EndoVE endosCopic Treatment for Oesophageal and Gastric canceR

Study Overview
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Brief Summary
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This project aims to establish the safety and efficacy of treating patients with inoperable oesophageal cancer or gastric cancer, using an endoscopic electroporation system (EndoVE) to facilitate direct chemotherapy tumour absorption.

Detailed Description
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The use of electroporation has expanded over the last twenty years since its first clinically reported study in the treatment of head and neck cancer in 1991. In electroporation short high-voltage pulses are delivered directly to the tumour which transiently permeabilises the cell membranes enabling targeted cell death and also allowing otherwise non-permeant chemotherapeutic drugs to enter the cancer cells. The parameters of a successful electroporation process are determined by the strength of the electric field and the duration of the electrical field exposure. ePORE and EndoVE deliver electroporation parameters which successfully electroporate cells in the reversible electroporation range, whilst eliminating muscular contractions. Both devices are CE marked and will be used within the definition of their intended use. Currently over 150 sites in Europe are reported to be employing electroporation in the clinical management of head & neck, recurrent breast, malignant melanoma, colorectal, liver metastasis, pancreatic and inoperable glioma. The standard operating procedures for electroporation and electrochemotherapy were established during the EU funded ESOPE study which established the clinical application of electroporation in combination with cisplatin or bleomycin. The EndoVE device has already been used successfully in phase I studies in patients with inoperable oesophageal and colorectal cancer. No serious adverse events were noted with positive tumour regression observed after a single treatment. A patient recruited to the study will be requested to attend a pre-study visit where informed consent will be obtained before proceeding to review medical history and conduct a full clinical examination, full blood count, EKG and assessment of tumour volume via a CT. The procedure will happen no later than 28 days after the pre-study visit - Day 0. On the day of the procedure, a review of any changes which occurred since the pre-study visit will be conducted. The patient will be placed under General Anaesthetic or sedated before Bleomycin will be delivered intravenously. The patient will then be treated endoscopically with the EndoVE device. The EndoVE procedure should take no longer than 30 minutes. The patient will then be transferred to the step-down ward to monitor for any adverse events before being discharged. There will be a telephone follow up after 2 days, 7 days, 4 weeks and 8 weeks. The patient will be requested to attend the clinic for a 12-week follow up for clinical review,

Official Title
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EndoVE endosCopic Treatment for Oesophageal and Gastric canceR

Conditions
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Oesophageal Cancer, Oesophageal Disease, Gastric Cancer

Intervention / Treatment
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* Procedure: EndoVE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically verified oesophageal tumour Men or women aged at least 18 years of age. Patient has already received or been considered for surgery, and / or chemo-radiation. Performance status (Karnofsky > 60% or ECOG/WHO <2). Treatment free interval of at least 2 weeks after previously applied therapy. Patients must be mentally capable of understanding the information given. Patients must give written informed consent. Exclusion Criteria: Coagulation disorder. Patients with a clinically manifested arrhythmia or with a pacemaker. Patients with oesophageal stenosis that cannot be relieved via balloon dilation. Oesophageal tumour treated with radiotherapy in the previous 4 weeks. Patients with epilepsy. Pregnancy or lactation/breastfeeding. Patients known to be Hepatitis B/C or HIV positive. Concurrent treatment with an investigational medicinal product or participation in another clinical study. Patients with any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study requirements. Highly ulcerated oesophageal tissue. Contraindications for bleomycin use including acute pulmonary infection and severe pulmonary disease. Allergic reactions to bleomycin observed previously If a bleomycin cumulative dose of 400 x103 IU has been exceeded

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: EndoVE endosCopic Treatment for Oesophageal and Gastric canceR<br>The patient will be placed under General Anaesthetic or sedated before Bleomycin will be delivered intravenously. The patient will then be treated endoscopically with the EndoVE device. The EndoVE procedure should take no longer than 30 minutes. The patient will then be transferred to the step-down ward to monitor for any adverse events before being discharged. There will be a telephone follow up after 2 days, 7 days, 4 weeks and 8 weeks. The patient will be requested to attend the clinic for a 12-week follow up for clinical review. | Procedure: EndoVE<br>* On the day of the procedure, a review of any changes which occurred since the pre-study visit will be conducted. The patient will be placed under general anaesthesia or sedated before Bleomycin will be delivered intravenously. The patient will then be treated endoscopically with the EndoVE device. The EndoVE procedure should take no longer than 30 minutes.<br>* Other names: ePORE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events (CTCAE) | Safety evaluation will be performed via continuous assessment of safety parameters by reviewing events as they arise. The investigation will be put on hold if unacceptable safety issues are outstanding. Adverse Events (AE) and Serious Adverse Events (SAE) will be evaluated and graded according to Common Terminology Criteria for Adverse Events (CTCAE) | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of system in palliation of dysphagia | Change in dysphagia post treatment as measured by Ogilvie Dysphagia Score | 12 weeks | 
| Response Evaluation Criteria in Solid Tumours (RECIST) | Following CT scan at 12 weeks, a response evaluation will be conducted and reported. | 12 Weeks Post-Treatment | 
| Evaluation of Patient Reported Quality of Life (EORTC QLQ30) | Change in Quality of Life Patient Reported Outcomes as measured by European Organisation for Research and Treatment of Cancer (EORTC) QLQ30 | Baseline (Day 0), Day 0 + 2 days, Day 0 + 1 week, Day 0 + 4 Weeks, Day 0 + 8 Weeks, Day 0 + 12 Weeks | 
| Evaluation of Patient Reported Quality of Life (EORTC QLQ-OES18) | Change in Quality of Life Patient Reported Outcomes as measured by disease specific European Organisation for Research and Treatment of Cancer (EORTC) QLQ-OES18 | Baseline (Day 0), Day 0 + 2 days, Day 0 + 1 week, Day 0 + 4 Weeks, Day 0 + 8 Weeks, Day 0 + 12 Weeks | 
| Evaluation of Pain pre and post-treatment | Change in pain experienced by the patient before and after treatment as measured by Brief Pain Inventory | Day 0 Pre-treatment, Day 0 Post-Treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Palliation