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

NCT02151864 | Completed Phase 1 DMC

• 1 other identifier: 131053
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the safety and determine the maximum safe dose of an experimental drug called LDE225 (hedgehog inhibitor) in people with liver cancer. We have identified hedgehog dysregulation as a novel mechanism for hepatocarcinogenesis and hepatic fibrosis/cirrhosis. Therefore, we hypothesize that the hedgehog inhibitor may be an ideal drug target for treating both hepatocellular carcinoma (HCC) and Child-Pugh A cirrhosis (CPA).

Conditions

Hepatocellular Carcinoma; Cirrhosis

Keywords

liver cancer; cirrhosis; Child-Pugh A; Hedgehog

Outcome Measures

Primary Outcomes (1)

• Rate of dose limiting toxicities

  A dose limiting toxicity is a clinically significant adverse event (AE) occurring within 42 days of investigational treatment that is considered by the investigator to be possibly, probably, or definitely related to LDE225.

  occurring within 42 days of investigational treatment

Study Arms (1)

LDE225

EXPERIMENTAL

LDE225 200mg-800mg oral daily

Drug: LDE225

Interventions

LDE225 DRUG

LDE225 will be administered orally, on a continuous once daily dosing schedule at a dose determined by the cohort the patient is enrolled in until progression or unacceptable toxicity develops

Also known as: hedgehog inhibitor

LDE225

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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jason K. Sicklick, M.D.: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

UCSD Moores Cancer Center

La Jolla, California, 92093, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Fibrosis; Liver Neoplasms

Interventions

sonidegib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jason K. Sicklick, MD

  University of California Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor, Surgery

Study Record Dates

• First Submitted: May 28, 2014
• First Posted: May 30, 2014
• Study Start: July 1, 2014
• Primary Completion: December 1, 2016
• Study Completion: September 1, 2017
• Last Updated: March 5, 2019

Record last verified: 2019-03

Locations

US (1)