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Pilot Study: Safety and Feasibility of Using Sorafenib as Neoadjuvant Treatment Prior to Orthotopic Liver Transplantation (OLT) in Patients With Hepatocellular Carcinoma


Phase 0
18 Years
N/A
Not Enrolling
Both
Carcinoma, Hepatocellular

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Trial Information

Pilot Study: Safety and Feasibility of Using Sorafenib as Neoadjuvant Treatment Prior to Orthotopic Liver Transplantation (OLT) in Patients With Hepatocellular Carcinoma


Primary objective:

• To evaluate safety (including possible surgical complication) and feasibility of using
sorafenib as neo-adjuvant (bridging therapy) prior to orthotopic liver transplant(OLT).

The primary goal of this pilot study is to assess the safety and feasibility of treating
HCC patients with sorafenib prior to OLT, as determined by the number of patients
experiencing grade 4 hemorrhaging or bleeding post-operatively.

To achieve these goals a 2-stage accrual design will be used with a maximum accrual goal of
10 patients. Initially 5 patients will be entered on-study. If more than one patient
experiences grade 4 hemorrhaging/bleeding following OLT the trial will be closed and
sorafenib will not be considered safe and/or feasible. If no patient experiences this event
5 additional patients will be enrolled. At the end of the study sorafenib will be considered
safe and feasible in this setting if no patient experience grade 4 hemorrhaging/bleeding
following transplant. With this design, and assuming at least 3 of the 5 patients in each
cohort undergo OLT, the likelihood of stopping early is <.04 if the underlying risk
hemorrhages/bleeding are low (<5% each) whereas there is a >.42 chance of early termination
if the risks are substantial (e.g. >.20 likelihood of dose limiting toxicity and >.30
likelihood of >grade 4 hemorrhages/bleeding). Overall the likelihood of accepting or not
accepting sorafenib as safe and feasible are >.84, and <.16, respectively under these
conditions.

Secondary objectives:

- Drop out rate

- Time to progression prior to orthotopic liver transplant (OLT)

- Waiting time.

Inclusion 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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Adverse events associated with technical aspects of the operation

Outcome Description:

To assess the safety and feasibility of treating HCC patients with sorafenib prior to OLT, as determined by the number of patients experiencing grade 4 hemorrhaging needing blood trnasfusion, thrombosis of vascular graft structures, stenosis of vascular anastomosis or biliary leaks or anastomotic biliary stenosis.

Outcome Time Frame:

post-transplant

Safety Issue:

Yes

Principal Investigator

Robert Pelley, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

CCF Taussig Cancer Solid Tumor Oncology

Authority:

United States: Institutional Review Board

Study ID:

CASE2209

NCT ID:

NCT01337492

Start Date:

September 2010

Completion Date:

January 2012

Related Keywords:

  • Carcinoma, Hepatocellular
  • Hepatocellular Carcinoma
  • Orthotopic Liver Transplant
  • Carcinoma
  • Carcinoma, Hepatocellular

Name

Location

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer CenterCleveland, Ohio  44195