Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05819606 |
| Other study ID # |
5641 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 15, 2023 |
| Est. completion date |
April 15, 2024 |
Study information
| Verified date |
April 2023 |
| Source |
Fondazione Policlinico Universitario Agostino Gemelli IRCCS |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The primary aim of this large prospective study consists of exploring the correlation among
Volumetric and Radiomic parameters extracted from staging PSMA PET/CT Imaging versus
conventional baseline clinical biochemical data, conventional imaging and the aggressiveness
of the tumor based on the post-surgical-Gleason Score (GS) in patients with intermediate/high
risk prostate cancer (PCa).
Secondarily, Volumetric and Radiomic features extracted from the same PET images will be
compared with the amount of the Circulating Tumor Cells (CTCs), with the expression of
specific receptors on CTCs surface,
Possible mutations encoding androgen receptors (AR) on CTCs surface, and with PSMA density on
primary tumor cells provided by the Immunohistochemistry method (IHC) applied on
post-surgical histological samples.
According to PET images, Volumes of interest (VOI) encompassing the whole prostate with foci
of PSMA uptake suspected for PCa will be drawn to extract semiquantitative and radiomic PET
features.
The association between PSMA PET radiomics and CTCs molecular and genomic panel at staging
could potentially lead to a more personalized and more effective therapeutic chances.
Description:
Background and rationale:
Besides PET semiquantitative assessment, new radiomic parameters could be extracted from
baseline PET/CT images. Radiomics is a high-through put approach that translates medical
images into minable data by extracting many quantitative features describing the intensity,
shape, and heterogeneity of targeted lesions. Radiomic models could indirectly be an
expression of tumor biology behavior and could be considered an additional support, together
with clinical and histological data, to help the clinicians in the diagnostic iter. Recently
PSMA PET metrics were suggested to predict high-risk pathological tumor features in primary
PC patients. As far we know, no large studies have been published about the integration of
PSMA PET/CT radiomic and CTCs amount and their molecular characteristics. This project aims
to gap this knowledge, studying a large dataset of patients in our referral university
hospital by an experienced multidisciplinary team.
OBJECTIVES Primary objective consists of exploring any correlation among volumetric and
radiomic parameters extracted from volume of Interest (VOIs) within the whole prostate from
staging PSMA, PET/CT imaging with baseline conventional clinical, biochemical, radiologic and
histological data in a large prospective consecutive cohort of patients with
intermediate/high risk prostate cancer before radical prostatectomy.
Secondary Objectives: Volumetric and radiomic features extracted from same VOIs will be
compared with the amount of CTCs and with the expression of specific receptors and their
potential mutations on CTCs surface.
METHODS Study design: This is an observational, prospective and monocentric study.
Population: Patients with newly diagnosed biopsy confirmed intermediate/high risk PCa will be
consecutively enrolled.
All patients will undergo a multiparametric MRI (mpMRI) examination at Radiology Department
and a PET/CT with PSMA radioligands for staging in the PET/CT Center, both in the Fondazione
Policlinico Universitario A. Gemelli IRCCS (Rome, Italy). After PET scan all patients will be
eligible for radical prostatectomy.
Study duration: 12 months
Patients Inclusion criteria:
- Age ≥ 18 years old
- Able to sign informed consent
- Biopsy-confirmed intermediate/high risk prostate cancer
- Good compliance to undergo mpMRI scan and PET/CT scan
- Eligible for radical prostatectomy
Patients Exclusion criteria:
- Contraindication to mpMRI (such. Metal implants and/or pacemaker)
- Poor compliance to undergo PET/CT (i.e.claustrophobia)
Variables and procedures
The following clinical conventional parameters will be collected:
age, results of DRE, Prostate-Specific Antigen (PSA) levels, results from mpMRI (PIRADS
categories from 1 to 5 according to v2.1 and biopsy-based Gleason Score (GS).
Furthermore, the amount of circulating tumor cells by the bloodstream peripheral samples
(CTCs), as well as the overexpression of specific receptors on the CTCs surface, such as the
epidermal grow factor receptor (EGFR), PSMA receptor will be assessed.
Genomic data, in terms of possible presence of AR mutation on CTCs will be collected.
ENDPOINTS Primary endpoint
- Association among conventional PET parameters and first-order radiomic features
(tSUVmax, tSUVmean, tMTV, tTLA, tSkewness, tKurtosis) and advances ones, extracted from
VOIs within the whole prostate gland) with PSA, bioptical and post-surgical GS and
positive/negative mpMRI and DRE Secondary endpoints
- Association among above-mentioned PET parameters with the amount of CTCs and with the
expression of specific receptors and their potential mutations on CTCs surface.
Sample size calculation A prospective cohort of 160 patients will be enrolled to develop a
baseline radio-genomic model which is compared to the conventional clinical and histological
parameters at staging, according to the medium per-year number of available PET scans and
current data available on literature.
In depth, Sample size is determined on an AUC measure equal to 0.93 (Zamboglu et al., 2019),
by considering the dichotomized Gleason Score (>=8) as primary outcome, a significance level
(alpha) equal to 0.05, an expected power of the test (1- probability of type II error) equal
to 0.95, and a K=controls/cases ratio equal to 4. Accounting for this, the sample size is
equal to 160.
Randomization: Not any randomization is considered in this protocol
Expected results and impact. Staging PSMA PET/CT metric applied on prostate with suspected
neoplastic involvement would have the potential to predict the extent (in terms of lymph node
involvement or distant metastases) and the aggressiveness of disease based on histological
post-surgical specimen GS, as well as on the PSMA overexpression in percentage on tumor cell
surface assessed by IHC. PSMA PET/CT metric could be associated to consistent amount of CTCs
at diagnosis, as well as increased PSMA OR EGFR expressed on CTCs surface, so paving the way
for a radiogenomic panel, which would lead to a more personalized and more effective
therapeutic chances.
