Primary Objective: • To evaluate the ability to concentrate the radiotracer in prostatic cancer lesions ( with respect to accumulation in background tissues) by prostatic artery injection (PAI), especially within the prostate gland compared to…
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Increase the ratio target (prostate cancer lesion) vs. non-target to
background (gluteal muscle and blood pool) accumulation by 30% with
intra-arterial compared to systemic administration evaluated on PET/CT images
using SUV(mean and/ or max)
Secondary outcome
• Lower the ratio target vs. non-target tissue accumulation, especially to the
kidneys and salivary glands, by 30% compared to systemic administration
evaluated via the radiation measured on PET/CT images SUV(mean and/ or max).
• Detection of new lesions in the primary prostate tumor within the prostate
gland or local lymph node identification / micro metastasis after local
administration compared to standard of care systemic administration
• Registration on the number and severity of adverse events (AEs, SAEs and
SUSARs) with intra-arterial compared to systemic administration
• Evaluation of accumulation patterns on PET/CT in the prostate bed after
intra-arterial compared to systemic administration derived by image-based
heterogeneity parameters.
• Estimation of 177Lu-PSMA radiation dose using 18F-DCFPyL accumulation
patterns on PET/CT after intra-arterial vs. systemic administration.
Background summary
Prostate cancer (PCa) is the most common non-cutaneous neoplasm in men.For
patients with local, advanced, or recurrent PCa, there is a great need for the
development and implementation of new treatments that can help to identify and
target the tumor cells.
In 2018 the *image of the year* at the SNMMI was a PSMA PET before and after
lutetium-177 PSMA617 theranostics in 8 patients with metastatic prostate cancer
who exhausted standard therapeutic options with extraordinary results.
Currently the phase III Vision trial is trying to prove scientifically that
this should be standard care in patients with local or of local-regional
disease or distant spread with minimal toxicity.
A peptide small molecule which specifically targets Prostate-Specific Membrane
Antigen (PSMA) trans-membrane antigen which is up regulated on PCa cells has
been developed and used clinically for accurate whole-body positron emission
tomography (PET) imaging. The systemic administration of this PSMA targeting
agent has yielded tremendous clinical success in both imaging and treating PCa
due to its high tumour sensitivity and rapid pharmacokinetic elimination.
However, one limitation is the uptake of the tracer by non-target tissue.
From experience with the minimally invasive transcatheter treatment of liver
tumours, we know that chemotherapy or radiation can be concentrated within a
tumour via directed intra-arterial administration. This technique isolates the
tumour from the systemic circulation, resulting in the concentration of
therapeutic treatment with minimal to no risk of adverse events related to
non-target administration. It is hypothesized a similar procedure can be
successfully utilized in the prostate for both imaging and treatment whereby a
PSMA targeting radiopharmaceutical is directly delivered in an intra-arterial
fashion within the prostatic artery. This minimally invasive procedure will
increase the local concentration of the tracer and allow the tracer to interact
with the providing a superior first pass uptake for the radiopharmaceutical.
Improving the tumour to background ratio for superior imaging and eventually
allowing the substitution of a treatment radionuclide for this procedures
application as a means of localized treatment. Our study aims to determine the
feasibility with intra-arterial injection of 18F-DCFPyL PSMA as a means to
concentration of the tracer within the prostate gland and (loco) regional lymph
nodes and lower the uptake in non-target tissue. And at last to see whether
there are new tumour sites within the prostate or not identified lymph nodes/
micro metastasis.
Study objective
Primary Objective:
• To evaluate the ability to concentrate the radiotracer in prostatic cancer
lesions ( with respect to accumulation in background tissues) by prostatic
artery injection (PAI), especially within the prostate gland compared to
standard systemic intra-venous (IV) administration.
Secondary Objectives:
• To evaluate the PET/CT targeting characteristics of prostatic artery
injection (PAI) with 18F-DCFPyL to non-target tissue; especially to the kidneys
and salivary glands in comparison with IV administration .
• Correlation of 18F-DCFPyL uptake in prostatic lesions and lymph node after
IV and PAI injections with standard multi-parametric MRI
• To evaluate adverse events (AEs, SAEs and SUSARs) after IV and PAI
administration of 18F-DCFPyL
• Show the difference in accumulation pattern for IA vs IV administration of
18F-DCFPyL in the prostate bed.
• Ability to calculate the optimal therapeutic radiation dose for 177Lu-PSMA
therapy
Study design
Phase IIb proof of concept study with one cohort.
Intervention
For this study a catheter directed angiography of the prostate arteries will be
performed in each patient. Direct arterial administration of radiotracer into
the vascular bed of the prostate gland via the prostate artery (both sides).
There will be no changes to the vascularity of the prostate. After the
angiography a PET/CT will be completed.
Study burden and risks
The patient has one extra visit to the hospital as an outpatient procedure for
6 hrs. There is no hospital stay required. The patient will undergo an
additional minimally invasive procedure consisting of an angiogram of the
pelvis and prostate, this procedure uses radiation for imaging of 16-17mSv. No
change in the available treatments or side effects related to the PAI are
expected. The risks of this procedure are small and include damage to a vessel,
bleeding, infection, kidney injury, and anaphylaxis, however these
complications are extremely rare (e.g. less than 1-2%).
18F-DCFPyL PSMA is a commonly employed clinical radiotracer with an excellent
safety profile and low radiation dose of 2-3 mSv. The potential radiation dose
that will be encounter by the prostate with complete absorption of the entire
radiotracer dose within the prostate is safe and negligible, in this extreme
case the radiation dose will have no effect on the prostate or surrounding
pelvic organs.
The patient will undergo a PET/CT scan after the angiography.
Plesmanlaan 121
Amsterdam 1066 CX
NL
Plesmanlaan 121
Amsterdam 1066 CX
NL
Listed location countries
Age
Inclusion criteria
• Age >70 years
• Confirmed histological diagnosis of PCa
• All (T) (N) (M) stages
• The Eastern Cooperative Oncology Group (ECOG) performance status <= 2
• Received a baseline multi-parametric MRI and 18F-DCFPyL PET scan <= 6 month
prior to inclusion in our study done in NKI-AVL
• Demonstrate adequate hematologic and organ function, defined by the following
laboratory results.
• All screening laboratory tests should be performed within 30 days prior to
the procedure:
o Absolute neutrophil count (ANC) >= 1500 cells/µL
o Platelet count >= 100.000/µL
o Hemoglobin >= 5.6 mmol/L
o AST and ALT <= 3 (x ULN)
o Serum bilirubin <= 1.5 (x ULN)
o Serum Creatinine <= 1.5 x ULN OR measured of calculated creatinine clearance
(GFR can also be used in place of creatinine or CrCl) >= 40 mL/min for subject
with creatinine levels.
• Signed Informed Consent Form
Exclusion criteria
• History of concomitant malignancies
• Severe allergy for iodine-based contrast agents
• Prior treatments with brachytherapy or prostatectomy
• Inability to undergo intra-arterial procedure secondary to vascular
abnormalities
• Body weight over 150 kg
• Severe allergy for I.V. contrast used in angiography
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-001219-26-NL |
| CCMO | NL73434.031.20 |