Trial of Sorafenib in Hepatocellular Cancer (HCC) Transplant Patients

Sponsor

Columbia University (Other)

Overall Status

Completed

CT.gov ID

NCT00997022

Collaborator

Bayer (Industry), Amgen (Industry)

Enrollment

Locations

Arm

Duration (Months)

4.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This Phase I study of sorafenib in high risk hepatocellular cancer patients after liver transplantation will study 24 subjects for about 5 years. Each subject will receive sorafenib for 6 months. Safety and effectiveness on the post transplant, high risk HCC patients will be studied.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Cancer	Drug: Sorafenib	Phase 1

Detailed Description

Sorafenib (BAY 43-9006) is an oral multi-kinase inhibitor with effects on tumor proliferation and angiogenesis. Sorafenib is approved for the treatment of patients with advanced renal cancer and unresectable hepatocellular carcinoma (HCC). The recommended daily dose of Sorafenib is 400 mg (2 x 200 mg tablets) taken twice daily without food (at least 1 hour before or 2 hours after a meal). Studies of single-agent sorafenib showed treatment was well-tolerated with manageable side effects. The results seen with sorafenib in the Phase III (SHARP) trial suggest that VEGF and RAF kinase inhibition prolong survival in patients with advanced HCC. It is not known whether a drug which is considered primarily cytostatic will be effective in preventing cancer recurrences in the setting of minimal residual disease.

This is a phase I, single center, open-label, dose-escalation study to determine the maximum tolerated dose (MTD) and overall safety profile of daily sorafenib as therapy to prevent HCC recurrence in liver transplant subjects with high-risk HCC. For each subject, the study will consist of two phases: a treatment phase and an extension phase.

Study Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I Open-Label, Dose-Finding Study of BAY 43-9006 (Sorafenib) in High-risk Hepatocellular Cancer Patients After Liver Transplantation

Study Start Date :

May 1, 2009

Actual Primary Completion Date :

May 1, 2015

Actual Study Completion Date :

May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sorafenib Daily sorafenib taken orally	Drug: Sorafenib Dose escalation: Dose level 1: 200mg of sorafenib daily Dose level 2: 200mg of sorafenib BID (twice daily) Dose level 3: 200mg QAM (taken every morning) and 400mg QPM (taken every evening) Dose level 4: 400mg BID (twice daily) Other Names: Nexavar

Arm

Intervention/Treatment

Experimental: Sorafenib

Daily sorafenib taken orally

Drug: Sorafenib

Dose escalation: Dose level 1: 200mg of sorafenib daily Dose level 2: 200mg of sorafenib BID (twice daily) Dose level 3: 200mg QAM (taken every morning) and 400mg QPM (taken every evening) Dose level 4: 400mg BID (twice daily)

Other Names:

Nexavar

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of daily sorafenib [Every two weeks throughout six cycles]

Secondary Outcome Measures

Duration of disease free survival [Every three months for 2 years]
Duration of progression free survival [Every three months for 2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥18 years old
ECOG Performance Status 0-2
Post liver transplant and have explants with histologically confirmed hepatocellular carcinoma.
No evidence of HCC disease at study entry by imaging
Eligible to start 4 weeks post transplant (29 days post transplant) as long as they are on stable doses of immunosuppressants.
"High risk" for recurrence after transplantation
Received prior surgical resection, chemoembolization or other local therapy prior to transplant.
Have Child-Pugh Class A or compensated Child-Pugh Class B liver dysfunction at the start of therapy
Have adequate bone marrow, liver and renal function as assessed by the following:
Hemoglobin ≥ 8.0 g/dl
Absolute neutrophil count (ANC) ≥ 1,500/mm3
Platelet count ≥ 75,000/mm3
Total bilirubin ≤ 1.5 times ULN
ALT and AST ≤ 5 x ULN
Creatinine ≤ 1.5 times ULN
Albumin ≥ 2.5 mg/dl
Women of childbearing potential must have a negative serum pregnancy test performed within 14 days prior to the 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.
Exhibit the ability to understand and willingness to sign a written informed consent regarding the study and alternative treatments.
INR < 1.5 or a PT/PTT within normal limits.

Exclusion Criteria:

Cardiac disease: Congestive heart failure > class II NYHA.
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.
Active clinically serious infection > CTCAE Grade 2.
Thromboembolic events such as a cerebrovascular accident (including transient ischemic attacks) within the past 6 months.
Any hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of study drug.
Serious non-healing wound, ulcer, or bone fracture within 4 weeks of first dose of study drug.
Evidence or history of bleeding diathesis or coagulopathy within 4 weeks of first dose of study drug.
Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
Use of St. John's Wort or rifampin within 4 weeks of first dose of study drug.
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.
Patients who are pregnant or breastfeeding. Breastfeeding should be discontinued if the patient is to be treated.
Prior malignancy treated during the prior 5-years (other than localized non-melanoma carcinoma of the skin).
Any condition or social situation that may limit patient's compliance with the study regimen
Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis prior to enrollment.
Known human immunodeficiency virus (HIV) infection (hepatitis B and hepatitis C infection will not be exclusion criteria.
Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of study drug.
Any malabsorption problem which in the investigator's opinion would prevent adequate absorption of the sorafenib.
On M-Tor inhibitors

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Southern California	Los Angeles	California	United States	90089
2	University of California, Los Angeles	Los Angeles	California	United States	90095
3	Columbia University Medical Center	New York	New York	United States	10032