Bladder CancerICH-MIM-01NCT04256616
Immunogenic Cell Death as a Novel Mechanism of Mitomycin C Activity in Bladder Cancer
An observational study of Bladder Cancer, run by Istituto Clinico Humanitas at 1 site in Italy.
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). Read more about this study
- Who is it for?
- Ages 40 years and olderHealthy volunteers can take part
- Conditions the study is for
- Bladder Cancer
- How many people
- 110 participants
- Where
- 1 siteItaly
- Study dates
- 27 Jun 2018to 30 Sep 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: 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.
Who may be able to join
- 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
Who cannot join
- 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:
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Humanitas reseach hospital (ICH)
Rozzano, Milan, 20089
Maria Rescigno, PhD, +390282245431, maria.rescigno@hunimed.eu
About this study
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
Read the 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).
- Conditions
- Bladder Cancer
- Being tested
- 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.
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.Other
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. | |
| 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
MMC-induced ICD
The main aim of this study is to evaluate whether MMC is able to trigger ICD in patient-derived neoplastic tissues.
Measured: 3 years
Secondary outcomes (2)
ICD signature analyzed by RNAseq analysis
Identify an expression profile that is common to all tumors that undergo ICD upon MMC treatment ('ICD signature')
Measured: 3 years
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
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2020
- Study start27 Jun 2018
- Primary completion1 Sep 2020 (estimated)
- Study completion30 Sep 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- More trials run by Istituto Clinico HumanitasThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Clinico Humanitas
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michele Tedeschi, Istituto Clinico Humanitas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04256616
- Sponsor's protocol ID
- 2041
- Acronym
- ICH-MIM-01
- Status last verified
- Jul 2020
- First submitted
- 3 Feb 2020
- Last updated
- 7 Jul 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Research outcome
Publications
Oresta B, Pozzi C, Braga D, Hurle R, Lazzeri M, Colombo P, Frego N, Erreni M, Faccani C, Elefante G, Barcella M, Guazzoni G, Rescigno M. Mitochondrial metabolic reprogramming controls the induction of immunogenic cell death and efficacy of chemotherapy in bladder cancer. Sci Transl Med. 2021 Jan 6;13(575):eaba6110. doi: 10.1126/scitranslmed.aba6110.
PubMed 33408185
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunogenic Cell Death as a Novel Mechanism of Mitomycin C Activity in Bladder Cancer
- ClinicalTrials.gov ID
- NCT04256616
- Acronym / sponsor ID
- ICH-MIM-01 / 2041
- Conditions
- Bladder Cancer
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- Istituto Clinico HumanitasUniversity, hospital or other
- Study start
- 27 Jun 2018 (actual)
- Primary completion
- 1 Sep 2020 (estimated)
- Study completion
- 30 Sep 2020 (estimated)
- First posted
- 5 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bladder cancer 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.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 |
| Controls- Healthy subjects | – | 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.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. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 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.
Key inclusion criteria (3 listed)
- Male and females, > 40 years old
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Other | Bladder cancer patients, Controls- Healthy subjects |
Primary outcome
MMC-induced ICD
Time frame: 3 years
The main aim of this study is to evaluate whether MMC is able to trigger ICD in patient-derived neoplastic tissues.
2 secondary outcomes
ICD signature analyzed by RNAseq analysis
Time frame: 3 years
Microbiota study
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2020.
- Derived from this study: PubMed 33408185Oresta B, Pozzi C, Braga D, Hurle R, Lazzeri M, Colombo P, Frego N, Erreni M, Faccani C, Elefante G, Barcella M, Guazzoni G, Rescigno M. Mitochondrial metabolic reprogramming controls the induction of immunogenic cell death and efficacy of chemotherapy in bladder cancer. Sci Transl Med. 2021 Jan 6;13(575):eaba6110. doi: 10.1126/scitranslmed.aba6110.
- Individual participant dataSharing planned: No. Research outcome
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Bladder Cancer, run by Istituto Clinico Humanitas at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Maria Rescigno, PhD (+390282245431, maria.rescigno@hunimed.eu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MMC-induced ICD (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04256616, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2020.