Gene Electrotransfer to Muscle With Plasmid AMEP in Patients With Disseminated Cancer
19 de junio de 2014 actualizado por: Copenhagen University Hospital at Herlev
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).
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Intervencionista
Inscripción (Actual)
7
Fase
- Fase 1
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Herlev, Dinamarca, 2730
- Depart. of Oncology, Copenhagen Universtiy Hospital Herlev
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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.
- 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.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Safety of the trial treatment
Periodo de tiempo: From treatment to last follow up, planned 8 weeks.
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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.
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From treatment to last follow up, planned 8 weeks.
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Efficacy of the trial treatment
Periodo de tiempo: PET/CT scan 4 weeks, 8 weeks and 12 weeks after trial treatment.
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PET/CT scan will be evaluated using RECIST 1.1 (CT) and PERCIST (PET)
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PET/CT scan 4 weeks, 8 weeks and 12 weeks after trial treatment.
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Pharmacokinetics
Periodo de tiempo: Pre-dose, 2, 6 and 24 hours after dose, day 8, 15, 22, 29 and 8 weeks after treatment.
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Measurements of plasma and urine plasmid AMEP concentrations.
Measurements of plasma and urine protein AMEP concentrations
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Pre-dose, 2, 6 and 24 hours after dose, day 8, 15, 22, 29 and 8 weeks after treatment.
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Discomfort associated with the treatment procedure
Periodo de tiempo: Scoring 'immediately after treatment', '30 min after treatment' '6 hours after treatment' and 'pain in the past 24 hours', and day 8.
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The patient completes VAS (Visual Analogue Scale) scores pain related to the treatment area at abovementioned time points.
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Scoring 'immediately after treatment', '30 min after treatment' '6 hours after treatment' and 'pain in the past 24 hours', and day 8.
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Safety
Periodo de tiempo: Day after treatment and 14 days after treatment
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MR scan of treated region (thigh muscle) in order to assess potential intramuscular edema or hematoma
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Day after treatment and 14 days after treatment
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Investigador principal: Julie Gehl, MD DMSci, Department of Oncology, Copenhagen University Hospital Herlev
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de julio de 2012
Finalización primaria (Anticipado)
1 de mayo de 2015
Finalización del estudio (Anticipado)
1 de mayo de 2015
Fechas de registro del estudio
Enviado por primera vez
16 de julio de 2012
Primero enviado que cumplió con los criterios de control de calidad
10 de agosto de 2012
Publicado por primera vez (Estimar)
14 de agosto de 2012
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
20 de junio de 2014
Última actualización enviada que cumplió con los criterios de control de calidad
19 de junio de 2014
Última verificación
1 de junio de 2014
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- AA 1201
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
Ensayos clínicos sobre Plasmid AMEP
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Lisa H. Butterfield, Ph.D.National Cancer Institute (NCI)TerminadoCarcinoma hepatocelular | Cáncer de hígado | Cáncer de hígado | Hepatoma | Cáncer hepatocelular | Cáncer hepático | Carcinoma de células hepáticas | Cáncer Hepatocelular | Cáncer de hígado en adultos | Carcinoma de células hepáticas en adultos | Cáncer de hígado | Neoplasias De Hígado | Neoplasias hepáticas | Neoplasias...Estados Unidos