Bladder CancerNCT06341478
Investigator Grant (IG) 2022 27746
A study testing various neoadjuvant therapies in people with Bladder Cancer, run by IRCCS San Raffaele at 1 site in Italy.
Trial summary
Background: Muscle-invasive bladder cancer (MIBC) is a systemic disease as >40% of patients (pts) ultimately develop recurrence after radical cystectomy (RC). For pts who cannot receive or refuse cisplatin-based chemotherapy there is no standard-of-care neoadjuvant therapy. 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?
- various neoadjuvant therapies
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 153 participants
- Where
- 1 siteItaly
- Study dates
- 15 Mar 2024to 15 Mar 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Inclusion in NureCombo (NCT04876313), SURE-01 (NCT05226117), and SURE-02 (NCT05535218) clinical trials or candidates to radical cystectomy as per routine clinical practice.
- 2. Histopathologically-confirmed urothelial carcinoma (UC). 3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 4. Clinical stage T2-T4N0M0, muscle-invasive bladder cancer (MIBC)
Who cannot join
- Refusal to partecipate to the above studies
- Unavailability of baseline tumor and blood samples
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Rossella Miotti, PhD contact
Italy1 site, 1 recruiting
- Recruiting
IRCCS Ospedale San Raffaele
Milan, Mi, 20132
Andrea Necchi, MD, +390226435789, necchi.andrea@hsr.it
Rossella Miotti, PhD, miotti.rossella@hsr.it
About this study
Official title: Understanding Tumor and Immune Dynamics and Predicting Response to Various Perioperative Therapies in Patients With Muscle-invasive Bladder Cancer
Background:
Muscle-invasive bladder cancer (MIBC) is a systemic disease as >40% of patients (pts) ultimately develop recurrence after radical cystectomy (RC). For pts who cannot receive or refuse cisplatin-based chemotherapy there is no standard-of-care neoadjuvant therapy. Single-agent pembrolizumab, given neoadjuvantly in patients with T2-4N0M0 MIBC, documented a 42% pathologic complete response-rate (ypT0N0) in a previous AIRC-supported trial (PURE-01, NCT02736266; PMID: 30343614). However, there is a huge proportion of pts who do not benefit from single-agent immunotherapy. Antibody-drug conjugates (ADC) represent the next wave of MIBC treatment revolution. An umbrella of various neoadjuvant therapies including the ADC Sacituzumab govitecan (SG), SG plus pembrolizumab, and chemoimmunotherapy combination has been established to improve our knowledge on MIBC biology and to improve the outcomes.
Read more
Hypothesis:
By developing a robust biomarker program associated with therapeutic benefit of novel therapies or their combinations, along with an imaging biomarker development, the investigators will be able to identify suitable tumor characteristics for personalizing perioperative therapies in MIBC, coupled with the possibility to predict the pathological response to treatment.
Aims:
The project is aimed at characterizing the tumor and microenvironment characteristics of muscle-invasive bladder cancer, with a special focus on their changes induced by various neoadjuvant therapies preceding radical cystectomy.
The investigators will aim to evaluate the tumor and immune profile on matched pre- vs post-therapy samples and noninvasively monitor the response to treatment with the use of radiological assessments.
Experimental design:
The investigators will access tumor samples from matched pre-therapy (transurethral resection of the bladder tumor) and post-therapy (radical cystectomy) surgical interventions. They will also analyze the imaging analyses of combined bladder multiparametric MRI/Fluorodeoxyglucose Positron Emission Tomography (PET) scans pre-post neoadjuvant therapies, and will associate the data with the pathological response to treatment, expanding our previously reported work (PMID: 31882281).
Biomarker analyses will include the following: i.) multiplex immunofluorescence assays will allow the investigators defining the immune contexture of tumor lesion; ii.) multiparametric flow cytometry will allow the phenotypic and functional analysis of peripheral blood cells at single cell level; iii.) a whole transcriptome assay will enable investigators to assign specific molecular subtypes to pathological response and outcome, as previously reported (PMID: 33785257; 32165065).
Expected results:
The investigators will expect to identify the tumor characteristics and immune-profiling enabling them to delineate the selection of patients most suited for certain novel perioperative therapies, thus anticipating the developments in clinical research that are being conducted worldwide in MIBC.
The investigators will be also able to develop noninvasive tools for pathological complete response identification, thus enabling them to develop a next-generation of clinical trials aimed at sparing any radical local therapy on the bladder tumor.
Impact on cancer:
In principle, the present personalized strategy yields the potential to enhance the therapeutic standards achievable with RC alone as well as with single-agent immunotherapy and RC.
- Conditions
- Bladder Cancer
- Being tested
- various neoadjuvant therapies
- 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.
various neoadjuvant therapiesDrug
Radical cystectomy, Sacituzumab Govitecan (SG), SG + pembrolizumab, nivolumab+abraxane
| Study group | Role | What they receive |
|---|---|---|
| Radical cystectomy | Active comparator | Radical cystectomy and pelvic lymphadenectomy upfront, according to the standar-of-care management Receives: Drug: various neoadjuvant therapies |
| Sacituzumab Govitecan | Experimental | SURE-01 trial: 4 courses of sacituzumab Govitecan, intravenously, at the dose of 7.5 mg/Kg on Day 1 and 8, every 21 days. Receives: Drug: various neoadjuvant therapies |
| Sacituzumab Govitecan + pembrolizumab | Experimental | SURE-02 trial: 4 courses of sacituzumab Govitecan, intravenously, at the dose of 7.5 mg/Kg on Day 1 and 8, every 21 days, added to pembrolizumab, intravenously, at the dose of 200 mg every 21 days, followed by radical cystectomy. After cystectomy, 13 courses of 200 mg pembrolizumab, intravenously, every 21 days. Receives: Drug: various neoadjuvant therapies |
| Nivolumab + abraxane | Experimental | NureCombo trial: 4 cycles of 360 mg nivolumab, every 3 weeks, added to nab-paclitaxel 125 mg/m2 on days 1 and 8, every 21 days, before radical cystectomy. After cystectomy, 13 courses of 360 mg nivolumab, intravenously, every 21 days. Receives: Drug: various neoadjuvant therapies |
What is being measured
The primary outcome is the main question the study is designed to answer.
Predictors of immune response to experimental combination therapies in MIBC.
Proportion of polymorphonuclear (PMN) cells, PMN-myeloid-derived suppressor cells (MDSCs), and intermediate monocytes (CD14+CD16+) in baseline blood samples of pathological complete responders compared to non-complete responders (pathological partial responders, pPR) and pathological nonresponders (pNR, ypT≥2N0 and ypN+).
Measured: Baseline (pre-therapy) to radical cystectomy
Genomic predictors of response to experimental combination therapies in MIBC.
Proportion of gene mutations and fusions in baseline tumor samples of pathological complete responders compared to non-complete responders (pathological partial responders, pPR) and pathological nonresponders (pNR, ypT≥2N0 and ypN+).
Measured: Baseline (pre-therapy) to radical cystectomy
Transcriptomic predictors of response to experimental combination therapies in MIBC.
Proportion of single gene or gene pathways signature scores in baseline tumor samples of pathological complete responders compared to non-complete responders (pathological partial responders, pPR) and pathological nonresponders (pNR, ypT≥2N0 and ypN+).
Measured: Baseline (pre-therapy) to radical cystectomy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2024
- Study start15 Mar 2024
- Primary completion15 Mar 2026 (estimated)
- Study completion15 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Post-hoc biomarker analyses of ongoing phase 2 studies
- Masking
- None (open label)
- Enrolment
- 153 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrea Necchi, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06341478
- Sponsor's protocol ID
- IG-2022-27746
- Status last verified
- Mar 2024
- First submitted
- 19 Mar 2024
- Last updated
- 2 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Understanding Tumor and Immune Dynamics and Predicting Response to Various Perioperative Therapies in Patients With Muscle-invasive Bladder Cancer
- ClinicalTrials.gov ID
- NCT06341478
- Acronym / sponsor ID
- IG-2022-27746
- Conditions
- Bladder Cancer
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 153 participants (estimated)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Study start
- 15 Mar 2024 (actual)
- Primary completion
- 15 Mar 2026 (estimated)
- Study completion
- 15 Mar 2027 (estimated)
- First posted
- 2 Apr 2024 (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.
Background:
Muscle-invasive bladder cancer (MIBC) is a systemic disease as >40% of patients (pts) ultimately develop recurrence after radical cystectomy (RC). For pts who cannot receive or refuse cisplatin-based chemotherapy there is no standard-of-care neoadjuvant therapy. Single-agent pembrolizumab, given neoadjuvantly in patients with T2-4N0M0 MIBC, documented a 42% pathologic complete response-rate (ypT0N0) in a previous AIRC-supported trial (PURE-01, NCT02736266; PMID: 30343614). However, there is a huge proportion of pts who do not benefit from single-agent immunotherapy. Antibody-drug conjugates (ADC) represent the next wave of MIBC treatment revolution. An umbrella of various neoadjuvant therapies including the ADC Sacituzumab govitecan (SG), SG plus pembrolizumab, and chemoimmunotherapy combination has been established to improve our knowledge on MIBC biology and to improve the outcomes.
Hypothesis:
By developing a robust biomarker program associated with therapeutic benefit of novel therapies or their combinations, along with an imaging biomarker development, the investigators will be able to identify suitable tumor characteristics for personalizing perioperative therapies in MIBC, coupled with the possibility to predict the pathological response to treatment.
Aims:
The project is aimed at characterizing the tumor and microenvironment characteristics of muscle-invasive bladder cancer, with a special focus on their changes induced by various neoadjuvant therapies preceding radical cystectomy.
The investigators will aim to evaluate the tumor and immune profile on matched pre- vs post-therapy samples and noninvasively monitor the response to treatment with the use of radiological assessments.
Experimental design:
The investigators will access tumor samples from matched pre-therapy (transurethral resection of the bladder tumor) and post-therapy (radical cystectomy) surgical interventions. They will also analyze the imaging analyses of combined bladder multiparametric MRI/Fluorodeoxyglucose Positron Emission Tomography (PET) scans pre-post neoadjuvant therapies, and will associate the data with the pathological response to treatment, expanding our previously reported work (PMID: 31882281).
Biomarker analyses will include the following: i.) multiplex immunofluorescence assays will allow the investigators defining the immune contexture of tumor lesion; ii.) multiparametric flow cytometry will allow the phenotypic and functional analysis of peripheral blood cells at single cell level; iii.) a whole transcriptome assay will enable investigators to assign specific molecular subtypes to pathological response and outcome, as previously reported (PMID: 33785257; 32165065).
Expected results:
The investigators will expect to identify the tumor characteristics and immune-profiling enabling them to delineate the selection of patients most suited for certain novel perioperative therapies, thus anticipating the developments in clinical research that are being conducted worldwide in MIBC.
The investigators will be also able to develop noninvasive tools for pathological complete response identification, thus enabling them to develop a next-generation of clinical trials aimed at sparing any radical local therapy on the bladder tumor.
Impact on cancer:
In principle, the present personalized strategy yields the potential to enhance the therapeutic standards achievable with RC alone as well as with single-agent immunotherapy and RC.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Post-hoc biomarker analyses of ongoing phase 2 studies
| Arm | Type | Receives |
|---|---|---|
| Radical cystectomy | Active comparator | Drug: various neoadjuvant therapiesRadical cystectomy and pelvic lymphadenectomy upfront, according to the standar-of-care management |
| Sacituzumab Govitecan | Experimental | Drug: various neoadjuvant therapiesSURE-01 trial: 4 courses of sacituzumab Govitecan, intravenously, at the dose of 7.5 mg/Kg on Day 1 and 8, every 21 days. |
| Sacituzumab Govitecan + pembrolizumab | Experimental | Drug: various neoadjuvant therapiesSURE-02 trial: 4 courses of sacituzumab Govitecan, intravenously, at the dose of 7.5 mg/Kg on Day 1 and 8, every 21 days, added to pembrolizumab, intravenously, at the dose of 200 mg every 21 days, followed by radical cystectomy. After cystectomy, 13 courses of 200 mg pembrolizumab, intravenously, every 21 days. |
| Nivolumab + abraxane | Experimental | Drug: various neoadjuvant therapiesNureCombo trial: 4 cycles of 360 mg nivolumab, every 3 weeks, added to nab-paclitaxel 125 mg/m2 on days 1 and 8, every 21 days, before radical cystectomy. After cystectomy, 13 courses of 360 mg nivolumab, intravenously, every 21 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Inclusion in NureCombo (NCT04876313), SURE-01 (NCT05226117), and SURE-02 (NCT05535218) clinical trials or candidates to radical cystectomy as per routine clinical practice.
- 2. Histopathologically-confirmed urothelial carcinoma (UC). 3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 4. Clinical stage T2-T4N0M0, muscle-invasive bladder cancer (MIBC)
Key exclusion criteria (2 listed)
- Refusal to partecipate to the above studies
- Unavailability of baseline tumor and blood samples
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 |
|---|---|---|
| various neoadjuvant therapiesRadical cystectomy, Sacituzumab Govitecan (SG), SG + pembrolizumab, nivolumab+abraxane | Drug | Nivolumab + abraxane, Radical cystectomy, Sacituzumab Govitecan, Sacituzumab Govitecan + pembrolizumab |
Primary outcome
Predictors of immune response to experimental combination therapies in MIBC.
Time frame: Baseline (pre-therapy) to radical cystectomy
Proportion of polymorphonuclear (PMN) cells, PMN-myeloid-derived suppressor cells (MDSCs), and intermediate monocytes (CD14+CD16+) in baseline blood samples of pathological complete responders compared to non-complete responders (pathological partial responders, pPR) and pathological nonresponders (pNR, ypT≥2N0 and ypN+).
Genomic predictors of response to experimental combination therapies in MIBC.
Time frame: Baseline (pre-therapy) to radical cystectomy
Proportion of gene mutations and fusions in baseline tumor samples of pathological complete responders compared to non-complete responders (pathological partial responders, pPR) and pathological nonresponders (pNR, ypT≥2N0 and ypN+).
Transcriptomic predictors of response to experimental combination therapies in MIBC.
Time frame: Baseline (pre-therapy) to radical cystectomy
Proportion of single gene or gene pathways signature scores in baseline tumor samples of pathological complete responders compared to non-complete responders (pathological partial responders, pPR) and pathological nonresponders (pNR, ypT≥2N0 and ypN+).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2024.
- Individual participant dataSharing planned: No
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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.
Rossella Miotti, PhD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing various neoadjuvant therapies in people with Bladder Cancer, run by IRCCS San Raffaele 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 2 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: looking for participants now, as of the sponsor's last update on 2 Apr 2024. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Andrea Necchi, MD (+390226435789, necchi.andrea@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Predictors of immune response to experimental combination therapies in MIBC. (time frame: Baseline (pre-therapy) to radical cystectomy). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Apr 2024.