Histopathologic Effect of Calcium Electroporation on Cancer in the Skin

Cancer Clinical Trial

— CAEP-B  

Official title:

Phase II Investigation of the Histopathologic Effect of Calcium Electroporation on Cancer in the Skin (CAEP-B)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04259658
• Other study ID #: REG-114-2019
• Status: Completed
• Phase: Phase 2
• Start date: April 20, 2020
• Est. completion date: July 27, 2023

Study information

• Verified date: October 2023
• Source: Zealand University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: July 27, 2023
• Est. primary completion date: October 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cancer

Intervention

Combination Product:
• Calcium electroporation
Patients with cutaneous metastases will be treated with calcium electroporation.

Locations

Country	Name	City	State
Denmark	Dept. of Clinical oncology and Palliative Care	Næstved

Sponsors (1)

Lead Sponsor	Collaborator
Zealand University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

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