NCT01203787

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P50-P75 for phase_4 hepatocellular-carcinoma

Timeline
Completed

Started Dec 2010

Typical duration for phase_4 hepatocellular-carcinoma

Geographic Reach
1 country

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 10, 2010

Completed
6 days until next milestone

First Posted

Study publicly available on registry

September 16, 2010

Completed
3 months until next milestone

Study Start

First participant enrolled

December 1, 2010

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2014

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2014

Completed
12 months until next milestone

Results Posted

Study results publicly available

February 11, 2015

Completed
Last Updated

March 5, 2015

Status Verified

February 1, 2015

Enrollment Period

3.1 years

First QC Date

September 10, 2010

Results QC Date

January 27, 2015

Last Update Submit

February 13, 2015

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular CarcinomaHCCLiver Cancer

Outcome Measures

Primary Outcomes (2)

  • Total (Cumulative) Dose Delivery of Sorafenib

    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.

    4 months-1/12/2010-1/27/14

  • Cumulative Dose of Sorafenib

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

    11/22/2010-1/27/14

Secondary Outcomes (5)

  • Safety and Efficacy of Sorafenib Dosing Regimens

    Baseline-End of Treatment (11/22/2010-3/10/2014)

  • 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

  • Frequency and Severity of Adverse Events According to National Cancer Institute- CTCAE

    11/22/2010-3/10/2014

  • Number of Subjects With Dose Interruptions

    Baseline-End of Treatment (11/22/2010-3/10/2014)

  • Number of Subjects With Dose Reductions

    11/22/2010-3/10/2014

Study Arms (2)

Sorafenib Standard Dosing Regimen

ACTIVE COMPARATOR

Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24

Drug: Sorafenib Ramp-Up Regimen

Sorafenib Ramp-Up Regimen

EXPERIMENTAL

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

Interventions

Sorafenib Standard Dosing RegimenDRUG

Sorafenib 400 mg twice daily until wk 24 or end of treatment

Also known as: Nexavar(Bay43-9006)
Sorafenib Ramp-Up Regimen
Sorafenib Ramp-Up RegimenDRUG

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

Also known as: Nexavar (Bay43-9006)
Sorafenib Standard Dosing Regimen

Eligibility Criteria

Age20 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • Hemoglobin \> 8.5 g/dl
  • Absolute neutrophil count (ANC) \> 1,500/mm3
  • Platelet count \> 50,000/mm3
  • Total bilirubin \< 3 mg/dl
  • ALT and AST ( \< 5 x ULN)
  • 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.
  • +3 more criteria

You may not qualify if:

  • 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
  • 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.
  • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
  • Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
  • 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.
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

University of Florida Hepatology

Gainesville, Florida, 32610-0277, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Florida Hospital Transplant Center

Orlando, Florida, 32804, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Drexel University College of Medicine

Philadelphia, Pennsylvania, 19107, United States

Location

University of Texas Health Science Center Houston

Houston, Texas, 77030, United States

Location

Brooke Army Medical Center

San Antonio, Texas, 78234, United States

Location

MeSH Terms

Conditions

Carcinoma, HepatocellularLiver Neoplasms

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea CompoundsUreaAmidesOrganic ChemicalsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsNiacinamideNicotinic AcidsAcids, HeterocyclicHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-Ring

Results Point of Contact

Title
Roniel Cabrera, MD
Organization
UNIVERSITY OF FLORIDA
RONIEL.CABRERA@MEDICINE.UFL.EDU
352-273-9468

Study Officials

  • David R Nelson, MD

    University of Florida

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 10, 2010

First Posted

September 16, 2010

Study Start

December 1, 2010

Primary Completion

January 1, 2014

Study Completion

March 1, 2014

Last Updated

March 5, 2015

Results First Posted

February 11, 2015

Record last verified: 2015-02

Locations

US(9)