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Sorafenib Dose Ramp-Up in Hepatocellular Carcinoma (HCC)

Information source: University of Florida
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Hepatocellular Carcinoma

Intervention: Sorafenib Standard Dosing Regimen (Drug); Sorafenib Ramp-Up Regimen (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: University of Florida

Official(s) and/or principal investigator(s):
David R Nelson, MD, Principal Investigator, Affiliation: University of Florida

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.

Clinical Details

Official title: Multicenter, Randomized Pilot Study of the Effect of Sorafenib Dosing Schedule on Tolerability and Drug Delivery

Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Total (Cumulative) Dose Delivery of Sorafenib

Cumulative Dose of Sorafenib

Secondary outcome:

Safety and Efficacy of Sorafenib Dosing Regimens

Safety of Dosing Regimens as Assessed by the Frequency and Severity of Adverse Events According to National Cancer Institute- CTCAE

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

Number of Subjects With Dose Interruptions

Number of Subjects With Dose Reductions

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

Minimum age: 20 Years. Maximum age: 75 Years. Gender(s): Both.

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.

Locations and Contacts

University of Florida Hepatology, Gainesville, Florida 32610-0277, United States

Mayo Clinic, Jacksonville, Florida 32224, United States

Florida Hospital Transplant Center, Orlando, Florida 32804, United States

Tampa General Hospital, Tampa, Florida 33606, United States

Loyola University Medical Center, Maywood, Illinois 60153, United States

Henry Ford Health System, Detroit, Michigan 48202, United States

Drexel University College of Medicine, Philadelphia, Pennsylvania 19107, United States

University of Texas Health Science Center Houston, Houston, Texas 77030, United States

Brooke Army Medical Center, San Antonio, Texas 78234, United States

Additional Information

Starting date: December 2010
Last updated: February 13, 2015

Page last updated: August 23, 2015

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