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Trial registered on ANZCTR


Registration number
ACTRN12607000172404
Ethics application status
Approved
Date submitted
14/03/2007
Date registered
16/03/2007
Date last updated
1/12/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
A trial of clofazimine in Lipiodol injection in patients with inoperable Hepatocellular carcinoma
Scientific title
A phase 1 open label dose escalation study to determine safety and tolerability of Clofazimine in Lipiodol (PI-166) injection in patients with unresectable Hepatocellular Carcinoma.
Universal Trial Number (UTN)
Trial acronym
CFZ 101
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatocellular Carcinoma 1687 0
Condition category
Condition code
Cancer 1782 1782 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This trial will be a dose escalation of a single dose of clofazimine administered in a fixed volume of lipiodol. In eligible patients with unresectable hepatocellular carcinoma, a single injection of clofazimine in lipiodol (PI-166) will be administered via the hepatic artery. During the dose escalation phase, cohort size will be one patient. If a drug related toxicity is observed the cohort size will be expanded to 3 patients. The starting dose of clofazimine will be 3mg escalating to dose levels of 6, 10, 18, 30, 50, 75, 98, 120, 150 mg. Patients will be assessed for safety and tolerability for 4 weeks post the injection or until adverse events are resolved. The pharmacokinetics of clofazimine will also be assessed during this time. If the first dose of clofazimine in lipiodol injection is well tolerated patients may receive upto 3 additional doses at the same dose level, at intervals not less than 6 weeks between doses.
Intervention code [1] 1645 0
None
Comparator / control treatment
No comparator.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 2489 0
To determine the maximum tolerated dose of clofazimine in lipiodol injection as a single injection. The maximum tolerated dose will be determined as the dose level below the dose where a drug related toxicitiy/dose limiting toxicity occurs in 2 or more patients in a cohort and is defined as a grade 3 non haematological toxicity or grade 4 haematological toxicity considered to be possibly/probably or certainly related to the study drug.
Timepoint [1] 2489 0
Assessments will occur on the day of treatment and on days 2, 3, 4, 7, 14, 21 and 28 post the treatment.
Primary outcome [2] 2490 0
Patients will be assessed for safety and tolerability for weeks post the injection.
Timepoint [2] 2490 0
Assessments will occur on the day of treatment and on days 2, 3, 4, 7, 14, 21 and 28 post the treatment.
Secondary outcome [1] 4294 0
1. to assess safety and tolerability of intrahepatic arterial injection of clofazimine in lipiodol injection.
Timepoint [1] 4294 0
Subjects will be assessed for side effects related to the study treatment ( vital signs, full blood count, biochemistry etc) on day 2, 3, 4, 7, 14, 21 and 28 days. On day 28 patients will undergo a CT scan/angiogram to assess the extent of the primary malignant disease and presence of metastatic disease following the study treatment based on the Response Evaluation Criteria in Solid Tumours (RECIST) criteria.
Secondary outcome [2] 4295 0
2. To assess the pharmacokinetics of clofazimine in lipiodol injection administered via intrahepatic arterial injection.
Timepoint [2] 4295 0
Blood will be drawn for pharmacokinetic studies at the following time points: immediately before the study drug is administered , at 1 and 4 hours and day 2, 3, 4, 7, 14, 21 and 28 post study drug administration.

Eligibility
Key inclusion criteria
1. confirmed diagnosis of progressive unresectable hepatocellular carcinoma.2. measurable disease or elevated tumour markers.3. Lipiodol avid tumour.4. Eastern Cooperative Oncology Group Performance Scale 0-2. 5. Voluntary written Informed consent. 6. liver function tests stable within the previous 4 weeks. 7. Patent hepatic artery and portal vein (demonstrated by angiography with in the previous 4 weeks).
Minimum age
18 Years
Maximum age
Not stated
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Clinically significant non- malignant disease.2. Prior therapy for the primary cancer in the previous 4 weeks (including lipiodol injection).3. Major surgery within the past 4 weeks.4. hepatic encephalopathy or coagulopathy (INR greater than 2)5. Variceal bleeding in the previous 4 weeks6. women who are pregnant or breastfeeding.7.History of allergy and or hypersensitivity to iodine, Lipiodol or clofazimine.8. elevated liver function tests greater than 10 times normal9. uncontrolled infection in the past 4 weeks.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
10/01/2003
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 1932 0
Commercial sector/Industry
Name [1] 1932 0
Progen Pharmaceuticals Ltd
Country [1] 1932 0
Australia
Funding source category [2] 4038 0
Commercial sector/Industry
Name [2] 4038 0
Progen Pharmaceuticals Ltd
Country [2] 4038 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Progen Pharmaceuticals Ltd
Address
16 Benson Street Toowong Brisbane 4066
Country
Australia
Secondary sponsor category [1] 1744 0
None
Name [1] 1744 0
not applicable
Address [1] 1744 0
Country [1] 1744 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 3598 0
St George Hospital - The UNSW Human Research Ethics Committee/ SESAHS.
Ethics committee address [1] 3598 0
St George Hospital, Kogarah, NSW
Ethics committee country [1] 3598 0
Australia
Date submitted for ethics approval [1] 3598 0
Approval date [1] 3598 0
18/11/2002
Ethics approval number [1] 3598 0
02/107
Ethics committee name [2] 3599 0
Princess Alexandra Hospitl - PAH Research Ethics Committee
Ethics committee address [2] 3599 0
Princess Alexandra Hospital, Woolloongabba, Qld
Ethics committee country [2] 3599 0
Australia
Date submitted for ethics approval [2] 3599 0
Approval date [2] 3599 0
30/03/2004
Ethics approval number [2] 3599 0
2004/028
Ethics committee name [3] 3600 0
Monash Medical Centre - Southern Health Human Research Ethics Committee
Ethics committee address [3] 3600 0
Monash Medical Centre, Melbourne, Victoria
Ethics committee country [3] 3600 0
Australia
Date submitted for ethics approval [3] 3600 0
Approval date [3] 3600 0
03/09/2004
Ethics approval number [3] 3600 0
04070A

Summary
Brief summary
Hepatocellualr carcinoma (HCC) is a highly lethal disease with few effective treatment options. It has been established that clofazimine can control the growth of HCC cell lines in vitro and in pre clinical animal models. This study aims to treat patients with unresectable primary HCC with escalating doses of clofazimine delivered in Lipiodol and administered via the hepatic artery under computerised tomography (CT) guidance. The maximum tolerated dose will be established using cohorts of one to six patients. Safety and tolerability will also be assessed in eligible patients. Each cycle of treatment will be 28 days in length and patients may receive up to 4 additional treatments if the study treatment is well tolerated. This study commenced recruitment in January 2003 and is currently recruiting patients into the final dose level cohort.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 27579 0
Address 27579 0
Country 27579 0
Phone 27579 0
Fax 27579 0
Email 27579 0
Contact person for public queries
Name 10834 0
Barbara Hicks
Address 10834 0
16 Benson Street
Toowong QLD 4066
Country 10834 0
Australia
Phone 10834 0
+61 7 3842 3333
Fax 10834 0
+61 7 37209587
Email 10834 0
[email protected]
Contact person for scientific queries
Name 1762 0
Barbara Hicks
Address 1762 0
16 Benson Street
Toowong QLD 4066
Country 1762 0
Australia
Phone 1762 0
+61 7 3842 3333
Fax 1762 0
+61 7 37209587
Email 1762 0
[email protected]

No information has been provided regarding IPD availability


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No Supporting Document Provided



Results publications and other study-related documents

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