A Phase I Study of the Safety and Tolerability of Four Doses of Cetuximab (C225) in Patients With Advanced Solid Tumors
- Determine the maximum tolerated dose of cetuximab in patients with advanced solid
- Evaluate the safety and tolerability of this drug in these patients.
- Develop a detailed scale for assessment of rash in these patients.
- Investigate potential predictors of response using correlative studies on patient
tissue, buccal mucosa, and blood samples.
- Obtain preliminary efficacy data and evaluate the relationship of efficacy to grade of
- Correlate downstream markers (e.g., pMAPK, pAKT, and Ki-67) and the presence of
epidermal growth factor receptor (EGFR) polymorphisms with clinical response and/or
- Examine the levels of downstream marker proteins in buccal cells obtained pre- and
- Correlate basal p27 expression levels with response and/or survival.
- Determine if the presence of a K-RAS mutation influences response or survival outcome.
- Correlate the presence or absence of mutant K-RAS tumor DNA shed into patient plasma
with response and/or outcome.
- Correlate levels of cytokines and chemokines with rash and clinical response.
OUTLINE: This is an open-label, dose-escalation study.
Patients receive cetuximab IV over 90 minutes once weekly for 4 weeks. Treatment repeats
every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable
Cohorts of 3-6 patients receive escalating doses of cetuximab until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
Patients undergo blood and buccal mucosa collection at baseline and prior to courses 2 and 3
of treatment for molecular correlative studies. Archival tumor tissue specimens are also
used for molecular correlative studies. Immunologic correlative studies are performed using
patient blood samples.
After completion of study treatment, patients are followed periodically for survival.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of cetuximab
Angela Davies, MD
University of California, Davis
United States: Food and Drug Administration
|University of California Davis Cancer Center||Sacramento, California 95817|