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

NCT01337492 | Terminated Early Phase 1 DMC

• 1 other identifier: CASE2209
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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).

Conditions

Carcinoma, Hepatocellular

Keywords

Hepatocellular Carcinoma; Orthotopic Liver Transplant

Outcome Measures

Primary Outcomes (1)

• 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.

  post-transplant

Secondary Outcomes (3)

• Time to progression prior to OLT

  10 - 12 months

• Drop Out Rate

  10-12 months

• Waiting Time

  10-12 months

Study Arms (1)

Sorafenib

EXPERIMENTAL

Drug: Nexavar

Interventions

Nexavar DRUG

400 mg of Sorafenib

Sorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• Bayer: collaborator
• Onyx Therapeutics, Inc.: collaborator

Study Sites (1)

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Robert Pelley, MD

  CCF Taussig Cancer Solid Tumor Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2011
• First Posted: April 19, 2011
• Study Start: September 1, 2010
• Primary Completion: May 1, 2011
• Study Completion: January 1, 2012
• Last Updated: March 21, 2012

Record last verified: 2012-03

Locations

US (1)