Ignite Creation Date:
2024-05-06 @ 8:26 PM
Last Modification Date:
2024-10-26 @ 3:28 PM
Study NCT ID:
NCT06388252
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
2024-04-29
First Post:
2024-04-24
Brief Title:
Electrochemotherapy Induces Changes in the Tumor Microenvironment of Cutaneous and Subcutaneous Metastases in Patients With Cutaneous Melanoma
Sponsor:
Institute of Oncology Ljubljana
Organization:
Institute of Oncology Ljubljana
Study Overview
Official Title:
Electrochemotherapy Induces Changes in the Tumor Microenvironment of Cutaneous and Subcutaneous Metastases in Patients With Cutaneous Melanoma
Status:
ENROLLING_BY_INVITATION
Status Verified Date:
2024-03
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:
In the last 10 years the treatment of metastatic cutaneous melanoma has changed dramatically The new systemic treatment with immunotherapy has led to a dramatic improvement in quality of life and overall survival Systemic treatment means that the patient receives the drug as an infusion into a vein Unfortunately we know that immunotherapy is not equally successful in all patients Recent studies have shown that the success of the treatment is not only influenced by the cellular composition of the metastasis but also by its surroundings This is called tumor microenvironment Depending on the differences in the composition of this microenvironment some metastases can be described as immunologically hot and others as immunologically cold Immunologically hot metastases respond better to immunotherapy than immunologically cold metastases
Studies have shown that with some interventions we can change the tumor microenvironment from being immune-cold to being immune-hot Electrochemotherapy is one of the interventions that might improve the efficacy of immunotherapy in cutaneous melanoma Electrochemotherapy is an established method for the local treatment of tumors in which only a certain tumor is treated with special electrodes to which a weak electric current is applied We hypothesize that electrochemotherapy stimulates the bodys own immune response and enables more effective treatment Since immunotherapy also stimulates the bodys own immune response to cutaneous melanoma cells the interaction of the two drugs could be even more successful Recent research results support this assumption
The primary objective is to evaluate the changes in the tumor microenvironment of cutaneous and subcutaneous melanoma metastases induced by electrochemotherapy based on the histologic analysis of treated and untreated metastases before and after treatment The secondary aim is to determine whether the changes in the tumor microenvironment differ depending on the chemotherapeutic agent used
The results will help us to better understand the synergistic effects of electrochemotherapy and immunotherapy on cutaneous melanoma metastases The combination of systemic immunotherapy and electrochemotherapy could become an important treatment method for patients with metastatic melanoma
Studies have shown that with some interventions we can change the tumor microenvironment from being immune-cold to being immune-hot Electrochemotherapy is one of the interventions that might improve the efficacy of immunotherapy in cutaneous melanoma Electrochemotherapy is an established method for the local treatment of tumors in which only a certain tumor is treated with special electrodes to which a weak electric current is applied We hypothesize that electrochemotherapy stimulates the bodys own immune response and enables more effective treatment Since immunotherapy also stimulates the bodys own immune response to cutaneous melanoma cells the interaction of the two drugs could be even more successful Recent research results support this assumption
The primary objective is to evaluate the changes in the tumor microenvironment of cutaneous and subcutaneous melanoma metastases induced by electrochemotherapy based on the histologic analysis of treated and untreated metastases before and after treatment The secondary aim is to determine whether the changes in the tumor microenvironment differ depending on the chemotherapeutic agent used
The results will help us to better understand the synergistic effects of electrochemotherapy and immunotherapy on cutaneous melanoma metastases The combination of systemic immunotherapy and electrochemotherapy could become an important treatment method for patients with metastatic melanoma
Detailed Description:
The study is prospective The primary objective is to evaluate the changes in the tumor microenvironment of cutaneous and subcutaneous melanoma metastases induced by electrochemotherapy ECT based on the histologic analysis of treated and untreated metastases before and after treatment The secondary aim is to determine whether the changes in the tumor microenvironment differ depending on the chemotherapeutic agent used
In the study 10-15 patients will be enrolled and devided in two arms ECT with bleomycin and ECT with cysplatin
ECT will be offered to patients with cuteaneous melanoma and at least 5 in-transit or distant cutaneous andor subcutaneous melanoma metastases regardless of previous treatments The decision will be made in a multidisciplinary tumor board The choice of chemotherapeuthic drug will depend on the size andnumber of lesions to be treated Inclusion in the study has no influence on the decision regarding the timing of treatment with immunotherapy Treatment with immunotherapy will later be included as a factor in the statistical analysis
ECT will be performed according to the standard operating procedures for the treatment of cutaneous and subcutaneous tumors with ECT ECT will be performed within 8 - 28 minutes after intravenous bolus administration of bleomycin 15000 IUm2 BSA or directly after the intratumorally administration of cysplatin 05-2 mgcm3 tumor CliniporatorTM IGEA SPA Carpi Italy will be used to apply the pulses 8 pulses 1300 Vcm 100 μs 5 kHz Triggering of the electrical pulses will be synchronized with ECG signals through the ECG triggering device AccuSync to avoid delivery of pulses in vulnerable period of the heart The type of electrode used will be selected according to the size and location of the tumors
One cutaneoussubcutaneous metastasis will be excised before ECT One treated cutaneoussubcutaneous metastasis will be excised 2-4 and 9-13 days after the procedure An untreated cutaneoussubcutaneous metastasis will be excised on day 9-13 The excisions will be performed under local anesthesia All patients will be enrolled in the study after the procedures and the study have been explained to them in detail and they have signed an informed consent form A venous blood sample will be taken at the same time points before ECT 2-4 days and 9-13 days after ECT
Histological examination assessment of the degree of regression and the presence of tumor infiltrating lymphocytes TIL will be performed according to standardized procedures on 2-3 μm thick tissue sections previously fixed in formalin and embedded in paraffin FFPE stained with the hematoxylin-eosin HE staining method
Immunohistochemical characterization of the tumor microenvironment will be performed on 2-4 μm thick tissue sections pre-fixed in formalin and embedded in paraffin We will use commercially available primary monoclonal antibodies to define the tumor inflammatory infiltrate stroma and vasculature We will use the following antibodies CD3 CD4 CD8 CD56 CD163 FoxP3 ERG PGM1 CD274 PD-L1 The choice of antibodies used and the method of pathohistologic analysis may change depending on the results Specific binding of primary antibodies will be visualized using the recommended three-step detection system OptiView DAB IHC Detection Kit Cat No 760-700 manufactured by Ventana ROCHE inc Tucson AZ USA according to the manufacturers instructions The analysis will be performed by two independent pathologists
We will also collect the information about previous treatments for cutaneous melanoma and photographic documentation of the effectiveness of ECT treatment Patients will also fill out internationally recognized validated quality of life questionnaires EORTC QLQ-C 30 and EQ-5D-5L at entollment after ECT 3 months 6 months and 12 months after ECT and then once a year during the follow-up period
In the study 10-15 patients will be enrolled and devided in two arms ECT with bleomycin and ECT with cysplatin
ECT will be offered to patients with cuteaneous melanoma and at least 5 in-transit or distant cutaneous andor subcutaneous melanoma metastases regardless of previous treatments The decision will be made in a multidisciplinary tumor board The choice of chemotherapeuthic drug will depend on the size andnumber of lesions to be treated Inclusion in the study has no influence on the decision regarding the timing of treatment with immunotherapy Treatment with immunotherapy will later be included as a factor in the statistical analysis
ECT will be performed according to the standard operating procedures for the treatment of cutaneous and subcutaneous tumors with ECT ECT will be performed within 8 - 28 minutes after intravenous bolus administration of bleomycin 15000 IUm2 BSA or directly after the intratumorally administration of cysplatin 05-2 mgcm3 tumor CliniporatorTM IGEA SPA Carpi Italy will be used to apply the pulses 8 pulses 1300 Vcm 100 μs 5 kHz Triggering of the electrical pulses will be synchronized with ECG signals through the ECG triggering device AccuSync to avoid delivery of pulses in vulnerable period of the heart The type of electrode used will be selected according to the size and location of the tumors
One cutaneoussubcutaneous metastasis will be excised before ECT One treated cutaneoussubcutaneous metastasis will be excised 2-4 and 9-13 days after the procedure An untreated cutaneoussubcutaneous metastasis will be excised on day 9-13 The excisions will be performed under local anesthesia All patients will be enrolled in the study after the procedures and the study have been explained to them in detail and they have signed an informed consent form A venous blood sample will be taken at the same time points before ECT 2-4 days and 9-13 days after ECT
Histological examination assessment of the degree of regression and the presence of tumor infiltrating lymphocytes TIL will be performed according to standardized procedures on 2-3 μm thick tissue sections previously fixed in formalin and embedded in paraffin FFPE stained with the hematoxylin-eosin HE staining method
Immunohistochemical characterization of the tumor microenvironment will be performed on 2-4 μm thick tissue sections pre-fixed in formalin and embedded in paraffin We will use commercially available primary monoclonal antibodies to define the tumor inflammatory infiltrate stroma and vasculature We will use the following antibodies CD3 CD4 CD8 CD56 CD163 FoxP3 ERG PGM1 CD274 PD-L1 The choice of antibodies used and the method of pathohistologic analysis may change depending on the results Specific binding of primary antibodies will be visualized using the recommended three-step detection system OptiView DAB IHC Detection Kit Cat No 760-700 manufactured by Ventana ROCHE inc Tucson AZ USA according to the manufacturers instructions The analysis will be performed by two independent pathologists
We will also collect the information about previous treatments for cutaneous melanoma and photographic documentation of the effectiveness of ECT treatment Patients will also fill out internationally recognized validated quality of life questionnaires EORTC QLQ-C 30 and EQ-5D-5L at entollment after ECT 3 months 6 months and 12 months after ECT and then once a year during the follow-up period
Study Oversight
Has Oversight DMC:
None
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?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 0120-29720233 | OTHER | National Medical Ethics Committee of the Republic of Slovenia | None |