Sorafenib Dose Ramp-Up in Hepatocellular Carcinoma (HCC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01203787
First received: September 10, 2010
Last updated: May 20, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Hepatocellular Carcinoma
Drug: Sorafenib Standard Dosing Regimen
Drug: Sorafenib Ramp-Up Regimen
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter, Randomized Pilot Study of the Effect of Sorafenib Dosing Schedule on Tolerability and Drug Delivery

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Total (cumulative) dose delivery of sorafenib [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and Efficacy of Sorafenib Dosing Regimens [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]

Enrollment: 120
Study Start Date: December 2010
Study Completion Date: May 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Sorafenib Standard Dosing Regimen
Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24
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)
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
Drug: Sorafenib Standard Dosing Regimen
Sorafenib 400 mg twice daily until wk 24 or end of treatment
Other Name: Nexavar(Bay43-9006)

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT01203787

Locations
United States, Florida
University of Florida Hepatology
Gainesville, Florida, United States, 32610-0277
Mayo Clinic
Jacksonville, Florida, United States, 32224
Florida Hospital Transplant Center
Orlando, Florida, United States, 32804
Tampa General Hospital
Tampa, Florida, United States, 33606
United States, Illinois
Loyola University Medical Center
Maywood, Illinois, United States, 60153
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Pennsylvania
Drexel University College of Medicine
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
University of Texas Health Science Center Houston
Houston, Texas, United States, 77030
Brooke Army Medical Center
San Antonio, Texas, United States, 78234
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: David R Nelson, MD University of Florida
  More Information

No publications provided

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01203787     History of Changes
Other Study ID Numbers: ONC-2010-19
Study First Received: September 10, 2010
Last Updated: May 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Florida:
Hepatocellular Carcinoma
HCC
Liver Cancer

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Carcinoma
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
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 September 16, 2014