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

NCT06738797 | Recruiting

• 1 other identifier: NIMAO/2023-2/NH01
• Study Type: observational
• Target: 32
• Locations: 1 country
• Sites: 5

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.

Conditions

Urogenital Neoplasms

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (30)

• Histology of cells

  Inclusion

• Presence of an aggressive minority component

  Inclusion

• Type of other component

  Inclusion

• Tumor grade

  Inclusion

• PD1/PDL1 status

  Inclusion

Study Arms (1)

Patients with urothelial carcinoma

Diagnostic Test: SPHERTEST test

Interventions

SPHERTEST test DIAGNOSTIC_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.

Patients with urothelial carcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead

Study Sites (5)

Institut du Cancer de Montpellier

Montpellier, France

NOT YET RECRUITING

Institut Régional du Cancer de Montpellier

Montpellier, France

NOT YET RECRUITING

Centre Antoine Lacassagne

Nice, France

NOT YET RECRUITING

CHU de Nimes

Nîmes, France

RECRUITING

Iuct Oncopole

Toulouse, France

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Venous blood sampling (5 EDTA tubes of 4 ml or 20 ml in total) before and after initiation of immunotherapy. Stool sampling at the patient's home using a dedicated kit before starting immunotherapy and then before cycle 4 ( of treatment.

MeSH Terms

Conditions

Urogenital Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Nadine Houede

  CHU de Nimes

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nadine Houede

CONTACT

04.66.68.33.01; nadine.houede@chu-nimes.fr

Study Design

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

Study Record Dates

• First Submitted: December 10, 2024
• First Posted: December 18, 2024
• Study Start: December 12, 2024
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: January 28, 2026

Record last verified: 2026-01

Locations

FR (5)