Spanish Study for Molecular Characterization of Thyroid Carcinoma

Active, not recruiting

• Conditions: Medullary Thyroid Carcinoma; Differentiated Thyroid Carcinoma
• Interventions: Other: Immunohistochemistry (IHC); Other: Fluorescence In-Situ Hybridization (FISH); Other: Oncomine Focus Assay Platform with 52 genes

• Registration Number: NCT04970134
• Lead Sponsor: Grupo Español de Tratamiento de Tumores de Cabeza y Cuello

Brief Summary

This project is a retrospective observational study based on the molecular characterization of a Spanish population of patients with refractory radio-iodine differentiated thyroid cancer (DTC) and medullary thyroid carcinoma (MTC) with advanced and / or metastatic disease undergoing systemic treatment, or under clinical observation.

Three diagnostic techniques will be performed on formalin-fixed paraffin embedded (FFPE) tumor samples from the study population: immunohistochemistry (IHC), fluorescence by in situ hybridization (FISH) as well as Next-Generation Sequencing (NGS) techniques by means of DNA and RNA analysis (Ion Platform Torrent - Oncomine Focus Assay, 52 gene detection). The results of each patient will be compared in order to correlate the results of each method.

Detailed Description

Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) techniques will be carried out to identify NTRK and RET alterations. NTRK alterations will be identified using IHC techniques (NTRK over-expression), and FISH techniques (break-apart method). RET alterations will also be identified using the FISH technique (break-apart method).

At the same time, DNA and RNA will be extracted for sequencing techniques using the Oncomine Focus Assay platform, including 52 genes (35 Hotspot genes, 19 Copy number variants and 23 Gene fusions, including NTRK and RET).

Study Timeline

• Study Start: 2021-06-14
• Study First Submitted: 2021-07-16
• Study First Submitted QC: 2021-07-16
• Study First Posted: 2021-07-21
• Primary Completion: 2023-01-25
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-19
• Last Update Posted: 2023-04-20
• Study Completion: 2024-03

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

1. All participants must be over 18 years old
2. Obtaining the informed consent signed by the patient or his legal representative.
3. Have a paraffinized tumor sample available for analysis in the central laboratory, preferably from total thyroidectomy.
4. Life expectancy greater than 6 months.
5. Thyroid carcinoma with a date of initial histological diagnosis before January 1, 2021 of the types:

(1) Differentiated thyroid carcinoma (DTC) refractory to radio-iodine, including papillary carcinomas, follicular carcinomas, poorly differentiated thyroid carcinomas, and the corresponding different variants. The radio-refractoriness criteria will be defined by medical criteria and / or by decision of the tumor committee (depending on the organization of each hospital) or (2) Medullary thyroid carcinoma (MTC). 6. Potential candidate patients must meet at least one of the following premises:

1. Patients with advanced / metastatic disease in wait & see follow-up.
2. Patients with advanced / metastatic disease currently undergoing treatment or in progression to any type of multikinase inhibitor, such as, for example: sorafenib, lenvatinib, cabozantinib, axitinib, vandetanib, ...
3. Patients with advanced / metastatic disease under treatment or in progression to treatments that inhibit immune checkpoints (anti programed death (PD-1) or its ligand (PD-L1), anti Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), others) or who are participating in clinical trial regimen. They must be patients who have previously progressed to multikinase inhibitors.

Exclusion Criteria

1. Patients affected by other malignant histologies not mentioned in the previous section (eg melanoma, lymphoma, sarcoma, ...) or benign tumors exclusively of the thyroid gland.
2. Patients with radioiodine sensitive differentiated thyroid carcinoma or anaplastic thyroid carcinomas.
3. Patients with refractory radioiodine differentiated thyroid carcinoma and advanced medullary thyroid carcinomas with the possibility of local ablative treatment with radical or curative intent (surgery, radiosurgery, radio-ablation, ...).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Thyroid carcinoma	Oncomine Focus Assay Platform with 52 genes	Advanced and / or metastatic thyroid carcinoma with initial histological diagnosis date before January 1, 2021 of the types: Differentiated thyroid carcinoma (DTC) refractory to radio-iodine, including papillary carcinomas, follicular carcinomas, poorly differentiated carcinomas of the thyroid and the different corresponding variants. Medullary thyroid carcinoma (MTC).
Thyroid carcinoma	Immunohistochemistry (IHC)	Advanced and / or metastatic thyroid carcinoma with initial histological diagnosis date before January 1, 2021 of the types: Differentiated thyroid carcinoma (DTC) refractory to radio-iodine, including papillary carcinomas, follicular carcinomas, poorly differentiated carcinomas of the thyroid and the different corresponding variants. Medullary thyroid carcinoma (MTC).
Thyroid carcinoma	Fluorescence In-Situ Hybridization (FISH)	Advanced and / or metastatic thyroid carcinoma with initial histological diagnosis date before January 1, 2021 of the types: Differentiated thyroid carcinoma (DTC) refractory to radio-iodine, including papillary carcinomas, follicular carcinomas, poorly differentiated carcinomas of the thyroid and the different corresponding variants. Medullary thyroid carcinoma (MTC).

Primary Outcome Measures

Name	Time	Method
Progression free survival (PFS)	Throughout the study. Approximately 2 years	Time from start of data capture (retrospectively) to progression disease. Patients may be stratified in subgroups attending to their histologic subtype and molecular genetic profile.
Objective response rate	Throughout the study. Approximately 2 years	Response to systemic treatments received if available. Patients may be stratified in subgroups attending to their histologic subtype and molecular genetic profile.
Overall survival (OS)	Throughout the study. Approximately 2 years	Time from start of data capture (retrospectively) to death. Patients may be stratified in subgroups attending to their histologic subtype and molecular genetic profile.
Prevalence of genetic alterations	Throughout the study. Approximately 2 years	Frequency of genetic alterations in the study population determined by the molecular genetic interventions: IHC, FISH and NGS

Trial Locations

Locations (12)

Institut Català d'Oncologia Girona - ICO Girona; 🇪🇸 Girona, Spain

Hospital universitario Marqués de Valdecilla; 🇪🇸 Santander, Spain

Consorci Corporació Sanitària Parc Taulí de Sabadell; 🇪🇸 Sabadell, Barcelona, Spain

Hospital Universitario Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Clínic de Barcelona; 🇪🇸 Barcelona, Spain

Hospital Universitario Miguel Servet; 🇪🇸 Zaragoza, Spain

Hospital Universitario Ramón y Cajal; 🇪🇸 Madrid, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Fundació Althaia; 🇪🇸 Manresa, Barcelona, Spain

Hospital General Universitario de Valencia; 🇪🇸 Valencia, Spain

Hospital Universitario y Politécnico La Fe; 🇪🇸 Valencia, Spain

Hospital Universitario Durán i Reinals; 🇪🇸 L'Hospitalet De Llobregat, Barcelona, Spain