Precision Medicine Applied to Locally Advanced Thyroid Cancer Using Tumor-derived Organoids and In-vitro Sensitivity Testing: a Phase 2a, Single-center, Open-label, and Non-comparative Study

West China Hospital1 个研究点分布在 1 个国家目标入组 75 人开始时间: 2021年6月1日最近更新: 2024年12月5日

适应症

干预措施

试验速览

阶段: 2 期
状态: 招募中
发起方: West China Hospital
入组人数: 75
试验地点: 1
主要终点: Progress-free survival

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The current study aims to explore the potential advantages of anti-cancer therapy that is implemented based on drug sensitivity testing. This pertains to individuals with locally advanced thyroid cancer who have undergone conventional therapy in the past or unresectable patients .

详细描述

This research trial aims to determine the efficacy of organoid-guided targeted therapy for patients with locally advanced thyroid cancer. We will also investigate the variables affecting the effectiveness of targeted therapy for locally advanced thyroid cancer that is guided by organoids. Additionally, side effects related to the medication are also studied.

The following are the main questions that the trial seeks to address:

Can patients' tumor sizes be shrunk by taking medications that were found to be sensitive by organoid screening? Can patients' survival outcomes be improved by the medications that organoid screening found as sensitive? What aspects of the medications shown to be responsive by organoid screening are impacting their clinical efficacy? Is it possible for organoid-based drugs screening to guide treatment which lower surgical risk and make cancers that are now incurable into manageable ones? To ascertain the efficacy of the screened sensitive drugs in treating locally advanced thyroid cancer, researchers will measure the tumor size before and after taking the organoid-screened sensitive targeted drugs, assess the risk of radical resection, and document the survival outcomes of enrolled patients.

To further elucidate the parameters impacting the efficacy and prognosis, prognostic analysis based on clinical and pathological data, such as pathological type, gene mutation, age, tumor size, distant metastasis, and involvement of the trachea, esophagus, or major artery, will also be conducted.

The sample size for this study was determined based on the objective response rate (ORR) observed in our preliminary pilot study, which indicated an ORR of 22%. For papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), and poorly differentiated thyroid carcinoma (PDTC), we aimed to detect a treatment effect with a minimum ORR of 12%, consistent with results from the previous multicenter, randomized, double-blind, placebo-controlled phase 3 trial (DECISION). For anaplastic thyroid carcinoma (ATC) and medullary thyroid carcinoma (MTC), we aimed to detect a treatment effect with a minimum ORR of 1%, considered the threshold for clinical efficacy.

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Adult participants who have either been initially diagnosed with locally advanced thyroid cancer or have experienced persistent or recurrent thyroid cancer, including cervical nodal recurrence. Types of pathology include:
•Papillary thyroid carcinoma (PTC)
•Follicular thyroid carcinoma (FTC)
•Medullary thyroid carcinoma (MTC)
•Poorly differentiated thyroid carcinoma (PDTC)
•Anaplastic thyroid carcinoma (ATC)
•Evidence of extrathyroidal extension and/or locally invasive disease and deemed at risk for R2 resection by treating team on clinical and/or fiberoptic examination and/or radiographic evaluation in the primary or recurrent setting. Evidence of "at risk for R2 resection" includes:
•Vocal cord paralysis by fiberoptic examination
•Extrathyroid and/or extranodal extension on CT or MRI, including tracheal and/or laryngeal cartilage invasion, esophageal involvement, and/or involvement of perithyroid muscles (e.g. strap, sternocleidomastoid, inferior constrictor muscles) or bone involvement
•Extension into the mediastinum with visceral and/or vascular involvement
•Involvement of the carotid artery or other major vessel by 180 degrees or more
•Other factors that make the participant to be "at risk for R2 resection" may be allowed, after discussion with the study's principal investigator.
•There is at least one measurable lesion according to the Modified Response Evaluation Criteria in Solid Tumors (mRECIST).
•Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤
•Normal organ and bone marrow function.
•Adequate end-organ function (including bone marrow, coagulation, renal, liver and cardiac) 28 days prior to the study registration.
•Ability to swallow pills.
•Signed informed consent form.
•Expected survival time of more than 2 months.

排除标准

•Patients with contraindications specified in the drug instructions for the targeted drugs involved in the corresponding organoid drug sensitivity tests.
•Patients with incomplete clinical data.
•Patients with severe organ dysfunction, metabolic diseases, or other conditions significantly affecting survival.
•Other active malignant disease requiring therapy.
•Females who are pregnant or breastfeeding.
•Patients without target lesions.
•Patients deemed unsuitable for inclusion by the researchers.