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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат AL2846 Capsules
  AL2846 Capsule is a multi - target tyrosine kinase inhibitor, which has significant inhibitory effects on c-Mesenchymal-epithelial transition factor (c - MET), stem cell factor receptor (c - KIT), VEGFR1 and Ret Proto-Oncogene (RET).
• Препарат AL2846 Placebo
  AL2846 Placebo without drug substance.

Первичные конечные точки

• Progression - Free Survival (PFS) evaluated by the Independent Review Committee (IRC) [Срок оценки: 34 months]

Вторичные конечные точки (6)

• Overall Survival (OS) [Срок оценки: 34 months]
• Compare the Progression - Free Survival (PFS) evaluated by the researchers in the treatment group and the placebo group [Срок оценки: 34 months]
• Compare the objective response rate (ORR) between the treatment group and the placebo group [Срок оценки: 34 months]
• Compare the Disease Control Rate (DCR) between the treatment group and the placebo group [Срок оценки: 34 months]
• Compare the Duration of Response (DOR) between the treatment group and the placebo group [Срок оценки: 34 months]
• Evaluate the safety of AL2846 capsules compared with placebo in subjects with locally advanced or metastatic iodine - refractory differentiated thyroid cancer who have failed previous VEGFR - targeted therapy [Срок оценки: 34 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 35 центров

• The Second Hospital Of Anhui Medical University — Хэфэй
• cancer hospital Chinese academy of medical sciences — Пекин
• The Southwest Hospital of Amu — Чунцин
• Fujian Medical University Union Hospital — Фучжоу
• Gansu Provincial Cancer Hospital — Lanzhou
• Sun Yat-sen University Cancer Center — Гуанчжоу
• Affiliated Hospital of Guilin Medical University — Gui'lin
• The Second Affiliated Hospital Of GXUST — Liuzhou
• … и ещё 27 центров

Идентификаторы

NCT: NCT06860971 · AL2846-III-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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