Immunogenic Cell Death as a Novel Mechanism of Mitomycin C Activity in Bladder Cancer (ICH-MIM-01)
Aperçu de l'étude
Statut
Les conditions
Description détaillée
Urothelial or transitional cell carcinoma of the bladder is the fourth most common cancer in males worldwide, with about 60-80% of newly diagnosed patients having non-muscle-invasive bladder cancer (NMIBC). NMIBC management consist in transurethral resection of bladder tumor (TURBT) followed by adjuvant intravesical treatment with the chemotherapeutic agent Mitomycin C (MMC) or the immunotherapy bacillus Calmette-Guérin. These therapies result in low progression rates, but are not efficacious in all patients, leading to high tumor recurrence. Immunogenic cell death (ICD) may be one of the mechanisms of action of MMC intravesical therapy in bladder cancer.
The primary objective of the study is to evaluate whether MMC is able to trigger ICD in patient-derived neoplastic tissues. As secondary targets we aim to:
- identify an expression profile that is common to all tumors that undergo ICD upon MMC treatment ('ICD signature'),
- asses the genetic and environmental factors- urinary microbiome composition- responsible for MMC treatment efficacy,
- evaluate whether ICD induction correlates with clinical staging and response (clinical endpoints for MMC-treated patients are recurrence at three month and one year after enrollment).
Type d'étude
Inscription (Anticipé)
Contacts et emplacements
Lieux d'étude
-
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Milan
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Rozzano, Milan, Italie, 20089
- Recrutement
- Humanitas reseach hospital (ICH)
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
Méthode d'échantillonnage
Population étudiée
80 patients with carcinoma of the bladder; divided in 20 patients Ta (low grade), 20 patients Ta/T1 (high grade) and 20 patients T2. Only for liquid samples collection we will include 20 CIS (carcinoma in situ) patients.
30 age and sex-matched subjects not suffering from carcinoma of the bladder, already hospitalized in ICH; we expect to enroll 24 males and 6 females of which 10 of 40- 60 years old, 10 of 60-70 years old, 10 of >70 years old.
La description
Inclusion Criteria:
- Male and females, > 40 years old
For bladder cancer patients:
- bladder cancer patients- patinets with first tumor occurrence or patient with a recurrence after more than 2 years from the removal of the prior malignancy
Exclusion Criteria:
- Treated with immunomodulatory agents at time of enrollment or in the two months before enrollment
- Treated with antibiotics at time of enrollment or during the month before enrollment
- Positive history of sexually transmitted diseases
- Urinary infection ongoing or recent (during the three months before enrollment)
- Suffering from chronic intestinal inflammation
ONLY for controls:
- Treated with immunomodulatory agents at time of enrollment or in the two months before enrollment
- Treated with antibiotics at time of enrollment or during the month before enrollment
- Positive history of sexually transmitted diseases
- Urinary infection ongoing or recent (during the three months before enrollment)
- Suffering from chronic intestinal inflammation
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
Intervention / Traitement |
|---|---|
|
Bladder cancer patients
80 patients with carcinoma of the bladder; divided in 20 patients Ta (low grade), 20 patients Ta/T1 (high grade) and 20 patients T2.
Only for liquid samples collection we will include 20 CIS (carcinoma in situ) patients
|
urine collection: DNA is isolated from urine samples (catheterized, washout, midstream) and the 16S rRNA gene is sequenced. Specimen collection: Specimens collected during TURBT are selected by a pathologist and trasferred to the laboratory. The tissues are treated ex vivo with MMC. |
|
Controls- Healthy subjects
30 age and sex-matched subjects not suffering from carcinoma of the bladder, already hospitalized in ICH; we expect to enroll 24 males and 6 females of which 10 of 40- 60 years old, 10 of 60-70 years old, 10 of >70 years old.
|
urine collection: DNA is isolated from urine samples (catheterized, washout, midstream) and the 16S rRNA gene is sequenced. Specimen collection: Specimens collected during TURBT are selected by a pathologist and trasferred to the laboratory. The tissues are treated ex vivo with MMC. |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
MMC-induced ICD
Délai: 3 years
|
The main aim of this study is to evaluate whether MMC is able to trigger ICD in patient-derived neoplastic tissues.
|
3 years
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
ICD signature analyzed by RNAseq analysis
Délai: 3 years
|
Identify an expression profile that is common to all tumors that undergo ICD upon MMC treatment ('ICD signature')
|
3 years
|
|
Microbiota study
Délai: 3 years
|
Verify the existance of urinary microbiome using catheterized urines and identify changes in urinary microbiome composition correlating with bldder cancer, MMC efficacy and staging/progression of the disease
|
3 years
|
Collaborateurs et enquêteurs
Parrainer
Publications et liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Anticipé)
Achèvement de l'étude (Anticipé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 2041
Plan pour les données individuelles des participants (IPD)
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Description du régime IPD
Informations sur les médicaments et les dispositifs, documents d'étude
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