Cetuximab in Treating Patients With Advanced Solid Tumors
RATIONALE: 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.
PURPOSE: This phase I trial is studying the side effects and best dose of cetuximab in treating patients with advanced solid tumors.
Unspecified Adult Solid Tumor, Protocol Specific
Genetic: molecular diagnostic method
Other: immunologic technique
Other: laboratory biomarker analysis
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of the Safety and Tolerability of Four Doses of Cetuximab (C225) in Patients With Advanced Solid Tumors|
- Maximum tolerated dose of cetuximab [ Time Frame: December 2007 ] [ Designated as safety issue: Yes ]
- Safety and tolerability of cetuximab [ Time Frame: December 2007 ] [ Designated as safety issue: Yes ]
- Potential predictors of response using correlative studies [ Time Frame: December 2007 ] [ Designated as safety issue: No ]
- Correlation of efficacy of cetuximab with grade of skin rash [ Time Frame: December 2007 ] [ Designated as safety issue: No ]
- Development of a detailed scale for assessing skin rash [ Time Frame: December 2007 ] [ Designated as safety issue: No ]
|Study Start Date:||December 2004|
|Study Completion Date:||December 2007|
|Primary Completion Date:||November 2007 (Final data collection date for primary outcome measure)|
|Experimental: Phase I dose escalation study||
Dose level 0: cetuximab 400 mg/m2 week 1, 250 mg/m2 weekly; Dose level 1: cetuximab 400 mg/m2 week 1, 300 mg/m2 weekly; Dose level 2: cetuximab 400 mg/m2 week 1, 350 mg/m2 weekly; Dose level 3: cetuximab 400 mg/m2 week 1, 400 mg/m2 weekly
Other Names:Genetic: molecular diagnostic method
Tissue and Blood Specimens; IHC Methodology; IHC Scoring; K-RAS Mutation AnalysisOther: immunologic technique
Peripheral Blood Mononuclear Cells (PBMC)Other: laboratory biomarker analysis
- Determine the maximum tolerated dose of cetuximab in patients with advanced solid tumors.
- 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 rash.
- 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 survival.
- Examine the levels of downstream marker proteins in buccal cells obtained pre- and post-treatment.
- 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 toxicity.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00376727
|United States, California|
|University of California Davis Cancer Center|
|Sacramento, California, United States, 95817|
|Study Chair:||Angela Davies, MD||University of California, Davis|