Идёт набор NCT06341478

Investigator Grant (IG) 2022 27746

Без фазы С лечением Bladder Cancer

Ориентир для пациента и семьи

Простыми словами

Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.

Что изучают: В протоколе указаны: various neoadjuvant therapies.
Кому может быть актуально: Состояния в реестре: Bladder Cancer. Базовые параметры: от 18 лет · Все.
Что важно проверить: Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
Где проводится: Италия
Следующий шаг: Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →

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Официальное название

Understanding Tumor and Immune Dynamics and Predicting Response to Various Perioperative Therapies in Patients With Muscle-invasive Bladder Cancer

Обзор

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.

Вмешательства

Препарат various neoadjuvant therapies
Radical cystectomy, Sacituzumab Govitecan (SG), SG + pembrolizumab, nivolumab+abraxane

Первичные конечные точки

Predictors of immune response to experimental combination therapies in MIBC. [Срок оценки: Baseline (pre-therapy) to radical cystectomy]
Genomic predictors of response to experimental combination therapies in MIBC. [Срок оценки: Baseline (pre-therapy) to radical cystectomy]
Transcriptomic predictors of response to experimental combination therapies in MIBC. [Срок оценки: Baseline (pre-therapy) to radical cystectomy]

Критерии участия

Критерии включения

Inclusion in NureCombo (NCT04876313), SURE-01 (NCT05226117), and SURE-02 (NCT05535218) clinical trials or candidates to radical cystectomy as per routine clinical practice.

2\. Histopathologically-confirmed urothelial carcinoma (UC). 3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 4. Clinical stage T2-T4N0M0, muscle-invasive bladder cancer (MIBC)