This phase I trial is studying the side effects and best dose of cixutumumab when given together with sorafenib tosylate in treating patients with advanced liver cancer. Monoclonal antibodies, such as cixutumumab, 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. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cixutumumab together with sorafenib tosylate may kill more tumor cells.
PRIMARY OBJECTIVES: I. To establish the maximum tolerated dose (MTD) of IMC-A12 given in conjunction with standard doses of sorafenib to patients with advanced hepatocellular carcinoma (HCC). II. To describe the toxicity and tolerance of IMC-A12 at each dose studied in combination with standard-dose sorafenib in patients with advanced HCC. III. To evaluate the impact of IMC-A12 on biomarkers related to the IGF-1R/IGF pathway which is thought relevant to HCC progression and drug resistance. IV. To obtain preliminary assessments of efficacy through description of progression-free survival (PFS) and objective response rate (RR). OUTLINE: This is a multicenter, dose-escalation study of cixutumumab followed by an extended accrual phase in which patients are treated at the maximum-tolerated dose. Patients receive cixutumumab IV over 1 hour on days 1, 8, 15, and 22 and oral sorafenib tosylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up periodically.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
21
City of Hope Comprehensive Cancer Center
Duarte, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
Penn State Hershey Cancer Institute-Clinical Trials Office
Hershey, Pennsylvania, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States
MTD defined as the highest IMC-A12 dose tested in which none or only one patient had a dose-limiting toxicity (DLT) attributed to IMC-A12 as assessed by NCI CTCAE version 4.0
The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by CTCAE and nadir or maximum values for the laboratory measures), time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.
Time frame: First 1 month of therapy
Toxicities and tolerability of this regimen as assessed by NCI CTCAE version 4.0
Time frame: 30 days
Impact of cixutumumab on biomarkers related to the IGF-1R/IGF pathway
Time frame: From baseline to up to 5 years
Objective response rate according to RECIST
Time frame: Up to 5 years
Progression-free rate according to the Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: Up to 5 years
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