A Phase II Clinical Trial of Fruquintinib as Third Line Treatment in Advanced Pancreatic Cancer

Inclusion Criteria: 1. 18-80 years old; 2. Locally advanced or recurrent/metastatic pancreatic adenocarcinoma confirmed by cytological or histopathological examination; 3. Have failed second-line chemotherapy (gemcitabine or 5-FU-based regiments) (the definition of treatment failure is: toxic and side effects are intolerable, disease progression during treatment, recurrence within six months after the end of adjuvant chemotherapy, or progression within three months after the end of palliative chemotherapy); prior chemotherapy are required to include gemcitabine or 5-FU or its derivatives; 4. With one or more measurable lesions, the longest diameter should be at least 10 mm measured by spiral CT scan, or at least 20 mm by conventional CT scan should be(RECIST standard, version 1.1); 5. ECOG score was 0-2; 6. Life expectancy ≥12 weeks; 7. The damage was recovered from other antitumor treatments, including the interval from nitroso or mitomycin to enrollment was ≥6 weeks, and the interval from other cytotoxic drugs, radiotherapy or surgery to enrollment was ≥4 weeks, and the wound was completely healed; 8. Acceptable hematologic, hepatic, and renal function within 7 days from screenin: absolute neutrophil count (ANC) ≥1.5x109 /L; Hemoglobin ≥ 9.0g/dL; Platelet count ≥80 x109 /L; Total bilirubin \< 1.5 times upper limit of normal (ULN); ALT and AST\< 2.5 x ULN (with liver metastasis \<5x ULN); Serum creatinine ≤1 x ULN, endogenous creatinine clearance rate \>50ml/min; 9. Women of reproductive age need to take effective contraceptive measures; 10. Participate in this study is voluntarily and sign informed consent. With good compliance to cooperate with the follow-up, participate should understand the purpose of this study and the necessary procedures. Exclusion Criteria: 1. A history of other malignant tumors in the past 5 year: however, localized tumor cured in the study is excluded, including cervical carcinoma in situ and skin basal cell carcinoma. 2. Patients with hypertension that could not be controlled by antihypertensive drug therapy (systolic blood pressure \>140mmHg, diastolic blood pressure \>90mmHg), coronary heart disease of grade 1 or above, arrhythmia of grade 1 or above (including prolonged QTc interval \> 450ms in males and \> 470ms in females) and cardiac dysfunction of grade 1 or above; 3. Symptomatic brain or meningeal metastases (except those with stable brain metastases for more than one month after treatment); 4. Have a history of uncontrolled epileptic seizures, central nervous system dysfunction, or mental disorders; 5. Uncontrolled pleural or abdominal effusion; 6. Undergoing kidney dialysis; 7. Severe or uncontrolled infection; 8. With multiple factors affecting oral medication (inability to swallow, chronic diarrhea and intestinal obstruction); 9. Abnormal coagulation function (PT\>16s, APTT\>43s, TT\>21s, Fbg\< 2g/L), bleeding tendency, receiving thrombolytic or anticoagulant treatment, and a history of thrombosis or embolism within six months; 10. Patients at risk of gastrointestinal bleeding should not be enrolled, including: (1) patients with active digestive ulcer lesions and fecal occult blood (2+ or above); (2) patients with history of black stools and hematemesis within 3 months; (3) Patients with gastrointestinal fistula or perforation. 11. Participated in other medicine clinical trials within four weeks. 12. Weight less than 40kg. 13. Urine protein ≥2+ by urine routine