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- Essai clinique NCT03397238
Myeloid Cell Reprogramming in Thyroid Carcinoma
Myeloid Cell Reprogramming in the Context of Radioiodine Therapy in Patients With Non-Medullary Thyroid Carcinoma
Aperçu de l'étude
Statut
Les conditions
Description détaillée
Description of the problem:
Non-medullary thyroid carcinoma (TC) is the most common endocrine malignancy and its incidence is one of the most rapidly increasing among the cancer types. For many patients with advanced and poorly differentiated tumors, treatment options are limited and the prognosis of advanced stage metastatic disease remains poor.
Envisioned solution/research direction:
To improve the patients outcome and identify novel therapeutic targets, one needs a 'systems understanding' of the pathophysiology of tumors, particularly the complex interaction of the malignant cells with other cell types in the tumor en the tumor environment (TME), especially immune cells. Tumor-associated macrophages (TAMs), the most dominant myeloid population in aggressive thyroid tumors, exhibit a distorted phenotype functioning predominantly as tumor enhancer. Despite the progress in understanding the importance of TAMs, the in-depth characterization of different TAMs populations is lacking and the mechanisms governing the functional polarization of TAMs are largely unknown. Understanding the interplay between TAMs and tumor cells represents a crucial step towards development of additional therapeutic strategies in cancer.
Hypothesis:
- We first propose that in advanced TC, not only TAMs, but also circulating monocytes and bone marrow (BM) myeloid progenitors are functionally reprogrammed by tumor-derived factors even before their recruitment in the TME.
- Radioactive iodide (I131)(RAI) is a very effective therapy for patients with TC, but is less effective in patients with advanced, metastatic tumors. We hypothesize that by exposing tumor antigens to the immune system, RAI might induce immunogenic effects at the level of the TME with reprogramming of both TAMs present in the TME and circulating monocytes, towards a tumor suppressive phenotype. This may further potentiate the effects of RAI. In addition this could be explored in the future as a basis for immunotherapy for tumors that are refractory to conventional treatment.
Type d'étude
Inscription (Réel)
Contacts et emplacements
Lieux d'étude
-
-
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Nijmegen, Pays-Bas, 6525GA
- Radboudumc
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-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
Méthode d'échantillonnage
Population étudiée
La description
Inclusion Criteria:
- Group 1:
Subject is newly diagnosed with TC, therapy-naive and is planned to receive conventional treatment by surgery followed by RAI; no evidence of local or distant metastases
- Group 2:
Subject has TC with evidence of distant metastases (either newly diagnosed or therapy-naive or patients with persistent or recurrent disease); at least 4 months since the previous treatment with RAI if applicable
- Group 3:
Subject is diagnosed with MNG, is euthyroid, and is planned to undergo surgery - Group 4: Subject is diagnosed with MNG, is euthyroid, and is planned to receive RAI treatment
- Group 5: Healthy individuals who are euthyroid and have no evidence of thyroid disease
Exclusion Criteria:
- Mentally incompetent
- Pregnant, trying to become pregnant or breastfeeding
- Known inflammatory or infectious diseases or an immunosuppressive status
- Using medication interfering with the immune system
- Reduced platelet counts or other conditions associated with an increased risk of bleeding
- Severe comorbidities: other active malignancy (except for basal cell carcinoma)
- Serious psychiatric pathology
- A self-reported alcohol consumption of >21 units per week
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
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Non-metastatic TC
blood withdrawal, bone marrow aspiration
|
Metastatic TC
blood withdrawal, bone marrow aspiration
|
MNG surgery
blood withdrawal, bone marrow aspiration
|
MNG RAI treatment
blood withdrawal
|
Healthy volunteers
blood withdrawal
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Transcriptional reprogramming of myeloid cells
Délai: baseline
|
RNAseq
|
baseline
|
Epigenetic reprogramming of myeloid cells
Délai: baseline
|
ATAC-seq
|
baseline
|
Functional reprogramming of myeloid cells
Délai: baseline
|
Cytokine response
|
baseline
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Metabolites
Délai: baseline
|
Presence and level metabolites
|
baseline
|
Change of reprogramming after RAI treatment
Délai: baseline and 7 days after RAI treatment
|
RNAseq
|
baseline and 7 days after RAI treatment
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Romana T Netea-Maier, Endocrinologist
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- NL62671.091.17
- 2017-3628 (Autre identifiant: CMO Arnhem-Nijmegen)
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Étudie un produit d'appareil réglementé par la FDA américaine
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