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

Official title

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

Overview

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.

Interventions

• Drug 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).
• Drug AL2846 Placebo
  AL2846 Placebo without drug substance.

Primary outcome measures

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

Secondary outcome measures (6)

• Overall Survival (OS) [Time frame: 34 months]
• Compare the Progression - Free Survival (PFS) evaluated by the researchers in the treatment group and the placebo group [Time frame: 34 months]
• Compare the objective response rate (ORR) between the treatment group and the placebo group [Time frame: 34 months]
• Compare the Disease Control Rate (DCR) between the treatment group and the placebo group [Time frame: 34 months]
• Compare the Duration of Response (DOR) between the treatment group and the placebo group [Time frame: 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 [Time frame: 34 months]

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 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.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 35 centers

• The Second Hospital Of Anhui Medical University — Hefei
• cancer hospital Chinese academy of medical sciences — Beijing
• The Southwest Hospital of Amu — Chongqing
• Fujian Medical University Union Hospital — Fuzhou
• Gansu Provincial Cancer Hospital — Lanzhou
• Sun Yat-sen University Cancer Center — Guangzhou
• Affiliated Hospital of Guilin Medical University — Gui'lin
• The Second Affiliated Hospital Of GXUST — Liuzhou
• … and 27 more centers

Identifiers

NCT: NCT06860971 · AL2846-III-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗