Immune Profiling After HDR in Local Relapsed Prostate Cancer

Prostate Cancer Clinical Trial

— PRIMUS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04247217
• Other study ID #: PRIMUS
• Status: Completed
• Start date: February 19, 2020
• Est. completion date: December 23, 2021

Study information

• Verified date: May 2022
• Source: Maastricht Radiation Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: December 23, 2021
• Est. primary completion date: December 23, 2021
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• PD-L1
• Prostate Cancer
• Prostatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
Netherlands	Maastro	Maastricht

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht Radiation Oncology

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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