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Trial registered on ANZCTR


Registration number
ACTRN12612000908831
Ethics application status
Approved
Date submitted
14/08/2012
Date registered
27/08/2012
Date last updated
27/08/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase I study of 4-(N-(S-penicillaminylacetyl)amino)
phenylarsonous acid (PENAO) given as a continuous intravenous infusion, to patients with advanced solid tumours
Scientific title
A Phase I study of 4-(N-(S-penicillaminylacetyl)amino)
phenylarsonous acid (PENAO) given as a continuous intravenous infusion, to patients with advanced solid tumours
Secondary ID [1] 281028 0
Nil
Universal Trial Number (UTN)
U1111-1133-4715
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Patients with advanced solid tumours 287164 0
Condition category
Condition code
Cancer 287485 287485 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid (PENAO)

PENAO will be administered as a continuous intravenous infusion, using a centrally placed infusion line and a portable pump. Patients will be enrolled and assessed in groups of 3 patients per cohort. If no defined severe toxicity is observed, then 3 new patients will be treated at the next higher dose level. If some defined severe toxicity is observed, the cohort may be expanded to 6 patients or recognised as the Maximum Active Drug Level. The starting dose of PENAO will be 2.0 mg/m2/day over 4 days (96 hours) in every 21 day cycle. Subsequent cohorts/groups of patients will receive the same daily dose over periods of 7 days, 14 days and 21 days. Once the feasibility of a 21 day infusion is determined, this schedule will be maintained and the daily dose will then be increased between cohorts. Subsequently daily dose increases are predefined in the protocol, and range between 30-40% of the previous safe dose.
Intervention code [1] 285487 0
Treatment: Drugs
Comparator / control treatment
No comparator/control treatment
Control group
Uncontrolled

Outcomes
Primary outcome [1] 287745 0
To define the recommended Phase II dose (RPTD) of PENAO as a 21 day continuous intravenous infusion, in patients with advanced solid tumours.

Dose escalation will occur through the defined dose levels, until the Maximum Active Dose Level (MADL) is defined. The dose level to be evaluated as the first candidate RPTD will be determined by which dose level has been designated the MADL.
The candidate RPTD will be expanded to assess and assure its tolerability over 2 cycles before it is declared the final RPTD.
Timepoint [1] 287745 0
During PENAO treatment, patients will be regularly evaluated on a weekly basis for adverse events, standard haematological and biochemical parameters, and pharmacokinetic endpoints.
Secondary outcome [1] 298766 0
To define the toxicity profile of PENAO.

During PENAO treatment, patients will be regularly evaluated for adverse events (by monitoring vitals and performing a physical exam), standard haematological and biochemical parameters (by blood tests), and pharmacokinetic endpoints (by blood and urine tests).
Timepoint [1] 298766 0
During PENAO treatment, patients will be regularly evaluated on a weekly basis for the length of the study.
Secondary outcome [2] 298767 0
To define the pharmacokinetics of PENAO as a continuous intravenous infusion.

During PENAO treatment, patients will be regularly evaluated for pharmacokinetic endpoints (by blood and urine tests).
Timepoint [2] 298767 0
Patients will be evaluated on a weekly basis for the first two cycles, and then at the start of each 21 day cycle from cycle 3.
Secondary outcome [3] 298768 0
To define the pharmacodynamic effects of PENAO.

Restaging will occur every two (2) cycles. FDG-PET scans will be performed for patients enrolled at Dose Levels 3 and above, at baseline, on Cycle 1 Day 8 and Cycle 3 Day 8. FLT-PET scans will be performed for eligible patients enrolled in the RPTD expanded cohort within 3 days of the FDG-PET scans.
Timepoint [3] 298768 0
Restaging will occur every two (2) cycles. FDG-PET scans will be performed for patients enrolled at Dose Levels 3 and above, at baseline, on Cycle 1 Day 8 and Cycle 3 Day 8. FLT-PET scans will be performed for eligible patients enrolled in the RPTD expanded cohort within 3 days of the FDG-PET scans.

Eligibility
Key inclusion criteria
1. Histologically or cytologically confirmed advanced solid tumour refractory to standard treatment or for which no standard treatment exists.
2. Patients with primary CNS malignancy must be seizure free for at least 28 days and on stable (i.e. not increasing) doses of anticonvulsants and corticosteroids in that time frame, and be on a maximum corticosteroid dose of 2 mg/day dexamethasone (or bioequivalent dose of other agent) at study enrolment.
3. Aged greater than or equal to 18 years.
4. ECOG performance status of 0 to 1.
5. Life expectancy of greater than 3 months.
6. GFR greater than equal to 65 mL/min
7. Normal cardiac function, parameters are defined.
8. Minimum intervals since most recent systemic and local therapies are defined.
9. Threshold haematological and biochemical parameters are defined.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Currently receiving therapeutic anticoagulant therapy.
2. Known HIV infection or active HBV infection.
3. Receiving medications associated with prolongation of Q-Tc interval.
4. Pre-existing > Grade I Peripheral Neuropathy.
5. Known brain metastases
6. Baseline proteinuria (by dipstick) or history of glomerular renal disease.
7. Body Mass Index >30.
8. History of allergic reactions to arsenic compound(s).
9. Uncontrolled intercurrent illness or psycho-social dysfunction.
10. Patients who are pregnant or breast feeding.

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)
Patients are indentified by researchers, and allocated to open treatment slots once meeting all screening criteria and registered.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
None
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
None
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
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)
VIC
Recruitment postcode(s) [1] 5587 0
3002
Recruitment postcode(s) [2] 5588 0
3052

Funding & Sponsors
Funding source category [1] 285814 0
Government body
Name [1] 285814 0
Cancer Institute of NSW
Address [1] 285814 0
Australian Technology Park
Level 9, 8 Central Avenue
EVELEIGH NSW 2015
AUSTRALIA
Country [1] 285814 0
Australia
Primary sponsor type
University
Name
University of NSW
Address
University of NSW
Sydney NSW 2052
Country
Australia
Secondary sponsor category [1] 284638 0
None
Name [1] 284638 0
Address [1] 284638 0
Country [1] 284638 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287827 0
Peter MacCallum Cancer Centre Human Research Ethics Committee
Ethics committee address [1] 287827 0
Peter MacCallum Cancer Centre
St Andrews Place
East Melbourne Victoria
Postal Address
Locked Bag 1 A'Beckett Street
Victoria 8006
Ethics committee country [1] 287827 0
Australia
Date submitted for ethics approval [1] 287827 0
01/12/2011
Approval date [1] 287827 0
21/05/2012
Ethics approval number [1] 287827 0
HREC/11/PMCC/37

Summary
Brief summary
The main aim of the study is to work out the safest dose of PENAO to give to patients. PENAO is an organoarsenic which means it is related to arsenic. There are other drugs in this class which are used to treat different forms of cancer. In this research study patients will be given a new drug, PENAO, for the first time. This drug has been previously safely tested in animals but has not been tested before in humans. Because of this, it is unknown what the most effective and safe dosage level should be. Secondly, the study aims to monitor patients to collect more information about how the drug is broken down by the body and do scans to observe whether the drug has an effect on tumours.
To date, this drug has been shown to slow or stop the growth of many different types of tumours when grown in mice.

PENAO is an experimental drug. This means that it is not an approved treatment for cancer in Australia or other parts of the world. This study drug was developed by a group of researchers at the University of NSW as an anti-cancer agent. This research and the clinical study are funded by the Cancer Institute of NSW.
Trial website
None
Trial related presentations / publications
None
Public notes

Contacts
Principal investigator
Name 34576 0
Address 34576 0
Country 34576 0
Phone 34576 0
Fax 34576 0
Email 34576 0
Contact person for public queries
Name 17823 0
Prof Phil Hogg
Address 17823 0
University of NSW
Sydney, NSW 2052
Country 17823 0
Australia
Phone 17823 0
(+61 2) 9385-1004
Fax 17823 0
(+61 2) 9385-1510
Email 17823 0
p.hogg@unsw.edu.au
Contact person for scientific queries
Name 8751 0
Prof Phil Hogg
Address 8751 0
University of NSW
Sydney, NSW 2052
Country 8751 0
Australia
Phone 8751 0
(+61 2) 9385-1004
Fax 8751 0
(+61 2) 9385-1510
Email 8751 0
p.hogg@unsw.edu.au

No information has been provided regarding IPD availability
Summary results
No Results