PRIMUS: Immune Profiling After HDR in Local Relapsed Prostate Cancer

Sponsor

Maastricht Radiation Oncology (Other)

Overall Status

Completed

CT.gov ID

NCT04247217

Collaborator

(none)

Enrollment

Location

22.1

Actual Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer PD-L1	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 Design

Study Type:

Observational

Actual Enrollment :

10 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Feb 19, 2020

Actual Primary Completion Date :

Dec 23, 2021

Actual Study Completion Date :

Dec 23, 2021

Outcome Measures

Primary Outcome Measures

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

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 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
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
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
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maastro	Maastricht		Netherlands	6229 ET

Sponsors and Collaborators

Maastricht Radiation Oncology

Investigators

Principal Investigator: Ben Vanneste, MD, PhD, Maastro

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Maastricht Radiation Oncology

ClinicalTrials.gov Identifier:

NCT04247217

Other Study ID Numbers:

PRIMUS

First Posted:

Jan 29, 2020

Last Update Posted:

May 26, 2022

Last Verified:

May 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Prostatic Neoplasms

Study Results

No Results Posted as of May 26, 2022