None listed
Conditions
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.
Interventions
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 leve
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.
Sponsors
Progen Pharmaceuticals Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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).
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.
Outcome results
None listed