Trial Title:
Efficacy of Organoid-Based Drug Screening to Guide Treatment for Locally Advanced Thyroid Cancer
NCT ID:
NCT06482086
Condition:
Locally Advanced Thyroid Gland Carcinoma
Conditions: Official terms:
Thyroid Neoplasms
Thyroid Diseases
Everolimus
Sorafenib
Apatinib
Lenvatinib
Trametinib
Dabrafenib
Pralsetinib
Entrectinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Anlotinib
Description:
8/10/12 mg qd, po. Stop the medication for one week after taking it for two weeks.
Arm group label:
Organoid-guided targeted therapeutic group
Intervention type:
Drug
Intervention name:
Lenvatinib
Description:
8/12 mg qd, po.
Arm group label:
Organoid-guided targeted therapeutic group
Intervention type:
Drug
Intervention name:
Sorafenib
Description:
0.4 g bid, po.
Arm group label:
Organoid-guided targeted therapeutic group
Intervention type:
Drug
Intervention name:
Donafenib
Description:
0.3 g bid, po.
Arm group label:
Organoid-guided targeted therapeutic group
Intervention type:
Drug
Intervention name:
Everolimus
Description:
10 mg qd, po.
Arm group label:
Organoid-guided targeted therapeutic group
Intervention type:
Drug
Intervention name:
Apatinib
Description:
500 mg qd, po.
Arm group label:
Organoid-guided targeted therapeutic group
Intervention type:
Drug
Intervention name:
Dabrafenib + Trametinib
Description:
Dabrafenib 150 mg bid, po+Trametinib 2 mg qd, po.
Arm group label:
Organoid-guided targeted therapeutic group
Intervention type:
Drug
Intervention name:
Cabozantinib
Description:
Cabozantinib 60mg qd, po.
Arm group label:
Organoid-guided targeted therapeutic group
Intervention type:
Drug
Intervention name:
Vandetanib
Description:
Vandetanib 300mg qd, po.
Arm group label:
Organoid-guided targeted therapeutic group
Intervention type:
Drug
Intervention name:
Entrectinib
Description:
Entrectinib 600mg qd，po.
Arm group label:
Organoid-guided targeted therapeutic group
Intervention type:
Drug
Intervention name:
Pralsetinib
Description:
400mg qd, po.
Arm group label:
Organoid-guided targeted therapeutic group
Intervention type:
Drug
Intervention name:
Larotrectinib
Description:
100mg qd，po
Arm group label:
Organoid-guided targeted therapeutic group
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
1. 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:
1. Papillary thyroid carcinoma (PTC)
2. Follicular thyroid carcinoma (FTC)
3. Medullary thyroid carcinoma (MTC)
4. Poorly differentiated thyroid carcinoma (PDTC)
5. Anaplastic thyroid carcinoma (ATC)
-
2. 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:
1. Vocal cord paralysis by fiberoptic examination
2. 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
3. Extension into the mediastinum with visceral and/or vascular involvement
4. Involvement of the carotid artery or other major vessel by 180 degrees or more
5. Other factors that make the participant to be "at risk for R2 resection" may be
allowed, after discussion with the study's principal investigator.
-
3. There is at least one measurable lesion according to the Modified Response
Evaluation Criteria in Solid Tumors (mRECIST).
-
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
-
5. Normal organ and bone marrow function.
-
6. Adequate end-organ function (including bone marrow, coagulation, renal, liver
and cardiac) 28 days prior to the study registration.
-
7. Ability to swallow pills.
-
8. Signed informed consent form.
-
9. Expected survival time of more than 2 months.
Exclusion Criteria:
-
1. Patients with contraindications specified in the drug instructions for the
targeted drugs involved in the corresponding organoid drug sensitivity tests.
-
2. Patients with incomplete clinical data.
-
3. Patients with severe organ dysfunction, metabolic diseases, or other conditions
significantly affecting survival.
-
4. Other active malignant disease requiring therapy.
-
5. Females who are pregnant or breastfeeding.
-
5. Patients without target lesions.
-
6. Patients deemed unsuitable for inclusion by the researchers.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
West China hospital
Address:
City:
Chengdu
Zip:
610041
Country:
China
Status:
Recruiting
Contact:
Last name:
Zhihui Li, Professor
Phone:
18980602027
Phone ext:
+86
Email:
rockoliver@vip.sina.com
Start date:
June 1, 2021
Completion date:
December 1, 2025
Lead sponsor:
Agency:
West China Hospital
Agency class:
Other
Source:
West China Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06482086
