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

University of Verona

Status: Active, not recruiting

Conditions: Metastatic Prostate Cancer

Treatments: Procedure: biopsy; Procedure: Prostate biopsy

Study type: Observational

Funder types: Other

Identifiers

NCT07352748

296CET

Details and patient eligibility

About

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.

Enrollment: 30 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

30 participants in 2 patient groups

Patients with histological diagnosis of advanced prostate cancer who started hormone therapy

Description:

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.

Treatment:

Procedure: biopsy

Patients due for prostate biopsy to confirm the diagnosis of a prostate adenocarcinoma at high risk

Description:

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.

Treatment:

Procedure: Prostate biopsy