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.

Overview

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.

Interventions

• 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.

Primary outcome measures

• SPHERTEST measurement of potential therapeutic efficacy [Time frame: Day 0]
• Progression-free survival [Time frame: Month 12]

Secondary outcome measures (12)

• Histology of cells [Time frame: Inclusion]
• Presence of an aggressive minority component [Time frame: Inclusion]
• Type of other component [Time frame: Inclusion]
• Tumor grade [Time frame: Inclusion]
• PD1/PDL1 status [Time frame: Inclusion]
• PDL1 score [Time frame: Inclusion]
• Type of metastatic involvement [Time frame: Inclusion]
• Primary tumor site [Time frame: Inclusion]
• Hemoglobin level [Time frame: Inclusion]
• Hemoglobin level [Time frame: Cycle 2 visit]
• Lactate dehydrogenase level [Time frame: Inclusion]
• Lactate dehydrogenase level [Time frame: Cycle 2 visit]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Case-only

Study locations

France · 5 centers

• Institut du Cancer de Montpellier — Montpellier
• Institut Régional du Cancer de Montpellier — Montpellier
• Centre Antoine Lacassagne — Nice
• CHU de Nimes — Nîmes
• Iuct Oncopole — Toulouse

Identifiers

NCT: NCT06738797 · NIMAO/2023-2/NH01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗