Clinical trial NCT06738797: Association Between the SPHERTEST in Vitro Test and Response to Checkpoint Inhibitor Treatments in Patients With Advanced or Metastatic Urothelial Carcinoma
Official title: 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.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Urogenital Neoplasms
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2024-12-18
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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.

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: SPHERTEST measurement of potential therapeutic efficacy
timeFrame: Day 0
measure: Progression-free survival
timeFrame: Month 12
Secondary outcomes:
measure: Histology of cells
timeFrame: Inclusion
measure: Presence of an aggressive minority component
timeFrame: Inclusion
measure: Type of other component
timeFrame: Inclusion
measure: Tumor grade
timeFrame: Inclusion
measure: PD1/PDL1 status
timeFrame: Inclusion
measure: PDL1 score
timeFrame: Inclusion
measure: Type of metastatic involvement
timeFrame: Inclusion
measure: Primary tumor site
timeFrame: Inclusion
measure: Hemoglobin level
timeFrame: Inclusion
measure: Hemoglobin level
timeFrame: Cycle 2 visit
measure: Lactate dehydrogenase level
timeFrame: Inclusion
measure: Lactate dehydrogenase level
timeFrame: Cycle 2 visit
measure: C-reactive protein level
timeFrame: Inclusion
measure: C-reactive protein level
timeFrame: Cycle 2 visit
measure: Neutrophil count
timeFrame: Inclusion
measure: Neutrophil count
timeFrame: Cycle 2 visit (cycles are spaced 3 weeks (pembrolizumab) or 2 weeks (avelumab) apart)
measure: Lymphocyte count
timeFrame: Inclusion
measure: Lymphocyte count
timeFrame: Cycle 2 visit (cycles are spaced 3 weeks (pembrolizumab) or 2 weeks (avelumab) apart)
measure: Number of lines of systemic treatment received in the metastatic phase
timeFrame: Inclusion
measure: Type of platinum salt received prior to immunotherapy
timeFrame: Inclusion
measure: Treatment regimen prior to anti-PD1 therapy
timeFrame: Inclusion
measure: Current treatment: whether treatment is combined with another molecule
timeFrame: Inclusion
measure: Antibiotics in the previous month
timeFrame: Inclusion
measure: Corticosteroid therapy > 10 mg prednisolone equivalent at immunotherapy initiation
timeFrame: Inclusion
measure: Taking an immunosuppressant other than corticosteroid therapy at immunotherapy initiation
timeFrame: Inclusion
measure: Any comedication at immunotherapy initiation
timeFrame: Inclusion
measure: Patient functioning level
timeFrame: Inclusion
measure: BCG vaccine
timeFrame: Inclusion
measure: Mitomycin therapy
timeFrame: Inclusion
measure: History of auto-immune disease
timeFrame: Inclusion
Other outcomes:
Locations:
city: Montpellier
country: France
facility: Institut du Cancer de Montpellier
city: Montpellier
country: France
facility: Institut Régional du Cancer de Montpellier
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Nimes
country: France
facility: CHU de Nimes
city: Toulouse
country: France
facility: Iuct Oncopole
Study officials:
affiliation: CHU de Nimes
name: Nadine Houede
role: PRINCIPAL_INVESTIGATOR
References: