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

Recruiting

• Conditions: Urogenital Neoplasms

• Registration Number: NCT06738797
• Lead Sponsor: Centre Hospitalier Universitaire de Nīmes

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-12-10
• Study Start: 2024-12-12
• Study First Submitted QC: 2024-12-13
• Study First Posted: 2024-12-18
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-11
• Last Update Posted: 2025-04-16
• Primary Completion: 2027-06
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 32

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
SPHERTEST measurement of potential therapeutic efficacy	Day 0	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"
Progression-free survival	Month 12	Yes/No according to RECIST criteria

Secondary Outcome Measures

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

Trial Locations

Locations (5)

Institut du Cancer de Montpellier; 🇫🇷 Montpellier, France

Institut Régional du Cancer de Montpellier; 🇫🇷 Montpellier, France

Centre Antoine Lacassagne; 🇫🇷 Nice, France

CHU de Nimes; 🇫🇷 Nimes, France

Iuct Oncopole; 🇫🇷 Toulouse, France