Metastatic Prostate CancerMOSAICNCT07352748
Exploiting Heterogeneity in Hormone Therapy Response to Reveal Early Determinants of Drug Resistance in Advanced PCa
An observational study of Metastatic Prostate Cancer, run by Universita di Verona at 1 site in Italy.
Trial summary
The goal of this observational study is to study intra-patient tumor and TME heterogeneity after initiation of hormonal therapy (ADT +- ARSI), while the patient is responding to treatment, to understand the drivers of hormonal therapy resistance and identify potential novel therapeutic targets in metastatic prostate… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Prostate Cancer
- What is being tested?
- biopsy and Prostate biopsy
- Type of treatment
- Surgery or procedure
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- 17 Oct 2024to 17 Oct 2026
- How long will I take part?
- 2 Years
- Phase
- Observational
- 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
- Men only
- No healthy volunteers
- Adult, Older adult
Study population: Patients with prostate cancer receiving care at Azienda Ospedaliera Universitaria Integrata di Verona, Italy.
Who may be able to join
- Patients with histological diagnosis of advanced prostate cancer (defined as the presence of metastatic disease, including both metastatic hormone naïve prostate cancer patients and metastatic castration resistant prostate cancer patients);
- Patients who started ADT or ADT plus AR inhibitor therapy (Enzalutamide, Darolutamide or Apalutamide or Abiraterone) in a standard therapy.
- Have accessible metastatic and/or primitive disease to perform a biopsy safely during hormonal therapy (ADT or ADT plus AR inhibitor therapy) and before hormonal therapy (alternatively, as a basal biopsy could be used archival FFPE or frozen tumor material left over from surgical procedures or previous biopsies, if available)
- Written acceptance of informed consent to be included in the present study.
- Aged 18 or over.
- Patients due for prostate biopsy to confirm the diagnosis of a prostate adenocarcinoma at high risk of metastatic disease. High risk is defined as follows:
Show all 10Show fewer
- PSA >=20ng/dL with or without imaging suggestive of metastatic prostate cancer OR
- PSA >=10 ng/mL and <= 20 ng/mL AND >=33% risk to have a high grade disease on prostate biopsy according to the MSKCC nomogram "Risk of high grade cancer of prostate biopsy" (https://www.mskcc.org/nomograms/prostate/biopsy_risk_dynamic).
- Written acceptance of informed consent to be included in the present study.
- Aged 18 or over
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
The goal of this observational study is to study intra-patient tumor and TME heterogeneity after initiation of hormonal therapy (ADT +- ARSI), while the patient is responding to treatment, to understand the drivers of hormonal therapy resistance and identify potential novel therapeutic targets in metastatic prostate cancer patients. The main question it aims to answer if intra-tumor adaptive mechanisms including expression of immune checkpoint proteins and changes in the tumor immune infiltrate are related to the induction of a senescent phenotype in response to hormonal therapy.
Participants will asked to provide an FFPE and/or fresh biopsy sample from the primary tumor or a metastatic site at baseline (before starting hormonal therapy) and during the course of hormonal therapy. Additionally, a maximum of 2 blood tubes (10ml) will be collected each time.
- Conditions
- Metastatic Prostate Cancer
- Being tested
- biopsy, Prostate biopsy
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
biopsyProcedure or surgery
A fresh tumor biopsies and an FFPE block will be taken at baseline (alternatively, as a basal biopsy could be used archival FFPE tumor material left over from surgical procedures or previous biopsies if available and if a fresh biopsy at baseline is not feasible or safe; in case of availability of frozen and FFPE archival blocks, 1 frozen block and 1 FFPE block will be used for the analyses) and after 2-4 weeks of hormonal treatment with ADT and/or AR inhibitors. Biopsies will be performed guided by ultrasound or CT, depending on location. From each Fresh biopsy, 2 core biopsies will be collected, 1 will be processed into an FFPE block, and the second will be processed according to freezing procedures.
Prostate biopsyProcedure or surgery
Fresh and FFPE block tumor biopsies at baseline
| Study group | Role | What they receive |
|---|---|---|
| Patients with histological diagnosis of advanced prostate cancer who started hormone therapy | A fresh tumor biopsies and FFPE block will be taken at baseline and after 4 weeks of hormone therapy and/or AR targeting agents. Blood samples for the isolation of plasma, serum and PBMC will be collected before the start of therapy and after 4 weeks of hormone therapy and/or AR targeting agents. The correlation of biopsies analyses and clinical data will advance the understanding of prostate cancer progression pathways and guide the design of subsequent studies in the field of personalized medicine. Receives: Procedure: biopsy | |
| Patients due for prostate biopsy to confirm the diagnosis of a prostate adenocarcinoma at high risk | A fresh tumor biopsies and FFPE block and blood samples for the isolation of plasma, serum and PBMC will be taken at baseline. This cohort was necessary because it is complex to intercept patients at the time they perform diagnostic biopsy and then obtain fresh biopsies pre-hormonal treatment. If patients of this group will metastasize, these patients will be incorpored in the other. Receives: Procedure: Prostate biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
A) Density of tumor-infiltrating immune cells
Description: Density of tumor-infiltrating lymphocytes (CD3+, CD4+, CD8+, FOXP3+) assessed by multiplex immunohistochemistry in tumor biopsies from patients under hormonal therapy.
Unit of Measure: Cells/mm²
Measured: From enrollment to 24 months
Tumor expression of Immune checkpoints
The investigators will pursue IHC assessment of immunomodulatory proteins. I will use a multiplexed customized IHC panel and the expression of the immunomodulatory proteins will be assessed in a semiquantitative manner (negative, 1+, 2+, 3+) in different tumor areas. I will compare the expression of immunomodulatory proteins assessed on human prostate cancer biopsies under hormonal treatment with same-patient pre-treatment therapy biopsies.
Measured: From enrollment to 24 months
Emergence of a senescent phenotype
The investigators will confirm in vivo, in human samples, the senescent phenotype described in prostate cancer preclinical models, assessing the SA-Beta-Gal activity on fresh OCT-embedded biopsies and/or testing the telomere shortening in FFPE biopsies, depending If will be feasible to collect both fresh frozen and FFPE cores biopsies.
Measured: From enrollment to 24 months
Changes in expression of prostate cancer-specific markers and therapeutic targets.
The investigators will also test the expression of prostate cancer specific markers PSMA, STEAP1, STEAP2 in response to AR blockade by IHC in pre-treatment vs post-treatment samples.
Measured: From enrollment to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2026
- Study start17 Oct 2024
- Primary completion11 Sep 2025
- Study completion17 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Prostate CancerStudies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- Universita di Verona
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Francesca Zacchi, Universita di Verona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07352748
- Sponsor's protocol ID
- 296CET
- Acronym
- MOSAIC
- Status last verified
- Jan 2026
- First submitted
- 23 Sep 2025
- Last updated
- 28 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploiting Heterogeneity in Hormone Therapy Response to Reveal Early Determinants of Drug Resistance in Advanced PCa
- ClinicalTrials.gov ID
- NCT07352748
- Acronym / sponsor ID
- MOSAIC / 296CET
- Conditions
- Metastatic Prostate Cancer
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Universita di VeronaUniversity, hospital or other
- Study start
- 17 Oct 2024 (actual)
- Primary completion
- 11 Sep 2025 (actual)
- Study completion
- 17 Oct 2026 (estimated)
- First posted
- 20 Jan 2026 (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 goal of this observational study is to study intra-patient tumor and TME heterogeneity after initiation of hormonal therapy (ADT +- ARSI), while the patient is responding to treatment, to understand the drivers of hormonal therapy resistance and identify potential novel therapeutic targets in metastatic prostate cancer patients. The main question it aims to answer if intra-tumor adaptive mechanisms including expression of immune checkpoint proteins and changes in the tumor immune infiltrate are related to the induction of a senescent phenotype in response to hormonal therapy.
Participants will asked to provide an FFPE and/or fresh biopsy sample from the primary tumor or a metastatic site at baseline (before starting hormonal therapy) and during the course of hormonal therapy. Additionally, a maximum of 2 blood tubes (10ml) will be collected each time.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Years
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with histological diagnosis of advanced prostate cancer who started hormone therapy | – | Procedure: biopsyA fresh tumor biopsies and FFPE block will be taken at baseline and after 4 weeks of hormone therapy and/or AR targeting agents. Blood samples for the isolation of plasma, serum and PBMC will be collected before the start of therapy and after 4 weeks of hormone therapy and/or AR targeting agents. The correlation of biopsies analyses and clinical data will advance the understanding of prostate cancer progression pathways and guide the design of subsequent studies in the field of personalized medicine. |
| Patients due for prostate biopsy to confirm the diagnosis of a prostate adenocarcinoma at high risk | – | Procedure: Prostate biopsyA fresh tumor biopsies and FFPE block and blood samples for the isolation of plasma, serum and PBMC will be taken at baseline. This cohort was necessary because it is complex to intercept patients at the time they perform diagnostic biopsy and then obtain fresh biopsies pre-hormonal treatment. If patients of this group will metastasize, these patients will be incorpored in the other. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with prostate cancer receiving care at Azienda Ospedaliera Universitaria Integrata di Verona, Italy.
Key inclusion criteria (10 listed)
- Patients with histological diagnosis of advanced prostate cancer (defined as the presence of metastatic disease, including both metastatic hormone naïve prostate cancer patients and metastatic castration resistant prostate cancer patients);
- Patients who started ADT or ADT plus AR inhibitor therapy (Enzalutamide, Darolutamide or Apalutamide or Abiraterone) in a standard therapy.
- Have accessible metastatic and/or primitive disease to perform a biopsy safely during hormonal therapy (ADT or ADT plus AR inhibitor therapy) and before hormonal therapy (alternatively, as a basal biopsy could be used archival FFPE or frozen tumor material left over from surgical procedures or previous biopsies, if available)
- Written acceptance of informed consent to be included in the present study.
- Aged 18 or over.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| biopsyA fresh tumor biopsies and an FFPE block will be taken at baseline (alternatively, as a basal biopsy could be used archival FFPE tumor material left over from surgical procedures or previous biopsies if available and if a fresh biopsy at baseline is not feasible or safe; in case of availability of frozen and FFPE archival blocks, 1 frozen block and 1 FFPE block will be used for the analyses) and after 2-4 weeks of hormonal treatment with ADT and/or AR inhibitors. Biopsies will be performed guided by ultrasound or CT, depending on location. From each Fresh biopsy, 2 core biopsies will be collected, 1 will be processed into an FFPE block, and the second will be processed according to freezing procedures. | Procedure or surgery | Patients with histological diagnosis of advanced prostate cancer who started hormone therapy |
| Prostate biopsyFresh and FFPE block tumor biopsies at baseline | Procedure or surgery | Patients due for prostate biopsy to confirm the diagnosis of a prostate adenocarcinoma at high risk |
Primary outcome
A) Density of tumor-infiltrating immune cells
Time frame: From enrollment to 24 months
Description: Density of tumor-infiltrating lymphocytes (CD3+, CD4+, CD8+, FOXP3+) assessed by multiplex immunohistochemistry in tumor biopsies from patients under hormonal therapy. Unit of Measure: Cells/mm²
Tumor expression of Immune checkpoints
Time frame: From enrollment to 24 months
The investigators will pursue IHC assessment of immunomodulatory proteins. I will use a multiplexed customized IHC panel and the expression of the immunomodulatory proteins will be assessed in a semiquantitative manner (negative, 1+, 2+, 3+) in different tumor areas. I will compare the expression of immunomodulatory proteins assessed on human prostate cancer biopsies under hormonal treatment with same-patient pre-treatment therapy biopsies.
Emergence of a senescent phenotype
Time frame: From enrollment to 24 months
The investigators will confirm in vivo, in human samples, the senescent phenotype described in prostate cancer preclinical models, assessing the SA-Beta-Gal activity on fresh OCT-embedded biopsies and/or testing the telomere shortening in FFPE biopsies, depending If will be feasible to collect both fresh frozen and FFPE cores biopsies.
Changes in expression of prostate cancer-specific markers and therapeutic targets.
Time frame: From enrollment to 24 months
The investigators will also test the expression of prostate cancer specific markers PSMA, STEAP1, STEAP2 in response to AR blockade by IHC in pre-treatment vs post-treatment samples.
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 28 Jan 2026.
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RecruitingPhase 2
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Active, not recruitingPhase 2
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Metastatic Prostate Cancer, run by Universita di Verona 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 10 inclusion and 0 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: under way, not looking for participants, as of the sponsor's last update on 28 Jan 2026. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
A) Density of tumor-infiltrating immune cells (time frame: From enrollment to 24 months). The study lists 4 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 28 Jan 2026.