Study of Anlotinib Hydrochloride Capsules in the Treatment of Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Carcinoma

Inclusion Criteria:

• Patients voluntarily participate in this study, sign the informed consent form and hadgood compliance;
• Aged 18 ~ 70 years old; Eastern Cooperative Oncology Group Performance Status (ECOGPS) score: 0~1; more than 6 months of expected survival ;
• Histopathologically confirmed locally advanced or metastatic differentiated thyroidcancer, radiographically documented disease progression within 18 months of absence ofradioactive iodine (RAI) therapy;
• Meet any of the following:

1. Lesions were not iodine-avid: no RAI uptake was confirmed after RAI scan in thepresence of a low-iodine diet, adequate thyroid stimulating hormone (TSH)elevation (≥ 30 mIU/L). The definition of no iodine uptake:
2. no iodine uptake initially;
3. exist of iodine uptake initially while lost subsequently;
4. partially uptake;
5. progression disease despite iodine uptake.
6. The cumulative dose of RAI was ≥ 600 mCi or 22 GBq, with an interval of at least 3 months.
7. Radiographically documented disease progression within 18 months of RAI therapydespite the presence of iodine-131 affinity at the time of RAI therapy;

• At least one measurable lesion according to Response Evaluation Criteria in SolidTumours (RECIST) 1.1.
• Major organ functions meet the following criteria within 7 days prior to treatment:

1. Blood routine test criteria (14 days without blood transfusion):
2. Hemoglobin (HB) ≥ 85 g/L;
3. Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L;
4. Platelet (PLT) ≥ 80 × 10^9/L
5. Biochemical tests need to meet the following criteria:
6. Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN);
7. Alanine aminotransferase (ALT) and aspartate aminotransferase AST ≤ 2 .5×ULN, ALT and AS if liver metastases T ≤ 5 ×ULN;
8. Serum creatinine (Cr) ≤ 1 .5 ×ULN or creatinine clearance (CCr) ≥ 60 Ml/min;

• Females of childbearing potential should agree to use contraceptive measures (such asintrauterine device, contraceptives or condoms) during the study and within 6 monthsafter the end of the study; have a negative serum or urine pregnancy test within 7days before study enrollment and must be non-lactating patients; and males shouldagree to use contraceptive measures during the study and within 6 months after the endof the study period.

Exclusion Criteria:

• Comorbidities and medical history:

1. A history of or concurrent with other malignancies within the past 3 years.Patients were eligible if they had disease-free survival (DFS) for 5 consecutiveyears in other malignancies treated by single surgery; Cured cervical carcinomain situ, non-melanoma skin cancer and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor infiltrating basementmembrane)];
2. Major surgical treatment, open biopsy, or significant traumatic injury within 28days before the start of study treatment;
3. Subjects with any severe and/or uncontrolled illness, including:
4. Patients with ≥ grade 2 myocardial ischemia or myocardial infarction,arrhythmia (including Corrected QT Interval (QTc)≥450ms(male), QTc≥ 470ms(female)) and ≥ grade 2 congestive heart failure (NYHA classification);
5. Severe active or uncontrolled infection (≥ grade 2 infection according toCommon Terminology Criteria for Adverse Events (CTCAE) );
6. Renal failure requiring hemodialysis or peritoneal dialysis;

• Patients with concomitant diseases that seriously endanger the safety of patients oraffect the completion of the study, or patients who are considered to be unsuitablefor enrollment for other reasons according to the judgment of the investigators.
• patients with previous treatment with anlotinib hydrochloride capsules or similarvascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI)small molecule drugs, such as vandetanib, Cabozantinib, lenvatinib, sunitinib, orsorafenib, etc.;