New Models for the Evaluation of Preclinical Treatment for Urothelial Carcinomas of the Upper Excretory Tract.

NCT ID: NCT04944550

Last Updated: 2022-09-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

20 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-03-01

Study Completion Date

2024-03-01

Brief Summary

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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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Detailed Description

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Conditions

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Upper Urinary Tract Urothelial Carcinoma Nephroureterectomy Tumor Xenograft Model

Study Design

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Observational Model Type

OTHER

Study Time Perspective

OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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INSERM U1194, Institut de Recherche en Cancérologie de Montpellier, Campus Val d'Aurelle, 34298 Montpellier cedex 5

UNKNOWN

Sponsor Role collaborator

Centre Hospitalier Universitaire de Nīmes

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nadine HOUEDE, Pr.

Role: PRINCIPAL_INVESTIGATOR

CHU de Nimes

Locations

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Centre Hospitalier Universitaire de Nîmes

Nîmes, Gard, France

Site Status RECRUITING

Countries

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France

Central Contacts

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Nadine HOUEDE, Pr.

Role: CONTACT

+33 4.66.68.33.01

Anissa MEGZARI, Mme.

Role: CONTACT

04.66.68.42.36

Facility Contacts

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Anissa MEZGARI

Role: primary

References

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Birtle A, Johnson M, Chester J, Jones R, Dolling D, Bryan RT, Harris C, Winterbottom A, Blacker A, Catto JWF, Chakraborti P, Donovan JL, Elliott PA, French A, Jagdev S, Jenkins B, Keeley FX Jr, Kockelbergh R, Powles T, Wagstaff J, Wilson C, Todd R, Lewis R, Hall E. Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial. Lancet. 2020 Apr 18;395(10232):1268-1277. doi: 10.1016/S0140-6736(20)30415-3. Epub 2020 Mar 5.

Reference Type BACKGROUND
PMID: 32145825 (View on PubMed)

Other Identifiers

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NIMAO/2020-2/NH01

Identifier Type: -

Identifier Source: org_study_id

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