Endoscopic Treatment of Inoperable Colorectal Cancer With the EndoVe System

NCT01172860 | Completed Phase 1 DMC

• 1 other identifier: EudraCT:2012-001248-23
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

A new approach to treating solid tumours (both operable and inoperable) has been carried out by the Cork Cancer Research Centre (CCRC) at the Mercy University Hospital, Cork, Ireland since 2002. The approach simply allows a greater concentration of chemotherapy drugs to enter the tumour cells rather than healthy cells. The uptake of the chemotherapeutic drug directly by the tumour is aided through applying short electric pulses to the tumor mass (referred to as - Electrochemotherapy or ECT). The pulses make the tumour 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. This approach to date has been limited to skin based tumours due to the requirement for the electrodes to be placed directly in contact with the tumour. Procedures with electrochemotherapy have 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. Case reports concerning other primary tumours have also been reported. The investigators have developed an endoscopic approach (EndoVe system) for delivering the electric pulses to internal cancers and are currently seeking to evaluate its efficacy in the treatment of inoperable colorectal cancer. The treatment procedure is similar to standard endoscopic colorectal examination (colonoscopy) with the added element of an intravenous injection of bleomycin followed after eight minutes by the delivery of electric pulses (each one less than 1msec in duration). The pulses are endoscopically delivered directly to the tumour mass. The entire procedure is minimally invasive and does not require intensive care follow up or stitches. If the treatment is successful the tumour will 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 reducing the size of the tumour.

Conditions

Colorectal Cancer

Keywords

Inoperable; Colorectal; Endoscopic; Electroporation; Outpatient

Outcome Measures

Primary Outcomes (2)

• Tumor regression

  Follow up examination of tumor volume following treatment via endoscopy and transrectal ultrasound.

  3 months

• treatment safety

  Evaluate safety of treatment approach at regular checkup intervals following treatment

  3 months

Study Arms (1)

EndoVe treatment

EXPERIMENTAL

Use of the EndoVe device to safely and effectively ablate rectal tumor tissue

Device: EndoVe endoscopic electroporation

Interventions

EndoVe endoscopic electroporation DEVICE

The EndoVe device enables the endoscopic treatment of gastrointestinal tumor tissues. The device is placed on the tumor tissue and an electrical pulse of less than 1msec is delivered. The tumor tissue becomes permeabilised and absorbs much greater concentrations of the drug than the surrounding healthy tissue

Also known as: EndoVe, Endoscope

EndoVe treatment

Eligibility Criteria

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

You may qualify if:

• Histologically verified colorectal tumour.
• Case reviewed by a multidisciplinary team (MDT) (surgery, radiology, oncology, gastroenterology) and there are no curable options with the standard of care. The MDT considers all available treatment options and enrolment to this study is agreed as being appropriate; Or the case is curable but patient refuses to undergo the standard of care. The MDT considers all possible alternatives, which are also discussed with the patient, and the MDT considers enrolment to this study as being the most appropriate option; Or patients with advanced local disease with impending obstruction on endoscopic evaluation who are otherwise not suitable for surgical intervention or stenting, the MDT would also consider these patients for enrolment into this study.
• Men or women aged at least 18 years.
• 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.
• a) A female of Non-Childbearing potential (i.e. physiologically incapable of becoming pregnant) is eligible to participate in the study if she:
• has had a hysterectomy
• has had a bilateral oophorectomy (ovariectomy) - has had a bilateral tubal ligation
• Is post-menopausal:

You may not qualify if:

• Coagulation disorder
• Patients with pre-existing renal dysfunction are excluded. \[Note: Creatinine clearance will be measured for all patients. For Bleomycin treatment: creatinine clearance must be greater than 40ml/min.\]
• Patients with a clinically manifested arrhythmia or with a pacemaker
• Patients with epilepsy.
• Pregnancy or lactation/breastfeeding.
• Patient known to be Hepatitis B/C or HIV positive.
• Concurrent treatment with an investigational medicinal product or participation in another clinical study.
• Patients who have undergone a regime of Bevacizumab in the previous 4 weeks.
• 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 inflamed colon tissue which is ulcerated and bleeding.
• Contraindications for bleomycin use including acute pulmonary infection and severe pulmonary disease.
• Contraindication for bleomycin use: allergic reactions to bleomycin observed in previous treatment.
• Contraindication for bleomycin use: if cumulative dose of 250mg BLM/m2 was previously exceeded.
• Patients with hypersensitivity to Cisplatin or other platinum compounds or to any of the excipients are to be excluded from receiving Cisplatin for the study.
• Cisplatin is contraindicated in combination with live vaccines, including yellow fever vaccine.

Sponsors & Collaborators

• Mercy University Hospital, Cork, Ireland: lead
• St. James's Hospital, Ireland: collaborator
• The Adelaide and Meath Hospital: collaborator

Study Sites (1)

Mercy University Hospital

Cork, cork4, Ireland

Location

Related Publications (10)

• Gargiulo M, Moio M, Monda G, Parascandolo S, Cubicciotti G. Electrochemotherapy: actual considerations and clinical experience in head and neck cancers. Ann Surg. 2010 Apr;251(4):773. doi: 10.1097/SLA.0b013e3181d64b81. No abstract available.

  PMID: 20375711 BACKGROUND

• Moller MG, Salwa S, Soden DM, O'Sullivan GC. Electrochemotherapy as an adjunct or alternative to other treatments for unresectable or in-transit melanoma. Expert Rev Anticancer Ther. 2009 Nov;9(11):1611-30. doi: 10.1586/era.09.129.

  PMID: 19895245 BACKGROUND

• Campana LG, Mocellin S, Basso M, Puccetti O, De Salvo GL, Chiarion-Sileni V, Vecchiato A, Corti L, Rossi CR, Nitti D. Bleomycin-based electrochemotherapy: clinical outcome from a single institution's experience with 52 patients. Ann Surg Oncol. 2009 Jan;16(1):191-9. doi: 10.1245/s10434-008-0204-8. Epub 2008 Nov 6.

  PMID: 18987914 BACKGROUND

• Quaglino P, Mortera C, Osella-Abate S, Barberis M, Illengo M, Rissone M, Savoia P, Bernengo MG. Electrochemotherapy with intravenous bleomycin in the local treatment of skin melanoma metastases. Ann Surg Oncol. 2008 Aug;15(8):2215-22. doi: 10.1245/s10434-008-9976-0. Epub 2008 May 23.

  PMID: 18498012 BACKGROUND

• Sadadcharam M, Soden DM, O'sullivan GC. Electrochemotherapy: an emerging cancer treatment. Int J Hyperthermia. 2008 May;24(3):263-73. doi: 10.1080/02656730701832334.

  PMID: 18393004 BACKGROUND

• Larkin JO, Collins CG, Aarons S, Tangney M, Whelan M, O'Reily S, Breathnach O, Soden DM, O'Sullivan GC. Electrochemotherapy: aspects of preclinical development and early clinical experience. Ann Surg. 2007 Mar;245(3):469-79. doi: 10.1097/01.sla.0000250419.36053.33.

  PMID: 17435555 BACKGROUND

• Mir LM, Morsli N, Garbay JR, Billard V, Robert C, Marty M. Electrochemotherapy: a new treatment of solid tumors. J Exp Clin Cancer Res. 2003 Dec;22(4 Suppl):145-8.

  PMID: 16767921 BACKGROUND

• Byrne CM, Thompson JF. Role of electrochemotherapy in the treatment of metastatic melanoma and other metastatic and primary skin tumors. Expert Rev Anticancer Ther. 2006 May;6(5):671-8. doi: 10.1586/14737140.6.5.671.

  PMID: 16759159 BACKGROUND

• Soden DM, Larkin JO, Collins CG, Tangney M, Aarons S, Piggott J, Morrissey A, Dunne C, O'Sullivan GC. Successful application of targeted electrochemotherapy using novel flexible electrodes and low dose bleomycin to solid tumours. Cancer Lett. 2006 Feb 8;232(2):300-10. doi: 10.1016/j.canlet.2005.03.057. Epub 2005 Jun 16.

  PMID: 15964138 BACKGROUND

• Snoj M, Rudolf Z, Cemazar M, Jancar B, Sersa G. Successful sphincter-saving treatment of anorectal malignant melanoma with electrochemotherapy, local excision and adjuvant brachytherapy. Anticancer Drugs. 2005 Mar;16(3):345-8. doi: 10.1097/00001813-200503000-00015.

  PMID: 15711188 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Endoscopes

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Equipment; Equipment and Supplies; Surgical Equipment

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 29, 2010
• First Posted: July 30, 2010
• Study Start: March 1, 2010
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: November 9, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will share

Locations

IE (1)