Clinical trial NCT04970134: Spanish Study for Molecular Characterization of Thyroid Carcinoma
Official title: Spanish Observational Study for MOLecular Characterization of THYroid Carcinoma MOLTHY Project
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Differentiated Thyroid Carcinoma
Medullary Thyroid Carcinoma
Keywords: advanced and/or metastatic disease
iodine refractory
Lead sponsor: Grupo Español de Tratamiento de Tumores de Cabeza y Cuello
Sponsor class: OTHER
First posted: 2021-07-21
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: It is estimated to include 150 patients over 18 years of age with thyroid carcinoma (radioiodine resistant differentiated thyroid carcinoma and medullary thyroid carcinoma) undergoing systemic treatment or under clinical follow-up.

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).

Eligibility criteria: 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, ...).

Primary outcomes:
measure: Progression free survival (PFS)
timeFrame: Throughout the study. Approximately 2 years
measure: Overall survival (OS)
timeFrame: Throughout the study. Approximately 2 years
measure: Objective response rate
timeFrame: Throughout the study. Approximately 2 years
measure: Prevalence of genetic alterations
timeFrame: Throughout the study. Approximately 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: L'Hospitalet De Llobregat
country: Spain
facility: Hospital Universitario Durán i Reinals
state: Barcelona
city: Manresa
country: Spain
facility: Fundació Althaia
state: Barcelona
city: Sabadell
country: Spain
facility: Consorci Corporació Sanitària Parc Taulí de Sabadell
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Girona
country: Spain
facility: Institut Català d'Oncologia Girona - ICO Girona
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Santander
country: Spain
facility: Hospital universitario Marqués de Valdecilla
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
affiliation: Hospital Clinic of Barcelona
name: Neus Basté Rotllan, M.D. Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: