LDE225 in Patients With Advanced or Metastatic Hepatocellular Carcinoma and Child-Pugh A/B7 Cirrhosis

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring liver cancer, cirrhosis, Child-Pugh A, Hedgehog Read More

Inclusion Criteria:

• Age 18 years or older
• Pathological confirmation of advanced or metastatic HCC
• HCC not amenable to surgical resection, liver transplantation, chemoembolization, or ablation therapy
• Patients with Child-Pugh A and Child-Pugh B7 (if due to low albumin but not elevated INR or bilirubin) cirrhosis are allowed.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• At least one measurable site of disease (as defined by Response Evaluation Criteria in Solid Tumors)
• Patients with adequate bone marrow, liver and renal function
• Inability to tolerate first-line treatment with sorafenib
• Patient amenable to liver tumor biopsy

Exclusion Criteria:

• Child-Pugh B or Child-Pugh C cirrhosis
• Patients with known Gilbert's Syndrome
• Ongoing alcohol use or abuse defined as > an average of 2 alcoholic beverages daily
• Patients who have had major surgery within 4 weeks of initiation of study medication
• Patients with known brain metastases
• Patients with concurrent uncontrolled medical conditions that may interfere with their participation in the study
• Patients with known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness
• Patients with Hepatitis B and/or Hepatitis C infection are excluded if they are on any of the following viral suppressive agents: boceprevir (Victrelis), ribavirin (Rebetol, Ribatab, Ribasphere), telaprevir (Incivek)
• Patients unable to take oral drugs or with lack of physical integrity of the upper gastrointestinal tract or known malabsorption syndromes
• Patients who have previously been treated with systemic LDE225 or with other Hh pathway inhibitors
• Patients who have neuromuscular disorders or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis
• Patients who are planning on embarking on a new strenuous exercise regimen after initiation of study treatment
• Patients who have taken part in an experimental drug study within 4 weeks of initiating study treatment with LDE225
• Patients who are receiving other anti-neoplastic therapy concurrently or within 2 weeks of starting study treatment with LDE225
• Patients who are receiving any anti-coagulation or anti-platelet therapy
• Patients who are receiving treatment with medications known to be strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4/5) or drugs metabolized by cytochrome P450 2B6 (CYP2B6) or cytochrome P450 2C9 (CYP2C9) that have narrow therapeutic index, and that cannot be discontinued before starting study treatment with LDE225
• Impaired cardiac function or clinically significant heart disease
• Patients with contraindications for MRI and/or MRI contrast agents
• Pregnant or nursing (lactating) women
• Women of child-bearing potential must use highly effective contraception during the study and through 6 months after the final dose of study treatment
• Sexually active males who are unwilling to use a condom during intercourse while taking drug and for 6 months after stopping investigational medications and agree not to father a child in this period