Confirmatory Trial in the Evaluation of Ca Electroporation for the Treatment of Cutaneous Metastases

NCT03628417 | Completed Results DMC

• 1 other identifier: 032104/2016/OTIG
• Study Type: interventional
• Target: 7
• Locations: 0 countries
• Sites: N/A

Brief Summary

Electroporation is a method that can facilitate transport of molecules across the cell membrane and into the cell by means of electrical pulses. The method can be used with molecules that normally have difficulty passing the cell membrane such as chemotherapy (electrochemotherapy). Electrochemotherapy (ECT) is used in cancer therapy, where chemotherapy is administered intratumoral or intravenous, then followed by electrical pulses applied directly on the tumor. The chemotherapy accumulates in the cancer cells which results in an increased cytotoxic effect. The most used chemotherapeutic drug used in electrochemotherapy is bleomycin. Electrochemotherapy is a well-documented local treatment form for especially cutaneous tumors. Today, the treatment is used mostly in palliative care in more than 140 centres around Europe. In vitro and in vivo studies have shown that the combination of calcium and electroporation is an effective method in killing cancer cells without serious side effects.This new combination opens the possibility of replacing bleomycin with calcium in treatments with electroporation. Calcium electroporation is a local treatment where calcium is administered intratumoral and followed by electrical pulses applied on the tumor. The preclinical studies have shown that there is a difference in sensitivity in tumor cells and normal cells, as normal cells tolerate the treatment better than tumor cells (own data manuscript in preparation). The studies have also shown that there is no cell injury by calcium injection without electroporation, the investigators therefore expect that the treatment only will cause minor side effects. Calcium electroporation would be possible to use on patients for whom chemotherapy is contradicted e.g. severe lung functions impairment, pregnant woman etc. Calcium electroporation is a simple and unexpensive cancer treatment that does not involve any administration of cytotoxic chemotherapy, and can be performed by surgeons, radiologists as well as oncologists. Both electroporation equipment and calcium are already being used in the clinic, so the treatment can easily be implemented.

Conditions

Cutaneous Melanoma

Keywords

cutaneous metastases; calcium electroporation; bleomycin electroporation

Outcome Measures

Primary Outcomes (1)

• Response Rate (RECIST1.1) of Calcium Electroporation and Bleomycin Based Electrochemotherapy on Cutaneous Metastases at Day 180.

  Documentation was done with digital color photography, including a ruler to estimate tumor size. Primary evaluation of the response was based on criteria similar RECIST 1.1 guidelines and defined as complete response (CR) - disappearance of the lesion, partial response (PR) - at least 30% decrease in the largest diameter of the lesion, progressive disease - at least 20% increase in the largest diameter of the lesion and stable disease - neither 30% decrease nor 20% increase of the largest diameter of the lesion. Change in the largest diameter:

  180 days after treatment

Secondary Outcomes (1)

• Adverse Events for Calcium Electroporation and Bleomycin Based Electrochemotherapy. The Adverse Reactions Are Classified According to CTCAE Version 4.0 (Common Terminology Criteria for Adverse Events).

  180 days after treatment

Other Outcomes (1)

• The Tertiary Outcome is to Register if Calcium Affects the Current Strength in Electroporation Treatments.

  Day 0 - During Ca-electroporation and bleomycin based electrochemotherapy interventions

Study Arms (2)

Calcium Electroporation

EXPERIMENTAL

Calcium Calcium chloride 220 mmol/L (9 mg/ml): * Tumor \< 0.5 cm³ - 1 ml/cm³ tumor volume * Tumor \> 0.5 cm³ - 0,5 ml/cm³ tumor volume Tumor volume = ab²π/6 (a = longest diameter, b = longest diameter perpendicular to "a")

Procedure: Calcium Electroporation

Bleomycin based electrochemotherapy

EXPERIMENTAL

Bleomycin Bleomycin 1000 IU/ml: * Tumor \< 0.5 cm³ - 1 ml/cm³ tumor volume * Tumor \> 0.5 cm³ - 0,5 ml/cm³ tumor volume Tumor volume = ab²π/6 (a = longest diameter, b = longest diameter perpendicular to "a") Maximum of injected bleomycin per tumor will be 1500 IU and total dose per treatment 7500 IU. Normal maximum limit for bleomycin is 15.000 IU/m² body surface area.

Procedure: Bleomycin based electrochemotherapy

Interventions

Calcium Electroporation PROCEDURE

If the patient agrees biopsies will be performed from the tumor area before and after electroporation during local anaesthesia. Maximum of 8 biopsies will be done, depending on the patient's number of metastases. All patient's regardless of the number of metastases will have one biopsy from area treated with calcium and one from area treated with bleomycin, after the randomization code is revealed at day 180. Patients with more than 6 metastases: One to two biopsies before treatment, one to two biopsies one week after treatment from metastases treated with calcium and bleomycin respectively. All biopsies will be handled according to current guidelines and analyzed by a pathologist for amount of tumor tissue, inflammation, fibrosis and necrosis.

Calcium Electroporation

Bleomycin based electrochemotherapy PROCEDURE

If the patient agrees biopsies will be performed from the tumor area before and after electroporation during local anaesthesia. Maximum of 8 biopsies will be done, depending on the patient's number of metastases. All patient's regardless of the number of metastases will have one biopsy from area treated with calcium and one from area treated with bleomycin, after the randomization code is revealed at day 180. Patients with more than 6 metastases: One to two biopsies before treatment, one to two biopsies one week after treatment from metastases treated with calcium and bleomycin respectively. All biopsies will be handled according to current guidelines and analyzed by a pathologist for amount of tumor tissue, inflammation, fibrosis and necrosis.

Bleomycin based electrochemotherapy

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years.
• Verified cutaneous metastases of any histology.
• At least one cutaneous metastases between 0.5 to 3 cm and accessible to electroporation.
• The patient should have been offered current standard treatment. If there is no further standard treatment to offer, or if the patient does not want to receive this, the patient may be included in the trial.
• Treatment free interval of more than two weeks. However, patients treated with Navelbine (Vinorelbine) Capecitabine (Xeloda) or weekly paclitaxel (Taxol) can continue these treatments, if there is no regression of cutaneous metastases. Other medical cancer treatments such as endocrine treatment, targeted treatment and radiotherapy to another area may also continue.
• Performance status World Health Organization (WHO) ≤ 2.
• Expected survival of \> 3 months.
• Platelets ≥ 50 billion/L, international normalized ratio (INR) \< 1.5. Medical correction is allowed, e.g. correction of a high INR using vitamin K.
• Sexually active men and women who can become pregnant should use adequate contraception during this trial (pill, spiral, injection of prolonged progestin, subdermal implantation, hormone-containing vaginal devices, transdermal patches).
• The patient should be able to understand the information.
• Signed informed consent.

You may not qualify if:

• Previous bleomycin treatment with more than 200,000 U/m² .
• History of severe allergic reactions associated with bleomycin.
• Coagulation disorder which cannot be corrected.
• Pregnancy and lactation.
• Participating in other clinical trials involving experimental drugs or involved in a trial within 4 weeks prior to study drug administration.

Sponsors & Collaborators

• Szeged University: lead

Related Publications (2)

• Falk H, Forde PF, Bay ML, Mangalanathan UM, Hojman P, Soden DM, Gehl J. Calcium electroporation induces tumor eradication, long-lasting immunity and cytokine responses in the CT26 colon cancer mouse model. Oncoimmunology. 2017 Mar 17;6(5):e1301332. doi: 10.1080/2162402X.2017.1301332. eCollection 2017.

  PMID: 28638724 BACKGROUND

• Agoston D, Baltas E, Ocsai H, Ratkai S, Lazar PG, Korom I, Varga E, Nemeth IB, Dosa-Racz Viharosne E, Gehl J, Olah J, Kemeny L, Kis EG. Evaluation of Calcium Electroporation for the Treatment of Cutaneous Metastases: A Double Blinded Randomised Controlled Phase II Trial. Cancers (Basel). 2020 Jan 10;12(1):179. doi: 10.3390/cancers12010179.

  PMID: 31936897 DERIVED

Related Links

• Calcium electroporation for treatment of cutaneous metastases; a randomized double-blinded phase II study, comparing the effect of calcium electroporation with electrochemotherapy

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

The study has certain limitations, like the small number of enrolled metastases, and the use of different electrodes.

Results Point of Contact

• Title: Principal Investigator, Assistant Professor
• Organization: Szeged University

kis.erika.gabriella@med.u-szeged.hu

+36-62-545-259

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Assistant Professor

Model Details: This randomized double blinded phase II study is comparing the effect of calcium electroporation with ECT with bleomycin on patients with cutaneous metastases of any histology where the metastases are randomized by block randomization and are done separately in each patient.

Study Record Dates

• First Submitted: November 7, 2017
• First Posted: August 14, 2018
• Study Start: September 20, 2016
• Primary Completion: June 4, 2019
• Study Completion: June 4, 2019
• Last Updated: January 2, 2020
• Results First Posted: January 2, 2020

Record last verified: 2019-12