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Trial Title:
PSMA Expression and PSMA PET Imaging in Soft Tissue Sarcomas and Urothelial Cell Carcinomas
NCT ID:
NCT05522257
Condition:
Sarcoma,Soft Tissue
Urothelial Carcinoma
Conditions: Official terms:
Carcinoma
Sarcoma
Carcinoma, Transitional Cell
Conditions: Keywords:
Prostate Specific Membrane Antigen
Soft Tissue Sarcoma
Urothelial Carcinoma
Urothelial Neoplasm
Transitional Cell Carcinoma
PSMA
PSMA PET/CT
JK-PSMA-7
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
This pilot study is a single centre, open-label, phase II study in patients with advanced
soft tissue sarcoma (cohort 1) and advanced urothelial cell carcinoma (cohort 2). It is a
non-randomized, non-blinded, prospective pilot study to assess the level of PSMA
expression and the feasibility of PSMA-targeted theranostics in these patient groups. In
all patients that are included in this pilot study, immunohistochemical PSMA staining
will be performed on their biopsy material. In case of high PSMA expression, as defined
by previous literature, a [18F]-JK-PSMA-7 PET/CT scan will be made to assess the level of
tracer uptake in the malignant lesion(s). The expected duration of recruitment is 1 year
and 9 months. An early stopping rule of 5 negative PSMA PET/CT scans is implemented in
this study, for each cohort.
Primary purpose:
Diagnostic
Masking:
None (Open Label)
Intervention:
Intervention type:
Diagnostic Test
Intervention name:
[18F]-JK-PSMA-7 PET/CT scan
Description:
A [18F]-JK-PSMA-7 PET/CT scan will be made to assess the level of tracer uptake in the
malignant lesion(s). We expect to make a [18F]-JK-PSMA-7 PET/CT scan in 15 out of 60
patients per cohort.
Arm group label:
Advanced soft tissue sarcoma (n=60) and advanced urothelial cell carcinoma (n=60)
Summary:
This pilot study aims to investigate the PSMA expression in the biopsy material of
advanced soft tissue sarcomas and advanced urothelial cell carcinomas, and in case of
high PSMA expression (as defined by previous literature), to investigate whether this
correlates with high tracer uptake on PSMA-targeted PET. This way, (a subset of) patients
can be selected that could benefit from radionuclide targeted therapy in the future.
Detailed description:
Background:
Patients with metastatic soft tissue sarcoma and metastatic urothelial cell carcinoma
have a poor prognosis, with a five-year survival rate of 16% and 6%, respectively. This
is due to limited treatment options and low response rates to systemic chemotherapy of
approximately 25% in soft tissue sarcomas and 40-50% in urothelial cell carcinomas. In
these patient groups there is a high need for new effective treatment options that can
decrease burden of disease and increase survival benefit.
Prostate specific membrane antigen (PSMA) is a transmembrane metallopeptidase that is
overexpressed in prostate cancer cells. For diagnostic purposes, PET/CT scans that target
PSMA have found their way into the clinical routine of prostate cancer patients. However,
currently we know that despite the name, PSMA is not prostate cancer specific. It is also
found in the tumour-associated blood vessels of a wide variety of other tumours,
including soft tissue sarcomas and urothelial cell carcinomas. In many different sarcoma
types, PSMA expression is seen in the neovasculature with the highest detection rate of
46-60% in high grade and undifferentiated sarcomas (e.g. pleomorphic sarcoma types). The
PSMA expression rate in the neovasculature of urothelial cell carcinomas still varies in
literature, however, the most recently published article showed that PSMA expression was
found in 93% of urothelial cell carcinoma tissues. Additionally, PSMA expression was seen
in the tumour cells itself in 79% of the tissues. Because of the unique expression
pattern which seems to be limited to tumour cells and tumour-associated endothelial
cells, PSMA may represent an interesting target for molecular imaging using
PSMA-targeting PET scans, and eventually for radionuclide targeted therapy, when coupled
to an alpha- or beta-emitter. [225Act]-PSMA and [177Lu]-PSMA therapy have shown promising
results in the treatment of advanced prostate cancer patients and might offer perspective
and increase quality of life in patients with advanced soft tissue sarcoma and urothelial
cell carcinoma, as well.
Objective of the study:
This pilot study aims to investigate the PSMA expression in the biopsy material of
advanced soft tissue sarcomas and advanced urothelial cell carcinomas, and in case of
high PSMA expression (as defined by previous literature), to investigate whether this
correlates with high tracer uptake on PSMA-targeted PET. This way, (a subset of) patients
can be selected that could benefit from radionuclide targeted therapy in the future.
Study design:
This pilot study is a single centre, open-label, non-randomized, non-blinded phase II
study with two patient cohorts.
Study population:
The study population comprises sixty adult patients with diagnosis of advanced (locally
irresectable or metastasized) soft tissue sarcoma (cohort 1) and sixty adult patients
with diagnosis of advanced (muscle invasive or metastasized) urothelial cell carcinoma
(cohort 2). The expected duration of recruitment is 1 year and 9 months.
Intervention:
In all included patients, biopsy material is obtained as part of routine clinical
practice. For this study, immunohistochemical PSMA staining will be performed on these
biopsy materials. If the biopsy material shows high PSMA expression (as defined by
previous literature), a [18F]-JK-PSMA-7 PET/CT scan will be made to assess the level of
tracer uptake in the malignant lesion(s). We expect to make a [18F]-JK-PSMA-7 PET/CT scan
in 15 out of 60 patients in each cohort.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age >/= 18 years at the time of informed consent.
- Diagnosis of advanced (locally irresectable or metastasized) soft tissue sarcoma
(cohort 1) or advanced (muscle invasive or metastasized) urothelial cell carcinoma
(cohort 2).
- Voluntary agreement to provide written informed consent and the willingness and
ability to comply with all aspects of the protocol.
- Recent (< 8 weeks) standard imaging (with CT or [18F]-FDG PET/CT) with measurable
disease (lesion diameter > 1 cm).
- Biopsy available of primary tumour and/or metastasis
- WHO performance status of 0-2
- Either:
- No previous systemic therapy for advanced soft tissue sarcoma or advanced
urothelial cell carcinoma, or;
- Previous systemic therapy for advanced soft tissue sarcoma or advanced
urothelial cell carcinoma with progression of disease during systemic therapy
or progression of disease after discontinuation of systemic therapy, or;
- Previous systemic therapy for advanced soft tissue sarcoma or advanced
urothelial cell carcinoma with partial response or stable disease, where the
last dose of systemic therapy was given > 8 weeks before.
Exclusion Criteria:
- Women who are pregnant and/or lactating.
- Medical or psychiatric conditions that compromise the patient's ability to give
informed consent.
- Known hypersensitivity to drugs comparative to [18F]-JK-PSMA-7, any of their
excipients or to any component of [18F]-JK-PSMA-7.
- Inability to undergo PET/CT scanning, e.g. claustrophobia, weight limits or
inability to tolerate lying down for the duration of a PET/CT scan (~30 minutes).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Leiden University Medical Centre
Address:
City:
Leiden
Zip:
2333 ZA
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Fleur Kleiburg, drs
Phone:
+31715262810
Email:
F.Kleiburg@lumc.nl
Start date:
August 1, 2022
Completion date:
June 1, 2024
Lead sponsor:
Agency:
Leiden University Medical Center
Agency class:
Other
Source:
Leiden University Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05522257