Pilot Study Sorafenib as Bridge to Orthotopic Liver Transplantation (OLT)

• Status: Terminated
• Trial end date: 2012-01-01
• Target enrollment: 0
• Participant gender: All

Summary

Patients with either histological confirmation or clinical diagnosis who are candidate for orthotopic liver transplant(OLT) will receive Sorafenib 400mg 2 x day (BID) as a neoadjuvant (bridging) treatment until transplant. If patient progresses or falls outside of the Milan criteria on sorafenib patient can be treated per physician's discretion using local therapy. Patient will be followed until 30 days after the orthotopic liver transplant (OLT).

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Case Comprehensive Cancer Center
• Collaborators: Bayer; Onyx Therapeutics, Inc.
• Treatments: Sorafenib

Criteria

Inclusion criteria:

• Age > 18 years old

• Confirmation of diagnosis of Hepato Cellular Carcinoma (HCC) and within Milan criteria awaiting liver transplant or going through evaluation for Liver Transplant.

• Either histological confirmation or clinical diagnosis by American Association for the Study of Liver Diseases(AASLD) criteria (see Appendix 1) in cirrhotic subjects is required. For subjects without cirrhosis histological confirmation is mandatory.

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

• Child Pugh A or B (Total point of 7 will be allowed See appendix for scoring system). (ONLY 4 patients with Child Pugh B7 will be allowed.)

• Adequate bone marrow, liver and renal function as assessed by the following:

• Hemoglobin > 8.5 g/dl

• Absolute neutrophil count (ANC) > 1,500/mm3

• Platelet count > 60,000/mm3

• Total bilirubin < 1.5 times Upper Limits of Normal (ULN)

• ALT and AST < 2.5 times the Upper Limits of Normal (ULN) ( < 5 x ULN for patients with liver involvement)

• Creatinine < 1.5 times Upper Limits of Normal (ULN)

• Women of childbearing potential must have 2 negative serum pregnancy test performed. The first test within 7-10 days prior to the start of treatment. The second test within 24 hours prior to start of treatment.

• Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least three months after the last administration of sorafenib.

• Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.

Exclusion Criteria

• Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.

• Prior use of sorafenib

• Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.

• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.

• Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.

• Known human immunodeficiency virus (HIV) infection.

• Active clinically serious infection > CTCAE Grade 2 except for Except Hepatitis B(HBV) or Hepatitis C (HCV)

• Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.

• Serious non-healing wound, ulcer, or bone fracture.

• Evidence or history of bleeding diathesis

• Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.

• Use of St. John's Wort or rifampin (rifampicin).

• Known or suspected allergy to sorafenib or any agent given in the course of this trial.

• Any condition that impairs patient's ability to swallow whole pills.