Treatment of advanced thyroid cancer with AL2846 capsules

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

This study is testing if AL2846 capsules can help people with advanced thyroid cancer that hasn't responded to other treatments live longer without their cancer getting worse.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 144 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. (Industry-sponsored)
• Locations: 35 sites (Hefei, Anhui and 34 other locations)
• Trial ID: NCT06860971 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of AL2846 capsules in patients with advanced or metastatic differentiated thyroid carcinoma that is resistant to iodine treatment and has not responded to previous VEGFR-targeted therapies. Participants will be randomly assigned to receive either AL2846 or a placebo, and the primary goal is to determine if AL2846 can significantly extend progression-free survival compared to the placebo. The study involves patients aged 18 to 75 with specific eligibility criteria, including confirmed iodine-refractory status and measurable disease.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with advanced iodine-refractory differentiated thyroid carcinoma who have previously failed VEGFR-targeted therapy.

Not a fit: Patients with thyroid cancer that is not iodine-refractory or those who have not undergone prior VEGFR-targeted therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new option for patients with advanced thyroid cancer who have limited treatment alternatives.

How similar studies have performed: Other studies have explored treatments for iodine-refractory thyroid cancer, but the specific approach with AL2846 is novel.

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:

  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.

Where this trial is running

Hefei, Anhui and 34 other locations

• The Second Hospital Of Anhui Medical University — Hefei, Anhui, China (Not_yet_recruiting)
• cancer hospital Chinese academy of medical sciences — Beijing, Beijing Municipality, China (Not_yet_recruiting)
• The Southwest Hospital of Amu — Chongqing, Chongqing Municipality, China (Not_yet_recruiting)
• Fujian Medical University Union Hospital — Fuzhou, Fujian, China (Not_yet_recruiting)
• Gansu Provincial Cancer Hospital — Lanzhou, Gansu, China (Not_yet_recruiting)
• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Not_yet_recruiting)
• Affiliated Hospital of Guilin Medical University — Gui'lin, Guangxi, China (Not_yet_recruiting)
• The Second Affiliated Hospital Of GXUST — Liuzhou, Guangxi, China (Not_yet_recruiting)
• The First Affiliated Hospital of Hainan Medical University — Hainan, Haikou, China (Not_yet_recruiting)
• CangZhou Center Hospital — Cangzhou, Hebei, China (Not_yet_recruiting)
• Harbin Medical University cancer hospital — Harbin, Heilongjiang, China (Not_yet_recruiting)
• Henan Cancer Hospital — Zhengzhou, Henan, China (Not_yet_recruiting)
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Not_yet_recruiting)
• Hunan Cancer Hospital — Changsha, Hunan, China (Not_yet_recruiting)
• Nanjing First Hospital — Nanjing, Jiangsu, China (Not_yet_recruiting)
• The Affiliated Hospital of XuZhou Medical University — Xuzhou, Jiangsu, China (Not_yet_recruiting)
• The Second Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China (Not_yet_recruiting)
• JIANGXI cancer hospital — Nanchang, Jiangxi, China (Not_yet_recruiting)
• China-Japan Union Hospital of Jilin University — Changchun, Jilin, China (Not_yet_recruiting)
• JILIN cancer hospital — Changchun, Jilin, China (Not_yet_recruiting)
• Liaoning Cancer Hospital — Shengyang, Liaoning, China (Not_yet_recruiting)
• The First Affiliated Hospital of Xi'an Jiao Tong University — Xi'an, Shaani, China (Not_yet_recruiting)
• Xijing Hospital — Xi'an, Shaanxi, China (Not_yet_recruiting)
• Shaanxi Provincial People'S Hospital — Xi'an, Shaanxi, China (Not_yet_recruiting)
• The Second Hospital of Shandong University — Jinan, Shandong, China (Not_yet_recruiting)
• Shandong Cancer Hospital — Jinan, Shandong, China (Not_yet_recruiting)
• Weifang people's Hospital — Weifang, Shandong, China (Not_yet_recruiting)
• Shanghai Sixth People's Hospital — Shanghai, Shanghai Municipality, China (Not_yet_recruiting)
• Shanghai Jiaotong University School of Medicine, Tongji Hospital — Shanghai, Shanghai Municipality, China (Not_yet_recruiting)
• West China Hospital of Si chuan University — Chengdu, Sichuan, China (Not_yet_recruiting)
• Tianjin Cancer Hospital Airport Hospital — Tianjin, Tianjin Municipality, China (Not_yet_recruiting)
• Tianjin Medical University Cancer Institute&Hospital — Tianjin, Tianjin Municipality, China (Recruiting)
• Affiliated Tumor Hospital of Xinjiang Medical University — Ürümqi, Xinjiang, China (Not_yet_recruiting)
• Yunnan Cancer Hospital — Kunming, Yunnan, China (Not_yet_recruiting)
• Zhejiang Cancer Hospital — Hangzhou, Zhejiang, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Feng Shi, Master

Conditions Thyroid Cancer