Metastatic Malignant NeoplasmPhase 1NCT01664273
Gene Electrotransfer to Muscle With Plasmid AMEP in Patients With Disseminated Cancer
A Phase 1 study testing Plasmid AMEP in people with Metastatic Malignant Neoplasm, run by Copenhagen University Hospital at Herlev at 1 site in Denmark.
Trial summary
Gene transfer by electroporation (gene electrotransfer) uses short electric pulses to transiently permeabilise the cell membrane enabling passage of plasmid DNA into the cell cytosol. It is an efficient non-viral method for gene delivery to various tissues. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Malignant Neoplasm
- What is being tested?
- Plasmid AMEP
- Type of treatment
- Injection or infusion
- How many people
- 7 participants
- Where
- 1 siteDenmark
- Study dates
- Jul 2012to May 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years.
- Performance status < 1 (ECOG).
- Histologically confirmed malignant tumor (solid tumor) of any histology,
- Metastatic disease. Patients with asymptomatic brain metastases are eligible.
- Patient should have been offered standard treatment. Patient is eligible if no standard treatment is available or if the patient does not wish to receive standard treatment.
- Life expectancy ≥ 3 months.
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- Measurable disease defined as at least one measurable lesion according to RECIST 1.1
- Patient should have adequate organ function:
- Adequate bone marrow function: Neutrophil count ≥ 1.0 x 109/l (≤ grade 2 CTCAE 4.0); Platelet count ≥ 75 x 109/l (< grade 2 CTCAE 4.0); Hemoglobin ≥ 6,0 mmol/l.
- Liver: ALAT or ASAT < 3 ULN (< grade 2 CTCAE 4.0); Bilirubin ≤ 1,5 ULN (< grade 2 CTCAE 4.0); APTT within normal range; INR ≤ 1,2 (< grade 1 CTCAE 4.0)
- Kidney: Plasma creatinin ≤ 1.5 ULN (< grade 2 CTCAE 4.0)
- At least 4 weeks since any anti-cancer treatment.
- Men and women of reproductive age must use effective contraception during the study and at least 6 months after administration of plasmid AMEP.
- Patient should be able to understand the participant information and able to comply with protocol requirements and scheduled visits.
- Signed informed consent.
Who cannot join
- Allergy to the anaesthetic used.
- Clinical signs of active infection.
- Implanted pacemaker, defibrillator or any other implanted electronic device.
- Participation in other clinical trials involving experimental drugs or participation in a clinical trial within 4 weeks before initiation of study treatment.
- AMI (acute myocardial infarction), stroke or acute ischemic event within the last 6 months.
- Severe atherosclerosis, significant cardiovascular disease (NYHA III or IV) or significant arrhythmias.
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- Systolic blood pressure above 180 mm Hg and/or diastolic blood pressure above 110 mm Hg. If BP >180/110 mm Hg medical correction is allowed and the patient can be included when BP < 180/110 mm Hg.
- Pregnancy and lactation.
- Clinically significant coagulopathy.
- Treatment with anticoagulant drugs.
- Other disorders which the investigator finds incompatible with participation in the study.
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Depart. of Oncology, Copenhagen Universtiy Hospital Herlev
Herlev, 2730
About this study
Gene transfer by electroporation (gene electrotransfer) uses short electric pulses to transiently permeabilise the cell membrane enabling passage of plasmid DNA into the cell cytosol. It is an efficient non-viral method for gene delivery to various tissues. In this phase I dose-escalating study, patients will be treated with intramuscular gene electrotransfer of plasmid AMEP. Plasmid AMEP encodes protein AMEP which bind to α5β1 og αvβ3 integrins. Primary end point of the trial is safety and secondary end points are efficacy, pharmacokinetics and evaluation of potential discomfort associated with the treatment procedure using VAS (Visual Analogue Scale).
Read the detailed description
Cohorts of 3 patients will be treated with increasing doses of plasmid AMEP. Up to 12 patients will be treated.
Treatment procedure: Local anesthetic is applied to m. quadriceps femoris (thigh muscle) and the skin. An incision of the skin is performed followed by dissection until the muscle is exposed. The surgical procedure is performed by plastic surgeons.
Plasmid AMEP is injected intramuscularly and immediately followed by application of electric pulses via a needle electrode inserted into the muscle. A combination of one high voltage pulse (700V/cm, 100 µs) followed by one low voltage pulse (80 V/cm, 400 ms) will be applied. The wound is sutured and a dressing is applied. Treatment procedure is estimated to 30 minutes.
All patients are hospitalized for 24 hours after treatment for the purpose of evaluation of vital signs, physical examination, AE and SAE recording and pharmacokinetics sampling (blood and urine).
Blood biochemistry including LDH and CK is taken 24 hours post treatment. ECG will be taken before and after treatment. Patients score discomfort or pain from treated area using VAS.
- Conditions
- Metastatic Malignant Neoplasm
- Being tested
- Plasmid AMEP
- Keywords
- electroporation, gen electrotransfer, muscle, plasmid AMEP
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plasmid AMEPDrug
Cohorts of 3 patients will received increasing doses of plasmid AMEP:
50 μg, 100 μg, 250 μg and 500 μg. Starting dose will be the lowest dose.
Injection volume will remain constant at 200 μL.
Once-only treatment and intra-individual dose escalation will therefore not occur.
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of the trial treatment
Safety is evaluated by registration of adverse events (Adverse Events and Serious Adverse Events) using the CTCAE criteria version 4.0. Patients are seen in the out patient clinic once a week during the first month after treatment (at day 8, day 15, day 22, day 29) and 8 weeks after treatment. If no progression of the disease at 8 weeks, patients are seen at 12 weeks and then every three months until disease progression or death.
Measured: From treatment to last follow up, planned 8 weeks.
Secondary outcomes (4)
Efficacy of the trial treatment
PET/CT scan will be evaluated using RECIST 1.1 (CT) and PERCIST (PET)
Measured: PET/CT scan 4 weeks, 8 weeks and 12 weeks after trial treatment.
Pharmacokinetics
Measurements of plasma and urine plasmid AMEP concentrations. Measurements of plasma and urine protein AMEP concentrations
Measured: Pre-dose, 2, 6 and 24 hours after dose, day 8, 15, 22, 29 and 8 weeks after treatment.
Discomfort associated with the treatment procedure
The patient completes VAS (Visual Analogue Scale) scores pain related to the treatment area at abovementioned time points.
Measured: Scoring 'immediately after treatment', '30 min after treatment' '6 hours after treatment' and 'pain in the past 24 hours', and day 8.
Safety
MR scan of treated region (thigh muscle) in order to assess potential intramuscular edema or hematoma
Measured: Day after treatment and 14 days after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2012 (estimated)
- Study startJul 2012
- Primary completionMay 2015 (estimated)
- Study completionMay 2015 (estimated)
Why it stopped: Production of the IMP (plasmid AMEP) has been terminated by the supplier (BioAlliance Pharma)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Malignant NeoplasmStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital at Herlev
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Julie Gehl, MD DMSci, Principal investigator, Department of Oncology, Copenhagen University Hospital Herlev
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01664273
- Sponsor's protocol ID
- AA 1201
- Status last verified
- Jun 2014
- First submitted
- 16 Jul 2012
- Last updated
- 20 Jun 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gene Electrotransfer to Muscle With Plasmid AMEP in Patients With Disseminated Cancer
- ClinicalTrials.gov ID
- NCT01664273
- Acronym / sponsor ID
- AA 1201
- Conditions
- Metastatic Malignant Neoplasm
- Keywords
- electroporation, gen electrotransfer, muscle, plasmid AMEP
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Production of the IMP (plasmid AMEP) has been terminated by the supplier (BioAlliance Pharma)
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Copenhagen University Hospital at HerlevUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- May 2015 (estimated)
- Study completion
- May 2015 (estimated)
- First posted
- 14 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Gene transfer by electroporation (gene electrotransfer) uses short electric pulses to transiently permeabilise the cell membrane enabling passage of plasmid DNA into the cell cytosol. It is an efficient non-viral method for gene delivery to various tissues. In this phase I dose-escalating study, patients will be treated with intramuscular gene electrotransfer of plasmid AMEP. Plasmid AMEP encodes protein AMEP which bind to α5β1 og αvβ3 integrins. Primary end point of the trial is safety and secondary end points are efficacy, pharmacokinetics and evaluation of potential discomfort associated with the treatment procedure using VAS (Visual Analogue Scale).
Detailed description
Cohorts of 3 patients will be treated with increasing doses of plasmid AMEP. Up to 12 patients will be treated.
Treatment procedure: Local anesthetic is applied to m. quadriceps femoris (thigh muscle) and the skin. An incision of the skin is performed followed by dissection until the muscle is exposed. The surgical procedure is performed by plastic surgeons.
Plasmid AMEP is injected intramuscularly and immediately followed by application of electric pulses via a needle electrode inserted into the muscle. A combination of one high voltage pulse (700V/cm, 100 µs) followed by one low voltage pulse (80 V/cm, 400 ms) will be applied. The wound is sutured and a dressing is applied. Treatment procedure is estimated to 30 minutes.
All patients are hospitalized for 24 hours after treatment for the purpose of evaluation of vital signs, physical examination, AE and SAE recording and pharmacokinetics sampling (blood and urine).
Blood biochemistry including LDH and CK is taken 24 hours post treatment. ECG will be taken before and after treatment. Patients score discomfort or pain from treated area using VAS.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Age > 18 years.
- Performance status < 1 (ECOG).
- Histologically confirmed malignant tumor (solid tumor) of any histology,
- Metastatic disease. Patients with asymptomatic brain metastases are eligible.
- Patient should have been offered standard treatment. Patient is eligible if no standard treatment is available or if the patient does not wish to receive standard treatment.
Key exclusion criteria (11 listed)
- Allergy to the anaesthetic used.
- Clinical signs of active infection.
- Implanted pacemaker, defibrillator or any other implanted electronic device.
- Participation in other clinical trials involving experimental drugs or participation in a clinical trial within 4 weeks before initiation of study treatment.
- AMI (acute myocardial infarction), stroke or acute ischemic event within the last 6 months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Plasmid AMEPCohorts of 3 patients will received increasing doses of plasmid AMEP: 50 μg, 100 μg, 250 μg and 500 μg. Starting dose will be the lowest dose. Injection volume will remain constant at 200 μL. Once-only treatment and intra-individual dose escalation will therefore not occur. | Drug | – |
Primary outcome
Safety of the trial treatment
Time frame: From treatment to last follow up, planned 8 weeks.
Safety is evaluated by registration of adverse events (Adverse Events and Serious Adverse Events) using the CTCAE criteria version 4.0. Patients are seen in the out patient clinic once a week during the first month after treatment (at day 8, day 15, day 22, day 29) and 8 weeks after treatment. If no progression of the disease at 8 weeks, patients are seen at 12 weeks and then every three months until disease progression or death.
4 secondary outcomes
Efficacy of the trial treatment
Time frame: PET/CT scan 4 weeks, 8 weeks and 12 weeks after trial treatment.
Pharmacokinetics
Time frame: Pre-dose, 2, 6 and 24 hours after dose, day 8, 15, 22, 29 and 8 weeks after treatment.
Discomfort associated with the treatment procedure
Time frame: Scoring 'immediately after treatment', '30 min after treatment' '6 hours after treatment' and 'pain in the past 24 hours', and day 8.
Safety
Time frame: Day after treatment and 14 days after treatment
Results and safety
The study was stopped early (reason given: Production of the IMP (plasmid AMEP) has been terminated by the supplier (BioAlliance Pharma)). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julie Gehl, MD DMSci principal investigator
Department of Oncology, Copenhagen University Hospital Herlev
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Plasmid AMEP in people with Metastatic Malignant Neoplasm, run by Copenhagen University Hospital at Herlev at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Production of the IMP (plasmid AMEP) has been terminated by the supplier (BioAlliance Pharma)). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of the trial treatment (time frame: From treatment to last follow up, planned 8 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jun 2014.