Immune Profiling After HDR in Local Relapsed Prostate Cancer (PRIMUS)

Prostate Cancer Immune Profiling Before, During and After HDR-brachytherapy in Local Relapsed Prostate Cancer (PRIMUS-study)

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer; PD-L1
• Intervention / Treatment: Radiation: HDR salvage brachytherapy

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 Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands, 6229 ET
    • Maastro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Patients with local relapse of prostate cancer, who are candidate for a salvage HDR treatment will be asked to participate in this study at the time of intake.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expression of PD-(L)-1 receptor	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.	up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expression patterns of CXCL12	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	up to 28 days
Expression patterns of IL-23	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	up to 28 days
Expression patterns of MDSC	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	up to 28 days
Changes in T cell infiltration profiles	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	up to 28 days
Changes in HLA class I-A expression on tumor cells	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	up to 28 days
Changes in HLA class I-B expression on tumor cells	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	up to 28 days
Changes in HLA class I-C expression on tumor cells	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	up to 28 days

Collaborators and Investigators

• Sponsor: Maastricht Radiation Oncology
• Investigators: Principal Investigator: Ben Vanneste, MD, PhD, Maastro

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2020
• Primary Completion (Actual): December 23, 2021
• Study Completion (Actual): December 23, 2021

Study Registration Dates

• First Submitted: January 17, 2020
• First Submitted That Met QC Criteria: January 28, 2020
• First Posted (Actual): January 29, 2020

Study Record Updates

• Last Update Posted (Actual): May 26, 2022
• Last Update Submitted That Met QC Criteria: May 19, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: PRIMUS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No