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

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.

Sex

All

Minimum age

18 Years

Maximum age

100 Years

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

• BACKGROUNDFalk 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
• DERIVEDAgoston 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