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

Primary Purpose

Carcinoma, Hepatocellular

Status
Terminated
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Nexavar
Sponsored by
Case Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Hepatocellular focused on measuring Hepatocellular Carcinoma, Orthotopic Liver Transplant

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sorafenib

Arm Description

Outcomes

Primary Outcome Measures

Adverse events associated with technical aspects of the operation
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.

Secondary Outcome Measures

Time to progression prior to OLT
A measure of time after being put on transplant list until the disease is beyond Milan's criteria prior to OLT.
Drop Out Rate
This is the rate of subjects who were eligible for liver transplant but drop out secondary to disease progression while awaiting donor organ.
Waiting Time
This is number of months from the time patient get listed on the transplant list to the time patient under goes actual liver transplant.

Full Information

First Posted
January 19, 2011
Last Updated
March 20, 2012
Sponsor
Case Comprehensive Cancer Center
Collaborators
Bayer, Onyx Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01337492
Brief Title
Pilot Study Sorafenib as Bridge to Orthotopic Liver Transplantation (OLT)
Official Title
Pilot Study: Safety and Feasibility of Using Sorafenib as Neoadjuvant Treatment Prior to Orthotopic Liver Transplantation (OLT) in Patients With Hepatocellular Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2012
Overall Recruitment Status
Terminated
Why Stopped
slow accrual
Study Start Date
September 2010 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Case Comprehensive Cancer Center
Collaborators
Bayer, Onyx Therapeutics, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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).
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Hepatocellular
Keywords
Hepatocellular Carcinoma, Orthotopic Liver Transplant

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sorafenib
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Nexavar
Intervention Description
400 mg of Sorafenib
Primary Outcome Measure Information:
Title
Adverse events associated with technical aspects of the operation
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.
Time Frame
post-transplant
Secondary Outcome Measure Information:
Title
Time to progression prior to OLT
Description
A measure of time after being put on transplant list until the disease is beyond Milan's criteria prior to OLT.
Time Frame
10 - 12 months
Title
Drop Out Rate
Description
This is the rate of subjects who were eligible for liver transplant but drop out secondary to disease progression while awaiting donor organ.
Time Frame
10-12 months
Title
Waiting Time
Description
This is number of months from the time patient get listed on the transplant list to the time patient under goes actual liver transplant.
Time Frame
10-12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Pelley, MD
Organizational Affiliation
CCF Taussig Cancer Solid Tumor Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States

12. IPD Sharing Statement

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

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