Siliphos in Advanced Hepatocellular Carcinoma

NCT01129570 | Completed Phase 1 DMC

• 1 other identifier: AAAE7604
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

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

  Weeks 1, 3, 6, 9, and 12

Secondary Outcomes (5)

• Mean intra-patient percent change in AST, ALT and total serum bilirubin levels

  From baseline to 3 months

• Quality of life as measured by the FACT-hepatobiliary questionnaire

  From baseline to 3 months

• Plasma concentrations of silybinin, silybinin B, silibinin glucoronide, and silibinin sulfate

  From baseline to 3 months

• Mean intra-patient percent change in serum concentrations of CRP, IGF-1, and IGFBP-3

  From baseline to 3 months

• Tumor response as measured by RECIST criteria and AFP concentrations

  From baseline to 3 months

Study Arms (1)

Siliphos - dose escalation

EXPERIMENTAL

Drug: Silybin

Interventions

Silybin DRUG

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.

Also known as: Siliphos, Milk thistle, Advanced hepatocellular carcinoma

Siliphos - dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Abby Siegel: lead
• Lotte & John Hecht Memorial Foundation: collaborator

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Interventions

Silybin; milk-thistle extract; TXNIP protein, human

Intervention Hierarchy (Ancestors)

Silymarin; Flavonolignans; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Abby Siegel, MD, MS

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Clinical Medicine, Oncology

Study Record Dates

• First Submitted: April 12, 2010
• First Posted: May 24, 2010
• Study Start: February 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: November 25, 2013

Record last verified: 2013-11

Locations

US (1)