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

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
Phase II Study of Oxaliplatin, Capecitabine, and Cetuximab in Advanced Hepatocellular Carcinoma

Conditions
-----------------
Liver Cancer

Intervention / Treatment
-----------------
* Biological: cetuximab
* Drug: capecitabine
* Drug: oxaliplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
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 central nervous system (CNS) metastases (unless CNS metastases stable for > 3 months) PATIENT CHARACTERISTICS: Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Absolute neutrophil count (ANC) ≥ 1,500/mm³ Hemoglobin ≥ 9 g/dL Platelet count ≥ 100,000/mm³ Bilirubin ≤ 3 times ULN International normalized ratio (INR) ≤ 1.5 Aspartate aminotransferase (AST) and alanine aminotransferase (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 epidermal growth factor receptor (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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Single Arm Trial<br>Single Arm Trial | Biological: cetuximab<br>* 250 mg/m2, intravenously, once per week<br>* Other names: Erbitux;Drug: capecitabine<br>* 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.<br>* Other names: Xeloda;Drug: oxaliplatin<br>* 130 mg/m2, intravenously on Day 1 of each 21 day cycle<br>* Other names: Eloxatin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Response Rate | Radiographic response will be measured every six weeks while subject is on treatment. Response will be measured using RECIST criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. | 42 days (2 cycles) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Experiencing Adverse Events | Adverse events will be assessed using CTCAE criteria. | every 3 weeks of treatment with an average of 15 weeks on treatment | 
| Overall Survival | Overall survival will be calculated from time of enrollment to death or last contact date. | Median 23 month follow-up | 
| Time to Progression | Time to progression will be calculated from the time of enrollment until confirmed disease progression. Defined by RECIST (Response Evaluation Criteria in Solid Tumors), Progressive Disease (PD) - at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions. | Median 23 month follow-up | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
advanced adult primary liver cancer, localized unresectable adult primary liver cancer, recurrent adult primary liver cancer, adult primary hepatocellular carcinoma