a study of al2846 capsule versus placebo in the treatment of advanced radioiodine-refractory differentiated thyroid carcinoma

Conditions: Thyroid Cancer

Summary: 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.


Eligibility criteria:
inclusion criteria: * 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 \*\*1 or 2 prior lines of epidermal growth factor receptor tyrosine kinase inhibitor (egfr tki) therapy * confirmed iodine-refractory status, defined by \*\*one or more\*\* of the following: 1. lesions show no iodine uptake on post-iodine-131 therapy whole-body scan and are unlikely to benefit from further iodine-131 therapy. 2. previously iodine-avid lesions progressively lose iodine uptake after iodine-131 therapy. 3. mixed iodine-avid and non-iodine-avid lesions in the same patient with no biochemical response. 4. iodine-avid lesions with disease progression (radiologically confirmed) within 12 months. 5. 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: 1. hemoglobin (hgb) ≥90 g/l. 2. absolute neutrophil count (neut) ≥1.5×10⁹/l. 3. platelet count (plt) ≥90×10⁹/l. 4. total bilirubin (tbil) ≤1.5×uln. 5. alanine aminotransferase (alt) and aspartate transferase (ast) ≤2.5×uln. 6. creatinine clearance (ccr) ≥50 ml/min. 7. prothrombin time (pt), activated partial thromboplastin time (aptt), and international normalized ratio (inr) ≤1.5×uln (without anticoagulation therapy). 8. 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. exclusion criteria: * patients with undifferentiated thyroid carcinoma or medullary thyroid carcinoma; * patients who have had or currently have other malignancies. the following two situations are eligible for enrollment: other malignancies treated with a single surgery and achieving a disease - free survival (dfs) of 5 consecutive years; cured cervical carcinoma in situ, non - melanoma skin cancer, and superficial bladder tumors \[ta (non - invasive tumor), tis (carcinoma in situ), and t1 (tumor invading the basement membrane)\]. * those with multiple factors affecting oral medications (such as difficulty in swallowing, chronic diarrhea, and intestinal obstruction, etc.); * adverse reactions from previous treatments have not recovered to a common terminology criteria for adverse events (ctcae) version 5.0. grade score ≤ 1, except for grade 2 alopecia, grade 2 peripheral neuropathy, grade 2 anemia, non - clinically significant and asymptomatic grade 2 laboratory abnormalities, and hypothyroidism stabilized by hormone replacement therapy, and other toxicities judged by the investigator to have no safety risks. * known allergy to the excipient components of the study drug. * subjects who have participated in and used other anti - tumor clinical trial drugs within 4 weeks before randomization. * as judged by the investigator, there are situations that seriously endanger the safety of the subject or affect the subject's completion of the study.