Study of Apatinib in Patients With Differentiated Thyroid Cancer

Inclusion Criteria:

1. Locally advanced or metastatic differentiated thyroid cancer (papillary, follicular, Hurthle cells, poorly differentiated carcinoma). At least one measurable lesion (helical CT scan long diameter ≥10mm, meet the requirements of the standard Response Evaluation Criteria In Solid Tumors（RESCIST） version 1.1);
2. Disease progression within 14 months before inclusion;

3. Subjects must be 131I-refractory / resistant as defined by at least one of the following;

   • Lesions that do not demonstrate iodine uptake on any radioiodine scan
   • Subjects received a single radioactive iodine therapy within 12 months (≥ 3.7 Giga Becquerel (GBq) [≥ 100 millicurie (mCi) ]) and target lesion disease progression
   • Every two radioactive iodine treatment interval <12 months, doses ≥ 3.7 GBq [≥100 mCi], disease progress more than 12 months after at least once iodine therapy;
   • Received a total dose of radioactive iodine therapy ≥ 22.2 GBq (≥ 600 mCi)
4. main organs function is normal;
5. Eastern Cooperative Oncology Group（ECOG）Performance Status（PS） :0-2;
6. An expected survival of ≥ 3 months;
7. Pregnancy test (serum or urine) has to be performed for woman of childbearing age within 7 days before enrolment and the test result must be negative. They shall take appropriate methods for contraception during the study until the 8th week post the last administration of study drug. For men, (previous surgical sterilization accepted), shall agree to take appropriate methods of contraception during the study until the 8th week post the last administration of study drug;
8. Patient has to voluntarily join the study and sign the Informed Consent Form for the study;

Exclusion Criteria:

1. Other thyroid cancer histological subtypes (such as medullary carcinoma, lymphoma or sarcoma);
2. Received VEGFR inhibitor treatment within 1 month;
3. Subjects with poor-controlled arterial hypertension (systolic blood pressure> 140 mmHg and diastolic blood pressure > 90 mm Hg) despite standard medical management; Coronary heart disease greater than ClassII; II-level arrhythmia (including QT interval prolongation, for man ≥ 450 ms, for woman ≥ 470 ms) together with Class II cardiac dysfunction;
4. Factors that could have an effect on oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction);
5. Subjects with high gastrointestinal bleeding risk, including the following conditions: local active ulcer lesions with positive fecal occult blood test (++); history of black stool, or vomiting blood in the past 3 months;
6. Abnormal Coagulation (INR>1.5、APTT>1.5 UNL), with tendency of bleed;
7. Received anti-thyroid cancer chemotherapy treatment (allows the use of low-dose chemotherapy with radiation sensitizer) or thalidomide(or derivative) therapy;
8. Pregnant or lactating women;
9. Other conditions regimented at investigators' discretion.