Siliphos in Advanced Hepatocellular Carcinoma
Ključne besede
Povzetek
Opis
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.
Datumi
| Nazadnje preverjeno: | 10/31/2013 |
| Prvič predloženo: | 04/11/2010 |
| Predviden vpis oddan: | 05/20/2010 |
| Prvič objavljeno: | 05/23/2010 |
| Zadnja posodobitev oddana: | 11/20/2013 |
| Zadnja posodobitev objavljena: | 11/24/2013 |
| Dejanski datum začetka študija: | 01/31/2010 |
| Predvideni datum primarnega zaključka: | 05/31/2013 |
| Predvideni datum zaključka študije: | 05/31/2013 |
Stanje ali bolezen
Intervencija / zdravljenje
Drug: Siliphos - dose escalation
Faza
Skupine rok
| Roka | Intervencija / zdravljenje |
|---|---|
| Experimental: Siliphos - dose escalation | Drug: 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. |
Merila upravičenosti
| Starost, primerna za študij | 18 Years Za 18 Years |
| Spol, upravičen do študija | All |
| Sprejema zdrave prostovoljce | Da |
| Merila | 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 |
Izid
Primarni izidni ukrepi
1. The maximum tolerated dose of siliphos in patients with advanced hepatocellular carcinoma [Weeks 1, 3, 6, 9, and 12]
Ukrepi sekundarnega rezultata
1. Mean intra-patient percent change in AST, ALT and total serum bilirubin levels [From baseline to 3 months]
2. Quality of life as measured by the FACT-hepatobiliary questionnaire [From baseline to 3 months]
3. Plasma concentrations of silybinin, silybinin B, silibinin glucoronide, and silibinin sulfate [From baseline to 3 months]
4. Mean intra-patient percent change in serum concentrations of CRP, IGF-1, and IGFBP-3 [From baseline to 3 months]
5. Tumor response as measured by RECIST criteria and AFP concentrations [From baseline to 3 months]
