A Phase I Trial of Escalating Doses of the Anti-IGF-1R Monoclonal Antibody IMC-A12 and Standard Dose Sorafenib for Treatment of Advanced Hepatocellular Carcinoma
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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
First 1 month of therapy
UC Davis Comprehensive Cancer Center
United States: Food and Drug Administration
|UC Davis Comprehensive Cancer Center||Sacramento, California 95817|