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A Phase II Study of Sorafenib With Gemcitabine/Cisplatin in Advanced Hepatocellular Carcinoma

Phase 2
18 Years
80 Years
Open (Enrolling)
Hepatocellular Carcinoma

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Trial Information

A Phase II Study of Sorafenib With Gemcitabine/Cisplatin in Advanced Hepatocellular Carcinoma

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.

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

- 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).

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety of the combination of gemcitabine/cisplatin/sorafenib

Outcome Time Frame:

one year

Safety Issue:


Principal Investigator

Keith E. Stuart, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Lahey Clinic


United States: Institutional Review Board

Study ID:




Start Date:

February 2009

Completion Date:

December 2013

Related Keywords:

  • Hepatocellular Carcinoma
  • Treatment of advanced liver cancer
  • Carcinoma
  • Carcinoma, Hepatocellular



Lahey Clinic Burlington, Massachusetts  01805