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Siliphos in Advanced Hepatocellular Carcinoma

Primary Purpose

Advanced Hepatocellular Carcinoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Silybin
Sponsored by
Abby Siegel
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Hepatocellular Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Columbia University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Siliphos - dose escalation

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Mean intra-patient percent change in AST, ALT and total serum bilirubin levels
Fasting morning blood samples collected at baseline, weeks 1, 3, 6, 9, and 12
Quality of life as measured by the FACT-hepatobiliary questionnaire
Questionnaire administered at baseline, weeks 1, 6, and 12
Plasma concentrations of silybinin, silybinin B, silibinin glucoronide, and silibinin sulfate
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
Fasting morning blood samples collected at baseline, weeks 1, 3, 6, and 12
Tumor response as measured by RECIST criteria and AFP concentrations
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

Full Information

First Posted
April 12, 2010
Last Updated
November 21, 2013
Sponsor
Abby Siegel
Collaborators
Lotte & John Hecht Memorial Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT01129570
Brief Title
Siliphos in Advanced Hepatocellular Carcinoma
Official Title
Phase I Trial of Siliphos in Patients With Advanced Hepatocellular Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
November 2013
Overall Recruitment Status
Completed
Study Start Date
February 2010 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Abby Siegel
Collaborators
Lotte & John Hecht Memorial Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Hepatocellular Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Siliphos - dose escalation
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Silybin
Other Intervention Name(s)
Siliphos, Milk thistle, Advanced hepatocellular carcinoma
Intervention Description
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.
Primary Outcome Measure Information:
Title
The maximum tolerated dose of siliphos in patients with advanced hepatocellular carcinoma
Time Frame
Weeks 1, 3, 6, 9, and 12
Secondary Outcome Measure Information:
Title
Mean intra-patient percent change in AST, ALT and total serum bilirubin levels
Description
Fasting morning blood samples collected at baseline, weeks 1, 3, 6, 9, and 12
Time Frame
From baseline to 3 months
Title
Quality of life as measured by the FACT-hepatobiliary questionnaire
Description
Questionnaire administered at baseline, weeks 1, 6, and 12
Time Frame
From baseline to 3 months
Title
Plasma concentrations of silybinin, silybinin B, silibinin glucoronide, and silibinin sulfate
Description
Fasting morning blood samples collected at baseline, weeks 1, 3, 6, 9, and 12
Time Frame
From baseline to 3 months
Title
Mean intra-patient percent change in serum concentrations of CRP, IGF-1, and IGFBP-3
Description
Fasting morning blood samples collected at baseline, weeks 1, 3, 6, and 12
Time Frame
From baseline to 3 months
Title
Tumor response as measured by RECIST criteria and AFP concentrations
Description
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
Time Frame
From baseline to 3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Abby Siegel, MD, MS
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States

12. IPD Sharing Statement

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Siliphos in Advanced Hepatocellular Carcinoma

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