Immune Profiling After HDR in Local Relapsed Prostate Cancer

NCT ID: NCT04247217

Last Updated: 2022-05-26

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 10 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-02-19
• Study Completion Date: 2021-12-23

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.

Conditions

Prostate Cancer; PD-L1

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Interventions

HDR salvage brachytherapy

In patients receiving HDR salvage brachytherapy for locally relapsed prostate cancer serial biopsies will be performed at 4 different time points.

Intervention Type: RADIATION

Other Intervention Names

biopsies

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Maastricht Radiation Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ben Vanneste, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Maastro

Locations

Maastro

Maastricht, , Netherlands

Countries

Netherlands

Other Identifiers

PRIMUS

Identifier Type: -

Identifier Source: org_study_id