Clinical trial NCT06860971: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Thyroid Cancer
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-03-06
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Progression - Free Survival (PFS) evaluated by the Independent Review Committee (IRC)
timeFrame: 34 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 34 months
measure: Compare the Progression - Free Survival (PFS) evaluated by the researchers in the treatment group and the placebo group
timeFrame: 34 months
measure: Compare the objective response rate (ORR) between the treatment group and the placebo group
timeFrame: 34 months
measure: Compare the Disease Control Rate (DCR) between the treatment group and the placebo group
timeFrame: 34 months
measure: Compare the Duration of Response (DOR) between the treatment group and the placebo group
timeFrame: 34 months
measure: 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
timeFrame: 34 months
Other outcomes:
Locations:
city: Hefei
country: China
facility: The Second Hospital Of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: cancer hospital Chinese academy of medical sciences
state: Beijing
city: Chongqing
country: China
facility: The Southwest Hospital of Amu
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Lanzhou
country: China
facility: Gansu Provincial Cancer Hospital
state: Gansu
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Gui'lin
country: China
facility: Affiliated Hospital of Guilin Medical University
state: Guangxi
city: Liuzhou
country: China
facility: The Second Affiliated Hospital Of GXUST
state: Guangxi
city: Hainan
country: China
facility: The First Affiliated Hospital of Hainan Medical University
state: Haikou
city: Cangzhou
country: China
facility: CangZhou Center Hospital
state: Hebei
city: Harbin
country: China
facility: Harbin Medical University cancer hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Nanjing First Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of XuZhou Medical University
state: Jiangsu
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Nanchang
country: China
facility: JIANGXI cancer hospital
state: Jiangxi
city: Changchun
country: China
facility: China-Japan Union Hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: JILIN cancer hospital
state: Jilin
city: Shengyang
country: China
facility: Liaoning Cancer Hospital
state: Liaoning
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiao Tong University
state: Shaani
city: Xi'an
country: China
facility: Xijing Hospital
state: Shaanxi
city: Xi'an
country: China
facility: Shaanxi Provincial People'S Hospital
state: Shaanxi
city: Jinan
country: China
facility: The Second Hospital of Shandong University
state: Shandong
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Weifang
country: China
facility: Weifang people's Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Jiaotong University School of Medicine, Tongji Hospital
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital of Si chuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Cancer Hospital Airport Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute&Hospital
state: Tianjin
city: Ürümqi
country: China
facility: Affiliated Tumor Hospital of Xinjiang Medical University
state: Xinjiang
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
References: