Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Sorafenib Dose Ramp-Up in Hepatocellular Carcinoma (HCC)

This study has been completed.
Information provided by (Responsible Party):
University of Florida Identifier:
First received: September 10, 2010
Last updated: January 27, 2015
Last verified: January 2015

September 10, 2010
January 27, 2015
December 2010
January 2014   (final data collection date for primary outcome measure)
Total (Cumulative) Dose Delivery of Sorafenib [ Time Frame: 4 months-1/12/2010-1/27/14 ] [ Designated as safety issue: No ]
This outcome measure table shows the mean and median cumulative dose delivered to the subjects randomized to the standard dosing regimen (N=63) and ramp-up regimen (N=57) at 4 months of treatment.
Total (cumulative) dose delivery of sorafenib [ Time Frame: 4 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01203787 on Archive Site
Safety and Efficacy of Sorafenib Dosing Regimens [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Safety of Sorafenib was assessed by the type, frequency, and severity
Safety and Efficacy of Sorafenib Dosing Regimens [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
Sorafenib Dose Ramp-Up in Hepatocellular Carcinoma (HCC)
Multicenter, Randomized Pilot Study of the Effect of Sorafenib Dosing Schedule on Tolerability and Drug Delivery

Open-label study to evaluate the safety and tolerability of Sorafenib dose ramp-up (starting at a lower dose and then gradually increasing the dose) versus standard Sorafenib dosing in subjects with unresectable and/or metastatic hepatocellular carcinoma.

This is an open-label study that investigates the impact of a dose ramp-up strategy for sorafenib in patients with HCC. Clinical trial and post-marketing data suggest that sorafenib dose reductions and discontinuations due to adverse events are common and limit the drug's effectiveness. It is our hypothesis that a dose escalation strategy for sorafenib will improve the tolerability and allow a greater percentage of patients to remain on drug. The primary end-point of the study is the total accumulated and median daily dose of sorafenib delivered at month 2 and 4.

Phase 4
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Hepatocellular Carcinoma
  • Drug: Sorafenib Standard Dosing Regimen
    Sorafenib 400 mg twice daily until wk 24 or end of treatment
    Other Name: Nexavar(Bay43-9006)
  • Drug: Sorafenib Ramp-Up Regimen
    200 mg daily, Day 0-Day 13 200 mg twice daily, Day 14-Day 20 600 mg daily, Day 21-Day 27 400 mg twice daily, Day 28 until end of treatment400 mg twice daily
    Other Name: Nexavar (Bay43-9006)
  • Active Comparator: Sorafenib Standard Dosing Regimen
    Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24
    Intervention: Drug: Sorafenib Ramp-Up Regimen
  • Experimental: Sorafenib Ramp-Up Regimen
    200 mg daily from Day 0-Day 13 200 mg twice daily from Day 14-Day 20 600 mg daily from Day 21-Day 27 400 mg twice daily beginning Day 28 until end of treatment or Week 24
    Intervention: Drug: Sorafenib Standard Dosing Regimen
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
March 2014
January 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • HCC must be unresectable and/or metastatic
  • CPT score <9 at the time of screening (that is all Child A and Child B with a score of 7 or 8)
  • Age 20-75 years
  • Signed informed consent
  • EGD for variceal screening performed as per standard of care prophylaxis with non-selective beta-blockers or ligation
  • ECOG Performance Status ≤ 2.
  • Adequate bone marrow, liver and renal function as assessed by the following:

    1. Hemoglobin > 8.5 g/dl
    2. Absolute neutrophil count (ANC) > 1,500/mm3
    3. Platelet count > 50,000/mm3
    4. Total bilirubin < 3 mg/dl
    5. ALT and AST ( < 5 x ULN)
    6. Creatinine < 1.5 times ULN
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
  • Women of childbearing potential and non-surgically sterile 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.
  • INR< 2.3. 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 at least weekly, or as defined by the local standard of care, until INR is stable.
  • Life expectancy of at least 24 weeks

Exclusion Criteria:

  • Absence of informed consent
  • Child-Pugh score >9
  • ECOG PS >2
  • Active alcohol dependence per PI discretion
  • History of organ or bone marrow transplant
  • Plans to relocate from the study center within the period of the trial
  • Pregnancy or breastfeeding
  • Contraindications to sorafenib

    1. Cardiac disease: Congestive heart failure > class II 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.
    2. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
    3. Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
    4. 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.
  • Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
  • Bleeding

    1. Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug.
    2. Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug.
    3. Evidence or history of bleeding diathesis or coagulopathy
  • Serious non-healing wound, ulcer, or bone fracture.
  • Major surgery, open biopsy or significant traumatic injury within 4 weeks prior to 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.
  • Any malabsorption problem.
20 Years to 75 Years
Contact information is only displayed when the study is recruiting subjects
United States
University of Florida
University of Florida
Not Provided
Principal Investigator: David R Nelson, MD University of Florida
University of Florida
January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP