Trial of Sorafenib in Hepatocellular Cancer (HCC) Transplant Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Bayer
Onyx Pharmaceuticals
Information provided by (Responsible Party):
Abby Siegel, Columbia University
ClinicalTrials.gov Identifier:
NCT00997022
First received: October 14, 2009
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

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 Intervention Phase
Hepatocellular Cancer
Drug: Sorafenib - dose escalation
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Maximum tolerated dose of daily sorafenib [ Time Frame: Every two weeks throughout six cycles ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Duration of disease free survival and progression free survival [ Time Frame: Every three months for 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: January 2009
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 years old
  • ECOG Performance Status 0-2 (See Appendix I)
  • All patients will be post liver transplant and have explants with histologically confirmed hepatocellular carcinoma.
  • Patient should have no evidence of HCC disease at study entry by imaging
  • Patients will be eligible to start 4 weeks post transplant (29 days post transplant) as long as they are on stable doses of immunosuppressants. Patient must start treatment within 16 weeks (112 days) after transplant.
  • Patients must be deemed "high risk" for recurrence after transplantation, by either being outside Milan criteria before transplant or on explant, having tumors with micro or macrovascular invasion, and/or poorly differentiated tumor histology.
  • Patients may have received prior surgical resection, chemoembolization or other local therapy prior to transplant. They may not have received prior anti-angiogenic therapy, systemic targeted agents or systemic chemotherapy. They also may not have received M-Tor inhibitors.
  • Patients must have Child-Pugh Class A or compensated Child-Pugh Class B liver dysfunction at the start of therapy (See Appendix II).
  • Patients must 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.
  • Subjects must 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. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored carefully. Patients must be warned of possible increased risk of bleeding on the combination.

Exclusion Criteria:

  • Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have unstable angina (anginal symptoms at rest), new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
  • 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.
  • Patients may not be on M-Tor inhibitors
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00997022

Locations
United States, California
University of California, Los Angeles
Los Angeles, California, United States, 90095
University of Southern California
Los Angeles, California, United States, 90089
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Bayer
Onyx Pharmaceuticals
Investigators
Principal Investigator: Abby Siegel, MD, MS Columbia University
  More Information

No publications provided

Responsible Party: Abby Siegel, Assistant Professor of Clinical Medicine, Columbia University
ClinicalTrials.gov Identifier: NCT00997022     History of Changes
Other Study ID Numbers: AAAD3519
Study First Received: October 14, 2009
Last Updated: November 21, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
HCC
High-risk Hepatocellular Cancer

Additional relevant MeSH terms:
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 20, 2014