Gene Electrotransfer to Muscle With Plasmid AMEP in Patients With Disseminated Cancer
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Gene Electrotransfer to Muscle With Plasmid AMEP in Patients With Disseminated Cancer|
- Safety of the trial treatment [ Time Frame: From treatment to last follow up, planned 8 weeks. ] [ Designated as safety issue: Yes ]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.
- Efficacy of the trial treatment [ Time Frame: PET/CT scan 4 weeks, 8 weeks and 12 weeks after trial treatment. ] [ Designated as safety issue: No ]PET/CT scan will be evaluated using RECIST 1.1 (CT) and PERCIST (PET)
- Pharmacokinetics [ Time Frame: Pre-dose, 2, 6 and 24 hours after dose, day 8, 15, 22, 29 and 8 weeks after treatment. ] [ Designated as safety issue: No ]Measurements of plasma and urine plasmid AMEP concentrations. Measurements of plasma and urine protein AMEP concentrations
- 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. ] [ Designated as safety issue: No ]The patient completes VAS (Visual Analogue Scale) scores pain related to the treatment area at abovementioned time points.
- Safety [ Time Frame: Day after treatment and 14 days after treatment ] [ Designated as safety issue: Yes ]MR scan of treated region (thigh muscle) in order to assess potential intramuscular edema or hematoma
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||May 2015|
|Estimated Primary Completion Date:||May 2015 (Final data collection date for primary outcome measure)|
Drug: Plasmid AMEP
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01664273
|Depart. of Oncology, Copenhagen Universtiy Hospital Herlev|
|Herlev, Denmark, 2730|
|Principal Investigator:||Julie Gehl, MD DMSci||Department of Oncology, Copenhagen University Hospital Herlev|