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NCT Number: NCT04944550

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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Key information

Conditions

Upper Urinary Tract Urothelial Carcinoma Neoplasms Nephroureterectomy Tumor Xenograft Model

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Centre Hospitalier Universitaire de Nîmes

Nîmes, Gard, 30029, France

Who can participate

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Primary outcomes

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

    Time frame: 1-6 months after harvesting

    Microscopic observation of cells after staining with hematoxylin and eosin

  2. Study of genomes of tumor specimens

    Time frame: 1-6 months after harvesting

    Exome sequencing of DNA cells isolated from original patient tumor specimens.

  3. Alterations in the genomes of patient-derived xenograft tumor models

    Time frame: 1-6 months after harvesting

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

  4. Alterations in the genomes of patient-derived cell line models

    Time frame: 1-6 months after harvesting

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

  5. Study of the transcriptome of patient tumor specimens.

    Time frame: 1-6 months after harvesting

    RNA-sequencing of cells isolated from patient tumor specimens.

  6. Transcriptome of the patient-derived xenograft tumor models.

    Time frame: 1-6 months after harvesting

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

  7. Transcriptome of the patient-derived cell line models.

    Time frame: 1-6 months after harvesting

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

Secondary outcomes

  1. Sensitivity to Cisplatin: patient-derived cell line models

    Time frame: 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.

  2. Sensitivity to Carboplatin: patient-derived cell line models

    Time frame: 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.

  3. Sensitivity to Oxaliplatin: patient-derived cell line models

    Time frame: 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.

  4. Sensitivity to Gemcitabin: patient-derived cell line models

    Time frame: 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.

  5. Tumor size in non-treated patient-derived xenograft models

    Time frame: 1-6 months after harvesting

    The volume of tumors will be measured in mm3.

  6. Sensitivity to Cisplatin: tumor size in treated patient-derived xenograft models

    Time frame: 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.

  7. Sensitivity to Cisplatin: tumor growth rate in patient-derived xenograft models

    Time frame: 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.

  8. Sensitivity to Carboplatin: tumor size in treated patient-derived xenograft models

    Time frame: 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.

  9. Sensitivity to Carboplatin: tumor growth rate in treated patient-derived xenograft models

    Time frame: 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.

  10. Sensitivity to Oxiplatin: tumor size in treated patient-derived xenograft models

    Time frame: 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.

  11. Sensitivity to Oxiplatin: tumor growth rate in treated patient-derived xenograft models

    Time frame: 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.

  12. Sensitivity to Gemcitabine: tumor size in treated patient-derived xenograft models

    Time frame: 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.

  13. Sensitivity to Gemcitabin: tumor growth rate in treated patient-derived xenograft models

    Time frame: 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.

Other outcomes

  1. Patients' gender

    Time frame: Day 0

    The sex of patients will be recorded at the inclusion as Male/Female/Transgender

  2. Patients' age

    Time frame: Day 0

    The age of patients will be recorded at the inclusion in years

  3. Primitive tumor site

    Time frame: Day 0

    The site of the patient's primitive tumor will be recorded at the inclusion

  4. Infiltrative tumor

    Time frame: Day 0

    The tumor will be noted as infiltrative or not (YES/NO) at the inclusion.

Sponsors and collaborators

Lead sponsor

Centre Hospitalier Universitaire de Nīmes

Other

Collaborators

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

Registry information

Official study title

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

Acronym: CICLOP

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
Jun 29, 2021
Registry last updated
Jun 16, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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