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

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

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

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Combination product: Calcium electroporation

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 Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Næstved, Denmark
    • Dept. of Clinical oncology and Palliative Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Calcium electroporation treatment; Experimental treatment with calcium electroporation for cutaneous metastases.	Combination product: Calcium electroporation; Patients with cutaneous metastases will be treated with calcium electroporation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Molecular subtype classification	Gene expression profiling according to tumour histology.	3 months
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
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
Tumour regression	To describe presence of regressive changes including necrosis at different timepoints (percentage of tissue).	3 months
Residual tumour	To describe presence of residual tumour (yes/no) and description of topographical location.	3 months
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
Clinical response to intervention	To document evolution of tumours before and after treatment using digital photography including a ruler.	3 months
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
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
Tumour type	To establish number of treated tumours with complete response depending on tumour type.	3 months
Systemic immunologic response	To detect signs of systemic immunologic response from any routine scans before and after treatment in the inclusion period.	3 months
Importance of previous irradiation	To investigate differences in effect depending whether the treated tumour was in a previously irradiated area.	3 months
Adjacent non-tumour tissue	To evaluate effect on adjacent non-tumour tissue.	3 months
PD-L1 expression over time	To assess PD-L1 expression over time by biopsy.	3 months
Relation between change in PD-L1 expression and response	To investigate any relation between change in PD-L1 expression and tumour response.	3 months
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
PD-L1 expression of different tumour histologies	To describe PD-L1 expression on different cell types of the different tumour histologies investigated.	3 months
Western blotting	To examine frozen tissues samples by western blotting in order to support any of the above mentioned endpoints.	3 months
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
Current measurement	To measure current during treatment as indicated by the pulse generator.	1 month
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

Collaborators and Investigators

• Sponsor: Zealand University Hospital
• Investigators: Principal Investigator: Julie Gehl, MD, Zealand University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2020
• Primary Completion (Actual): October 19, 2022
• Study Completion (Actual): July 27, 2023

Study Registration Dates

• First Submitted: January 21, 2020
• First Submitted That Met QC Criteria: February 4, 2020
• First Posted (Actual): February 6, 2020

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: metastases; cancer; tumor infiltrating lymphocytes; calcium; electroporation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Calcium-Regulating Hormones and Agents; Calcium
• Other Study ID Numbers: REG-114-2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No