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 .
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
75
8/10/12 mg qd, po. Stop the medication for one week after taking it for two weeks.
8/12 mg qd, po.
0.4 g bid, po.
West China hospital
Chengdu, Sichuan, China
RECRUITINGObjective response rate
ORR is defined as the percentage of patients who achieve a response, which can either be complete response (complete disappearance of lesions) or partial response (reduction in the sum of maximal tumor diameters by at least 30% or more)
Time frame: Every 8 weeks until progression up to 3 years
Progress-free survival
PFS is defined as the time from the administration of the first dose to first disease progression or death.
Time frame: Every 8 weeks until progression or death up to 3 years
Overall R0/R1 resection rate
Defined as the proportion of patients who undergo R0/R1 resection among all patients.
Time frame: Up to 36 months.
Overall Survival
OS is defined as the time from the administration of the first dose to death.
Time frame: Up to 36 months.
Change in Surgical complexity and morbidity score (SCMS)
The Thyroid Neck Group Morbidity Complexity Scoring and MGH/MEE-MSK-MD Anderson (MMM) Surgical Morbidity Complexity Score (SMCS) are incorporated, specifying on scale with 5 levels of complexity and morbidity of the surgery \[mild (level 0), moderate (level 1), severe (level 2), very severe (level 3), and unresectable (level 4)\]. The surgical morbidity/complexity scores will be collected at enrollment, prior to surgery, and based on intraoperative findings. The change in SCMS will be reported as the median SCMS value. Determined by structures requiring resection, the score takes into account preoperatively radiographically defined structures judged to be requiring resection with surgical complexity of the given resection/potential for complications, and expected patient morbidity/change of function from the resection.
Time frame: Up to 36 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
0.3 g bid, po.
10 mg qd, po.
500 mg qd, po.
Dabrafenib 150 mg bid, po+Trametinib 2 mg qd, po.
Cabozantinib 60mg qd, po.
Vandetanib 300mg qd, po.
Entrectinib 600mg qd，po.
400mg qd, po.
100mg qd，po
Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v 5.0
Time frame: Up to 36 months