Association Between the SPHERTEST in Vitro Test and Response to Checkpoint Inhibitor Treatments in Patients With Advanced or Metastatic Urothelial Carcinoma (PROMES-URO)

Evaluation de l'Association Entre Les résultats d'un Test in Vitro en Cours de développement (SPHERTEST) et la réponse Aux Traitements Par Inhibiteur du Point de contrôle Chez Des Patients Atteints de Carcinome urothélial de Stade avancé ou métastatique.

First-line systemic treatments for bladder cancer are based on a combination of cytotoxic and immunotherapy, sequentially or concomitantly. Immune checkpoint inhibition (ICPI) is a powerful treatment for patients with metastatic urothelial carcinoma (UC). Since 2017, pembrolizumab (anti-PD1) can be offered as a second-line treatment after failure of platinum agents. In patients responding to platinum salts in first-line treatment, it is possible to maintain efficacy with maintenance treatment with another ICPI, avelumab (anti-PDL1). The phase III JAVELIN BLADDER 100 study compared avelumab to supportive care alone after successful platinum-based chemotherapy. At 30 months, 19.3% of patients were still in response compared to only 6.3% in the supportive care arm. However, biomarker analysis on tumor tissue did not show a robust signature on an individual scale. Recently, two phase 3 trials in first-line were presented at the ESMO 2023 congress. The first, in patients who could receive cisplatin-based chemotherapy, found a benefit on overall survival of adding Nivolumab in combination and then maintaining it for two years. The second proposed combined Enfortumab Vedotin and Pembrolizumab versus standard chemotherapy, with an overall survival for the study arm of more than 31 months. These trials confirm the essential role of immunotherapy in urothelial carcinomas. This progress is tempered by toxicity, cost and the lack of data on patient selection and treatment sequence. Although "prognostic" biomarkers have been identified, they cannot guide the choice of therapy, but only predict the expected outcomes, regardless of the treatment; biomarkers capable of predicting clinical benefit ("predictive") are urgently needed. It is therefore essential to identify a predictive signature at the individual level. The study authors have validated an in vitro model of heterotypic spheroids (SPHERTEST) composed of commercial urothelial carcinoma tumor cells and PBMCs from healthy donors. The aim of the study is to validate this model with PBMCs from UC patients to evaluate the effects of immunotherapy on the immune response and on tumor cell survival in vitro.

The study hypothesis is that the outcome of the pre-therapeutic test based on a heterotypic spheroid model with PBMC from patients with advanced or metastatic urothelial carcinoma (SPHERTEST) is related to the response to checkpoint inhibitor (CI) treatment.

Study Overview

• Status: Recruiting
• Conditions: Urogenital Neoplasms
• Intervention / Treatment: Diagnostic test: SPHERTEST test

• Study Type: Observational
• Enrollment (Estimated): 32

Contacts and Locations

• Study Contact: Name: Nadine Houede; Phone Number: 04.66.68.33.01; Email: nadine.houede@chu-nimes.fr

Study Locations

• France
  • Montpellier, France
    • Not yet recruiting
    • Institut Regional du Cancer de Montpellier
    • Contact: Céline GONGORA; Phone Number: 04.11.28.31.09; Email: celine.gongora@inserm.fr
  • Montpellier, France
    • Not yet recruiting
    • Institut du Cancer de Montpellier
    • Contact: Diego TOSI; Phone Number: 04.67.6.31.12; Email: diego.tosi@icm.unicancer.fr
  • Nice, France
    • Not yet recruiting
    • Centre Antoine Lacassagne
    • Contact: Delphine BORCHIELLINI; Phone Number: 04 92 03 10 00; Email: delphine.borchiellini@nice.unicancer.fr
  • Nîmes, France
    • Recruiting
    • CHU de Nîmes
    • Contact: Anissa Megzari; Phone Number: 04.66.68.42.36; Email: drc@chu-nimes.fr
  • Toulouse, France
    • Recruiting
    • IUCT Oncopole
    • Contact: Damien POUESSEL; Phone Number: 05.31.15.50.50; Email: pouessel.damien@iuct-oncopole.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of patients with advanced or metastatic urothelial carcinoma with an indication for treatment with an immune checkpoint inhibitor treated in the onco-urology departments of the Nîmes University Hospitals, the Antoine Lacassagne Center, the IUCT Toulouse and the Montpellier Regional Cancer Institute.

Description

Inclusion Criteria:

• Patient with histologically proven urothelial carcinoma, in a locally advanced or metastatic situation with indication for immunotherapy.
• The patient must have given their free and informed consent and signed the consent form
• The patient must be a member or beneficiary of a health insurance plan

Exclusion Criteria:

• The subject is participating in a category 1 or drug monotherapy interventional study, or is in a period of exclusion determined by a previous study
• It is impossible to give the subject informed information
• The patient is under safeguard of justice or state guardianship
• History of treatment with anti-PD1 or anti-PDL1 or anti-CTLA4 within the year.
• Pregnant, parturient or breastfeeding patient.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with urothelial carcinoma	Diagnostic test: SPHERTEST test; The SPHERETEST is an in vitro model of heterotypic spheroids composed of commercial urothelial carcinoma tumor cells and leukocyte mononuclear cells from healthy donors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SPHERTEST measurement of potential therapeutic efficacy	Yes/No. Differential in spheroid size before and after treatment according to the formula: R=M1-M0. R = test results, M0 = average spheroid size without immunotherapy treatment, M1 = average spheroid size with immunotherapy treatment. When R is ≤ 0, SPHERTEST = "yes" or "potential therapeutic efficacy". When R is > 0, SPHERTEST = "no" or "absence of potential therapeutic efficacy"	Day 0
Progression-free survival	Yes/No according to RECIST criteria	Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Histology of cells	Pure transitional cells vs predominantly transitional cells	Inclusion
Presence of an aggressive minority component	Yes/no	Inclusion
Type of other component	Micropapillary, microcystic, trophoblastic differentiation, epidermoid differentiation, nested, plasmacytoid, sarcomatoid, rhabdoid, lymphoepitheliomatoid, large cell, undifferentiated or neuroendocrine	Inclusion
Tumor grade	WHO grading	Inclusion
PD1/PDL1 status	Yes/no	Inclusion
PDL1 score	positive/negative	Inclusion
Type of metastatic involvement	Locally advanced (= local recurrence, or pelvic lymph node involvement) or Metastatic sites: liver, bone, lung, brain, extrapelvic lymph node, other	Inclusion
Primary tumor site	Bladder/Urethra/upper urinary tract/Urethra	Inclusion
Hemoglobin level	g/dL	Inclusion
Hemoglobin level	g/dL	Cycle 2 visit
Lactate dehydrogenase level	UI/L	Inclusion
Lactate dehydrogenase level	UI/L	Cycle 2 visit
C-reactive protein level	mg/L	Inclusion
C-reactive protein level	mg/L	Cycle 2 visit
Neutrophil count	G/L	Inclusion
Neutrophil count	G/L	Cycle 2 visit (cycles are spaced 3 weeks (pembrolizumab) or 2 weeks (avelumab) apart)
Lymphocyte count	G/L	Inclusion
Lymphocyte count	G/L	Cycle 2 visit (cycles are spaced 3 weeks (pembrolizumab) or 2 weeks (avelumab) apart)
Number of lines of systemic treatment received in the metastatic phase	0, 1, 2, ≥3	Inclusion
Type of platinum salt received prior to immunotherapy	Cisplatin or carboplatin	Inclusion
Treatment regimen prior to anti-PD1 therapy	Neoadjuvant with progression within 12 months / Adjuvant with progression within 12 months / Initially locally advanced/metastatic	Inclusion
Current treatment: whether treatment is combined with another molecule	Cisplatin / entoftumab-vedotin	Inclusion
Antibiotics in the previous month	Duration (days)	Inclusion
Corticosteroid therapy > 10 mg prednisolone equivalent at immunotherapy initiation	Yes/no	Inclusion
Taking an immunosuppressant other than corticosteroid therapy at immunotherapy initiation	Yes/no	Inclusion
Any comedication at immunotherapy initiation	Protein pump inhibitors / beta blockers / metformin / statin	Inclusion
Patient functioning level	ECOG Performance Status Scale (1-5)	Inclusion
BCG vaccine	Yes/no	Inclusion
Mitomycin therapy	Yes/no	Inclusion
History of auto-immune disease	Yes/no	Inclusion

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Nadine Houede, CHU de Nîmes

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2024
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: December 10, 2024
• First Submitted That Met QC Criteria: December 13, 2024
• First Posted (Actual): December 18, 2024

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Neoplasms
• Other Study ID Numbers: NIMAO/2023-2/NH01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No