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Trial registered on ANZCTR


Registration number
ACTRN12610000162011
Ethics application status
Approved
Date submitted
11/02/2010
Date registered
19/02/2010
Date last updated
29/08/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase I study of the Dz13 drug targeting the c-Jun gene in subjects with skin cance (nodular Basal Cell Carcinoma).
Scientific title
A phase I study to determine the safety and tolerability of Dz13 DNAzyme targeting c-Jun in subjects with nodular Basal Cell Carcinoma.
Secondary ID [1] 1409 0
nil.
Universal Trial Number (UTN)
U1111-1113-5815
Trial acronym
DISCOVER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Nodular Basal Cell Carcinoma (BCC) 256774 0
Condition category
Condition code
Cancer 256922 256922 0 0
Non melanoma skin cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 255981 0
Treatment: Drugs
Comparator / control treatment
No control treatment
Control group
Uncontrolled

Outcomes
Primary outcome [1] 257796 0
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).
Timepoint [1] 257796 0
1, 2, 4, 8, 12, 24 hours, 7 days, 14 days, 28 days post injection.
Primary outcome [2] 257797 0
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.
Timepoint [2] 257797 0
1, 2, 4, 8, 12, 24 hours, 7 days, 14 days, 28 days post injection.
Secondary outcome [1] 263207 0
To measure the level of Dz13 in serum following administration of a single dose of Dz13 complexed with DOPE/DOTAP via intra-tumoural injection.
Timepoint [1] 263207 0
30 min, 1, 2, 4, 8, 12, 24 hours, 7 days, 14 days, 28 days post injection.
Secondary outcome [2] 263208 0
To compare BCC histopathology and immunohistochemistry 14 days following Dz13 administration relative to baseline.
Timepoint [2] 263208 0
14 days post injection.

Eligibility
Key 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
Can healthy volunteers participate?
No
Key exclusion criteria
Women of childbearing potential.
Prior or co-existing malignancy.
Radiotherapy to >30% bone marrow in previous three months.
Known genetic predisposition to skin cancer.
Clinically significant non-malignant disease.
Current immunosuppression.
History of immune-mediated thrombocytopenia or other platelet disease.
History of drug abuse.
Enrollment in another clinical study using another investigational agent.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Study is not randomised.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Three dose cohorts (10 mcg, 30 mcg, 100 mcg) will receive Dz13.
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment postcode(s) [1] 2570 0
2050

Funding & Sponsors
Funding source category [1] 256480 0
Government body
Name [1] 256480 0
Cancer Institute NSW
Address [1] 256480 0
Australian Technology Park
Biomedical Building
Suite 101
1 Central Avenue
EVELEIGH NSW 2015
Country [1] 256480 0
Australia
Primary sponsor type
University
Name
University of New South Wales
Address
Sydney
NSW 2052
Country
Australia
Secondary sponsor category [1] 255787 0
None
Name [1] 255787 0
Address [1] 255787 0
Country [1] 255787 0
Other collaborator category [1] 1114 0
University
Name [1] 1114 0
University of Sydney
Address [1] 1114 0
Sydney
NSW 2006
Country [1] 1114 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258534 0
Sydney South West Area Health Service (SSWAHS) Royal Prince Alfred Hospital Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 258534 0
Research Development Office Level 3, Building 92 Royal Prince Alfred Hospital Missenden Road
CAMPERDOWN
NSW 2050
Ethics committee country [1] 258534 0
Australia
Date submitted for ethics approval [1] 258534 0
18/01/2010
Approval date [1] 258534 0
14/07/2010
Ethics approval number [1] 258534 0
EC00113

Summary
Brief 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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30812 0
Address 30812 0
Country 30812 0
Phone 30812 0
Fax 30812 0
Email 30812 0
Contact person for public queries
Name 14059 0
Prof. Levon Khachigian
Address 14059 0
UNSW
Centre for Vascular Research
Sydney
2052
Country 14059 0
Australia
Phone 14059 0
+61 2 9385 2537
Fax 14059 0
+61 2 9385 1389
Email 14059 0
l.khachigian@unsw.edu.au
Contact person for scientific queries
Name 4987 0
Prof. Levon Khachigian
Address 4987 0
UNSW
Centre for Vascular Research
Sydney
2052
Country 4987 0
Australia
Phone 4987 0
+61 2 9385 2537
Fax 4987 0
+61 2 9385 1389
Email 4987 0
l.khachigian@unsw.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary