Working… Menu

Siliphos in Advanced Hepatocellular Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01129570
Recruitment Status : Completed
First Posted : May 24, 2010
Last Update Posted : November 25, 2013
Lotte & John Hecht Memorial Foundation
Information provided by (Responsible Party):
Abby Siegel, Columbia University

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Advanced Hepatocellular Carcinoma Drug: Silybin Phase 1

Detailed Description:
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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Trial of Siliphos in Patients With Advanced Hepatocellular Carcinoma
Study Start Date : February 2010
Actual Primary Completion Date : June 2013
Actual Study Completion Date : June 2013

Arm Intervention/treatment
Experimental: Siliphos - dose escalation Drug: Silybin
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.
Other Names:
  • Siliphos
  • Milk thistle
  • Advanced hepatocellular carcinoma

Primary Outcome Measures :
  1. The maximum tolerated dose of siliphos in patients with advanced hepatocellular carcinoma [ Time Frame: Weeks 1, 3, 6, 9, and 12 ]

Secondary Outcome Measures :
  1. Mean intra-patient percent change in AST, ALT and total serum bilirubin levels [ Time Frame: From baseline to 3 months ]
    Fasting morning blood samples collected at baseline, weeks 1, 3, 6, 9, and 12

  2. Quality of life as measured by the FACT-hepatobiliary questionnaire [ Time Frame: From baseline to 3 months ]
    Questionnaire administered at baseline, weeks 1, 6, and 12

  3. Plasma concentrations of silybinin, silybinin B, silibinin glucoronide, and silibinin sulfate [ Time Frame: From baseline to 3 months ]
    Fasting morning blood samples collected at baseline, weeks 1, 3, 6, 9, and 12

  4. Mean intra-patient percent change in serum concentrations of CRP, IGF-1, and IGFBP-3 [ Time Frame: From baseline to 3 months ]
    Fasting morning blood samples collected at baseline, weeks 1, 3, 6, and 12

  5. Tumor response as measured by RECIST criteria and AFP concentrations [ Time Frame: From baseline to 3 months ]

    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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01129570

Layout table for location information
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Abby Siegel
Lotte & John Hecht Memorial Foundation
Layout table for investigator information
Principal Investigator: Abby Siegel, MD, MS Columbia University

Layout table for additonal information
Responsible Party: Abby Siegel, Assistant Professor of Clinical Medicine, Oncology, Columbia University Identifier: NCT01129570     History of Changes
Other Study ID Numbers: AAAE7604
First Posted: May 24, 2010    Key Record Dates
Last Update Posted: November 25, 2013
Last Verified: November 2013
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Protective Agents
Physiological Effects of Drugs