Clinical trial NCT04247217: Immune Profiling After HDR in Local Relapsed Prostate Cancer
Official title: Prostate Cancer Immune Profiling Before, During and After HDR-brachytherapy in Local Relapsed Prostate Cancer (PRIMUS-study)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Prostate Cancer
PD-L1
Lead sponsor: Maastricht Radiation Oncology
Sponsor class: OTHER
First posted: 2020-01-29
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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.

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.

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

Primary outcomes:
measure: Expression of PD-(L)-1 receptor
timeFrame: up to 28 days
Secondary outcomes:
measure: Expression patterns of CXCL12
timeFrame: up to 28 days
measure: Expression patterns of IL-23
timeFrame: up to 28 days
measure: Expression patterns of MDSC
timeFrame: up to 28 days
measure: Changes in T cell infiltration profiles
timeFrame: up to 28 days
measure: Changes in HLA class I-A expression on tumor cells
timeFrame: up to 28 days
measure: Changes in HLA class I-B expression on tumor cells
timeFrame: up to 28 days
measure: Changes in HLA class I-C expression on tumor cells
timeFrame: up to 28 days
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastro
Study officials:
affiliation: Maastro
name: Ben Vanneste, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: