Clinical trial NCT00483405: Oxaliplatin, Capecitabine, and Cetuximab in Treating Patients With Advanced Liver Cancer
Official title: Phase II Study of Oxaliplatin, Capecitabine, and Cetuximab in Advanced Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Liver Cancer
Keywords: advanced adult primary liver cancer
localized unresectable adult primary liver cancer
recurrent adult primary liver cancer
adult primary hepatocellular carcinoma
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Sanofi
name: Roche Pharma AG
name: Bristol-Myers Squibb
name: National Center for Research Resources (NCRR)
name: National Cancer Institute (NCI)
First posted: 2007-06-07
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Disease Response Rate
timeFrame: 42 days (2 cycles)
Secondary outcomes:
measure: Number of Subjects Experiencing Adverse Events
timeFrame: every 3 weeks of treatment with an average of 15 weeks on treatment
measure: Overall Survival
timeFrame: Median 23 month follow-up
measure: Time to Progression
timeFrame: Median 23 month follow-up
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Bert H. O'Neil, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Michael A. Morse, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sanoff HK, Bernard S, Goldberg RM, Morse MA, Garcia R, Woods L, Moore DT, O'Neil BH. Phase II Study of Capecitabine, Oxaliplatin, and Cetuximab for Advanced Hepatocellular Carcinoma. Gastrointest Cancer Res. 2011 May;4(3):78-83.