A Study of AL2846 Capsule Versus Placebo in the Treatment of Advanced Radioiodine-Refractory Differentiated Thyroid Carcinoma

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

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 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:

  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.

Conditions2

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