Electrochemotherapy on Head and Neck Cancer

A phase II clinical trial testing electrochemotherapy on mucosal recurrent head and neck cancer. Twenty-five patients will be treated. Primary outcome is tumour response on imaging. Secondary outcomes are response from tissue samples, VAS score, Quality of life evaluation and side effects to treatment.

Study Overview

• Status: Unknown
• Conditions: Head Neck Cancer
• Intervention / Treatment: Procedure: Electrochemotherapy; Device: Cliniporator; Drug: Bleomycin

Detailed Description

Electric pulses may be used to transiently permeabilise cell membranes, enabling passage of otherwise non-permeating molecules. This dramatically enhances the cytotoxic effect of certain chemotherapeutic agents, and is termed electrochemotherapy. Electrochemotherapy is now standardly used in the treatment of cutaneous metastases of various cancers in over 100 cancer centers around Europe.

The intention of this trial is to investigate the possible use of electrochemotherapy in recurrent head and neck cancer as a palliative treatment. Surgery and radiotherapy, with the possible addition of chemotherapy, cures a large part of patients with head and neck cancer. However, in the event of recurrence curative options may be exhausted and the patient is referred for palliative chemotherapy.

It is for this patient group, the investigators propose electrochemotherapy in a clinical trial.

The electrochemotherapy is administered as a once-only treatment, with possible retreatment after eight weeks. Under general anesthesia, chemotherapy is administered intravenously, followed by application of electric pulses to the tumour area. Before treatment, the location and spread of the tumour is determined by imaging.

The trial includes evaluation of response by MRI (magnetic resonance imaging) and PET/CT (Positron Emission Tomography - Computed Tomography) scans (base-line, 4 weeks, 8 weeks), tissue samples, as well as adverse events registration and questionnaires on quality of life. The planned study is a phase II clinical study, prospective, observational with up to 25 patients.

Treatments will be performed in collaboration between the Department of Oncology, Copenhagen University Hospital Herlev, which has extensive experience in electrochemotherapy, and the Department of Ear Nose and Throat Surgery at Copenhagen University Hospital Rigshospitalet, that has the surgical expertise and set-up needed.

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Christina C. Plaschke, MD; Phone Number: +45 29 25 92 45; Email: caroline@dadlnet.dk
• Study Contact Backup: Name: Irene Wessel, MD; Phone Number: +45 35 45 83 22; Email: irene.wessel.01@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Department of Otorhinolaryngology, Rigshospitalet, Copenhagen University Hospital
    • Contact: Christina C. Plaschke, MD; Phone Number: +45 29 25 92 45; Email: caroline@dadlnet.dk
    • Contact: Irene Wessel, MD; Phone Number: +45 35 45 83 22; Email: irene.wessel.01@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject age > 18 years.
2. Verified cancer of the head and neck area of any histology.
3. At least one tumour lesion should be accessible for electroporation.
4. Performance status WHO <= 2nd
5. Progressive and / or metastatic disease.
6. Expected survival of > 3 months.
7. Measurable disease is defined as at least one measurable lesion by RECIST 1.1.
8. A treatment-free interval of more than 4 weeks since chemotherapy or radiation therapy.
9. The participant should have been offered the current standard treatment. If there are no further standard treatment to offer or if the participant does not want to receive this, the participant may be included in the trial.
10. The participant should be able to understand the information for participants and be willing and able to comply with hospitalization in the treatment and the agreed follow-up visits and tests.
11. Platelets ≥ 50 billion / L, INR (international normalized ratio) > 1.5. Medical correction is permitted, e.g. correction using vitamin K.
12. Sexually active women who can become pregnant should use adequate contraception during this trial and 6 months after administration of bleomycin (pill, spiral, injection of prolonged progestin subdermal implantation, hormone-containing vaginal devices, transdermal patches).
13. Signed informed consent. -

Exclusion Criteria:

Participants should be excluded if they meet just one of the criteria stated below.

1. Symptomatic progression of the participants cancerous disease that requires another intervention.
2. Acute lung infection
3. Symptoms of lung function impairment. This triggers a lung function test (DLCO = diffusing capacity of the lungs for carbon monoxide), if moderate to severe the participant will be excluded.
4. Previous bleomycin treatment with cumulative dose more than 240,000 Units / m2.
5. History of severe allergic reactions associated with bleomycin.
6. Allergy to constituents of the planned anesthetic.
7. Coagulation disorder which can not be corrected.
8. Chronic renal dysfunction with creatinine> 150 micromoles / liter, will trigger a Cr-51-EDTA (Chromium-51-ethylenediamine tetra acetic acid) clearance. If this is too impaired, the participant is excluded.
9. Pregnancy or lactation.
10. While participation in other clinical trials involving experimental drugs or involved in a trial within 4 weeks prior to study drug administration.
11. Other disorders investigator finds incompatible with participation in the trial. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Electrochemotherapy; 25 patients treated with electrochemotherapy	Procedure: Electrochemotherapy; Electroporation by a device, Cliniporator, combined with chemotherapy, Bleomycin.; Other Names: electroporation with chemotherapy; eletropermeabilization with chemotherapy; Device: Cliniporator; Electric pulses , duration 100 microseconds, about 400 V given at 5000 Hz.; Drug: Bleomycin; Administered intravenously or injected into the tumour before electroporation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Tumour response from PET/CT scans (Positron Emission Tomography - Computed Tomography)	8 weeks after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumour response from MRI scans (Magnetic resonance imaging)		8 weeks after treatment
Tumour response from tissue samples	Still cancer activity or not	4 weeks after treatment
VAS score (Visual Analogue Scale)	Participant assessed	baseline, 4 weeks and 8 weeks after treatment
Quality of life	EORTC scores for head and neck (The European Organisation for Research and Treatment of Cancer)	baseline, 4 weeks and 8 weeks after treatment
CTCAE recordings (Common Terminology Criteria for Adverse Events)	side effects scored by CTCAE version 4.0	baseline, 4 weeks and 8 weeks after treatment

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: Copenhagen University Hospital at Herlev
• Investigators: Study Chair: Julie Gehl, MD, Denmark: Herlev and Gentofte Hospital, University of Copenhagen

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Anticipated): September 1, 2019
• Study Completion (Anticipated): September 1, 2019

Study Registration Dates

• First Submitted: September 6, 2015
• First Submitted That Met QC Criteria: September 14, 2015
• First Posted (Estimate): September 15, 2015

Study Record Updates

• Last Update Posted (Estimate): January 18, 2017
• Last Update Submitted That Met QC Criteria: January 17, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Electrochemotherapy; bleomycin; head neck cancer
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Antineoplastic Agents; Antibiotics, Antineoplastic; Bleomycin
• Other Study ID Numbers: HH1222

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided