Apatinib Combined With PD-1 in the Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma

Inclusion Criteria:

1. Male or female patients: 18-70 years old.
2. Pathologically diagnosed nasopharyngeal carcinoma.
3. Patients with nasopharyngeal carcinoma who have local recurrence after onecomprehensive treatment (clinical examination found definite local residual: clearresidual or cervical enlarged lymph node can be seen under electronicnasopharyngoscope).
4. Patients with nasopharyngeal carcinoma who have distant metastasis after onecomprehensive treatment (found distant metastasis by liver ultrasound, chest X-ray,bone scan or other examination (such as CT, MRI or PET/CT) as the clinician considersappropriate.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Estimated survival ≥6 months.
7. The function of the main organs is good, that is, one week before joining the group,the following requirements are met: Blood routine examination:Hemoglobin > 80 g/L(no blood transfusion within 14days);Neutrophils count > 1.5x10^9/L;Platelet count > 80x10^9/L; biochemicaltest:serum total bilirubin ≤1.5×ULN(upper limit of normal), ALT orAST≤3×ULN;Endogenous creatinine clearance ≥ 1.5×ULN;Acceptable clotting state: theinternational standardized ratio ((INR)), prothrombin time (PT) and activated partialthromboplastin time (APTT) of blood clots were less than 1.5 times of the upper limitof normal (ULN).
8. All women with fertility potential must undergo a urine or serum pregnancy test duringscreening and the results are negative.
9. The subjects voluntarily joined the study, signed the informed consent form, had goodcompliance and cooperated with the follow-up.

Exclusion Criteria:

1. Before treatment, MRI showed that the tumor may have invaded important blood vessels (such as enclosing the internal carotid artery / vein), or researchers have determinedthat the tumor is highly likely to invade important blood vessels and cause fatalmassive bleeding during treatment.
2. There was a history of severe bleeding, and any bleeding events with a serious gradeof 3 or more in CTCAE4.0 occurred within 4 weeks before screening.
3. Patients with hypertension who cannot be well controlled by antihypertensive therapyalone (systolic blood pressure > 140mmHg, diastolic blood pressure > 90mmHg); patientswith a history of unstable angina pectoris; patients newly diagnosed with anginapectoris within 3 months or myocardial infarction within 6 months before screening;arrhythmias (including QTcF: ≥ 450ms in males, ≥ 470ms in females) require long-termuse of antiarrhythmic drugs and New York Heart Association grade ≥ II cardiacinsufficiency.
4. Positive urine protein.
5. Patients with abnormal blood coagulation and bleeding tendency (14 days before signinginformed consent: INR is within the normal range without anticoagulant); patientstreated with anticoagulants or vitamin K antagonists such as warfarin, heparin ortheir analogues; On the premise that the international standardized ratio ofprothrombin time ((INR)) is less than 1.5, low-dose warfarin (1mg orally, once a day)or low-dose aspirin (daily dose not more than 100mg) is allowed for preventivepurposes.
6. Arteriovenous thrombosis occurred within one year before screening, such ascerebrovascular accident (including temporary ischemic attack), deep venous thrombosis (except venous thrombosis caused by intravenous catheterization due to earlychemotherapy) and pulmonary embolism.
7. Long-term unhealed wound or incomplete fracture.
8. Any factors that affect the oral drug, such as inability to swallow, chronic diarrheaand intestinal obstruction, etc.
9. For female subjects: women of childbearing age, it is not acceptable to use medicallyapproved contraception during the study treatment period and within 6 months after theend of the study treatment period;Patients with positive serum or urine pregnancytest;Nursing patients.Male subjects: patients who did not undergo surgicalsterilization or did not agree to use medically approved contraception during thestudy and within 6 months after the study.
10. Having a history of psychotropic substance abuse and unable to quit or having mentaldisorders.
11. Medical history of immunodeficiency, or other acquired, congenital immunodeficiencydisease, or history of organ transplantation.Any symptomatic autoimmune disease (suchas lupus, scleroderma, Crohn's disease, ulcerative colitis) that requiresadministration of >10mg of prednisone equivalent. Lower dose steroids for conditionssuch as hypophysitis are allowed.
12. Any serious harm to the subject's safety or evidence of significant medical illnessthat in the investigator's judgment will substantially increase the risk associatedwith the subject's participation in and completion of the study.
13. Any prior severe adverse event attributed to prior anti-PD1 therapy that, in thePrincipal investigator's opinion, would contraindicate pembrolizumab administrationsuch as:Grade 2 or higher pneumonitis、Grade 4 AST or ALT elevation、Grade 3 or highercolitis; Known active infection with Hepatitis B Virus (HBV), Hepatitis C Virus (HCV),or HIV. Cleared HBV/HCV infection is not an exclusion, nor is HIV infection withcluster of differentiations 4 (CD4) counts >500 and an undetectable viral load.
14. Active bacterial, viral, or fungal infections, requiring systemic therapy apart fromanti-viral maintenance therapy for HIV；or Uncontrolled activity infected.