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NCT Number: NCT07352748

Exploiting Heterogeneity in Hormone Therapy Response to Reveal Early Determinants of Drug Resistance in Advanced PCa

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Metastatic Prostate Cancer Genital Diseases Genital Diseases, Male Genital Neoplasms, Male Male Urogenital Diseases Neoplasms Neoplasms by Site Prostatic Diseases Prostatic Neoplasms Urogenital Diseases Urogenital Neoplasms

Age range

18 year and older

Sex eligibility

Male

Study type

Observational

Primary location

Università di Verona

Verona, VR, 37134, Italy

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Group A:

  • 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.

Inclusion criteria

Group B:

  • 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:
  • 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

Treatment and study plan

Biopsy

Procedure

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 biopsy

Procedure

Fresh and FFPE block tumor biopsies at baseline

Primary outcomes

  1. 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

  2. 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.

  3. 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.

  4. 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.

Sponsors and collaborators

Lead sponsor

Universita di Verona

Other

Registry information

Acronym: MOSAIC

Important dates

Study start
2024
Primary completion
2025
Study completion
2026
First posted
Jan 20, 2026
Registry last updated
Jan 28, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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