Clincosm LogoSign in Get a demo

Sorafenib Dose Ramp-Up in Hepatocellular Carcinoma (HCC)

Sponsor
University of Florida (Other)
Overall Status
Completed
CT.gov ID
NCT01203787
Collaborator
(none)
120
Enrollment
9
Locations
2
Arms
39
Duration (Months)
13.3
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase
  • Drug: Sorafenib Standard Dosing Regimen
  • Drug: Sorafenib Ramp-Up Regimen
 Phase 4

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Multicenter, Randomized Pilot Study of the Effect of Sorafenib Dosing Schedule on Tolerability and Drug Delivery
Study Start Date :
Dec 1, 2010
Actual Primary Completion Date :
Jan 1, 2014
Actual Study Completion Date :
Mar 1, 2014

Arms and Interventions

Arm Intervention/Treatment
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 Names:
  • 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 Names:
  • Nexavar(Bay43-9006)

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Total (Cumulative) Dose Delivery of Sorafenib [4 months-1/12/2010-1/27/14]

      This outcome measure table shows the 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.

    2. Cumulative Dose of Sorafenib [11/22/2010-1/27/14]

      Table below shows mean cumulative dose of sorafenib for each of the dosing regimens.

    Secondary Outcome Measures

    1. Safety and Efficacy of Sorafenib Dosing Regimens [Baseline-End of Treatment (11/22/2010-3/10/2014)]

      Safety of Sorafenib was assessed by the frequency and severity of adverse events according to NCI-CTCAE grading

    2. Safety of Dosing Regimens as Assessed by the Frequency and Severity of Adverse Events According to National Cancer Institute- CTCAE [11/22/2010-3/10/2014]

      The total number of CTCAE (Common Terminology Criteria) grade 4 adverse events was collected for each dosing regimen beginning at baseline until Week 24/Early Termination Visit.

    3. Frequency and Severity of Adverse Events According to National Cancer Institute- CTCAE [11/22/2010-3/10/2014]

      The total number of CTCAE (Common Terminology Criteria) grade 5 adverse events was collected for each dosing regimen beginning at baseline through 6 months of treatment.

    4. Number of Subjects With Dose Interruptions [Baseline-End of Treatment (11/22/2010-3/10/2014)]

    5. Number of Subjects With Dose Reductions [11/22/2010-3/10/2014]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 University of Florida Hepatology Gainesville Florida United States 32610-0277
    2 Mayo Clinic Jacksonville Florida United States 32224
    3 Florida Hospital Transplant Center Orlando Florida United States 32804
    4 Tampa General Hospital Tampa Florida United States 33606
    5 Loyola University Medical Center Maywood Illinois United States 60153
    6 Henry Ford Health System Detroit Michigan United States 48202
    7 Drexel University College of Medicine Philadelphia Pennsylvania United States 19107
    8 University of Texas Health Science Center Houston Houston Texas United States 77030
    9 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Florida
    ClinicalTrials.gov Identifier:
    NCT01203787
    Other Study ID Numbers:
    • ONC-2010-19
    First Posted:
    Sep 16, 2010
    Last Update Posted:
    Mar 5, 2015
    Last Verified:
    Feb 1, 2015
    Keywords provided by University of Florida
    Hepatocellular Carcinoma
    HCC
    Liver Cancer
    Additional relevant MeSH terms:
    Carcinoma
    Carcinoma, Hepatocellular
    Sorafenib

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Sorafenib Standard Dosing Regimen Sorafenib Ramp-Up Regimen
    Arm/Group Description Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24 200 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
    Period Title: Overall Study
    STARTED 63 57
    COMPLETED 32 30
    NOT COMPLETED 31 27

    Baseline Characteristics

    Arm/Group Title Sorafenib Standard Dosing Regimen Sorafenib Ramp-Up Regimen Total
    Arm/Group Description Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24 200 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 Total of all reporting groups
    Overall Participants 63 57 120
    Age (Count of Participants)
    <=18 years
    00
    0%
    00
    0%
    0
    0%
    Between 18 and 65 years
    39
    61.9%
    30
    52.6%
    69
    57.5%
    >=65 years
    24
    38.1%
    27
    47.4%
    51
    42.5%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    62.0
    (6.8)
    63.5
    (7.5)
    62.7
    (7.2)
    Sex: Female, Male (Count of Participants)
    Female
    12
    19%
    10
    17.5%
    22
    18.3%
    Male
    51
    81%
    47
    82.5%
    98
    81.7%
    Region of Enrollment (participants) [Number]
    United States
    63
    100%
    57
    100%
    120
    100%

    Outcome Measures

    1. Primary Outcome
    Title Total (Cumulative) Dose Delivery of Sorafenib
    Description This outcome measure table shows the 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.
    Time Frame 4 months-1/12/2010-1/27/14

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Sorafenib Standard Dosing Regimen Sorafenib Ramp-Up Regimen
    Arm/Group Description Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24 200 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
    Measure Participants 63 57
    Median (Full Range) [mg]
    49800
    38000
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sorafenib Standard Dosing Regimen, Sorafenib Ramp-Up Regimen
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0262
    Comments
    Method Wilcoxon rank sum test
    Comments
    2. Secondary Outcome
    Title Safety and Efficacy of Sorafenib Dosing Regimens
    Description Safety of Sorafenib was assessed by the frequency and severity of adverse events according to NCI-CTCAE grading
    Time Frame Baseline-End of Treatment (11/22/2010-3/10/2014)

    Outcome Measure Data

    Analysis Population Description
    The total number of CTCAE (Common Terminology Criteria) grade 3 adverse events was collected for each dosing regimen
    Arm/Group Title Sorafenib Standard Dosing Regimen Sorafenib Ramp-Up Regimen
    Arm/Group Description Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24 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 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 Sorafenib Standard Dosing Regimen: Sorafenib 400 mg twice daily until wk 24 or end of treatment
    Measure Participants 63 57
    Number [Grade 3 adverse events]
    92
    101
    3. Secondary Outcome
    Title Safety of Dosing Regimens as Assessed by the Frequency and Severity of Adverse Events According to National Cancer Institute- CTCAE
    Description The total number of CTCAE (Common Terminology Criteria) grade 4 adverse events was collected for each dosing regimen beginning at baseline until Week 24/Early Termination Visit.
    Time Frame 11/22/2010-3/10/2014

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Sorafenib Standard Dosing Regimen Sorafenib Ramp-Up Regimen
    Arm/Group Description Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24 200 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
    Measure Participants 63 57
    Number [Grade 4 adverse events]
    19
    15
    4. Secondary Outcome
    Title Frequency and Severity of Adverse Events According to National Cancer Institute- CTCAE
    Description The total number of CTCAE (Common Terminology Criteria) grade 5 adverse events was collected for each dosing regimen beginning at baseline through 6 months of treatment.
    Time Frame 11/22/2010-3/10/2014

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Sorafenib Standard Dosing Regimen Sorafenib Ramp-Up Regimen
    Arm/Group Description Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24 200 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
    Measure Participants 63 57
    Number [Grade 5 Adverse Events]
    9
    8
    5. Primary Outcome
    Title Cumulative Dose of Sorafenib
    Description Table below shows mean cumulative dose of sorafenib for each of the dosing regimens.
    Time Frame 11/22/2010-1/27/14

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Sorafenib Standard Dosing Regimen Sorafenib Ramp-Up Regimen
    Arm/Group Description Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24 200 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
    Measure Participants 63 57
    Mean (Standard Deviation) [mg]
    53692
    (33411)
    41523
    (28783)
    6. Secondary Outcome
    Title Number of Subjects With Dose Interruptions
    Description
    Time Frame Baseline-End of Treatment (11/22/2010-3/10/2014)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Sorafenib Standard Dosing Regimen Sorafenib Ramp-Up Regimen
    Arm/Group Description Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24 200 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
    Measure Participants 63 57
    Number [participants]
    29
    46%
    20
    35.1%
    7. Secondary Outcome
    Title Number of Subjects With Dose Reductions
    Description
    Time Frame 11/22/2010-3/10/2014

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Sorafenib Standard Dosing Regimen Sorafenib Ramp-Up Regimen
    Arm/Group Description Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24 200 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
    Measure Participants 63 57
    Number [participants]
    40
    63.5%
    34
    59.6%

    Adverse Events

    Time Frame Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
    Adverse Event Reporting Description
    Arm/Group Title Sorafenib Standard Dosing Regimen Sorafenib Ramp-Up Regimen
    Arm/Group Description Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24 200 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
    All Cause Mortality
    Sorafenib Standard Dosing Regimen Sorafenib Ramp-Up Regimen
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Sorafenib Standard Dosing Regimen Sorafenib Ramp-Up Regimen
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 16/63 (25.4%) 13/57 (22.8%)
    Blood and lymphatic system disorders
    Anemia 2/63 (3.2%) 2 0/57 (0%) 0
    Thrombocytopenia 1/63 (1.6%) 1 0/57 (0%) 0
    Cardiac disorders
    Acute congestive heart failure 1/63 (1.6%) 1 0/57 (0%) 0
    Chest pain 1/63 (1.6%) 1 0/57 (0%) 0
    Cardiac arrest 1/63 (1.6%) 1 0/57 (0%) 0
    Hypertension 0/63 (0%) 0 1/57 (1.8%) 1
    Hypotension 3/63 (4.8%) 3 0/57 (0%) 0
    Ear and labyrinth disorders
    Blurred vision 0/63 (0%) 0 1/57 (1.8%) 1
    Gastrointestinal disorders
    Abdominal pain 1/63 (1.6%) 1 0/57 (0%) 0
    Nausea 1/63 (1.6%) 1 0/57 (0%) 0
    Upper gastrointestinal bleed 1/63 (1.6%) 1 2/57 (3.5%) 2
    Vomiting 1/63 (1.6%) 1 0/57 (0%) 0
    General disorders
    Deterioration of condition 0/63 (0%) 0 1/57 (1.8%) 1
    Hypothermia 1/63 (1.6%) 1 0/57 (0%) 0
    Syncopal episode 1/63 (1.6%) 1 0/57 (0%) 0
    Hepatobiliary disorders
    Ascites 1/63 (1.6%) 1 1/57 (1.8%) 2
    Biliary obstruction 1/63 (1.6%) 1 0/57 (0%) 0
    Decompensated liver failure 1/63 (1.6%) 1 0/57 (0%) 0
    Encephalopathy 6/63 (9.5%) 6 1/57 (1.8%) 1
    Liver failure 0/63 (0%) 0 4/57 (7%) 4
    Infections and infestations
    Cellulitis 1/63 (1.6%) 1 0/57 (0%) 0
    Influenza 1/63 (1.6%) 1 0/57 (0%) 0
    Meningitis 1/63 (1.6%) 1 0/57 (0%) 0
    Pneumonia 1/63 (1.6%) 1 1/57 (1.8%) 1
    Sepsis 2/63 (3.2%) 2 1/57 (1.8%) 1
    Spontaneous bacterial perotinitis 1/63 (1.6%) 1 0/57 (0%) 0
    Urinary tract infection 0/63 (0%) 0 1/57 (1.8%) 1
    Injury, poisoning and procedural complications
    Drug toxicity 1/63 (1.6%) 1 0/57 (0%) 0
    Post-embolization syndrome 3/63 (4.8%) 3 0/57 (0%) 0
    Metabolism and nutrition disorders
    Dehydration 2/63 (3.2%) 2 1/57 (1.8%) 1
    Failure to thrive 1/63 (1.6%) 1 0/57 (0%) 0
    Musculoskeletal and connective tissue disorders
    Rib fracture 1/63 (1.6%) 1 0/57 (0%) 0
    Nervous system disorders
    Dizziness 1/63 (1.6%) 1 0/57 (0%) 0
    Vertigo 0/63 (0%) 0 1/57 (1.8%) 1
    Unsteady gait 0/63 (0%) 0 1/57 (1.8%) 1
    Renal and urinary disorders
    Acute renal failure 3/63 (4.8%) 3 0/57 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 1/63 (1.6%) 1 1/57 (1.8%) 1
    Pulmonary embolism 1/63 (1.6%) 1 0/57 (0%) 0
    Respiratory failure 2/63 (3.2%) 2 1/57 (1.8%) 1
    Skin and subcutaneous tissue disorders
    Abrasion 1/63 (1.6%) 1 0/57 (0%) 0
    Other (Not Including Serious) Adverse Events
    Sorafenib Standard Dosing Regimen Sorafenib Ramp-Up Regimen
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 62/63 (98.4%) 57/57 (100%)
    Blood and lymphatic system disorders
    anemia 18/63 (28.6%) 26 16/57 (28.1%) 19
    direct hyperbilirubinemia 24/63 (38.1%) 44 30/57 (52.6%) 51
    leukocytosis 0/63 (0%) 0 1/57 (1.8%) 1
    leukopenia 20/63 (31.7%) 29 11/57 (19.3%) 16
    lymphodenitis 1/63 (1.6%) 1 0/57 (0%) 0
    lymphopenia 0/63 (0%) 0 1/57 (1.8%) 1
    pancytopenia 1/63 (1.6%) 1 0/57 (0%) 0
    thrombocytopenia 30/63 (47.6%) 41 26/57 (45.6%) 39
    Cardiac disorders
    aortic stenosis 1/63 (1.6%) 1 0/57 (0%) 0
    atypical chest pain 1/63 (1.6%) 1 0/57 (0%) 0
    bradycardia 1/63 (1.6%) 1 0/57 (0%) 0
    chest pain 0/63 (0%) 0 4/57 (7%) 4
    edema 6/63 (9.5%) 6 4/57 (7%) 4
    hypertension 32/63 (50.8%) 56 29/57 (50.9%) 49
    hypotension 2/63 (3.2%) 2 2/57 (3.5%) 2
    palpitations 0/63 (0%) 0 1/57 (1.8%) 1
    systolic murmur 1/63 (1.6%) 1 0/57 (0%) 0
    tachycardia 1/63 (1.6%) 1 0/57 (0%) 0
    ventricular hypertrophy 1/63 (1.6%) 1 0/57 (0%) 0
    Ear and labyrinth disorders
    ear fullness 1/63 (1.6%) 1 1/57 (1.8%) 1
    ear pain 0/63 (0%) 0 1/57 (1.8%) 1
    hearing impairment 0/63 (0%) 0 1/57 (1.8%) 1
    otitis media 1/63 (1.6%) 1 0/57 (0%) 0
    tinnitus 1/63 (1.6%) 1 0/57 (0%) 0
    Endocrine disorders
    cold intolerance 1/63 (1.6%) 1 0/57 (0%) 0
    Diabetic neuropathy 1/63 (1.6%) 1 0/57 (0%) 0
    diabetes 1/63 (1.6%) 1 0/57 (0%) 0
    hyperglycemia 1/63 (1.6%) 1 0/57 (0%) 0
    Eye disorders
    blurred vision 0/63 (0%) 0 3/57 (5.3%) 3
    Cataract 1/63 (1.6%) 1 1/57 (1.8%) 1
    conjunctival hemorrhage 1/63 (1.6%) 1 0/57 (0%) 0
    conjunctivitis 1/63 (1.6%) 1 0/57 (0%) 0
    Gastrointestinal disorders
    abdominal bloating 1/63 (1.6%) 1 0/57 (0%) 0
    abdominal cramps 0/63 (0%) 0 5/57 (8.8%) 6
    abdominal pain 17/63 (27%) 22 21/57 (36.8%) 26
    amylase elevation 7/63 (11.1%) 11 6/57 (10.5%) 6
    anorexia 17/63 (27%) 20 13/57 (22.8%) 13
    bezoar 1/63 (1.6%) 1 0/57 (0%) 0
    cholecystitis 1/63 (1.6%) 1 0/57 (0%) 0
    cholelithiasis 1/63 (1.6%) 1 0/57 (0%) 0
    constipation 4/63 (6.3%) 4 6/57 (10.5%) 7
    diarrhea 24/63 (38.1%) 30 23/57 (40.4%) 28
    dry mouth 3/63 (4.8%) 3 2/57 (3.5%) 2
    dysgeusia 0/63 (0%) 0 1/57 (1.8%) 1
    dyspepsia 3/63 (4.8%) 3 1/57 (1.8%) 1
    dysphagia 1/63 (1.6%) 2 1/57 (1.8%) 1
    early satiety 2/63 (3.2%) 2 0/57 (0%) 0
    fecal incontinence 1/63 (1.6%) 1 0/57 (0%) 0
    flatulence 1/63 (1.6%) 1 0/57 (0%) 0
    gastrointestinal bleed 6/63 (9.5%) 6 3/57 (5.3%) 3
    gastroparesis 1/63 (1.6%) 1 0/57 (0%) 0
    g.i disturbance 1/63 (1.6%) 1 0/57 (0%) 0
    glossodynia 0/63 (0%) 0 1/57 (1.8%) 1
    hemorrhoids 1/63 (1.6%) 1 2/57 (3.5%) 3
    hiccups 2/63 (3.2%) 2 0/57 (0%) 0
    lipase elevation 22/63 (34.9%) 38 26/57 (45.6%) 49
    mucositis 0/63 (0%) 0 2/57 (3.5%) 2
    nausea 21/63 (33.3%) 24 19/57 (33.3%) 20
    oral hypersensitivity 1/63 (1.6%) 1 2/57 (3.5%) 2
    oral pain 0/63 (0%) 0 1/57 (1.8%) 1
    pancreatitis 1/63 (1.6%) 1 0/57 (0%) 0
    peptic ulcer 1/63 (1.6%) 1 0/57 (0%) 0
    perianal abcess 0/63 (0%) 0 1/57 (1.8%) 1
    peritoneal enlarged studding 1/63 (1.6%) 1 0/57 (0%) 0
    rectal fissue 0/63 (0%) 0 1/57 (1.8%) 1
    umbilical hernia 0/63 (0%) 0 1/57 (1.8%) 1
    vomiting 11/63 (17.5%) 11 9/57 (15.8%) 11
    General disorders
    bleeding gums 4/63 (6.3%) 5 0/57 (0%) 0
    chills 1/63 (1.6%) 1 2/57 (3.5%) 2
    dehydration 1/63 (1.6%) 1 0/57 (0%) 0
    epistaxis 3/63 (4.8%) 3 1/57 (1.8%) 1
    fatigue 22/63 (34.9%) 26 31/57 (54.4%) 37
    flu-like symptoms 0/63 (0%) 0 1/57 (1.8%) 1
    head cold 0/63 (0%) 0 1/57 (1.8%) 1
    lightheadedness 2/63 (3.2%) 2 0/57 (0%) 0
    night sweats 0/63 (0%) 0 1/57 (1.8%) 1
    tooth pain 1/63 (1.6%) 1 0/57 (0%) 0
    weight loss 40/63 (63.5%) 63 28/57 (49.1%) 39
    Hepatobiliary disorders
    ammonia elevation 2/63 (3.2%) 2 0/57 (0%) 0
    ascites 9/63 (14.3%) 9 9/57 (15.8%) 10
    asterexis 0/63 (0%) 0 1/57 (1.8%) 1
    ast elevation 1/63 (1.6%) 1 0/57 (0%) 0
    elevated INR 19/63 (30.2%) 24 15/57 (26.3%) 16
    encephalopathy 11/63 (17.5%) 11 7/57 (12.3%) 7
    gynecomastia 0/63 (0%) 0 2/57 (3.5%) 3
    hepatomegaly 2/63 (3.2%) 2 0/57 (0%) 0
    hypoalbuminemia 31/63 (49.2%) 43 27/57 (47.4%) 37
    jaundice 1/63 (1.6%) 1 1/57 (1.8%) 1
    left portal vein thrombosis 0/63 (0%) 0 1/57 (1.8%) 1
    liver failure 6/63 (9.5%) 6 5/57 (8.8%) 5
    palmer erythema 1/63 (1.6%) 1 0/57 (0%) 0
    spider angiomata 1/63 (1.6%) 1 0/57 (0%) 0
    splenomegaly 1/63 (1.6%) 1 2/57 (3.5%) 3
    total hyperbilirubinemia 32/63 (50.8%) 50 34/57 (59.6%) 53
    Immune system disorders
    allergic rhinitis 1/63 (1.6%) 1 0/57 (0%) 0
    Infections and infestations
    cellulitis 2/63 (3.2%) 2 0/57 (0%) 0
    fever 8/63 (12.7%) 10 2/57 (3.5%) 2
    gastritis 1/63 (1.6%) 2 2/57 (3.5%) 2
    MRSA 1/63 (1.6%) 1 0/57 (0%) 0
    oral thrush 0/63 (0%) 0 1/57 (1.8%) 1
    pneumonia 0/63 (0%) 0 2/57 (3.5%) 2
    ringworm 1/63 (1.6%) 1 0/57 (0%) 0
    sinusitis 0/63 (0%) 0 2/57 (3.5%) 2
    skull infection 0/63 (0%) 0 1/57 (1.8%) 1
    stye 0/63 (0%) 0 1/57 (1.8%) 2
    throat pain 2/63 (3.2%) 2 1/57 (1.8%) 1
    thrush 1/63 (1.6%) 1 0/57 (0%) 0
    upper respiratory infection 0/63 (0%) 0 1/57 (1.8%) 1
    Injury, poisoning and procedural complications
    hematuria with catherization 0/63 (0%) 0 1/57 (1.8%) 1
    post-tace syndrome 2/63 (3.2%) 3 1/57 (1.8%) 1
    Metabolism and nutrition disorders
    malnutrition 0/63 (0%) 0 1/57 (1.8%) 1
    temporal wasting 1/63 (1.6%) 1 0/57 (0%) 0
    Musculoskeletal and connective tissue disorders
    ankle pain 0/63 (0%) 0 1/57 (1.8%) 1
    arthralgias 1/63 (1.6%) 2 4/57 (7%) 4
    back pain 2/63 (3.2%) 2 2/57 (3.5%) 2
    collar bone pain 0/63 (0%) 0 1/57 (1.8%) 1
    groin pain 3/63 (4.8%) 3 2/57 (3.5%) 3
    knee pain 0/63 (0%) 0 1/57 (1.8%) 1
    leg pain 1/63 (1.6%) 1 0/57 (0%) 0
    muscle cramps 6/63 (9.5%) 6 10/57 (17.5%) 11
    myalgia 0/63 (0%) 0 1/57 (1.8%) 1
    nasal fracture 1/63 (1.6%) 1 0/57 (0%) 0
    nose tenderness 0/63 (0%) 0 1/57 (1.8%) 1
    pseudogout 1/63 (1.6%) 1 0/57 (0%) 0
    spinal spondolytis 0/63 (0%) 0 1/57 (1.8%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    skin cancer 1/63 (1.6%) 1 0/57 (0%) 0
    squamous cell carcinoma 1/63 (1.6%) 1 2/57 (3.5%) 2
    Nervous system disorders
    arm paresthesia 1/63 (1.6%) 1 0/57 (0%) 0
    dizziness 2/63 (3.2%) 2 2/57 (3.5%) 2
    face/mouth sensitivity 1/63 (1.6%) 1 0/57 (0%) 0
    facial droop 1/63 (1.6%) 1 0/57 (0%) 0
    headache 5/63 (7.9%) 5 7/57 (12.3%) 8
    impaired speech 1/63 (1.6%) 1 0/57 (0%) 0
    peripheral neuropathy 0/63 (0%) 0 1/57 (1.8%) 1
    sciatica 1/63 (1.6%) 1 0/57 (0%) 0
    seizure like activity 1/63 (1.6%) 1 0/57 (0%) 0
    somnolence 1/63 (1.6%) 1 1/57 (1.8%) 1
    unsteady gait 3/63 (4.8%) 3 2/57 (3.5%) 2
    vertigo 0/63 (0%) 0 1/57 (1.8%) 1
    Psychiatric disorders
    anxiety 2/63 (3.2%) 2 0/57 (0%) 0
    depression 6/63 (9.5%) 6 1/57 (1.8%) 1
    insomnia 4/63 (6.3%) 4 6/57 (10.5%) 6
    irritability 1/63 (1.6%) 1 0/57 (0%) 0
    mood alteration 1/63 (1.6%) 1 0/57 (0%) 0
    Renal and urinary disorders
    bacteuria 0/63 (0%) 0 1/57 (1.8%) 1
    creatinine elevation 1/63 (1.6%) 1 0/57 (0%) 0
    hematuria 0/63 (0%) 0 1/57 (1.8%) 1
    hyperkalemia 4/63 (6.3%) 4 1/57 (1.8%) 1
    hypokalemia 6/63 (9.5%) 6 1/57 (1.8%) 1
    hypomagnesemia 5/63 (7.9%) 8 5/57 (8.8%) 5
    hyponatremia 1/63 (1.6%) 1 1/57 (1.8%) 1
    hypophosphatemia 23/63 (36.5%) 37 23/57 (40.4%) 30
    kidney injury 1/63 (1.6%) 1 0/57 (0%) 0
    renal failure 1/63 (1.6%) 1 0/57 (0%) 0
    urinary incontinence 2/63 (3.2%) 2 1/57 (1.8%) 1
    urinary tract infection 2/63 (3.2%) 2 3/57 (5.3%) 4
    Reproductive system and breast disorders
    pelvic floor dysfunction 0/63 (0%) 0 1/57 (1.8%) 1
    scortal pain 1/63 (1.6%) 1 0/57 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    bronchitis 1/63 (1.6%) 1 1/57 (1.8%) 1
    chronic obstructive pulmonary disease 0/63 (0%) 0 1/57 (1.8%) 1
    cough 2/63 (3.2%) 2 2/57 (3.5%) 2
    diminished breath sounds 0/63 (0%) 0 1/57 (1.8%) 1
    dysphonia 4/63 (6.3%) 5 8/57 (14%) 8
    pulmonary edema 0/63 (0%) 0 1/57 (1.8%) 1
    shortness of breath 1/63 (1.6%) 1 4/57 (7%) 4
    Skin and subcutaneous tissue disorders
    abscess 2/63 (3.2%) 2 0/57 (0%) 0
    alopecia 13/63 (20.6%) 13 7/57 (12.3%) 7
    blister 2/63 (3.2%) 2 0/57 (0%) 0
    bruising 1/63 (1.6%) 1 0/57 (0%) 0
    contusion 0/63 (0%) 0 1/57 (1.8%) 2
    decubitus ulcer 0/63 (0%) 0 1/57 (1.8%) 1
    dry skin 2/63 (3.2%) 2 2/57 (3.5%) 2
    erythema 1/63 (1.6%) 1 0/57 (0%) 0
    hand-foot reaction 25/63 (39.7%) 37 24/57 (42.1%) 36
    hematoma 0/63 (0%) 0 1/57 (1.8%) 1
    keratosis 0/63 (0%) 0 1/57 (1.8%) 1
    nail changes 1/63 (1.6%) 1 1/57 (1.8%) 1
    oral aphthous ulcers 4/63 (6.3%) 4 5/57 (8.8%) 5
    poison ivy 0/63 (0%) 0 1/57 (1.8%) 1
    pruritus 6/63 (9.5%) 6 6/57 (10.5%) 6
    rash 12/63 (19%) 13 13/57 (22.8%) 18
    scalp hypersensitivity 1/63 (1.6%) 1 2/57 (3.5%) 2
    skin excoriation 1/63 (1.6%) 1 0/57 (0%) 0
    skin lesions 1/63 (1.6%) 1 0/57 (0%) 0
    skin ulcer 0/63 (0%) 0 1/57 (1.8%) 1
    telangiectasia 0/63 (0%) 0 2/57 (3.5%) 2

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Roniel Cabrera, MD
    Organization UNIVERSITY OF FLORIDA
    Phone 352-273-9468
    Email RONIEL.CABRERA@MEDICINE.UFL.EDU
    Responsible Party:
    University of Florida
    ClinicalTrials.gov Identifier:
    NCT01203787
    Other Study ID Numbers:
    • ONC-2010-19
    First Posted:
    Sep 16, 2010
    Last Update Posted:
    Mar 5, 2015
    Last Verified:
    Feb 1, 2015