Spanish Study for Molecular Characterization of Thyroid Carcinoma

Medullary Thyroid Carcinoma Clinical Trial

— MOLTHY  

Official title:

Spanish Observational Study for MOLecular Characterization of THYroid Carcinoma MOLTHY Project

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04970134
• Other study ID #: TTCC-2020-02
• Status: Active, not recruiting
• Start date: June 14, 2021
• Est. completion date: March 2024

Study information

• Verified date: April 2023
• Source: Grupo Español de Tratamiento de Tumores de Cabeza y Cuello
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: March 2024
• Est. primary completion date: January 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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, ...).

Related Conditions & MeSH terms

• Carcinoma
• Differentiated Thyroid Carcinoma
• Medullary Thyroid Carcinoma
• Thyroid Diseases
• Thyroid Neoplasms

Intervention

Other:
• Immunohistochemistry (IHC)
VENTANA pan-TRK technique (EPR17341) Assay, with Optiview DAB-detection kit and Optiview amplification kit. Using FFPE slices
• Fluorescence In-Situ Hybridization (FISH)
FISH using FFPE slices for genes: Neurotrophic tyrosin kinase 1 (NTRK1), Neurotrophic tyrosin kinase 3 (NTRK3) and rearranged during transfection (RET)
• Oncomine Focus Assay Platform with 52 genes
Oncomine Focus Assay Platform with 52 genes (35 Hotspot genes, 19 Copy number variants and 23 Gene fusions). Using FFPE slices

Locations

Country	Name	City	State
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Institut Català d'Oncologia Girona - ICO Girona	Girona
Spain	Hospital Universitario Durán i Reinals	L'Hospitalet De Llobregat	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Fundació Althaia	Manresa	Barcelona
Spain	Consorci Corporació Sanitària Parc Taulí de Sabadell	Sabadell	Barcelona
Spain	Hospital universitario Marqués de Valdecilla	Santander
Spain	Hospital General Universitario de Valencia	Valencia
Spain	Hospital Universitario y Politécnico La Fe	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
Grupo Español de Tratamiento de Tumores de Cabeza y Cuello

Country where clinical trial is conducted

Spain, 

Outcome

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