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Trial registered on ANZCTR


Registration number
ACTRN12608000082303
Ethics application status
Not yet submitted
Date submitted
12/02/2008
Date registered
13/02/2008
Date last updated
13/03/2008
Type of registration
Prospectively registered

Titles & IDs
Public title
Doxorubicin Transdrug® in Advanced Hepatocellular Carcinoma.
Scientific title
Evaluation of the efficacy and tolerance of Hepatic Intrarterial-Injection of Doxorubicin Transdrug® in Advanced Hepatocellular Carcinoma, to that of standard care. A Randomized, Multicentre Phase 2-3 Study.
Universal Trial Number (UTN)
Trial acronym
DOTAHCC1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HepatoCellular Carcinoma 2819 0
Condition category
Condition code
Cancer 2956 2956 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Hepatic Intrarterial-Injection of Doxorubicin Transdrug® at 30mg/m2. 3 courses, one course every 28 days.
Intervention code [1] 2555 0
Treatment: Drugs
Comparator / control treatment
Standard treatment
This includes Embolisation, Transarterial Chemoembolisation (TACE), Hepatic Intra-Arterial chemotherapy with or without Lipiodol®, Lipiocis®, Intravenous Chemotherapy and best supportive care (pain and symptoms management). Each hospital has their own procedures for each of these treatments, however, typically you will receive the treatment on one day and have a follow-up visit 4-6 weeks later. Treatment may then need to be repeated depending on disease progression.
Control group
Active

Outcomes
Primary outcome [1] 3835 0
Number of patients free of local progression at 3 months after randomisation (treatment group).
Timepoint [1] 3835 0
3 months after randomisation
Primary outcome [2] 3836 0
Number of patients free of local progression at 3 months after randomisation (control group).
Timepoint [2] 3836 0
3 months after randomisation
Secondary outcome [1] 6463 0
Comparison between the treated and control groups: progression free survival, overall survival, objective response rate, tolerance and quality of life
Timepoint [1] 6463 0
Every three months for 12 months and survivial until death.
Secondary outcome [2] 6464 0
To determine the pharmacokinetic profile of Doxorubicin Transdrug.
Timepoint [2] 6464 0
Detemrined at the end of the study.

Eligibility
Key inclusion criteria
Patients with hepatocellular carcinoma (HCC); Multinodular hepatocellular carcinoma more than one lesion) regardless of the number of lesions, but involves less than 50% of the liver mass; Child-Pugh score A (assessment of the prognosis of chronic liver disease, mainly cirrhosis); Left ventricular ejection fraction (LVEF) greater than or equal to 50% as determined by echocardiography/cardiac ultrasound (the amount of blood pumped out of a ventricle with each heart beat); Adequate pulmonary function; Platelets greater than or equal to 75 x 109L; Absolute neutrophil count (white blood cells)greater than or equal to 1,0 x 109L; Aspartate transaminase (AST) and/or Alanine transaminase (ALT) less than or equal to 5 times upper limit of normal (liver enzymes, determine the health of the liver); Prothrombin time ratio greater than 60% and Factor V greater than 60% (measure of blood clotting ability).
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Blood clots in the main blood vessels of the liver;
Risk for oesophageal bleeding;
Hepatocellular carcinoma developed on transplanted liver;
Presence of extra-hepatic metastases (cancer outside liver);
Patients able to benefit from hepatic transplantation, surgical resection, pure alcogol injection into tumour or radiofrequency ablation (tumour mass is heated by radiofrequency to a point where the cells die);
Patient having undergone a 450 mg/m² cumulated dose of doxorubicin;
Prior chemotherapy, transarterial chemoembolisation (TACE), embolisation, radiation therapy for hepatocellular carcinoma regardless of the time elapsed before the enrolment;
Patients who have benefited from surgical resection or percutaneous (alcohol and/or radiofrequency) treatment in the month preceding the enrolment;
Patients currently being treated with immunosuppressor agent (medication to suppress the immune system) and/or an anticoagulant (medication to thin your blood) that cannot be stopped;
Presence of cardiac abnormalities;
Patient with a life expectancy of less than 3 months;
Pregnant or breast-feeding women; Patients with mental deficiency preventing proper understanding of trial protocol requirements.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients who meet the inclusion/exclusion criteria can be randomised into the trial. The Investigator connects to the International Drug Development Institute web-based randomization tool to randomize the patient. Patients will be centrally randomised into two treatment groups with a ratio of 2:1 using study centre, performance status (ECOG score) and the CLIP score as stratification factors. The system will generate a unique Patient ID and assign a treatment group. A patient randomization confirmation in pdf format is sent to the investigator, that pharmacist and the Sponsor.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The Investigator connects to the International Drug Development Institute web-based randomization tool to randomize the patient. Patients will be centrally randomised into two treatment groups with a ratio of 2:1 using study centre, Performance status (ECOG score) and the CLIP score as stratification factors. The dynamic minimization will use a stochastic treatment allocation algorithm based on the variance method. The system will generate a unique Patient ID and assign a treatment group.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/04/2008
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 576 0
2217
Recruitment postcode(s) [2] 577 0
3084
Recruitment postcode(s) [3] 578 0
3004
Recruitment postcode(s) [4] 579 0
3050
Recruitment postcode(s) [5] 580 0
6160
Recruitment postcode(s) [6] 765 0
6009
Recruitment postcode(s) [7] 766 0
5000
Recruitment outside Australia
Country [1] 788 0
Germany
State/province [1] 788 0
Country [2] 789 0
France
State/province [2] 789 0
Country [3] 790 0
Belgium
State/province [3] 790 0
Country [4] 791 0
Italy
State/province [4] 791 0
Country [5] 792 0
United Kingdom
State/province [5] 792 0

Funding & Sponsors
Funding source category [1] 3080 0
Commercial sector/Industry
Name [1] 3080 0
BioAlliance Pharma
Country [1] 3080 0
France
Primary sponsor type
Commercial sector/Industry
Name
ORION Clinical Services (Australia) Pty Ltd
Address
Suite 115, 45 Glenferrie Road
MALVERN, VIC, 3144
Country
Australia
Secondary sponsor category [1] 2774 0
Commercial sector/Industry
Name [1] 2774 0
BioAlliance Pharma
Address [1] 2774 0
49 boulevard du General Martial Valin (1st floor), 75015 Paris, France
Country [1] 2774 0
France

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 5028 0
Ethics committee address [1] 5028 0
Ethics committee country [1] 5028 0
Date submitted for ethics approval [1] 5028 0
25/02/2008
Approval date [1] 5028 0
Ethics approval number [1] 5028 0

Summary
Brief summary
The objective of the trial is to compare the efficacy (based on time to progression of tumour) and tolerance of Hepatic Intra-Arterial injection of Doxorubicin Transdrug® every 4 weeks, up to 3 courses with control standard treatment according to each centre’s usual practice (including TACE). This is an open label, multicentre, randomized in two parallel groups, Phase 2-3 study. The trial is designed to be performed in two successive parts, Phase 2 and Phase 3. At the end of the Phase 2, the efficacy of Doxorubicin Transdrug® will be evaluated based on the rate of patient free of local progression 3 months after randomisation. If more than 66% of patients treated with Doxorubicin Transdrug® are free of local progression, the study will be pursued and patients included in the Phase 2 study will automatically be followed and analyzed in the Phase 3 study. A total of 200 patients will be accrued of whom 50 patients will be accrued for the Phase 2.

Patients satisfying inclusion and exclusion criteria will be centrally randomised to one of two treatments groups. Group A: Patients will receive a course of hepatic intra-arterial Doxorubicin Transdrug® on Day1. The treatment will be repeated every 4 weeks or until D90 (i.e. 3 months after randomization) for a total of 3 courses in the absence of disease progression or unacceptable toxicity. Group B: Patients will receive treatment according to each centre’s usual practice (including TACE), treatment will be repeated until D90 (i.e. 3 months after randomization) in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for one year.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28367 0
Address 28367 0
Country 28367 0
Phone 28367 0
Fax 28367 0
Email 28367 0
Contact person for public queries
Name 11524 0
Anna Tippett
Address 11524 0
Level 1, 141 Osborne Street
South Yarra, Vic, 3141
Country 11524 0
Australia
Phone 11524 0
03 9279 3947
Fax 11524 0
03 9867 1086
Email 11524 0
[email protected]
Contact person for scientific queries
Name 2452 0
Anna Tippett
Address 2452 0
Level 1, 141 Osborne Street
South Yarra, Vic, 3141
Country 2452 0
Australia
Phone 2452 0
03 9279 3947
Fax 2452 0
03 9867 1086
Email 2452 0
[email protected]

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No Supporting Document Provided



Results publications and other study-related documents

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