Electrochemotherapy as a Palliative Treatment for Brain Metastases

This study has been terminated.
(Due to slow patient recruitment)
Sponsor:
Collaborators:
Rigshospitalet, Denmark
Glostrup University Hospital, Copenhagen
Information provided by (Responsible Party):
Copenhagen University Hospital at Herlev
ClinicalTrials.gov Identifier:
NCT01322100
First received: March 23, 2011
Last updated: July 30, 2013
Last verified: July 2013
  Purpose

Because electrochemotherapy is a quick and effective treatment for cutaneous metastases, a novel electrode device has been developed for treatment in soft tissue such as the brain. Up to 18 patients will be treated in this phase I dose-escalating study of electrochemotherapy for brain metastases. Primary endpoint of the clinical trial is safety and secondary endpoint is efficacy. One brain metastasis is treated once-only with the electrode device guided stereotactically through a burr hole using CT monitoring. The patient will be fully anesthetized during the treatment procedure. Patients are followed up for 6 months with regard to neurological function, Barthel Index, steroid use and adverse effects registration (CTCAE). Tumor response will be evaluated by Magnetic Resonance imaging (MRI).


Condition Intervention Phase
Brain Metastases
CNS Metastases
Device: The Electroporation System
Drug: Bleomycin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Electrochemotherapy as a Palliative Treatment for Brain Metastases

Resource links provided by NLM:


Further study details as provided by Copenhagen University Hospital at Herlev:

Primary Outcome Measures:
  • Safety of the trial treatment. This is evaluated by adverse events registrations (CTCAE). [ Time Frame: From treatment to last follow up, planned 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Efficacy of the trial treatment. This is evaluated by target tumor response on Magnetic resonance imaging (MRI). [ Time Frame: Patients are evaluable 50 days after treatment ] [ Designated as safety issue: No ]

Enrollment: 1
Study Start Date: April 2011
Study Completion Date: July 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Device: The Electroporation System
    The Electroporation System comprises of 3 parts: 1.Switch Box, 2. Driver, 3. Brain Probe
    Drug: Bleomycin
    Bleomycin dosage for i.v. use is 15.000 IU/m2, and is administered 10-30 minutes before the electric pulses. Bleomycin dosage for intratumoral use is either 2.000 IU, 4.000 IU, or 6.000 IU per 3 ml, and 20 % of the calculated tumor volume is injected.
Detailed Description:

Electrochemotherapy is a cancer treatment modality comprising of a combination of electrical pulses delivered by electrodes and chemotherapy supplied either intravenously or intratumorally. It is a quick and effective treatment for cutaneous metastases < 3 cm with a complete response rate of 73 % after once-only treatment. The available electrode devices have so far only been applicable for cutaneous tumors. An electrode has now been developed in collaboration with a medico-technical company. An increasing number of cancer patients suffer from metastases to the brain due to e.g. better control of the systemic peripheral cancer disease. The prognosis for patients with brain metastases remains poor and research into new treatments are needed in this field.

Up to 18 patients will be treated in a dose-escalating study of electrochemotherapy for brain metastases. Primary endpoint of the clinical trial is safety and secondary endpoint is efficacy. One brain metastasis is treated once-only with the electrode device guided stereotactically through a burr hole using CT monitoring. The patient will be fully anesthetized during the treatment procedure. Patients are followed up for 6 months with regard to neurological function, Barthel Index, steroid use and adverse effects registration (CTCAE). Tumor response will be evaluated by Magnetic Resonance imaging (MRI).

The first 6 patients will receive an intravenous dose of bleomycin 15.000 IE/m2 before electric pulses. The following patients will receive an additional intratumoral injection of bleomycin of increasing concentration. The electrical pulses will consist of a series of high voltage pulses of 0.1 millisecond duration.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients > 18 years.
  • Performance status < 2 (ECOG - Eastern Cooperative Oncology Group).
  • Diagnosis of brain metastases originated from histological or cytological verified cancer of any histology.
  • Patients should have received whole-brain radiation therapy (WBRT) with a time interval of at least 2 months from completion of WBRT until inclusion in this study.
  • Patients must have been offered every available standard treatment.
  • Brain metastases to be treated must have a diameter of at least 10 millimetres and no more than 27 millimetres.
  • Brain metastases to be treated must be accessible for treatment.
  • Estimated life expectancy must be more than 3 months.
  • Patients must have adequate organ functions:

Adequate bone marrow reserve: Leucocytes (WBC) > 3.0 x 109/l, thrombocytes > 75 x 109/l, hemoglobin > 7 g/dl.

Hepatic: Alkaline phosphate, ALAT or ASAT and bilirubin must not be increased more than 2 times, pp > 40, APTT in normal range. Medical correction is allowed, e.g. correction of low pp using vitamin K.

Renal: if creatinin > 150 micromolar do a GFR examination (Chrome-EDTA).

  • Patients must not have a blood pressure (BP) over 180 mm Hg systolic and 110 mm Hg diastolic.
  • Sexually active men and women of childbearing potential must use adequate birth control during this study and 6 month after the administration of bleomycin (contraceptive pills, intrauterine devices, injection of prolonged gestagen, subdermal implantation, hormonal vaginal devices, transdermal patches).
  • Participating patients must be able to understand the patient information.
  • Participating patients must have signed a written informed consent and power of attorney prior to inclusion in this study.

Exclusion Criteria:

  • Acute lung infection.
  • Previous bleomycin treatment with more than 200.000 IU/m2.
  • Previous allergic reaction to bleomycin.
  • Allergy towards the sedation used.
  • Pregnancy or breastfeeding. Pregnancy in fertile women is excluded by a measurement of HCG in a blood sample. Sterile or infertile women are excluded from the requirement to use anticonception. To be considered sterile or infertile, the patient must have undergone surgical sterilization (vasectomy/bilateral tubectomy, hysterectomy and bilateral ovariectomy) or be post-menopausal defined as the absence of menstruation.
  • Treatment with G-CSF (Granulocyte Colony Stimulating Factor) or other cytokines.
  • Lung diffusion capacity (DLCO) below normal. DLCO is to be performed in case of suspected (anamnestic or clinical) reduced lung function.
  • Physician's assessment that meningeal carcinomatosis (leptomeningeal disease) is a likely cause of the patient's symptoms.
  • Treatment with anticoagulants (marevan, marcumar, innohep).
  • Allergic to nickel, chrome or cobalt.
  • Participation in another clinical study with an experimental drug up to 4 weeks prior to inclusion.
  • Illnesses, medical, social or physiological, that may affect the patient's ability to understand the patient information and participate in the follow-up.
  • Other serious systemic illnesses (i.e. active infection, abnormal EKG) that the investigator finds may affect the patient's safety and/or ability to complete the study.
  • Treatment with Immunosuppressant drugs such as methotrexate and cyclosporine during the study. Treatment with prednisolone is accepted during the study.
  • Implanted pacemaker, defibrillators or hearth valve prosthetics.
  • Implanted devices such as neurostimulators, eartransplants, insulinpump, metallic tracheostomy.
  • Catheters with metal such as Port á cath, Swan Ganz, P-dialysis cath., ventriculoatrial and -peritoneal shunts, bladder cath. with thermo-measurement.
  • Metallic clips/prosthetics/magnets from surgery such as neuro- or abdominal clips, tooth- or other prosthetics.
  • Disorganised metallic material such as metal fragments in the eyes, shrapnel, gun shot injuries.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01322100

Locations
Denmark
Rigshospitalet
Copenhagen, Denmark, 2100
Herlev Hospital
Herlev, Denmark, 2730
Sponsors and Collaborators
Copenhagen University Hospital at Herlev
Rigshospitalet, Denmark
Glostrup University Hospital, Copenhagen
Investigators
Principal Investigator: Julie Gehl, MD, DMSci Department of Oncology, Herlev Hospital
  More Information

Publications:
Responsible Party: Copenhagen University Hospital at Herlev
ClinicalTrials.gov Identifier: NCT01322100     History of Changes
Other Study ID Numbers: HJ 1020
Study First Received: March 23, 2011
Last Updated: July 30, 2013
Health Authority: Denmark: Danish Medicines Agency

Keywords provided by Copenhagen University Hospital at Herlev:
Brain Metastases, CNS Metastases

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms, Second Primary
Brain Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Bleomycin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014