- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT04944550
New Models for the Evaluation of Preclinical Treatment for Urothelial Carcinomas of the Upper Excretory Tract. (CICLOP)
Development of New Models for the Evaluation of Preclinical Treatment for Urothelial Carcinomas of the Upper Excretory Tract.
Upper Urinary Tract Urothelial Carcinomas are rare, aggressive tumors, accounting for 5 to 10% of all urothelial tumors. These include tumors which develop in the renal cavities (renal pelvis, calices) and ureteral tumors. Nephro-ureterectomy is the standard treatment but 80% of patients will have a relapse within 2 years. Only one trial has (Birtle et al. 2020), has shown the interest of postoperative chemotherapy. Neoadjuvant systemic treatment seems particularly interesting for a population which is going to undergo a nephronic loss and therefore reduction in kidney function which is likely to make patients ineligible for cisplatin. In favor of additional immunotherapy, it has been described that upper excretory tract tumors have a high immunogenic potential with a high rate of microsatellite instability.
From surgical samples of patient tumors obtained after nephroureterectomy or biopsy material collected before treatment, we are going to generate patient-derived cell lines and xenograft models in the mouse. A recent publication has demonstrated the feasibility of this approach by specifying that the capture rate of tumor cells is 50% for patient-derived xenografts and 25% for patient-derived cells (Coleman et al. 2020). As tumors harvested from biopsies do not grow in patient-derived xenografts,we plan to graft the biopsies onto chorioallantoic chicken embryo membranes, a model which has never been used for this indication and which is one of the original features of our approach. These three concomitant approaches will allow us to increase our chances of obtaining stable upper urinary tract urothelial carcinoma lines to be used for the screening and identification of new treatments or new combinations of molecules that would benefit patients with upper urinary tract urothelial carcinomas, knowing that very few studies dedicated to this type of cancer have been conducted or published due to the rarity of the disease and the lack of existing models published on the subject of these particular tumors.
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Aperçu de l'étude
Statut
Type d'étude
Inscription (Anticipé)
Contacts et emplacements
Coordonnées de l'étude
- Nom: Nadine HOUEDE, Pr.
- Numéro de téléphone: +33 4.66.68.33.01
- E-mail: nadine.houede@chu-nimes.fr
Sauvegarde des contacts de l'étude
- Nom: Anissa MEGZARI, Mme.
- Numéro de téléphone: 04.66.68.42.36
- E-mail: drc@chu-nimes.fr
Lieux d'étude
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Gard
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Nîmes, Gard, France, 30029
- Recrutement
- Centre Hospitalier Universitaire de Nîmes
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Contact:
- Anissa MEZGARI
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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:
- Patients treated consecutively at the Urology Andrology Department of Nîmes University Hospital for high grade carcinoma of the pelvis or renal ureter with an indication for total nephroureterectomy decided during a multidisciplinary meeting.
- Patient with a diagnosis of high-grade urothelial carcinoma of the pelvis or renal ureter confirmed by histology (biopsy, biopsy of the ureteroscopic) or by cytology with the presence of :
- High-grade disease on ureteroscopic biopsy OR ;
- High grade disease on urinary cytology AND infiltrating appearance of the renal pelvic wall / ureter on the scanner (the presence of hydronephrosis will be considered as pervasive by definition) with a negative cytoscopy.
Exclusion Criteria:
- Any patient who has undergone previous systemic treatment.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Histological characteristics of patient-derived xenograft models after staining.
Délai: 1-6 months after harvesting
|
Microscopic observation of cells after staining with hematoxylin and eosin
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1-6 months after harvesting
|
Study of genomes of tumor specimens
Délai: 1-6 months after harvesting
|
Exome sequencing of DNA cells isolated from original patient tumor specimens.
|
1-6 months after harvesting
|
Alterations in the genomes of patient-derived xenograft tumor models
Délai: 1-6 months after harvesting
|
Exome sequencing of DNA cells isolated from patient-derived xenograft tumor models.
|
1-6 months after harvesting
|
Alterations in the genomes of patient-derived cell line models
Délai: 1-6 months after harvesting
|
Exome sequencing of DNA cells isolated from patient-derived cell line models.
|
1-6 months after harvesting
|
Study of the transcriptome of patient tumor specimens.
Délai: 1-6 months after harvesting
|
RNA-sequencing of cells isolated from patient tumor specimens.
|
1-6 months after harvesting
|
Transcriptome of the patient-derived xenograft tumor models.
Délai: 1-6 months after harvesting
|
RNA-sequencing of cells isolated from patient-derived xenograft tumor models.
|
1-6 months after harvesting
|
Transcriptome of the patient-derived cell line models.
Délai: 1-6 months after harvesting
|
RNA-sequencing of cells isolated from patient-derived cell line models.
|
1-6 months after harvesting
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Sensitivity to Cisplatin: patient-derived cell line models
Délai: 6-8 months after harvesting
|
The MIC 50 test (Minimum Inhibitory Concentration required for cell growth to be inhibited by 50%) will be used in vitro to test the tumor cells' response to Cisplatin.
|
6-8 months after harvesting
|
Sensitivity to Carboplatin: patient-derived cell line models
Délai: 6-8 months after harvesting
|
The MIC 50 test (Minimum Inhibitory Concentration required for cell growth to be inhibited by 50%) will be used in vitro to test the tumor cells' response to Carboplatin.
|
6-8 months after harvesting
|
Sensitivity to Oxaliplatin: patient-derived cell line models
Délai: 6-8 months after harvesting
|
The MIC 50 test (Minimum Inhibitory Concentration required for cell growth to be inhibited by 50%) will be used in vitro to test the tumor cells' response to Oxaliplatin.
|
6-8 months after harvesting
|
Sensitivity to Gemcitabin: patient-derived cell line models
Délai: 6-8 months after harvesting
|
The MIC 50 test (Minimum Inhibitory Concentration required for cell growth to be inhibited by 50%) will be used in vitro to test the tumor cells' response to Gemcitabin.
|
6-8 months after harvesting
|
Tumor size in non-treated patient-derived xenograft models
Délai: 1-6 months after harvesting
|
The volume of tumors will be measured in mm3.
|
1-6 months after harvesting
|
Sensitivity to Cisplatin: tumor size in treated patient-derived xenograft models
Délai: 6-8 months after harvesting
|
To test the tumor cells' response to Cisplatin in xenograft models, the volume of tumors will be measured in mm3 and compared with the volume of tumors in the non-treated control group.
|
6-8 months after harvesting
|
Sensitivity to Cisplatin: tumor growth rate in patient-derived xenograft models
Délai: 6-8 months after harvesting
|
To test the tumor cells' response to Cisplatin in xenograft models, the Tumor Growth Inhibition index, which is defined as (1 - (mean volume of treated tumors)/(mean volume of control tumors)) × 100% will be used.
|
6-8 months after harvesting
|
Sensitivity to Carboplatin: tumor size in treated patient-derived xenograft models
Délai: 6-8 months after harvesting
|
To test the tumor cells' response to Carboplatin in xenograft models, the volume of tumors will be measured in mm3 and compared with the volume of tumors in the non-treated control group.
|
6-8 months after harvesting
|
Sensitivity to Carboplatin: tumor growth rate in treated patient-derived xenograft models
Délai: 6-8 months after harvesting
|
To test the tumor cells' response to Carboplatin in xenograft models, the Tumor Growth Inhibition index, which is defined as (1 - (mean volume of treated tumors)/(mean volume of control tumors)) × 100% will be used.
|
6-8 months after harvesting
|
Sensitivity to Oxiplatin: tumor size in treated patient-derived xenograft models
Délai: 6-8 months after harvesting
|
To test the tumor cells' response to Oxiplatin in xenograft models, the volume of tumors will be measured in mm and compared with the volume of tumors in the non-treated control group.
|
6-8 months after harvesting
|
Sensitivity to Oxiplatin: tumor growth rate in treated patient-derived xenograft models
Délai: 6-8 months after harvesting
|
To test the tumor cells' response to Oxiplatin in xenograft models, the Tumor Growth Inhibition index, which is defined as (1 - (mean volume of treated tumors)/(mean volume of control tumors)) × 100% will be used.
|
6-8 months after harvesting
|
Sensitivity to Gemcitabine: tumor size in treated patient-derived xenograft models
Délai: 6-8 months after harvesting
|
To test the tumor cells' response to Gemcitabine in xenograft models, the tumor volume will be measured in mm3 and compared with the volume of tumors in the non-treated control group.
|
6-8 months after harvesting
|
Sensitivity to Gemcitabin: tumor growth rate in treated patient-derived xenograft models
Délai: 6-8 months after harvesting
|
To test the tumor cells' response to Gemcitabin in xenograft models, the Tumor Growth Inhibition index, which is defined as (1 - (mean volume of treated tumors)/(mean volume of control tumors)) × 100% will be used.
|
6-8 months after harvesting
|
Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Patients' gender
Délai: Day 0
|
The sex of patients will be recorded at the inclusion as Male/Female/Transgender
|
Day 0
|
Patients' age
Délai: Day 0
|
The age of patients will be recorded at the inclusion in years
|
Day 0
|
Primitive tumor site
Délai: Day 0
|
The site of the patient's primitive tumor will be recorded at the inclusion
|
Day 0
|
Infiltrative tumor
Délai: Day 0
|
The tumor will be noted as infiltrative or not (YES/NO) at the inclusion.
|
Day 0
|
Collaborateurs et enquêteurs
Collaborateurs
Les enquêteurs
- Chercheur principal: Nadine HOUEDE, Pr., CHU de Nimes
Publications et liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Anticipé)
Achèvement de l'étude (Anticipé)
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
- NIMAO/2020-2/NH01
Informations sur les médicaments et les dispositifs, documents d'étude
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