Histopathologic Effect of Calcium Electroporation on Cancer in the Skin

Phase 2

Completed

• Conditions: Cancer
• Interventions: Combination Product: Calcium electroporation

• Registration Number: NCT04259658
• Lead Sponsor: Zealand University Hospital

Brief Summary

In this phase II study we investigate the effect of calcium electroporation on cancer in the skin investigated by histopathology.

Detailed Description

In this non randomized phase II study, we will explore histopathological tumour cell death mechanisms in 24 patients with breast cancer metastases or other cutaneous or subcutaneous malignancy. The primary endpoint of the biopsy study is to evaluate differences in tumour infiltrating lymphocyte (TIL) population in tissue samples from treated cancer tumours two days after calcium electroporation treatment compared to samples taken on the day of treatment before the calcium electroporation procedure. TIL content in biopsies will be evaluated by pathological examination and specified in percent of cells. Patients will be followed up to 3 months and depending on number of treated tumors, biopsies will be taken at different timepoints after one or two treatments with calcium electroporation. Other analyses will include differences regarding tumour type, immune marker expression levels over time, vascular effects and regressive changes as well as examining changes in systemic immunological markers.

Study Timeline

• Study First Submitted: 2020-01-21
• Study First Submitted QC: 2020-02-04
• Study First Posted: 2020-02-06
• Study Start: 2020-04-20
• Primary Completion: 2022-10-19
• Study Completion: 2023-07-27
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-02
• Last Update Posted: 2023-10-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

• Trial subject must be able to understand the participant information.
• Histologically verified cutaneous or subcutaneous, primary or secondary cancer of any histology.
• The patient can undergo any simultaneous medical treatment (endocrine therapy, chemotherapy, immunotherapy etc.).
• The patient can undergo radiation therapy during the study period, provided that the treatment field does not involve the treated area.
• Performance status ECOG/WHO ≤2
• At least one cutaneous or subcutaneous tumour measuring at least 5 mm.
• Both men and women who are sexually active must use safe contraception (contraceptive coil, deposit injection of gestagen, subdermal implantation, hormonal vaginal ring or transdermal patch.)
• Signed informed consent.

Exclusion Criteria

• Pregnancy or lactation
• Allergy to local anaesthesia

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Calcium electroporation treatment	Calcium electroporation	Experimental treatment with calcium electroporation for cutaneous metastases.

Primary Outcome Measures

Name	Time	Method
The effect of calcium electroporation on tumor infiltrating lymphocyte (TIL) population.	2 days	The primary endpoint of this study is to evaluate differences in TIL population in tissue samples from treated cancer tumours two days after calcium electroporation treatment compared to before treatment (biopsy taken on the day of treatment before the calcium electroporation procedure). TIL content in biopsies will be evaluated by pathological examination and expressed as percent of cells.

Secondary Outcome Measures

Name	Time	Method
Changes in immune markers	3 months	Protein expression levels of immune markers e.g. markers for the innate and adaptive immune system and markers of the STING pathway compared from before treatment and at different timepoints up to 3 months.
Tumour inflammation signature (TIS)	3 months	Gene expression signatures including the 18-gene TIS will be calculated as a weighted linear average of the constituent genes.
Size of lesion	3 months	To clinically measure changes in lesion size 1, 2 and 3 months after treatment using caliper measurement. Changes in size due to biopsies will be accounted for.
Clinical response to intervention	3 months	To document evolution of tumours before and after treatment using digital photography including a ruler.
PD-L1 expression in relation to cell types	3 months	To describe PD-L1 expression in relation to cell types found in the tumour environment
TIL population and tumour type	3 months	To describe any relation between change in TIL population (percentage of cells) and tumour type before and after calcium electroporation.
Vascular effects	3 months	To investigate vascular effects of calcium electroporation including changes in capillary structures by histochemical staining for endothelial biomarkers CD31 and/or CD34.
Importance of previous irradiation	3 months	To investigate differences in effect depending whether the treated tumour was in a previously irradiated area.
Adjacent non-tumour tissue	3 months	To evaluate effect on adjacent non-tumour tissue.
PD-L1 expression over time	3 months	To assess PD-L1 expression over time by biopsy.
Relation between change in PD-L1 expression and response	3 months	To investigate any relation between change in PD-L1 expression and tumour response.
Current measurement	1 month	To measure current during treatment as indicated by the pulse generator.
Complete disappearance of treated lesions (in relation to all lesions treated)	3 months	To sum number of lesions across all patients with complete remission after one or two treatments, respectively (expressed at percentage of all treated lesions).
Tumour type	3 months	To establish number of treated tumours with complete response depending on tumour type.
Tumour regression	3 months	To describe presence of regressive changes including necrosis at different timepoints (percentage of tissue).
PD-L1 expression of different tumour histologies	3 months	To describe PD-L1 expression on different cell types of the different tumour histologies investigated.
Systemic immune factors after calcium electroporation	3 months	Blood samples may be analyzed for NK cell- and T-cell gene expression levels. Levels before and after treatment will be compared.
PCR	3 months	To examine frozen tissues samples by PCR. Relevant gene expression will be compared before and after treatment in breast cancer and non breast cancer samples.
Molecular subtype classification	3 months	Gene expression profiling according to tumour histology.
Residual tumour	3 months	To describe presence of residual tumour (yes/no) and description of topographical location.
Complete response at patient level	3 months	To sum number of patients with complete response after one or two treatments, respectively. Complete response will be defined as disappearance of all target lesions.
Systemic immunologic response	3 months	To detect signs of systemic immunologic response from any routine scans before and after treatment in the inclusion period.
Western blotting	3 months	To examine frozen tissues samples by western blotting in order to support any of the above mentioned endpoints.

Trial Locations

Locations (1)

Dept. of Clinical oncology and Palliative Care; 🇩🇰 Næstved, Denmark