Siliphos in Advanced Hepatocellular Carcinoma
Milk thistle is an herbal drug that may have some liver protection properties and may reduce inflammation in the liver. It may also have anticancer effects. However milk thistle is not approved by the Food and Drug Administration for any medical purpose in the United States.
It has not been used in patients with liver cancer previously, to our knowledge, but there have been many studies of its use in patients with hepatitis and cirrhosis. Some of these studies have shown that milk thistle may help reduce elevated liver function tests.
Siliphos is a derivative of milk thistle that can be absorbed better than some other types of milk thistle. The investigators would like to perform a study to identify doses of siliphos that are safe to take in advanced liver cancer and to identify positive or negative side effects this compound may have. The investigators will be using this information in future studies to see if siliphos can be used as a therapy in patients with advanced liver cancer to reduce elevated liver function tests.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Trial of Siliphos in Patients With Advanced Hepatocellular Carcinoma|
- The maximum tolerated dose of siliphos in patients with advanced hepatocellular carcinoma [ Time Frame: Weeks 1, 3, 6, 9, and 12 ] [ Designated as safety issue: Yes ]
- Mean intra-patient percent change in AST, ALT and total serum bilirubin levels [ Time Frame: From baseline to 3 months ] [ Designated as safety issue: No ]Fasting morning blood samples collected at baseline, weeks 1, 3, 6, 9, and 12
- Quality of life as measured by the FACT-hepatobiliary questionnaire [ Time Frame: From baseline to 3 months ] [ Designated as safety issue: No ]Questionnaire administered at baseline, weeks 1, 6, and 12
- Plasma concentrations of silybinin, silybinin B, silibinin glucoronide, and silibinin sulfate [ Time Frame: From baseline to 3 months ] [ Designated as safety issue: No ]Fasting morning blood samples collected at baseline, weeks 1, 3, 6, 9, and 12
- Mean intra-patient percent change in serum concentrations of CRP, IGF-1, and IGFBP-3 [ Time Frame: From baseline to 3 months ] [ Designated as safety issue: No ]Fasting morning blood samples collected at baseline, weeks 1, 3, 6, and 12
- Tumor response as measured by RECIST criteria and AFP concentrations [ Time Frame: From baseline to 3 months ] [ Designated as safety issue: No ]
Fasting blood samples collected at baseline, weeks 1, 3, 6, 9, and 12 for AFP concentrations.
MRI of abdomen/pelvis & CT of chest at baseline and week 12
|Study Start Date:||February 2010|
|Study Completion Date:||June 2013|
|Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
|Experimental: Siliphos - dose escalation||
4 dose levels of siliphos: 2, 4, 8, and 12 grams daily in three divided doses. This study will follow a standard sequential Phase I dose escalation design.
Milk thistle (MT) has been historically used to treat patients with liver diseases, and has been shown to have antioxidant, anti inflammatory, and hepatoprotective properties. It may also have direct anticancer effects through inhibition of growth factors and promotion of cell cycle arrest. MT has been shown to improve LFTs in several studies of patients with cirrhosis. To our knowledge, there have been no published trials evaluating the clinical efficacy of MT in advanced HCC. We therefore propose a phase I study to identify the maximum tolerated dose (MTD) of silybinphosphatidylcholine (a commercially available preparation with increased bioavailability), in patients with advanced HCC. We will use a traditional dose escalation, open label design with a study intervention period of 3 months, followed by one year of observation, with a maximum total of 30 subjects, evaluating a dose range between 1 to 12 gm Siliphos. The data obtained from this study will be utilized in the future to evaluate MT efficacy in reducing liver function tests in advanced HCC, which will have significant implications in its use as a potential adjunctive agent in patients with currently limited treatment options.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01129570
|United States, New York|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|Principal Investigator:||Abby Siegel, MD, MS||Columbia University|