The purpose of this study is to test the safety of bevacizumab when given in combination with gemcitabine and oxaliplatin and to see what effects (good or bad) it has on patients with hepatocellular carcinoma.

Condition	Intervention	Phase
Hepatocellular Carcinoma	Drug: Gemcitabine  Drug: Oxaliplatin  Drug: Bevacizumab	Phase II

Further Study Details: 

Primary Outcomes: To assess the time to disease progression of gemcitabine, oxaliplatin and bevacizumab regimen in patients with hepatocellular carcinoma.
Secondary Outcomes: To evaluate the side effects of this drug combination in this population of patients as well as the response rate, duration of response and median survival.
Expected Total Enrollment:  30

• Treatment is given in cycles, each cycle (except for cycle 1) is 4 weeks long. Cycle 1 is only 2 weeks long.
• During cycle one only, bevacizumab will be given intravenously on day one. Two weeks after receiving bevacizumab, the patient will return to the clinic for treatment with all 3 study drugs.
• During cycle 2 and every cycle thereafter patients will receive; bevacizumab intravenously on day one and day 15; gemcitabine intravenously on day 2 and day 16; oxaliplatin intravenously on day 2 and day 16.
• The following evaluations will be conducted on day 1 and day 15 of each cycle (once every 2 weeks): physical examination, vital signs, medical history, blood tests and urine tests.
• Tumor measurements done by CT and/or MRI will be repeated at the end of cycle 3 and every 2 cycles thereafter.
• Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) of the liver and Perfusions CT scans will also be done on days 10-12 following bevacizumab treatment during cycle 1, and the Perfusion CT will be repeated at the end of cycle 3.
• Once study treatment is stopped the following evaluations will be performed: physical exam, vital signs, blood work, urine tests, CT scan of chest, abdomen and pelvis, and tumor measurements by CT or MRI scans.
• Follow-up will consist of physical examinations and blood tests every 6 months.
• Patients will continue to receive study treatment as long as there is no disease progression or unacceptable side affects.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Unresectable or metastatic hepatocellular carcinoma
• Measurable tumors
• Adequate hepatic function: total bilirubin < 3.0mg/dl; AST < 7x ULN
• Adequate bone marrow function: ANC > 1,000/mm3; platelets > 75,000/mm3
• INR < 1.5 for those who are not on anticoagulation
• Up to two prior chemotherapy regimens for hepatocellular carcinoma
• 18 years of age or older
• ECOG performance status of 0-1
• Life expectancy of > 12 weeks

Exclusion Criteria:

• Clinically apparent central nervous system metastases or carcinomatous meningitis
• Uncontrolled serious medical or psychiatric illness
• Pregnant or lactating women
• Current or recent (within 4 weeks of first study infusion) participation in experimental study drug
• Uncontrolled hypertension
• Significant proteinuria
• Serious, non-healing wound, ulcer, or bone fracture
• Evidence of bleeding diathesis or coagulopathy

Massachusetts
      Massachusetts General Hospital, Boston,  Massachusetts,  02114,  United States
      Dana-Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02115,  United States

Study chairs or principal investigators

Andrew Zhu, MD,  Principal Investigator,  Massachusetts General Hospital   

Study ID Numbers:  03-390
Last Updated:  September 1, 2005
Record first received:  August 31, 2005
ClinicalTrials.gov Identifier:  NCT00142467
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-09-13