A Randomized, Double-Blind, Multicenter Phase III Clinical Trial Evaluating AL2846 Capsule Versus Placebo in Patients With Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Carcinoma Who Failed Prior VEGFR-Targeted Therapy
This study aims to demonstrate that, in subjects with locally advanced or metastatic iodine - refractory differentiated thyroid cancer who have failed previous VEGFR - targeted therapy, AL2846 can significantly prolong progression - free survival (PFS) compared with placebo.
• Participants voluntarily join the study, sign the informed consent form, and demonstrate good compliance.
• Histologically or cytologically confirmed locally advanced or metastatic differentiated thyroid carcinoma (DTC).
• Age: 18 years ≤ age \<75 years (calculated based on the date of signing the informed consent form).
• Eastern Cooperative Oncology Group (ECOG) performance status score: 0-1.
• Anticipated survival \>12 weeks.
• At least one measurable lesion confirmed by RECIST 1.1 criteria.
• Disease progression (per RECIST 1.1) after receiving no more than 2 lines (no more than 3 types) lines of Vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR TKI) therapy
• Confirmed iodine-refractory status, defined by \*\*one or more\*\* of the following:
‣ Lesions show no iodine uptake on post-Iodine-131 therapy whole-body scan and are unlikely to benefit from further Iodine-131 therapy.
⁃ Previously iodine-avid lesions progressively lose iodine uptake after Iodine-131 therapy.
⁃ Mixed iodine-avid and non-iodine-avid lesions in the same patient with no biochemical response.
⁃ Iodine-avid lesions with disease progression (radiologically confirmed) within 12 months.
⁃ Cumulative Iodine-131 dose ≥600 mCi (22 GBq) with no disease response (radiologically confirmed).
• Thyroid stimulating hormone (TSH) ≤0.5 mIU/L under TSH-suppressive therapy.
• Laboratory parameters meeting the following criteria:
‣ Hemoglobin (HGB) ≥90 g/L.
⁃ Absolute neutrophil count (NEUT) ≥1.5×10⁹/L.
⁃ Platelet count (PLT) ≥90×10⁹/L.
⁃ Total bilirubin (TBIL) ≤1.5×ULN.
⁃ Alanine aminotransferase (ALT) and Aspartate transferase (AST) ≤2.5×ULN.
⁃ Creatinine clearance (CCR) ≥50 mL/min.
⁃ Prothrombin time (PT), Activated partial thromboplastin time (APTT), and International Normalized Ratio (INR) ≤1.5×ULN (without anticoagulation therapy).
⁃ Serum albumin (ALB) ≥30 g/L (no albumin infusion within 7 days prior to screening).
• For participants of childbearing potential: Agreement to use effective contraception during the study and for 6 months after study completion. Females must have a negative serum/urine pregnancy test within 7 days before enrollment; males must agree to effective contraception during and for 6 months post-study.