Clinical trial NCT06482086: Efficacy of Organoid-Based Drug Screening to Guide Treatment for Locally Advanced Thyroid Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Locally Advanced Thyroid Gland Carcinoma
Lead sponsor: West China Hospital
Sponsor class: OTHER
First posted: 2024-07-01
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Primary outcomes:
measure: Objective response rate
timeFrame: Every 8 weeks until progression up to 3 years
measure: Progress-free survival
timeFrame: Every 8 weeks until progression or death up to 3 years
measure: Overall R0/R1 resection rate
timeFrame: Up to 36 months.
Secondary outcomes:
measure: Overall Survival
timeFrame: Up to 36 months.
measure: Change in Surgical complexity and morbidity score (SCMS)
timeFrame: Up to 36 months
measure: Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v 5.0
timeFrame: Up to 36 months
Other outcomes:
Locations:
city: Chengdu
country: China
facility: West China hospital
state: Sichuan
Study officials:
affiliation: West China Hospital
name: Zhihui Li, Professor
role: STUDY_DIRECTOR
References: