Gene Electrotransfer to Muscle With Plasmid AMEP in Patients With Disseminated Cancer

NCT01664273 | Terminated Phase 1 DMC

• 1 other identifier: AA 1201
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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. 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).

Conditions

Metastatic Malignant Neoplasm

Keywords

electroporation; gen electrotransfer; muscle; plasmid AMEP

Outcome Measures

Primary Outcomes (1)

• 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.

  From treatment to last follow up, planned 8 weeks.

Secondary Outcomes (4)

• Efficacy of the trial treatment

  PET/CT scan 4 weeks, 8 weeks and 12 weeks after trial treatment.

• Pharmacokinetics

  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

  Scoring 'immediately after treatment', '30 min after treatment' '6 hours after treatment' and 'pain in the past 24 hours', and day 8.

• Safety

  Day after treatment and 14 days after treatment

Interventions

Plasmid AMEP DRUG

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Copenhagen University Hospital at Herlev: lead

Study Sites (1)

Depart. of Oncology, Copenhagen Universtiy Hospital Herlev

Herlev, 2730, Denmark

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Julie Gehl, MD DMSci

  Department of Oncology, Copenhagen University Hospital Herlev

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2012
• First Posted: August 14, 2012
• Study Start: July 1, 2012
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: June 20, 2014

Record last verified: 2014-06

Locations

DK (1)