Clinical Trials Details

Public Title   

A phase I study of the Dz13 drug targeting the c-Jun gene in subjects with skin cance (nodular Basal Cell Carcinoma). | DISCOVER

Contacts   

Prof. Levon Khachigian
UNSW
Centre for Vascular Research
Sydney
2052
+61 2 9385 2537 (phone)
+61 2 9385 1389 (fax)
l.khachigian@unsw.edu.au
Australia

Recruitment Status   

Completed

Focus of Trial   

Treatment: Targeted and biological therapies

Phase of Trial   

Phase 1

Cancer Stage   

Early or Local

Recruitment Dates   

Anticipated start date
06/09/2010

Anticipated end date
NA

Location of Trial   

NSW

Trial Summary   

The purpose of this study is to test the safety of a new treatment (Dz13 combined with DOPE and DOTAP) for nodular BCC, a form of skin cancer.
Dz13 is a small piece of DNA which binds to an mRNA molecule in the cell which in turn produces a specific protein known as c-Jun. The c-Jun gene is known to be abnormally active in many types of cancer cells, including BCC, causing the abnormal production of the c-Jun protein molecule. The c-Jun protein is involved in 'switiching on' other genes involved in cell growth, resulting in growth and spread of tumour cells. Dz13 binds to the c-Jun mRNA and chops it into two pieces, which disrupts production of the c-Jun protein and limits the growth and spread of the tumour. c-Jun is present at very low levels in normal adult tissues and is mostly expressed at high levels in tumour tissue. It is hypothesised that Dz13 will be able to stop the growth and spread of BCC and other skin tumours without significant toxicity. Dz13 has been shown in animal studies to be well tolerated at doses 35-fold higher than the highest dose that will be used in this study.

Description of the Study   


Description of the Control
No control treatment

Description of the Intervention
Dz13 DNAzyme complexed with the lipids DOPE and DOTAP administered as a single intratumoural injection. Three dose cohorts of 10 mcg, 30 mcg and 100 mcg Dz13.

Allocation to Intervention
Nonrandomised trial

Target Sample Size   

9

Primary Outcomes   

To determine the safety and tolerability of Dz13 complexed with DOPE/DOTAP administered as a single intra-tumoural injection as determined by adverse events (AEs), changes in vital signs, clinical laboratory tests and 12-lead electrcardiography (ECG).
1, 2, 4, 8, 12, 24 hours, 7 days, 14 days, 28 days post injection.

To determine the maximum tolerated dose of Dz13 complexed with DOPE/DOTAP administered as a single intra-tumoural injection as assessed by the incidence of dose limiting toxicity (DLT) events in each dose cohort.
1, 2, 4, 8, 12, 24 hours, 7 days, 14 days, 28 days post injection.

Secondary Outcomes   

To measure the level of Dz13 in serum following administration of a single dose of Dz13 complexed with DOPE/DOTAP via intra-tumoural injection.
30 min, 1, 2, 4, 8, 12, 24 hours, 7 days, 14 days, 28 days post injection.

To compare BCC histopathology and immunohistochemistry 14 days following Dz13 administration relative to baseline.
14 days post injection.

Side Effects   

Intervention arm: mild transient (less than 24 hours) injection site swelling, nausea and discomfort in one subject. No serious adverse events occurred in any of the nine subjects

Inclusion Criteria   

Histologically proven nodular BCC.
Measurable disease of 8-16 mm located on trunk or limbs.
Presence of dividing cells as identified histologically.

Minimum Age:
18 Years

Maximum Age:
No limit

Gender:
Both males and females

Cost and Time Commitments   

Similar cost as usual care
More time commitment than usual care
Additional travel commitments

Ethics Approval   

Yes

Trial Sponsors   

Primary Sponsor:
University
University of New South Wales
Sydney
NSW 2052
Australia

Secondary Sponsor:
None




Other Collaborator:
University
University of Sydney
Sydney
NSW 2006
Australia

Funding Source   

Government body
Cancer Institute NSW
Australian Technology Park
Biomedical Building
Suite 101
1 Central Avenue
EVELEIGH NSW 2015
Australia