Precision Medicine Applied to Locally Advanced or Metastatic Poorly Differentiated or Anaplastic Thyroid Cancer Using Tumor Derived Organoids and In-vitro Sensitivity Testing: a Phase 2, Single-center, Open-label, and Non-comparative Study
Overview
- Phase
- Phase 2
- Intervention
- Cyclophosphamide+Pemetrexed+5-Fluorouracil
- Conditions
- Locally Advanced Thyroid Gland Carcinoma
- Sponsor
- West China Hospital
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Objective response rate (ORR)
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
Brief Summary
The current study aims to explore the potential advantages of chemotherapy that is implemented based on drug sensitivity testing. This pertains to individuals with locally advanced or metastatic poorly differentiated or anaplastic 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 chemotherapy for patients with locally advanced or metastatic poorly differentiated or anaplastic thyroid cancer. Currently, there are numerous clinical trials evaluating various molecularly targeted therapies for refractory, poorly differentiated thyroid cancer. Preoperative personalized targeted neoadjuvant therapy has been established as a critical approach in managing advanced thyroid cancer. However, clinical trials investigating personalized chemotherapy to guide the treatment of thyroid cancer remain scarce. Tumor organoids represent a sophisticated three-dimensional pathological model that preserves the histological and molecular characteristics of the original tumor. These models can be utilized to assess the in vitro efficacy of multiple anticancer drugs. The investigators' objective is to validate the effectiveness and safety of selecting and processing chemotherapeutic agents through drug susceptibility testing, thereby ensuring pragmatic and precise treatment tailored to individual patients' needs. The investigators will also investigate the variables affecting the effectiveness of chemotherapy that is guided by organoids. Additionally, side effects related to the medication are also studied.
Investigators
Li Zhihui
Dean of the Thyroid Surgery Department
West China Hospital
Eligibility Criteria
Inclusion Criteria
- •At least 18 years of age on the day of signing informed consent
- •Cytologically confirmed thyroid neoplasm, including papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), poorly differentiated thyroid carcinoma (PDTC), medullary thyroid carcinoma (MTC), anaplastic thyroid carcinoma (ATC)
- •Patients defined as poorly differentiated iodine-refractory thyroid tumors with inoperable locally advanced disease or metastases. The primary tumor may or may not be removed, but the risk of aerodigestive compression or bleeding should be excluded.
- •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 (exclusive of complete encasement)
- •Other factors that make the participant to be "at risk for R2 resection" may be allowed, after discussion with the study's principal investigator
- •At least one measurable lesion as defined by RECIST v1.1
Exclusion Criteria
- •Radiographically identified following findings: intraluminal airway tumor, complete carotid encasement/infiltration
- •Patients with contraindications to the involved chemotherapy drugs (such as severe coagulopathy, severe liver function impairment, etc.)
- •Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment
- •Gastrointestinal malabsorption or any other condition that in the opinion of the investigator might affect the absorption of study drug
- •Patients with serious internal medicine underlying diseases, serious organ dysfunction, metabolic diseases or other diseases that seriously affect survival
- •If \> 1 + proteinuria on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein ≥1g/24 h will be ineligible
- •Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment
- •Active hemoptysis (bright red blood ≥ 1/2 teaspoon) or other uncontrolled bleeding within 21 days prior to the study registration
- •Arterial/venous thromboembolic events in the last 12 months Treatment within 30 days prior to study registration with anticoagulant or antiplatelet therapy, apart from aspirin 81 mg daily
- •Active uncontrolled systemic bacterial, viral, or fungal infection, or serious ongoing intercurrent illness
Arms & Interventions
Organoid-guided chemotherapeutic group
Patients who take the recommended chemothetapy drugs regularly based on sensitivity analysis.
Intervention: Cyclophosphamide+Pemetrexed+5-Fluorouracil
Organoid-guided chemotherapeutic group
Patients who take the recommended chemothetapy drugs regularly based on sensitivity analysis.
Intervention: Cyclophosphamide+Doxorubicin+5-Fluorouracil
Organoid-guided chemotherapeutic group
Patients who take the recommended chemothetapy drugs regularly based on sensitivity analysis.
Intervention: Vindesine + Cisplatin
Organoid-guided chemotherapeutic group
Patients who take the recommended chemothetapy drugs regularly based on sensitivity analysis.
Intervention: Doxorubicin + Cisplatin
Organoid-guided chemotherapeutic group
Patients who take the recommended chemothetapy drugs regularly based on sensitivity analysis.
Intervention: Doxorubicin + Cyclophosphamide + Cisplatin
Organoid-guided chemotherapeutic group
Patients who take the recommended chemothetapy drugs regularly based on sensitivity analysis.
Intervention: Docetaxel + Doxorubicin
Organoid-guided chemotherapeutic group
Patients who take the recommended chemothetapy drugs regularly based on sensitivity analysis.
Intervention: Paclitaxel + Carboplatin
Organoid-guided chemotherapeutic group
Patients who take the recommended chemothetapy drugs regularly based on sensitivity analysis.
Intervention: Paclitaxel + Doxorubicin
Organoid-guided chemotherapeutic group
Patients who take the recommended chemothetapy drugs regularly based on sensitivity analysis.
Intervention: Paclitaxel + Cisplatin
Organoid-guided chemotherapeutic group
Patients who take the recommended chemothetapy drugs regularly based on sensitivity analysis.
Intervention: Gemcitabine alone
Outcomes
Primary Outcomes
Objective response rate (ORR)
Time Frame: Every 2 months until 12 months
To evaluate the efficacy of chemotherapy per RECIST (standard Response Evaluation Criteria in Solid Tumors \[RECIST 1.1\]), the percentages of patients will report that fall into each of the four categories: complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD)
Secondary Outcomes
- Progression free survival (PFS)(Up to 2 years post treatment)
- Overall survival (OS)(Up to 2 years post treatment)
- R0/R1 resection rates(From the date of enrollment to the date of surgery, up to 12 months)
- Incidence of adverse events(Every 2 months until 12 months)
- Quality of life(Every 2 months until 12 months)