Immunogenic Cell Death as a Novel Mechanism of Mitomycin C Activity in Bladder Cancer

Bladder Cancer Clinical Trial

— ICH-MIM-01  

Official title:

Immunogenic Cell Death as a Novel Mechanism of Mitomycin C Activity in Bladder Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04256616
• Other study ID #: 2041
• Status: Recruiting
• Start date: June 27, 2018
• Est. completion date: September 30, 2020

Study information

• Verified date: July 2020
• Source: Istituto Clinico Humanitas
• Contact: Maria Rescigno, PhD
• Phone: +390282245431
• Email: maria.rescigno[@]hunimed.eu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The principal objective of this study consists in the assessment of Immunogenic Cell Death (ICD) induction in neoplastic tissues derived from bladder cancer patients treated ex vivo with Mitomycin C (MMC). The evaluation is performed using cellular and molecular analyses of treated versus untreated samples derived from the same patient

Description:

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:

1. identify an expression profile that is common to all tumors that undergo ICD upon MMC treatment ('ICD signature'),

2. asses the genetic and environmental factors- urinary microbiome composition- responsible for MMC treatment efficacy,

3. 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: September 30, 2020
• Est. primary completion date: September 1, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Other:
• This is an observational study that does not concern a direct intervention on patients and control subjects and does not interfere with the clinical management of 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.

Locations

Country	Name	City	State
Italy	Humanitas reseach hospital (ICH)	Rozzano	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Istituto Clinico Humanitas

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MMC-induced ICD	The main aim of this study is to evaluate whether MMC is able to trigger ICD in patient-derived neoplastic tissues.	3 years
Secondary	ICD signature analyzed by RNAseq analysis	Identify an expression profile that is common to all tumors that undergo ICD upon MMC treatment ('ICD signature')	3 years
Secondary	Microbiota study	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