NCT06482086

Efficacy of Organoid-Based Drug Screening to Guide Treatment for Locally Advanced Thyroid Cancer

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 75 (estimated)
• Sponsor: West China Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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 .

Detailed description

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. To achieve a one-sided 95% confidence interval (α = 0.05), the Clopper-Pearson method was used to calculate the confidence interval for a proportion. This method ensured that the lower bound of the 95% confidence interval would exceed the minimum ORR (12% for PTC, FTC, and PDTC; 1% for ATC and MTC). The calculation indicated that a total of 42 samples are needed for PTC, FTC, and PDTC, while 5 samples are required for both MTC and ATC. Considering a 10% dropout rate and an 80% success rate for organoid drug sensitivity tests, a total of 59 samples are needed for PTC, FTC, and PDTC, while 7 samples are required for both MTC and ATC.

Conditions

• Locally Advanced Thyroid Gland Carcinoma

Interventions

Type	Name	Description
DRUG	Anlotinib	8/10/12 mg qd, po. Stop the medication for one week after taking it for two weeks.
DRUG	Lenvatinib	8/12 mg qd, po.
DRUG	Sorafenib	0.4 g bid, po.
DRUG	Donafenib	0.3 g bid, po.
DRUG	Everolimus	10 mg qd, po.
DRUG	Apatinib	500 mg qd, po.
DRUG	Dabrafenib + Trametinib	Dabrafenib 150 mg bid, po+Trametinib 2 mg qd, po.
DRUG	Cabozantinib	Cabozantinib 60mg qd, po.
DRUG	Vandetanib	Vandetanib 300mg qd, po.
DRUG	Entrectinib	Entrectinib 600mg qd，po.
DRUG	Pralsetinib	400mg qd, po.
DRUG	Larotrectinib	100mg qd，po

Timeline

• Start date: 2021-06-01
• Primary completion: 2024-12-01
• Completion: 2025-12-01
• First posted: 2024-07-01
• Last updated: 2024-12-05

Locations

1 site across 1 country: China