Cutaneous Malignant MelanomaNCT06388252
Electrochemotherapy Changes in Tumor Microenvironment of Cutaneous and Subcutaneous Metastases in Melanoma Patients
A study testing Electrochemotherapy with Intratumoral Cysplatin and Electrochemotherapy with Intravenous Bleomycin in people with Cutaneous Malignant Melanoma, run by Institute of Oncology Ljubljana at 1 site in Slovenia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Cutaneous Malignant Melanoma
- What is being tested?
- Electrochemotherapy with Intratumoral Cysplatin and Electrochemotherapy with Intravenous Bleomycin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteSlovenia
- Study dates
- 10 Nov 2023to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- more than 4 cytologically and/or histologically confirmed intransit or distant cutaneous/subcutaneous cutaneous melanoma metastases
- ECT should be proposed as a treatment in the multidisciplinary tumor board
- cutaneous/subcutaneous melanoma metastases, that can be excised under local anesthesia with primary wound closure, minimal morbidity of the procedure (risk of complications < 5%) and nocosmetic or functional consequences of the procedure
- stage IIIB, IIIC or IV of the disease
- age over 18 years
- performance status World Health Organization more than 2
- patients must give informed consent
Who cannot join
- age less than 18 years
- polimorbidity
- performance status World Health Organization more than 2
- high risk for intervention under general anesthesia;
- wound closure would require coverage with a skin graft or local flap;
- undesirable cosmetic or functional consequences would be expected (face, extensor side of joints)
- patients incapable of understanding the aim of the study or disagree with the entering into the clinical study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Electrochemotherapy Induces Changes in the Tumor Microenvironment of Cutaneous and Subcutaneous Metastases in Patients With Cutaneous Melanoma
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, investigators 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 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. Investigators hypothesize that electrochemotherapy stimulates the body's own immune response and enables more effective treatment. Since immunotherapy also stimulates the body's own immune response to cutaneous melanoma cells, the interaction of the two drugs could be even more successful. Recent research results support this assumption.
Read more
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 Investigators 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.
Read the 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 and/or 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 and number 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 (15.000 IU/m2 BSA) or directly after the intratumorally administration of cysplatin (0,5-2 mg/cm3 tumor). CliniporatorTM (IGEA S.P.A., Carpi, Italy) will be used to apply the pulses (8 pulses, 1300 V/cm, 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 cutaneous/subcutaneous metastasis will be excised before ECT. One treated cutaneous/subcutaneous metastasis will be excised 2-4 and 9-13 days after the procedure. An untreated cutaneous/subcutaneous 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. Investigators 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 manufacturer's instructions. The analysis will be performed by two independent pathologists.
Investigators 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.
- Conditions
- Cutaneous Malignant Melanoma
- Being tested
- Electrochemotherapy with Intratumoral Cysplatin, Electrochemotherapy with Intravenous Bleomycin
- Keywords
- In-transit melanoma metastases, Cutaneous and subcutaneous melanoma metastases, Electrochemotherapy, Bleomycin, Cysplatin
- Medical subject headings
- Melanoma, Cutaneous Malignant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Electrochemotherapy with Intratumoral CysplatinProcedure or surgery
ECT will be performed directly after the intratumorally administration of cysplatin (0,5-2 mg/cm3 tumor). CliniporatorTM (IGEA S.P.A., Carpi, Italy) will be used to apply the pulses (8 pulses, 1300 V/cm, 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.
Electrochemotherapy with Intravenous BleomycinProcedure or surgery
ECT will be performed within 8 - 28 minutes after intravenous bolus administration of bleomycin (15.000 IU/m2 BSA). CliniporatorTM (IGEA S.P.A., Carpi, Italy) will be used to apply the pulses (8 pulses, 1300 V/cm, 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.
| Study group | Role | What they receive |
|---|---|---|
| Electrochemotherapy with Intratumoral Cysplatin | Active comparator | ECT will be performed directly after the intratumorally administration of cysplatin (0,5-2 mg/cm3 tumor). CliniporatorTM (IGEA S.P.A., Carpi, Italy) will be used to apply the pulses (8 pulses, 1300 V/cm, 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. Receives: Procedure: Electrochemotherapy with Intratumoral Cysplatin |
| Electrochemotherapy with Intravenous Bleomycin | Active comparator | ECT will be performed within 8 - 28 minutes after intravenous bolus administration of bleomycin (15.000 IU/m2 BSA). CliniporatorTM (IGEA S.P.A., Carpi, Italy) will be used to apply the pulses (8 pulses, 1300 V/cm, 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. Receives: Procedure: Electrochemotherapy with Intravenous Bleomycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Tumor-Infiltrating Lymphocytes (TIL) Score Assessed by MIA Scoring System (Azimi et al.)
Tumor-infiltrating lymphocytes (TILs) will be evaluated semi-quantitatively using the MIA scoring system (Azimi et al.) in tissue samples from treated and untreated cutaneous/subcutaneous melanoma metastases. Assessment will be performed independently by two experienced pathologists.
Measured: Before electrochemotherapy (baseline), 2-4 days after electrochemotherapy, and 9-13 days after electrochemotherapy
Lymphocyte and Macrophage Distribution Density in Tumor Microenvironment Assessed by Park CH Method
Distribution densities of lymphocytes and macrophages in the tumor microenvironment will be estimated according to Park CH et al. in biopsies of treated and untreated melanoma metastases. Assessment will be performed independently by two experienced pathologists.
Measured: Before electrochemotherapy (baseline), 2-4 days after electrochemotherapy, and 9-13 days after electrochemotherapy
Number of Immune Marker-Positive Cells per mm² in Tumor Tissue Assessed by Immunohistochemistry (IHC)
The number of CD3+, CD4+, CD8+, CD56+, CD163+, FoxP3+, PGM1+, and PD-L1 (CD274)+ cells per mm² will be quantified by immunohistochemistry (IHC) in tissue samples from treated and untreated melanoma metastases. Results will be evaluated independently by two experienced pathologists.
Measured: Before electrochemotherapy (baseline), 2-4 days after electrochemotherapy, and 9-13 days after electrochemotherapy
Secondary outcomes (2)
Difference in Change of Tumor-Infiltrating Lymphocytes (TIL) Score (MIA Scoring) Between Bleomycin and Cisplatin Electrochemotherapy
Changes in semi-quantitative tumor-infiltrating lymphocyte (TIL) score assessed using the MIA scoring system (Azimi et al.) will be compared between patients treated with electrochemotherapy using intravenous bleomycin versus intratumoral cisplatin.
Measured: Before electrochemotherapy (baseline), 2-4 days after electrochemotherapy, and 9-13 days after electrochemotherapy
Difference in Immune Cell Density and Immune Marker-Positive Cells per mm² Between Bleomycin and Cisplatin Electrochemotherapy
Changes in lymphocyte/macrophage distribution density (Park CH method) and the number of immune marker-positive cells per mm² assessed by immunohistochemistry (CD3, CD4, CD8, CD56, CD163, FoxP3, ERG, PGM1, PD-L1/CD274) will be compared between patients treated with electrochemotherapy using intravenous bleomycin versus intratumoral cisplatin.
Measured: Before electrochemotherapy (baseline), 2-4 days after electrochemotherapy, and 9-13 days after electrochemotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2024
- Study start10 Nov 2023
- Primary completion30 Sep 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (28)Papers the sponsor has linked to this study.
- Other trials for Cutaneous Malignant MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Model description
- Electrochemotherapy with intratumoural cysplatin is recommended for smaller (less than 3 cm) and fewer tumours (up to 10 lesions), while electrochemotherapy with intravenous bleomycin is preferable for multiple and larger tumours.
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institute of Oncology Ljubljana
- Sponsor type
- University, hospital or other
- Collaborators
- Slovenian Research Agency
- Responsible party
- Sponsor
- Investigators
- Barbara Perić, Principal investigator, Dep. of Surgical Oncology, Institute of Oncology Ljubljana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06388252
- Sponsor's protocol ID
- ERID-KSOPR-0049/2023
- Other IDs
- 0120-297/2023/3
- Status last verified
- Feb 2026
- First submitted
- 24 Apr 2024
- Last updated
- 19 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Zadnik V, Primic Zakelj M, Lokar K, Jarm K, Ivanus U, Zagar T. Cancer burden in slovenia with the time trends analysis. Radiol Oncol. 2017 Feb 22;51(1):47-55. doi: 10.1515/raon-2017-0008. eCollection 2017 Mar 1.
PubMed 28265232Littman DR. Releasing the Brakes on Cancer Immunotherapy. Cell. 2015 Sep 10;162(6):1186-90. doi: 10.1016/j.cell.2015.08.038.
PubMed 26359975Goggins CA, Khachemoune A. The use of electrochemotherapy in combination with immunotherapy in the treatment of metastatic melanoma: a focused review. Int J Dermatol. 2019 Aug;58(8):865-870. doi: 10.1111/ijd.14314. Epub 2018 Nov 26.
PubMed 30479009Garbe C, Amaral T, Peris K, Hauschild A, Arenberger P, Basset-Seguin N, Bastholt L, Bataille V, Del Marmol V, Dreno B, Fargnoli MC, Forsea AM, Grob JJ, Hoeller C, Kaufmann R, Kelleners-Smeets N, Lallas A, Lebbe C, Lytvynenko B, Malvehy J, Moreno-Ramirez D, Nathan P, Pellacani G, Saiag P, Stratigos AJ, Van Akkooi ACJ, Vieira R, Zalaudek I, Lorigan P; European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization for Research and Treatment of Cancer (EORTC). European consensus-based interdisciplinary guideline for melanoma. Part 2: Treatment - Update 2022. Eur J Cancer. 2022 Jul;170:256-284. doi: 10.1016/j.ejca.2022.04.018. Epub 2022 May 24.
PubMed 35623961Quaglino P, Mortera C, Osella-Abate S, Barberis M, Illengo M, Rissone M, Savoia P, Bernengo MG. Electrochemotherapy with intravenous bleomycin in the local treatment of skin melanoma metastases. Ann Surg Oncol. 2008 Aug;15(8):2215-22. doi: 10.1245/s10434-008-9976-0. Epub 2008 May 23.
PubMed 18498012Kunte C, Letule V, Gehl J, Dahlstroem K, Curatolo P, Rotunno R, Muir T, Occhini A, Bertino G, Powell B, Saxinger W, Lechner G, Liew SH, Pritchard-Jones R, Rutkowski P, Zdzienicki M, Mowatt D, Sykes AJ, Orlando A, Mitsala G, Rossi CR, Campana L, Brizio M, de Terlizzi F, Quaglino P, Odili J; InspECT (the International Network for Sharing Practices on Electrochemotherapy). Electrochemotherapy in the treatment of metastatic malignant melanoma: a prospective cohort study by InspECT. Br J Dermatol. 2017 Jun;176(6):1475-1485. doi: 10.1111/bjd.15340. Epub 2017 Apr 26.
PubMed 28118487Campana LG, Valpione S, Mocellin S, Sundararajan R, Granziera E, Sartore L, Chiarion-Sileni V, Rossi CR. Electrochemotherapy for disseminated superficial metastases from malignant melanoma. Br J Surg. 2012 Jun;99(6):821-30. doi: 10.1002/bjs.8749. Epub 2012 Apr 17.
PubMed 22508342Cadossi R, Ronchetti M, Cadossi M. Locally enhanced chemotherapy by electroporation: clinical experiences and perspective of use of electrochemotherapy. Future Oncol. 2014 Apr;10(5):877-90. doi: 10.2217/fon.13.235.
PubMed 24799067Mali B, Jarm T, Snoj M, Sersa G, Miklavcic D. Antitumor effectiveness of electrochemotherapy: a systematic review and meta-analysis. Eur J Surg Oncol. 2013 Jan;39(1):4-16. doi: 10.1016/j.ejso.2012.08.016. Epub 2012 Sep 11.
PubMed 22980492Gehl J, Sersa G, Matthiessen LW, Muir T, Soden D, Occhini A, Quaglino P, Curatolo P, Campana LG, Kunte C, Clover AJP, Bertino G, Farricha V, Odili J, Dahlstrom K, Benazzo M, Mir LM. Updated standard operating procedures for electrochemotherapy of cutaneous tumours and skin metastases. Acta Oncol. 2018 Jul;57(7):874-882. doi: 10.1080/0284186X.2018.1454602. Epub 2018 Mar 25.
PubMed 29577784Sersa G, Teissie J, Cemazar M, Signori E, Kamensek U, Marshall G, Miklavcic D. Electrochemotherapy of tumors as in situ vaccination boosted by immunogene electrotransfer. Cancer Immunol Immunother. 2015 Oct;64(10):1315-27. doi: 10.1007/s00262-015-1724-2. Epub 2015 Jun 12.
PubMed 26067277Polajzer T, Jarm T, Miklavcic D. Analysis of damage-associated molecular pattern molecules due to electroporation of cells in vitro. Radiol Oncol. 2020 Jul 29;54(3):317-328. doi: 10.2478/raon-2020-0047.
PubMed 32726295Sersa G, Ursic K, Cemazar M, Heller R, Bosnjak M, Campana LG. Biological factors of the tumour response to electrochemotherapy: Review of the evidence and a research roadmap. Eur J Surg Oncol. 2021 Aug;47(8):1836-1846. doi: 10.1016/j.ejso.2021.03.229. Epub 2021 Mar 11.
PubMed 33726951Ursic K, Kos S, Kamensek U, Cemazar M, Miceska S, Markelc B, Bucek S, Staresinic B, Kloboves Prevodnik V, Heller R, Sersa G. Potentiation of electrochemotherapy effectiveness by immunostimulation with IL-12 gene electrotransfer in mice is dependent on tumor immune status. J Control Release. 2021 Apr 10;332:623-635. doi: 10.1016/j.jconrel.2021.03.009. Epub 2021 Mar 8.
PubMed 33705828Tremble LF, O'Brien MA, Soden DM, Forde PF. Electrochemotherapy with cisplatin increases survival and induces immunogenic responses in murine models of lung cancer and colorectal cancer. Cancer Lett. 2019 Feb 1;442:475-482. doi: 10.1016/j.canlet.2018.11.015. Epub 2018 Nov 22.
PubMed 30472183
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Electrochemotherapy Induces Changes in the Tumor Microenvironment of Cutaneous and Subcutaneous Metastases in Patients With Cutaneous Melanoma
- ClinicalTrials.gov ID
- NCT06388252
- Acronym / sponsor ID
- ERID-KSOPR-0049/2023
- Conditions
- Cutaneous Malignant Melanoma
- Keywords
- In-transit melanoma metastases, Cutaneous and subcutaneous melanoma metastases, Electrochemotherapy, Bleomycin, Cysplatin
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Institute of Oncology LjubljanaUniversity, hospital or other
- Collaborators
- Slovenian Research Agency
- Study start
- 10 Nov 2023 (actual)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 29 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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, investigators 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 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. Investigators hypothesize that electrochemotherapy stimulates the body's own immune response and enables more effective treatment. Since immunotherapy also stimulates the body's 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 Investigators 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 and/or 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 and number 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 (15.000 IU/m2 BSA) or directly after the intratumorally administration of cysplatin (0,5-2 mg/cm3 tumor). CliniporatorTM (IGEA S.P.A., Carpi, Italy) will be used to apply the pulses (8 pulses, 1300 V/cm, 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 cutaneous/subcutaneous metastasis will be excised before ECT. One treated cutaneous/subcutaneous metastasis will be excised 2-4 and 9-13 days after the procedure. An untreated cutaneous/subcutaneous 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. Investigators 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 manufacturer's instructions. The analysis will be performed by two independent pathologists.
Investigators 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 design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Electrochemotherapy with intratumoural cysplatin is recommended for smaller (less than 3 cm) and fewer tumours (up to 10 lesions), while electrochemotherapy with intravenous bleomycin is preferable for multiple and larger tumours.
| Arm | Type | Receives |
|---|---|---|
| Electrochemotherapy with Intratumoral Cysplatin | Active comparator | Procedure: Electrochemotherapy with Intratumoral CysplatinECT will be performed directly after the intratumorally administration of cysplatin (0,5-2 mg/cm3 tumor). CliniporatorTM (IGEA S.P.A., Carpi, Italy) will be used to apply the pulses (8 pulses, 1300 V/cm, 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. |
| Electrochemotherapy with Intravenous Bleomycin | Active comparator | Procedure: Electrochemotherapy with Intravenous BleomycinECT will be performed within 8 - 28 minutes after intravenous bolus administration of bleomycin (15.000 IU/m2 BSA). CliniporatorTM (IGEA S.P.A., Carpi, Italy) will be used to apply the pulses (8 pulses, 1300 V/cm, 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. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- more than 4 cytologically and/or histologically confirmed intransit or distant cutaneous/subcutaneous cutaneous melanoma metastases
- ECT should be proposed as a treatment in the multidisciplinary tumor board
- cutaneous/subcutaneous melanoma metastases, that can be excised under local anesthesia with primary wound closure, minimal morbidity of the procedure (risk of complications < 5%) and nocosmetic or functional consequences of the procedure
- stage IIIB, IIIC or IV of the disease
- age over 18 years
Key exclusion criteria (7 listed)
- age less than 18 years
- polimorbidity
- performance status World Health Organization more than 2
- high risk for intervention under general anesthesia;
- wound closure would require coverage with a skin graft or local flap;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Electrochemotherapy with Intratumoral CysplatinECT will be performed directly after the intratumorally administration of cysplatin (0,5-2 mg/cm3 tumor). CliniporatorTM (IGEA S.P.A., Carpi, Italy) will be used to apply the pulses (8 pulses, 1300 V/cm, 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. | Procedure or surgery | Electrochemotherapy with Intratumoral Cysplatin |
| Electrochemotherapy with Intravenous BleomycinECT will be performed within 8 - 28 minutes after intravenous bolus administration of bleomycin (15.000 IU/m2 BSA). CliniporatorTM (IGEA S.P.A., Carpi, Italy) will be used to apply the pulses (8 pulses, 1300 V/cm, 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. | Procedure or surgery | Electrochemotherapy with Intravenous Bleomycin |
Primary outcome
Change in Tumor-Infiltrating Lymphocytes (TIL) Score Assessed by MIA Scoring System (Azimi et al.)
Time frame: Before electrochemotherapy (baseline), 2-4 days after electrochemotherapy, and 9-13 days after electrochemotherapy
Tumor-infiltrating lymphocytes (TILs) will be evaluated semi-quantitatively using the MIA scoring system (Azimi et al.) in tissue samples from treated and untreated cutaneous/subcutaneous melanoma metastases. Assessment will be performed independently by two experienced pathologists.
Lymphocyte and Macrophage Distribution Density in Tumor Microenvironment Assessed by Park CH Method
Time frame: Before electrochemotherapy (baseline), 2-4 days after electrochemotherapy, and 9-13 days after electrochemotherapy
Distribution densities of lymphocytes and macrophages in the tumor microenvironment will be estimated according to Park CH et al. in biopsies of treated and untreated melanoma metastases. Assessment will be performed independently by two experienced pathologists.
Number of Immune Marker-Positive Cells per mm² in Tumor Tissue Assessed by Immunohistochemistry (IHC)
Time frame: Before electrochemotherapy (baseline), 2-4 days after electrochemotherapy, and 9-13 days after electrochemotherapy
The number of CD3+, CD4+, CD8+, CD56+, CD163+, FoxP3+, PGM1+, and PD-L1 (CD274)+ cells per mm² will be quantified by immunohistochemistry (IHC) in tissue samples from treated and untreated melanoma metastases. Results will be evaluated independently by two experienced pathologists.
2 secondary outcomes
Difference in Change of Tumor-Infiltrating Lymphocytes (TIL) Score (MIA Scoring) Between Bleomycin and Cisplatin Electrochemotherapy
Time frame: Before electrochemotherapy (baseline), 2-4 days after electrochemotherapy, and 9-13 days after electrochemotherapy
Difference in Immune Cell Density and Immune Marker-Positive Cells per mm² Between Bleomycin and Cisplatin Electrochemotherapy
Time frame: Before electrochemotherapy (baseline), 2-4 days after electrochemotherapy, and 9-13 days after electrochemotherapy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2026.
- Background: PubMed 28265232Zadnik V, Primic Zakelj M, Lokar K, Jarm K, Ivanus U, Zagar T. Cancer burden in slovenia with the time trends analysis. Radiol Oncol. 2017 Feb 22;51(1):47-55. doi: 10.1515/raon-2017-0008. eCollection 2017 Mar 1.
- Background: PubMed 26359975Littman DR. Releasing the Brakes on Cancer Immunotherapy. Cell. 2015 Sep 10;162(6):1186-90. doi: 10.1016/j.cell.2015.08.038.
- Background: PubMed 30479009Goggins CA, Khachemoune A. The use of electrochemotherapy in combination with immunotherapy in the treatment of metastatic melanoma: a focused review. Int J Dermatol. 2019 Aug;58(8):865-870. doi: 10.1111/ijd.14314. Epub 2018 Nov 26.
- Background: PubMed 35623961Garbe C, Amaral T, Peris K, Hauschild A, Arenberger P, Basset-Seguin N, Bastholt L, Bataille V, Del Marmol V, Dreno B, Fargnoli MC, Forsea AM, Grob JJ, Hoeller C, Kaufmann R, Kelleners-Smeets N, Lallas A, Lebbe C, Lytvynenko B, Malvehy J, Moreno-Ramirez D, Nathan P, Pellacani G, Saiag P, Stratigos AJ, Van Akkooi ACJ, Vieira R, Zalaudek I, Lorigan P; European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization for Research and Treatment of Cancer (EORTC). European consensus-based interdisciplinary guideline for melanoma. Part 2: Treatment - Update 2022. Eur J Cancer. 2022 Jul;170:256-284. doi: 10.1016/j.ejca.2022.04.018. Epub 2022 May 24.
- Background: PubMed 18498012Quaglino P, Mortera C, Osella-Abate S, Barberis M, Illengo M, Rissone M, Savoia P, Bernengo MG. Electrochemotherapy with intravenous bleomycin in the local treatment of skin melanoma metastases. Ann Surg Oncol. 2008 Aug;15(8):2215-22. doi: 10.1245/s10434-008-9976-0. Epub 2008 May 23.
- Background: PubMed 28118487Kunte C, Letule V, Gehl J, Dahlstroem K, Curatolo P, Rotunno R, Muir T, Occhini A, Bertino G, Powell B, Saxinger W, Lechner G, Liew SH, Pritchard-Jones R, Rutkowski P, Zdzienicki M, Mowatt D, Sykes AJ, Orlando A, Mitsala G, Rossi CR, Campana L, Brizio M, de Terlizzi F, Quaglino P, Odili J; InspECT (the International Network for Sharing Practices on Electrochemotherapy). Electrochemotherapy in the treatment of metastatic malignant melanoma: a prospective cohort study by InspECT. Br J Dermatol. 2017 Jun;176(6):1475-1485. doi: 10.1111/bjd.15340. Epub 2017 Apr 26.
- Background: PubMed 22508342Campana LG, Valpione S, Mocellin S, Sundararajan R, Granziera E, Sartore L, Chiarion-Sileni V, Rossi CR. Electrochemotherapy for disseminated superficial metastases from malignant melanoma. Br J Surg. 2012 Jun;99(6):821-30. doi: 10.1002/bjs.8749. Epub 2012 Apr 17.
- Background: PubMed 24799067Cadossi R, Ronchetti M, Cadossi M. Locally enhanced chemotherapy by electroporation: clinical experiences and perspective of use of electrochemotherapy. Future Oncol. 2014 Apr;10(5):877-90. doi: 10.2217/fon.13.235.
- Background: PubMed 22980492Mali B, Jarm T, Snoj M, Sersa G, Miklavcic D. Antitumor effectiveness of electrochemotherapy: a systematic review and meta-analysis. Eur J Surg Oncol. 2013 Jan;39(1):4-16. doi: 10.1016/j.ejso.2012.08.016. Epub 2012 Sep 11.
- Background: PubMed 29577784Gehl J, Sersa G, Matthiessen LW, Muir T, Soden D, Occhini A, Quaglino P, Curatolo P, Campana LG, Kunte C, Clover AJP, Bertino G, Farricha V, Odili J, Dahlstrom K, Benazzo M, Mir LM. Updated standard operating procedures for electrochemotherapy of cutaneous tumours and skin metastases. Acta Oncol. 2018 Jul;57(7):874-882. doi: 10.1080/0284186X.2018.1454602. Epub 2018 Mar 25.
- Background: PubMed 26067277Sersa G, Teissie J, Cemazar M, Signori E, Kamensek U, Marshall G, Miklavcic D. Electrochemotherapy of tumors as in situ vaccination boosted by immunogene electrotransfer. Cancer Immunol Immunother. 2015 Oct;64(10):1315-27. doi: 10.1007/s00262-015-1724-2. Epub 2015 Jun 12.
- Background: PubMed 32726295Polajzer T, Jarm T, Miklavcic D. Analysis of damage-associated molecular pattern molecules due to electroporation of cells in vitro. Radiol Oncol. 2020 Jul 29;54(3):317-328. doi: 10.2478/raon-2020-0047.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Barbara Perić principal investigator
Dep. of Surgical Oncology, Institute of Oncology Ljubljana
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Electrochemotherapy with Intratumoral Cysplatin and Electrochemotherapy with Intravenous Bleomycin in people with Cutaneous Malignant Melanoma, run by Institute of Oncology Ljubljana at 1 site in Slovenia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 19 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Slovenia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Tumor-Infiltrating Lymphocytes (TIL) Score Assessed by MIA Scoring System (Azimi et al.) (time frame: Before electrochemotherapy (baseline), 2-4 days after electrochemotherapy, and 9-13 days after electrochemotherapy). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06388252, which also lists 28 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2026.