Oxaliplatin, Capecitabine, and Cetuximab in Treating Patients With Advanced Liver Cancer

• Number of subjects experiencing adverse events [ Time Frame: every 3 weeks of treatment ] [ Designated as safety issue: Yes ]
  Adverse events will be assessed using CTCAE critera.
• Overall Survival [ Time Frame: time of enrollment until death ] [ Designated as safety issue: No ]
  Overall survival will be calculated from time of enrollment to death or last contact date.
• Time to progression [ Time Frame: Enrollment until confirmed disease progression ] [ Designated as safety issue: No ]
  Time to progression will be calculated from the time of enrollment until confirmed disease progression

• Safety every 3 weeks during treatment
• Survival
• Time to progression

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving chemotherapy together with a monoclonal antibody may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving oxaliplatin and capecitabine together with cetuximab works in treating patients with advanced liver cancer.

OBJECTIVES:

Primary

• Determine the response rate in patients with advanced hepatocellular carcinoma and hepatic dysfunction treated with oxaliplatin, capecitabine, and cetuximab.

Secondary

• Determine the safety of this regimen in these patients.
• Determine the overall survival of patients treated with this regimen.
• Determine the time to tumor progression in patients treated with this regimen.

OUTLINE: This is an open label, nonrandomized study.

Patients receive oral capecitabine twice daily on days 1-14, cetuximab IV over 60-120 minutes on days 1, 8, and 15, and oxaliplatin IV over 120 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 3-4 weeks and then every 3 months thereafter.

• Biological: cetuximab
  250 mg/m2, intravenously, once per week
  Other Name: Erbitux
• Drug: capecitabine
  850 mg/m2, orally, twice daily (dose rounded to accommodate 150 mg and 500 mg tablet sizes. Capecitabine given on days 1-14 of 21 day cycle.
  Other Name: Xeloda
• Drug: oxaliplatin
  130 mg/m2, intravenously on Day 1 of each 21 day cycle
  Other Name: Eloxatin

DISEASE CHARACTERISTICS:

• Meets 1 of the following criteria:

  • Histologically confirmed hepatocellular carcinoma
  • Alpha-fetoprotein (AFP) > 400 ng/mL with compatible mass by CT scan or MRI
• Metastatic disease OR not a candidate for surgical resection or immediate liver transplantation
• At least 1 site of measurable disease OR evaluable disease (AFP 2 times upper limit of normal [ULN])
• No evidence of CNS metastases (unless CNS metastases stable for > 3 months)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• ANC ≥ 1,500/mm³
• Hemoglobin ≥ 9 g/dL
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 3 times ULN
• INR ≤ 1.5
• AST and ALT ≤ 5 times ULN
• Creatinine clearance > 50 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known hypersensitivity to capecitabine, cetuximab, or oxaliplatin or to other murine products
• No comorbid condition which is deemed by the investigator to have a life expectancy of < 6 months
• No New York Heart Association class III-IV coronary artery disease and/or heart failure
• No variceal bleeding within the past 60 days
• No other cancer within the past 5 years except cervical intraepithelial neoplasia, nonmelanoma skin cancer, ductal carcinoma in situ, chronic lymphocytic leukemia, or treated localized prostate cancer with a normal prostate specific antigen level
• No active drug or alcohol abuse
• No prior allergic reaction to a therapeutic antibody
• No serious, uncontrolled infection
• No history of uncontrolled seizures, CNS disorders, or psychiatric disability that, in the opinion of the investigator, would preclude study participation or compliance
• No other serious uncontrolled medical condition that, in the opinion of the investigator, would preclude study participation
• No lack of physical integrity of the upper gastrointestinal tract
• No malabsorption syndrome
• No known existing uncontrolled coagulopathy

PRIOR CONCURRENT THERAPY:

• At least 4 weeks since prior participation in an investigational drug trial
• At least 4 weeks since prior major surgery and recovered
• At least 4 weeks since prior embolization, resection, or ablation
• No prior EGFR-targeting therapy
• No prior systemic chemotherapy or hepatic artery infusion of chemotherapy
• No concurrent phenytoin

• No concurrent therapeutic warfarin

  • Low-dose non-therapeutic warfarin to maintain patency of venous access devices allowed