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Phase I Trial of Siliphos in Patients With Advanced Hepatocellular Carcinoma

Phase 1
18 Years
Open (Enrolling)
Advanced Hepatocellular Carcinoma

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Trial Information

Phase I Trial of Siliphos in Patients With Advanced Hepatocellular Carcinoma

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.

Inclusion Criteria:

- Age ≥18 years

- ECOG performance score of 0-3

- Expected survival of >12 weeks

- Subjects with advanced HCC or locally advanced, unresectable HCC

- Elevated LFTs (including at least one of the following: TBili >1.5 times the upper
limit of normal; serum AST >2.5 times the upper limit of normal

- HCC diagnosed/defined based on either biopsy, or by suggestive radiologic imaging
according to the AASLD guidelines (arterial enhancement with venous washout) or an
AFP >200 ng/ml

- Subjects must have measurable disease that can be accurately measured in at least one
dimension (with at least >20mm diameter in the longest dimension by conventional
imaging or >10 mm by helical CT)

- Elevated liver enzymes that are either due to underlying liver disease and/or tumor
which is not amenable to stenting after discussion with interventional GI and/or IR

- Subjects must demonstrate an ability to understand the consent process and
willingness to sign a written informed consent form

- Subjects must agree to use birth control pills or other active contraception during
active study treatment

Exclusion Criteria:

- Pregnant women or women currently breastfeeding will be excluded from this study
because the effects of silybin on pregnant women and/or nursing infants are not known

- Subjects must have < grade 4 hepatic toxicity

- Known brain metastases because of poor prognosis and as patients with brain
metastases often develop neurological dysfunction that may confound evaluation of
neurologic and other adverse side effects

- History of allergic reactions to the study medication

- Uncontrolled concurrent illness including, but not limited to: ongoing active
infection (including SBP), symptomatic congestive heart failure, unstable angina,
active cardiac arrhythmia, or psychiatric illness that would limit compliance with
study requirements

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The maximum tolerated dose of siliphos in patients with advanced hepatocellular carcinoma

Outcome Time Frame:

Weeks 1, 3, 6, 9, and 12

Safety Issue:


Principal Investigator

Abby Siegel, MD, MS

Investigator Role:

Principal Investigator

Investigator Affiliation:

Columbia University


United States: Food and Drug Administration

Study ID:




Start Date:

February 2010

Completion Date:

February 2015

Related Keywords:

  • Advanced Hepatocellular Carcinoma
  • Carcinoma
  • Carcinoma, Hepatocellular



Columbia University Medical CenterNew York, New York  10032