Immune Profiling After HDR in Local Relapsed Prostate Cancer

Completed

• Conditions: Prostate Cancer; PD-L1

• Registration Number: NCT04247217
• Lead Sponsor: Maastricht Radiation Oncology

Brief Summary

Immunotherapy is currently revolutionizing the field in oncology. However, prostate cancer until now fails to respond to classical IO, like PD-1 and CTLA-4 inhibitors. Radiotherapy (RT) delivered to the primary tumor impacts both tumor cells and surrounding stromal cells. Radiation damage to cancer cells exposes tumor-specific antigens leading to increased visibility to the immune system by improved priming and activation of cytotoxic T cells. RT-induced modulation of the tumor microenvironment may also facilitate the recruitment and infiltration of immune cells by increasing the expression or T-cell attracting chemokines and by increasing T-cell docking molecules on the endothelial cells like VCAM-1. The main-hypothesis is that HDR-brachytherapy will turn an immunologically "cold" (no T-cell infiltrations) prostate cancer into an immunologically "hot" (CD4 and CD8-cell infiltrations) tumor, creating leverage points for different forms of IO.

Detailed Description

Prospective analysis of biopsies from 10 patients with local recurrence in the prostate selected for salvage HDR brachytherapy in MAASTRO Clinic, Maastricht. HDR treatment is standard in Maastro Clinic for local relapses of prostate cancer after previously irradiation (internal or external).

Biopsies will be taken at 4 different time points (before and after the 1st fraction; before the 2nd and 3rd fraction of the salvage treatment).

Several immunotyping (expression of PD-(L)-1, CXCL12, IL-23 receptor, etc.) and HLA class I expression will be performed on the biopsies. In addition, HLA genotypes will be determined on DNA isolated from pheripheral blood.

The plasma and the biopsies will be stored for eventually additional research.

Study Timeline

• Study First Submitted: 2020-01-17
• Study First Submitted QC: 2020-01-28
• Study First Posted: 2020-01-29
• Study Start: 2020-02-19
• Primary Completion: 2021-12-23
• Study Completion: 2021-12-23
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-19
• Last Update Posted: 2022-05-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 10

Inclusion Criteria

• Local relapse of prostate cancer, who is candidate for a salvage HDR treatment:

• Biochemical relapse (PSA increase)

• Local relapse on imaging: PSMA scan, mp-MRI

• Pathology proven relapse

  • Willing and able to comply with the study prescriptions.
  • 18 years or older
  • Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion Criteria

• Not eligible for proposed (HDR brachytherapy) treatment:

  • Life expectancy < 10 years
  • Distant Metastasis
  • Recently TURP with big urethral defect
  • Not able to stop anticoagulants
  • Flow < 10 ml/sec • No compliance to study procedure

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Expression of PD-(L)-1 receptor	up to 28 days	Expression of PD-(L)-1 receptor induced by HDR-brachytherapy in prostate tumor biopsies of local relapses of prostate cancer of 10 patients at 4 different time points.

Secondary Outcome Measures

Name	Time	Method
Changes in HLA class I-B expression on tumor cells	up to 28 days	Changes in HLA class I-B expression on tumor cells induced by HDR-brachytherapy in prostate tumor biopsies of local relapses of prostate cancer of 10 patients at 4 different time points
Expression patterns of CXCL12	up to 28 days	Expression of CXCL12 receptor induced by HDR-brachytherapy in prostate tumor biopsies of local relapses of prostate cancer of 10 patients at 4 different time points
Expression patterns of MDSC	up to 28 days	Expression of MDSC receptor induced by HDR-brachytherapy in prostate tumor biopsies of local relapses of prostate cancer of 10 patients at 4 different time points
Expression patterns of IL-23	up to 28 days	Expression of IL-23 receptor induced by HDR-brachytherapy in prostate tumor biopsies of local relapses of prostate cancer of 10 patients at 4 different time points
Changes in HLA class I-C expression on tumor cells	up to 28 days	Changes in HLA class I-C expression on tumor cells induced by HDR-brachytherapy in prostate tumor biopsies of local relapses of prostate cancer of 10 patients at 4 different time points
Changes in T cell infiltration profiles	up to 28 days	Changes in T cell infiltration profiles induced by HDR-brachytherapy in prostate tumor biopsies of local relapses of prostate cancer of 10 patients at 4 different time points
Changes in HLA class I-A expression on tumor cells	up to 28 days	Changes in HLA class I-A expression on tumor cells induced by HDR-brachytherapy in prostate tumor biopsies of local relapses of prostate cancer of 10 patients at 4 different time points

Trial Locations

Locations (1)

Maastro; 🇳🇱 Maastricht, Netherlands