ICH-MIM-01: Immunogenic Cell Death as a Novel Mechanism of Mitomycin C Activity in Bladder Cancer

Sponsor

Istituto Clinico Humanitas (Other)

Overall Status

Unknown status

CT.gov ID

NCT04256616

Collaborator

(none)

110

Enrollment

Location

27.1

Anticipated Duration (Months)

4.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer	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.

Detailed 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:

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).

Study Design

Study Type:

Observational

Anticipated Enrollment :

110 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Jun 27, 2018

Anticipated Primary Completion Date :

Sep 1, 2020

Anticipated Study Completion Date :

Sep 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
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	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.
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.	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.

Arm

Intervention/Treatment

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

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.

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.

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.

Outcome Measures

Primary Outcome Measures

MMC-induced ICD [3 years]
The main aim of this study is to evaluate whether MMC is able to trigger ICD in patient-derived neoplastic tissues.

Secondary Outcome Measures

ICD signature analyzed by RNAseq analysis [3 years]
Identify an expression profile that is common to all tumors that undergo ICD upon MMC treatment ('ICD signature')
Microbiota study [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Humanitas reseach hospital (ICH)	Rozzano	Milan	Italy	20089

Sponsors and Collaborators

Istituto Clinico Humanitas

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Michele Tedeschi, Head of Clinical Research, Istituto Clinico Humanitas

ClinicalTrials.gov Identifier:

NCT04256616

Other Study ID Numbers:

2041

First Posted:

Feb 5, 2020

Last Update Posted:

Jul 7, 2020

Last Verified:

Jul 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Urinary Bladder Neoplasms

Study Results

No Results Posted as of Jul 7, 2020