Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Bleomycin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Application of Reversible Electroporation (Electrochemotherapy) with Bleomycin

Electrochemotherapy with Bleomycin

Electrochemotherapy is a type of electroporation that allows the delivery of drugs to the cells through the local creation of pores in the cell membrane. The electric pulses can be applied directly to the neoplastic cells, allowing for the local concentration of a possible chemotherapeutic agent administered through the bloodstream. This technique does not use heat nor other thermal energies and it is performed using special needles/electrodes linked to a generator ("porator").

In this study this technique will be applied on unresectable pancreatic cancer, already submitted to neoadjuvant treatment and still unresectable, through laparotomy. Bleomycin will be the chemotherapeutic agent.

Electrochemoterapy With Bleomycin for the Treatment of Unresectable Pancreatic Cancer

A Clinical Trial Using Electrochemotherapy With Bleomycin for the Treatment of Non-metastatic Unresectable Pancreatic Cancer

Number of adverse events related with electrochemotherapy (within 12 months after treatment) are registered and analyzed according to the CTCAE version 4.0. Complications are distinct in early (during hospitalization) and late (bile duct stenosis) that may appear during follow-up

Number of procedures planned actually performed

Analysis of effects of electrochemotherapy on tumor using RECIST criteria

Analysis of quality of life using the Karnovsky performance index

Analysis of quality of life using the pain numeric scale

Survival analysis through the calculation of overall survival

Survival analysis through the calculation of progression free survival survival

Study of adaptive immunity through the sampling of Interleukin6 and Heat shock protein 70 levels at baseline and post-procedure

IGEA

Universita di Verona

Symptoms and General Pathology

Neoplastic Processes

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Intestinal Diseases

Rectal Diseases

Antibodies

Immunoglobulins

Systemic injection of bleomycin followed by electroporation of the primary tumor. Bleomycin administration: 15.000 IU/m2 BSA.

BSA by Du Bois formula.

Electrochemotherapy with bleomycin

Electroporation using an endoscopic electroporation device

EndoVE

Ismail Gögenur, MD, DMSc

Rasmus P Vogelsang, MD

Julie Gehl, MD, DMSc

Ismail Gögenur, Professor

The purpose of this study is to evaluate the efficacy and safety of neoadjuvant electrochemotherapy on locally advanced rectal cancer (UICC II-III) in an intended curative clinical setting, using an endoscopic electroporation device (EndoVE).

Electroporation of cancer cells allows for a greater concentration of chemotherapy drugs to enter the tumor cells. The uptake of the chemotherapeutic drug is aided through the application of short electric pulses to the tumor mass (referred to as - Electrochemotherapy or ECT). The pulses make the tumor cells more porous which allows the drug easier access into the cancer cells, whereas other tissues and organs in the body remain relatively poor at absorbing the drug, thereby reducing the potential side effects on healthy tissues. Procedures with electrochemotherapy have previously been applied to human patients in other countries of the EU, the US and Japan.

The drug concentration used is significantly reduced due to the more targeted absorption by the tumor and this significantly reduces side effects normally associated with chemotherapy.

A large number of preclinical and clinical Phase I and I/II studies have demonstrated the efficiency and safety of ECT. These studies have included patients with melanoma, head and neck squamous cell carcinoma, merkel cell carcinomas, basal cell carcinoma and adenocarcinoma nodules.

An endoscopic system (EndoVE ) for delivering the electric pulses to gastrointestinal tumors has recently been developed. The treatment procedure is similar to standard endoscopic colorectal examination (therapeutic colonoscopy) with the added element of an intravenous injection of bleomycin followed by the delivery of electric pulses (each one less than 1msec in duration). The pulses are endoscopically delivered directly to the tumor mass. The entire procedure is minimally invasive and completely ambulatory. A successful treatment will cause the tumor to shrink in size in the weeks following the procedure.

The objective of this study is to investigate the efficacy and safety of this approach in downsizing locally advanced rectal tumors prior to intended curative surgery.

Time frame:

1. All patients will be treated with standard neoadjuvant chemoradiation therapy prior to enrollment in this trial.
2. Alle patients will have PET/MRI scans performed twice to evaluate treatment response (before and after ECT)
3. ECT treatment will be performed 4 weeks prior to surgery outlined by MDT.
4. Alle patients will be followed up for 3 months.

Endoscopic Assisted Electrochemotherapy in Addition to Neoadjuvant Treatment of Locally Advanced Rectal Cancer

Endoscopic Assisted Electrochemotherapy in Addition to Neoadjuvant Treatment of Locally Advanced Rectal Cancer: a Randomized Clinical Phase II Trial

Number of participants with histopathologic tumor regression following elctrochemotherapy as assesed by histopathological evaluation of Tumor Regression Grade (Mandard Classification, TRG 1-5)

Number of participants with treatment-related adverse events as assesed by CTCAE version 4.0

Number of participants with compromized surgery following electrochemotherapy assesed by R1 resection rate, CRM involvement, non-mesorectal resection plane, and post operative complications according to Clavien-Dindo Classification

Tumor regression as assesed by tumor stage (T-stage)

Tumor immunologic infiltration as assesed by the Immunoscore through immunohistochemical analysis

Herlev Hospital

Rigshospitalet, Denmark

Zealand University Hospital

Skin and Connective Tissue Diseases

Neoplasm Metastasis

Skin Neoplasms

Skin Diseases

Bone Density Conservation Agents

Calcium

Calcium, Dietary

Hormones

The metastases will be treated with intratumoral injection of calcium chlorid followed by electrotransfer.

It is a once-only treatment. Calcium chlorid concentration: 9mg/ml. Total dose: 0,5ml/cm3 tumor volume.

The metastases will be treated with intratumoral injection of bleomycin followed by electrotransfer.

It is a once only treatment. bleomycin concentration: 1000 IU/ml. Total dose: o,5 ml/cm3 tumor volume.

Intratumoral injection, once only treatment.

Calcium electroporation

Intratumoral injection, once only treatment

Julie Gehl

The purpose of this study is to evaluate the effect of calcium electroporation on cutaneous metastases, and compare calcium electroporation with standard treatment: electrochemotherapy.

Double-blinded phase II clinical study. We will compare the effect of calcium electroporation for the treatment of cutaneous metastases with standard treatment: electrochemotherapy with intratumoral injection of bleomycin. Separate randomisation will be performed and the lesions will be treated with either intratumoral injection of calcium or bleomycin. It is a once only treatment and the patients will be followed up for 6 months.

It is a non-inferiority study and we accept a difference in response on 15%.

Patients with cutanoues tumors of any cancer histology were included, and metastases were marked, numbered and photographed. Syringes with either calcium or bleomycin were prepared by a pharmacist, blinded for the treating clinician. After injection of study drug (calcium or bleomycin), electroporation was performed. Metastases were followed and at the 6 month follow-up response was recorded for treated metastases and the actual drug used for each metastasis was revealed.

The patient and treating doctor only knew the size of the treated tumor, and the injection volume, but not the content of the syringe (either calcium or bleomycin).

Calcium Electroporation for Treatment of Cutaneous Metastases

It is a non-inferiority study, and we accept a difference in response on 15%.

Response evaluated by "Response Evaluation Criteria in Solid Tumors" (RECIST) guidelines version 1.1.

Describe adverse events using Common Terminology for Adverse Events, version 4.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Electrochemoterapy With Bleomycin for the Treatment of Unresectable Pancreatic Cancer	NCT03225781	Pancreatic Canc...	Electrochemothe...	18 Years - 80 Years	Universita di Verona
Endoscopic Assisted Electrochemotherapy in Addition to Neoadjuvant Treatment of Locally Advanced Rectal Cancer	NCT03040180	Locally Advance... Electrochemothe... Neoadjuvant The... Down Staging	Electrochemothe... EndoVE	18 Years -	Zealand University Hospital
Electrochemoterapy With Bleomycin for the Treatment of Unresectable Pancreatic Cancer	NCT03225781	Pancreatic Canc...	Electrochemothe...	18 Years - 80 Years	Universita di Verona
Endoscopic Assisted Electrochemotherapy in Addition to Neoadjuvant Treatment of Locally Advanced Rectal Cancer	NCT03040180	Locally Advance... Electrochemothe... Neoadjuvant The... Down Staging	Electrochemothe... EndoVE	18 Years -	Zealand University Hospital
Calcium Electroporation for Treatment of Cutaneous Metastases	NCT01941901	Cutaneous Metas...	Calcium electro... Electrochemothe...	18 Years -	Herlev Hospital
Calcium Electroporation for Treatment of Cutaneous Metastases	NCT01941901	Cutaneous Metas...	Calcium electro... Electrochemothe...	18 Years -	Herlev Hospital

Spots Global Cancer Trial Database for electrochemotherapy with bleomycin