal jugular artery/vein) at diagnosis; or tumor that, in the judgment of the investigator, likely to invade main vessels and cause life-threatening hemorrhage events during study
3. History of serious hemorrhage events or grade 3 or higher hemorrhage within 4 weeks prior to registration
4. Hypertension that couldn't be well controlled with single medication; unstable angina; angina diagnosed within the last 3 months; myocardial infarction within the last 6 months; cardiac arrhythmia that need long-term medication; grade 2 or higher cardiac dysfunction (NYHA)
5. Proteinuria
6. Coagulation dysfunction or predisposition to hemorrhage; on treatment of anticoagulation medication or vitamin K antagonist; low dose warfarin (1mg po qd) or aspirin (less than 100mg daily) were permitted as long as the international normalized ratio (INR) = < 1.5
7. Thrombosis within the last 1 year, except cured vein thrombosis related to vein indwelling catheter
8. Unhealed bone fracture or chronic unhealed wound
9. Illness that would interfere with oral medication, including dysphagia, chronic diarrhea, or ileus
10. Pregnant or lactating women
11. Women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception during and within 6 months after study
12. Current drug abuse or mentally disabled
13. History of congenital or acquired immune deficiency disease or organ transplantation
14. Major medical illness, which in the investigator's opinion would endanger the patients or interfere with the completion of therapy and follow up