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

NCT04944550 | Unknown

• 1 other identifier: NIMAO/2020-2/NH01
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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. .

Conditions

Upper Urinary Tract Urothelial Carcinoma; Nephroureterectomy; Tumor; Xenograft Model

Outcome Measures

Primary Outcomes (7)

• Histological characteristics of patient-derived xenograft models after staining.

  Microscopic observation of cells after staining with hematoxylin and eosin

  1-6 months after harvesting

• Study of genomes of tumor specimens

  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

  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

  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.

  RNA-sequencing of cells isolated from patient tumor specimens.

  1-6 months after harvesting

• Transcriptome of the patient-derived xenograft tumor models.

  RNA-sequencing of cells isolated from patient-derived xenograft tumor models.

  1-6 months after harvesting

• Transcriptome of the patient-derived cell line models.

  RNA-sequencing of cells isolated from patient-derived cell line models.

  1-6 months after harvesting

Secondary Outcomes (13)

• Sensitivity to Cisplatin: patient-derived cell line models

  6-8 months after harvesting

• Sensitivity to Carboplatin: patient-derived cell line models

  6-8 months after harvesting

• Sensitivity to Oxaliplatin: patient-derived cell line models

  6-8 months after harvesting

• Sensitivity to Gemcitabin: patient-derived cell line models

  6-8 months after harvesting

• Tumor size in non-treated patient-derived xenograft models

  1-6 months after harvesting

Other Outcomes (4)

• Patients' gender

  Day 0

• Patients' age

  Day 0

• Primitive tumor site

  Day 0

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of patients treated consecutively at the Urology Andrology department of Nîmes University Hospital for high-grade carcinomas of the pelvis or renal ureter for whom a total nephroureterectomy has been indicated during a multidisciplinary meeting. The tumor samples used for our study come from specimens removed surgically. Patients must not have undergone any prior systemic treatment.

You may qualify if:

• 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.

You may not qualify if:

• Any patient who has undergone previous systemic treatment.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead
• INSERM U1194, Institut de Recherche en Cancérologie de Montpellier, Campus Val d'Aurelle, 34298 Montpellier cedex 5: collaborator

Study Sites (1)

Centre Hospitalier Universitaire de Nîmes

Nîmes, Gard, 30029, France

RECRUITING

Related Publications (1)

• 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.

  PMID: 32145825 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Tumor samples removed by nephroureterctomy will be evaluated at Nîmes University Hospital's Pathological Anatomy and Cytology Department. Part of the tumors are dissected into 2-3 mm3 fragments and quickly transported in cold Roswell Park Memorial Institute medium or a phosphate-buffered saline environment to the animal lab for subcutaneous grafting on mice or to the "Resistance to innovative treatments and therapies" team for soft cell dissociation. Cell suspensions will then be transported on ice to our collaborators at Inovotion Laboratories for grafting into the chorioallantoid membrane of chicken embryos, or used for cold in vitro culture at the animal lab for subcutaneous grafts (patient-derived xenograft models).

MeSH Terms

Conditions

Neoplasms

Study Officials

• Nadine HOUEDE, Pr.

  CHU de Nimes

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nadine HOUEDE, Pr.

CONTACT

+33 4.66.68.33.01; nadine.houede@chu-nimes.fr

Anissa MEGZARI, Mme.

CONTACT

04.66.68.42.36; drc@chu-nimes.fr

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2021
• First Posted: June 29, 2021
• Study Start: March 1, 2021
• Primary Completion: September 1, 2023
• Study Completion: March 1, 2024
• Last Updated: September 28, 2022

Record last verified: 2022-09

Locations

FR (1)