NCT06341478

Investigator Grant (IG) 2022 27746

Recruiting now NA Last updated 2 April 2024

What this trial tests

NA trial testing various neoadjuvant therapies in Bladder Cancer in 153 participants. Currently enrolling.

Timeline

15 March 2024

Primary endpoint
15 March 2026

15 March 2027

Quick facts

Lead sponsor	IRCCS San Raffaele
Phase	NA
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	other
Enrollment	153
Start date	15 March 2024
Primary completion	15 March 2026
Estimated completion	15 March 2027
Sites	1 location across Italy

Drugs / interventions tested

• various neoadjuvant therapies — full drug profile →

Conditions studied

• Bladder Cancer — all drugs for Bladder Cancer →

Sponsor

IRCCS San Raffaele — full company profile →

Who can join

18 and older, any sex, with Bladder Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Background:

Muscle-invasive bladder cancer (MIBC) is a systemic disease as \>40% of patients (pts) ultimately develop recurrence after radical cystectomy (RC). For pts who cannot receive or refuse cisplatin-based chemotherapy there is no standard-of-care neoadjuvant therapy. Single-agent pembrolizumab, given neoadjuvantly in patients with T2-4N0M0 MIBC, documented a 42% pathologic complete response-rate (ypT0N0) in a previous AIRC-supported trial (PURE-01, NCT02736266; PMID: 30343614). However, there is a huge proportion of pts who do not benefit from single-agent immunotherapy. Antibody-drug conjugates (ADC) represent the next wave of MIBC treatment revolution. An umbrella of various neoadjuvant therapies including the ADC Sacituzumab govitecan (SG), SG plus pembrolizumab, and chemoimmunotherapy combination has been established to improve our knowledge on MIBC biology and to improve the outcomes.

Hypothesis:

By developing a robust biomarker program associated with therapeutic benefit of novel therapies or their combinations, along with an imaging biomarker development, the investigators will be able to identify suitable tumor characteristics for personalizing perioperative therapies in MIBC, coupled with the possibility to predict the pathological response to treatment.

Aims:

The project is aimed at characterizing the tumor and microenvironment characteristics of muscle-invasive bladder cancer, with a special focus on their changes induced by various neoadjuvant therapies preceding radical cystectomy.

The investigators will aim to evaluate the tumor and immune profile on matched pre- vs post-therapy samples and noninvasively monitor the response to treatment with the use of radiological assessments.

Experimental design:

The investigators will access tumor samples from matched pre-therapy (transurethral resection of the bladder tumor) and post-therapy (radical cystectomy) surgical interventions. They will also analyze the imaging analyses of combined bladder multiparametric MRI/Fluorodeoxyglucose Positron Emission Tomography (PET) scans pre-post neoadjuvant therapies, and will associate the data with the pathological response to treatment, expanding our previously reported work (PMID: 31882281).

Biomarker analyses will include the following: i.) multiplex immunofluorescence assays will allow the investigators defining the immune contexture of tumor lesion; ii.) multiparametric flow cytometry will allow the phenotypic and functional analysis of peripheral blood cells at single cell level; iii.) a whole transcriptome assay will enable investigators to assign specific molecular subtypes to pathological response and outcome, as previously reported (PMID: 33785257; 32165065).

Expected results:

The investigators will expect to identify the tumor characteristics and immune-profiling enabling them to delineate the selection of patients most suited for certain novel perioperative therapies, thus anticipating the developments in clinical research that are being conducted worldwide in MIBC.

The investigators will be also able to develop noninvasive tools for pathological complete response identification, thus enabling them to develop a next-generation of clinical trials aimed at sparing any radical local therapy on the bladder tumor.

Impact on cancer:

In principle, the present personalized strategy yields the potential to enhance the therapeutic standards achievable with RC alone as well as with single-agent immunotherapy and RC.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Progress and Innovative Combination Therapies in Trop-2-Targeted ADCs.
   Jiang Y, Zhou H, Liu J, Ha W, et al · · 2024 · cited 11× · PMID 38794221 · DOI 10.3390/ph17050652