Ignite Creation Date:
2025-12-24 @ 6:31 PM
Ignite Modification Date:
2026-01-04 @ 5:50 PM
Study NCT ID:
NCT05522257
Status:
COMPLETED
Last Update Posted:
2024-12-09
First Post:
2022-08-16
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
PSMA Expression and PSMA PET Imaging in Soft Tissue Sarcomas and Urothelial Cell Carcinomas
Sponsor:
Leiden University Medical Center
Organization:
Study Overview
Official Title:
Expression of Prostate Specific Membrane Antigen (PSMA) in Soft Tissue Sarcomas and Urothelial Cell Carcinomas: Implications for Tumour-specific Molecular Imaging and Treatment?
Status:
COMPLETED
Status Verified Date:
2024-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
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.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: