Phase II Study of Single-Agent Cetuximab for Treatment of High-Risk Pre-malignant Upper Aerodigestive Lesions
- To determine the histologic response rate in patients with high-risk, premalignant
lesions of the upper aerodigestive tract treated with cetuximab.
- To determine the clinical response rate in these patients.
- To determine if patterns of EGFR component expression are altered in these patients.
- To determine the change in status of genetic alterations, including loss of
heterozygosity, in these patients.
OUTLINE: This is a multicenter study. Patients are stratified by lesion type (diffuse
dysplasia vs recurrent dysplasia vs dysplastic lesions with 3p or 9p loss of heterozygosity
[LOH]). Patients are randomized to 1 of 2 arms.
- Arm I (treatment): Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22,
29, 36, 43, and 50 in the absence of disease progression or unacceptable toxicity.
- Arm II (control): Patients receive regular follow-up care. Patients have the option of
receiving cetuximab after completion of the study.
In both arms, patients with persistent or recurrent high-grade dysplasia or dysplastic
lesions with 3p or 9p LOH undergo surgical resection, if feasible, after week 8.
Tumor biopsy samples are obtained at baseline* and after week 8 for histologic and biomarker
correlative studies. Tissue samples are analyzed by histopathology to determine histologic
changes in post-treatment lesions and by IHC to measure expression and activation of EGFR
signaling pathway components. LOH studies are also performed.
NOTE: *Paraffin-embedded tissue from the original diagnostic biopsy may be used for baseline
assessment, if the diagnostic biopsy was performed within 3 months prior to study entry.
After completion of study therapy, patients are followed at approximately 1 month, every 3
months for 2 years, and then every 6 months for up to 5 years as per routine standard of
Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Objective response based on histologic grade
End of Treatment of Observation
Joseph Califano, MD
Sidney Kimmel Comprehensive Cancer Center
United States: Food and Drug Administration
|University of Michigan Comprehensive Cancer Center||Ann Arbor, Michigan 48109-0752|
|University of Chicago Cancer Research Center||Chicago, Illinois 60637|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|
|NYU Cancer Institute at New York University Medical Center||New York, New York 10016|
|Hollings Cancer Center at Medical University of South Carolina||Charleston, South Carolina 29425|
|Greenebaum Cancer Center at University of Maryland Medical Center||Baltimore, Maryland 21201|
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|
|Lucille P. Markey Cancer Center at University of Kentucky||Lexington, Kentucky 40536-0093|
|UPMC Cancer Centers||Pittsburgh, Pennsylvania 15232|