A Multicenter, Phase II Clinical Trial to Evaluate the Efficacy and Safety of ST-1898 Tablets in Patients With Locally Advanced or Metastatic RAIR-DTC After Failure of at Least First-line TKI Systemic Therapy
ST-1898, a multi-targeted tyrosine kinase inhibitor, has demonstrated strong inhibitory activity for VEGFR2, c-MET, AXL, PDGFRA, RET, KIT, etc. The primary purpose of this study is to evaluate the efficacy of ST-1898 tablets in patients with locally advanced or metastatic RAIR-DTC after failure of at least first-line TKI systemic therapy. All subjects will receive ST-1898 180 mg orally once daily until disease progression or intolerable toxicity.
⁃ Age \>= 18 years
⁃ Life expectancy of twelve weeks or more
⁃ Histologically or cytologically confirmed locally advanced or metastatic DTC that cannot be removed by surgery or radiotherapy, including papillary thyroid cancer, follicular thyroid cancer, hurthle cell thyroid cancer or poorly differentiated thyroid cancer.
⁃ At least one measurable lesion according to RECIST 1.1
⁃ Participants must be radioiodine (131I)- refractory / resistant as defined by at least one of the following criteria:
∙ One or more measurable lesions that do not demonstrate iodine uptake on any radioiodine scan.
‣ One or more measurable lesions that has progressed as per RECIST 1.1 within 14 months of 131I therapy（3.7\
• 4 GBq or100\
⁃ 200 mCi）,despite demonstration of radioiodine avidity at the time of that treatment by pre- or post-treatment scanning.
‣ Cumulative activity of 131I of \> 22 GBq or 600 mCi, with the last dose administered at least 6 months prior to study entry
⁃ Patients with DTC must have progressed on after at least first-line TKI systemic therapy.
⁃ Tumor tissue sections available (Formalin fixed and paraffin-embedded wax chunks of tumor tissue or unstained specimen).
⁃ Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
⁃ TSH-suppression therapy is well tolerated with thyroid stimulating hormone (TSH) \< 0.5 mU/L;
‣ The patient has adequate organ and bone marrow function as follows:
• Adequate bone marrow function (without transfusion or growth factor support within 2 weeks): hemoglobin ≥ 90 g/L, absolute neutrophil count (ANC) ≥ 1.5 ×109/L and platelets ≥ 90 × 109/L;
∙ Adequate liver function: Bilirubin ≤ 1.5 × upper limit of normal (ULN); Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 3 × ULN (≤ 5 × ULN if participant has liver metastases);
∙ Adequate renal function: Serum creatinine ≤1.5 ×ULN or creatinine clearance≥50 mL/min per the Cockcroft-Gault formula;
∙ Adequate blood coagulation function: International Normalized Ratio (INR) ≤ 1.5 and Activated partial thromboplastin time (APTT) ≤1.5 ULN（except for the prophylactic use of anticoagulants）
∙ Adequate cardiac function: Left ventricular ejection fraction (LVEF) ≥50%;
∙ Participants having≤ 1 + proteinuria or ≥2+ proteinuria with urine protein \< 1 g/24 hour (h).
‣ Ability to understand and the willingness to sign a written informed consent document. The results of routine examination during the corresponding window period before screening are acceptable.
‣ Women with child-bearing potential and men must agree to use adequate contraception (e.g., hormonal contraceptives, male or female condom, or abstinence) during the course of the study and for at least 3 months following the last dose of study drug. Women with childbearing potential must have a negative serum pregnancy test within 7 days before first study treatment.