Study of Sorafenib, Gemcitabine, and Cisplatin in Advanced Hepatocellular Carcinoma (HCC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00808145
Recruitment Status : Withdrawn (Lack of enrollment, many screen failures and non eligible study participants)
First Posted : December 15, 2008
Last Update Posted : October 22, 2014
Information provided by (Responsible Party):
Lahey Clinic

Brief Summary:
This study will look at the safety and efficacy of treating advanced hepatocellular carcinoma in patients who have not yet received systemic chemotherapy. Previous local treatment of hepatic lesions is permitted The treatment will use a combination of three FDA approved chemotherapy drugs, Gemcitabine, Cisplatin and Sorafenib. Sorafenib is FDA approved for the treatment of hepatocellular cancer, gemcitabine and cisplatin are not approved for the treatment of hepatocellular cancer.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: Gemcitabine / Cisplatin / Sorafenib Phase 2

Detailed Description:
This study will look at the effectiveness and safety of combining gemcitabine, cisplatin and sorafenib for the treatment of advanced hepatocellular carcinoma in patients with advanced disease who are chemo naive. Sorafenib has shown an increase in median survival but only tumor shrinkage by RECIST criteria. Since much of the morbidity and mortality of this disease occurs due to continued tumor growth in an already compromised liver, decreasing the size of the tumors might have significant impact on survival. The addition of traditional cytoxic agents might cause measureable tumor response and add to the survival benefit already seen with sorafenib. Gemcitabine and cisplatin are agents commonly used for systemic treatment of this disease and have demonstrated some effectiveness in disease control rate and median time to progression. Gemcitabine/Cisplatin have been used safely in combination with sorafenib in patients with lung cancer.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Sorafenib With Gemcitabine/Cisplatin in Advanced Hepatocellular Carcinoma
Study Start Date : February 2009
Actual Primary Completion Date : October 2014
Actual Study Completion Date : October 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Gemcitabine/Cisiplatin/Sorafenib
All eligible patients will receive intravenous gemcitabine/cisplatin + daily oral sorafenib until disease progression occurs
Drug: Gemcitabine / Cisplatin / Sorafenib
All patients will receive gemcitabine 1000mg/m2 cisplatin 30mg/m2 sorafenib 400mg orally twice daily
Other Names:
  • nexavar - sorafenib
  • gemzar - gemcitabine
  • cisplatin

Primary Outcome Measures :
  1. Safety of the combination of gemcitabine/cisplatin/sorafenib [ Time Frame: one year ]

Secondary Outcome Measures :
  1. Effectiveness of gemcitabine/cisplatin/sorafenib in shrinking tumors extending time to progression of disease [ Time Frame: 6 months ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Hepatocellular carcinoma: diagnosed histologically, cytologically, or clinically by a rising AFP > 500 ng/ml in the setting of cirrhosis and a radiographically compatible lesion.
  • No prior systemic therapy; local therapy such as chemoembolization, radiofrequency ablation or cryoablation is allowed.
  • Measurable disease > 1 cm by CT or MRI. Lesions which have received local therapy do not qualify as measurable target lesions.
  • Age > 18 years old
  • ECOG Performance Status 0 or 1
  • Child-Pugh status A and B
  • Adequate bone marrow, liver and renal function as assessed by the following:

    • Hemoglobin ≥ 9.0 g/dl
    • Absolute neutrophil count (ANC) ≥ 1,250/mm3
    • Platelet count ≥ 80,000/mm3
    • Total bilirubin ≤ 3.0 mg/dl
    • ALT and AST ≤ 5 times the ULN
    • Amylase and lipase ≤ 1.5 times ULN
    • Creatinine ≤ 1.5 times ULN
  • Resolution of all acute toxic effects of any prior local treatment to CTC Adverse Events grade £1.
  • 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 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 < 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR or PT and PTT should be measured prior to initiation of sorafenib and monitored at Day 1 and Day 8 of each cycle.

Exclusion Criteria:

  • Prior surgery, radiation or local therapy within 4 weeks.
  • Prior treatment with either sorafenib, gemcitabine, or cisplatin
  • 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.
  • Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
  • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
  • Uncontrolled hypertension defined as sustained 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.
  • Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
  • Serious non-healing wound, ulcer, or bone fracture.
  • Evidence or history of bleeding diathesis or coagulopathy
  • Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
  • Use of St. John's Wort or rifampin (rifampicin).
  • Known or suspected allergy to sorafenib, cisplatin, or gemcitabine.
  • Any condition that impairs patient's ability to swallow whole pills.
  • Any malabsorption problem.
  • Uncontrolled ascites (defined as not easily controlled with diuretic treatment).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00808145

United States, Massachusetts
Lahey Clinic
Burlington, Massachusetts, United States, 01805
Sponsors and Collaborators
Lahey Clinic
Principal Investigator: Keith E. Stuart, M.D. Lahey Clinic

Responsible Party: Lahey Clinic Identifier: NCT00808145     History of Changes
Other Study ID Numbers: 2008-108
First Posted: December 15, 2008    Key Record Dates
Last Update Posted: October 22, 2014
Last Verified: October 2014

Keywords provided by Lahey Clinic:
Treatment of advanced liver cancer

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Vitamin B Complex
Growth Substances