Bladder CancerMITOMARKER-MIMNCT04256122
Expression of Markers Related to Mitochondrial Functionality in Carcinoma of the Urinary Bladder: Comparative Retrospective Analysis Between Recurrent Tumors ("Non-responders") and Non-recurrent Tumors ("Responders") After Intravesical Treatment With Chemotherapy or Immunotherapy
An observational study of Bladder Cancer, run by Istituto Clinico Humanitas at 1 site in Italy.
Trial summary
Retrospective monocentric study evaluating different immunohistochemical phenotypes related to mitochondrial functions with treatment outcomes Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer
- What is being tested?
- No intervantion on patients. retrospective study is performed on paraffin embedded tumor tissue specimens routinely collected during TURBT.
- How many people
- 200 participants
- Where
- 1 siteItaly
- Study dates
- 22 Oct 2019to 31 Dec 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 18 years and older
- All sexes
- Adult, Older adult
Study population: Patients with NMIBC at first diagnosis, pTa/pT1 (primary tumors) treated with MMC or BCG after TURBT will be selected from the institutional patient registry.
Who may be able to join
- >18 years of age at diagnosis
- Histologically confirmed NMIBC urothelial carcinoma of the urinary bladder (pTa, pT1, CIS)
- Primary NMIBC or not treated secondary NMIBC, after a primary non-invasive malignancy
- Patients underwent TURBT for NMIBC at Humanitas between 2000 and 2019
- Patients that received intravesical instillations with either MMC or BCG after TURBT at Humanitas between 2000 and 2019
- Written informed consent to research purpose
Show all 11Show fewer
- For non-recurrent tumors ("responders"):
- Patient treated with adjuvant MMC or BCG that did not experience recurrence for at least 42 months after TURBT
- Patients are tumor-free at the moment of the analysis
- For recurrent tumors ("non-responders"):
- Patient treated with adjuvant MMC or BCG that experienced recurrence in the first 24 months after TURBT.
Who cannot join
- Previous malignancies other that bladder cancer
- Patients with a history of treated bladder cancer recurrences
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
Retrospective monocentric study evaluating different immunohistochemical phenotypes related to mitochondrial functions with treatment outcomes
Read the detailed description
About 80% of newly diagnosed patients have non-muscle-invasive bladder cancer (NMIBC), including papillary lesions confined to the urothelium (stage Ta) or invading the lamina propria (stage T1), and carcinoma in situ (CIS). These tumors show low progression rates, but high recurrence. In particular, patients with multifocal high-grade urothelial carcinoma have a high risk of both recurrence (∼70% after 1 yr) and progression (5% after 1 yr). Initial NMIBC management is a transurethral resection of bladder tumor (TURBT), followed by adjuvant intravesical treatment with the chemotherapeutic agent Mitomycin C (MMC) or the immunotherapy Bacillus Calmette-Guérin (BCG). However, these therapies lead to variable clinical responses and patients recur shortly after surgery. Despite both therapies have been used for decades in the treatment of NMIBC, at the moment it is not possible to predict after initial staging which patients will benefit from them since neither resistance mechanisms nor genetic markers associated to relapse have been identified yet.
In a preliminary analysis, the invesitigators found that low expression of several proteins involved in mitochondrial functions correlate with a worst prognosis in bladder cancer patients. The aim of this study is to detect markers of mitochondrial dysfunction by immunohistochemistry in recurrent tumors ("non-responders") and non-recurrent tumors ("responders") after intravesical treatment with chemotherapy or immunotherapy, and determine the prognostic relevance of these different markers.
- Conditions
- Bladder Cancer
- Being tested
- No intervantion on patients. retrospective study is performed on paraffin embedded tumor tissue specimens routinely collected during TURBT.
- 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.
No intervantion on patients. retrospective study is performed on paraffin embedded tumor tissue specimens routinely collected during TURBT.Other
evaluate an immunophenotypical profile related to mitochondrial functions in tumors responders vs non-responder to intravescical chemotherapy or immunotherapy. Verify the possible prognostic differences in clinical behavior between the two populations.
| Study group | Role | What they receive |
|---|---|---|
| Responder patients | Patients with NMIBC at first diagnosis, pTa/pT1 (primary tumors) treated with MMC or BCG after TURBT will be selected from the institutional patient registry.
* Patient treated with adjuvant MMC or BCG that did not experience recurrence for at least 42 months after TURBT
* Patients are tumor-free at the moment of the analysis Receives: Other: No intervantion on patients. retrospective study is performed on paraffin embedded tumor tissue specimens routinely collected during TURBT. | |
| Non responder patients | Patients with NMIBC at first diagnosis, pTa/pT1 (primary tumors) treated with MMC or BCG after TURBT will be selected from the institutional patient registry.
o Patient treated with adjuvant MMC or BCG that experienced recurrence in the first 24 months after TURBT. Receives: Other: No intervantion on patients. retrospective study is performed on paraffin embedded tumor tissue specimens routinely collected during TURBT. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immunohistochemestry analysis of biomarkers
perform an immunophenotypical analysis to assess the expression of key proteins involved in mitochondrial functionality in recurrent tumors ("non-responders") and non-recurrent tumors ("responders") after intravesical treatment with chemotherapy or immunotherapy.
Measured: 1 year
Secondary outcomes (1)
Correlation of biomarker expression with outcome
- To correlate the resulting phenotype with clinical/pathological response to adjuvant treatments (time to recurrence and presence of recurrence).
Measured: 1 year
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 start22 Oct 2019
- Primary completion31 Oct 2020 (estimated)
- Study completion31 Dec 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
- Retrospective
- Enrolment
- 200 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
- NCT04256122
- Sponsor's protocol ID
- 1191
- Acronym
- MITOMARKER-MIM
- Status last verified
- Feb 2020
- First submitted
- 3 Feb 2020
- Last updated
- 17 Feb 2020
- Results posted
- No
- Data monitoring committee
- 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 17 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Expression of Markers Related to Mitochondrial Functionality in Carcinoma of the Urinary Bladder: Comparative Retrospective Analysis Between Recurrent Tumors ("Non-responders") and Non-recurrent Tumors ("Responders") After Intravesical Treatment With Chemotherapy or Immunotherapy
- ClinicalTrials.gov ID
- NCT04256122
- Acronym / sponsor ID
- MITOMARKER-MIM / 1191
- Conditions
- Bladder Cancer
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Istituto Clinico HumanitasUniversity, hospital or other
- Study start
- 22 Oct 2019 (actual)
- Primary completion
- 31 Oct 2020 (estimated)
- Study completion
- 31 Dec 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.
Retrospective monocentric study evaluating different immunohistochemical phenotypes related to mitochondrial functions with treatment outcomes
Detailed description
About 80% of newly diagnosed patients have non-muscle-invasive bladder cancer (NMIBC), including papillary lesions confined to the urothelium (stage Ta) or invading the lamina propria (stage T1), and carcinoma in situ (CIS). These tumors show low progression rates, but high recurrence. In particular, patients with multifocal high-grade urothelial carcinoma have a high risk of both recurrence (∼70% after 1 yr) and progression (5% after 1 yr). Initial NMIBC management is a transurethral resection of bladder tumor (TURBT), followed by adjuvant intravesical treatment with the chemotherapeutic agent Mitomycin C (MMC) or the immunotherapy Bacillus Calmette-Guérin (BCG). However, these therapies lead to variable clinical responses and patients recur shortly after surgery. Despite both therapies have been used for decades in the treatment of NMIBC, at the moment it is not possible to predict after initial staging which patients will benefit from them since neither resistance mechanisms nor genetic markers associated to relapse have been identified yet.
In a preliminary analysis, the invesitigators found that low expression of several proteins involved in mitochondrial functions correlate with a worst prognosis in bladder cancer patients. The aim of this study is to detect markers of mitochondrial dysfunction by immunohistochemistry in recurrent tumors ("non-responders") and non-recurrent tumors ("responders") after intravesical treatment with chemotherapy or immunotherapy, and determine the prognostic relevance of these different markers.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Responder patients | – | Other: No intervantion on patients. retrospective study is performed on paraffin embedded tumor tissue specimens routinely collected during TURBT.Patients with NMIBC at first diagnosis, pTa/pT1 (primary tumors) treated with MMC or BCG after TURBT will be selected from the institutional patient registry. * Patient treated with adjuvant MMC or BCG that did not experience recurrence for at least 42 months after TURBT * Patients are tumor-free at the moment of the analysis |
| Non responder patients | – | Other: No intervantion on patients. retrospective study is performed on paraffin embedded tumor tissue specimens routinely collected during TURBT.Patients with NMIBC at first diagnosis, pTa/pT1 (primary tumors) treated with MMC or BCG after TURBT will be selected from the institutional patient registry. o Patient treated with adjuvant MMC or BCG that experienced recurrence in the first 24 months after TURBT. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Patients with NMIBC at first diagnosis, pTa/pT1 (primary tumors) treated with MMC or BCG after TURBT will be selected from the institutional patient registry.
Key inclusion criteria (11 listed)
- >18 years of age at diagnosis
- Histologically confirmed NMIBC urothelial carcinoma of the urinary bladder (pTa, pT1, CIS)
- Primary NMIBC or not treated secondary NMIBC, after a primary non-invasive malignancy
- Patients underwent TURBT for NMIBC at Humanitas between 2000 and 2019
- Patients that received intravesical instillations with either MMC or BCG after TURBT at Humanitas between 2000 and 2019
Key exclusion criteria (2 listed)
- Previous malignancies other that bladder cancer
- Patients with a history of treated bladder cancer recurrences
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 |
|---|---|---|
| No intervantion on patients. retrospective study is performed on paraffin embedded tumor tissue specimens routinely collected during TURBT.evaluate an immunophenotypical profile related to mitochondrial functions in tumors responders vs non-responder to intravescical chemotherapy or immunotherapy. Verify the possible prognostic differences in clinical behavior between the two populations. | Other | Non responder patients, Responder patients |
Primary outcome
Immunohistochemestry analysis of biomarkers
Time frame: 1 year
perform an immunophenotypical analysis to assess the expression of key proteins involved in mitochondrial functionality in recurrent tumors ("non-responders") and non-recurrent tumors ("responders") after intravesical treatment with chemotherapy or immunotherapy.
1 secondary outcome
Correlation of biomarker expression with outcome
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 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 11 inclusion and 2 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 17 Feb 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?
Immunohistochemestry analysis of biomarkers (time frame: 1 year). 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 NCT04256122, 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 17 Feb 2020.