Trial Information

Comparison of FLT and FDG PET in the Evaluation of Response to Cetuximab, Cisplatin and Radiation Therapy in Advanced Head and Neck Malignancies or Response to Standard Chemo-radiotherapy in Esophageal Malignancies

OBJECTIVES:

Primary

- To assess whether 3'-deoxy-3'-[18F] fluorothymidine (FLT) and fludeoxyglucose F 18
(FDG) PET scans can be used to identify patients with advanced squamous cell carcinoma
of the oropharynx, larynx, or hypopharynx who have a biochemical response after 2 weeks
of induction therapy with cetuximab.

- To assess whether FLT and FDG PET imaging-based response after 20-30 Gy of radiotherapy
is predictive of disease control at 6 months after completion of therapy.

Secondary

- To assess whether FLT and FDG PET imaging-based response after cetuximab therapy and/or
20-30 Gy of radiotherapy is predictive of pathologic complete response in these
patients.

- To assess whether FLT and FDG PET imaging-based response after cetuximab therapy and/or
20-30 Gy of radiotherapy is predictive of disease-free survival at 2 years in these
patients.

- To correlate suppression of FLT uptake after cetuximab therapy with thymidine kinase 1
activity and/or expression, proliferation, microvessel density, apoptosis, and
signaling pathway analyses.

- To correlate suppression of FDG uptake after cetuximab therapy with expression of
hexokinases, glucose transporter proliferation, microvessel density, apoptosis, and
signaling pathway analyses.

- To test and refine the ability of a novel commercial software package to quantify
treatment-induced structural and functional/molecular volumetric and sub-volumetric
change.

- To develop a working method for expressing change and predicting outcome.

OUTLINE: Patients receive cetuximab IV on days 1 and 8 of course 1. Beginning in course 2
and all subsequent courses, patients receive cetuximab IV and cisplatin IV over 2 hours on
day 1 and undergo radiotherapy once daily 5 days a week for 7 weeks. Treatment repeats every
7 days for a total of 8 courses in the absence of disease progression or unacceptable
toxicity.

Patients undergo 3'-deoxy-3'-[18F] fluorothymidine and fludeoxyglucose F 18 (FDG) PET scans
at baseline, after the second dose of cetuximab, after 20-30 Gy of radiotherapy, and then at
6 weeks and 6 months after completion of radiotherapy.

Patients undergo tumor tissue biopsies at baseline and after the first dose of cetuximab for
correlative laboratory studies. Samples are analyzed for proliferation (Ki-67 labeling
index), microvessel density (CD-31 staining), apoptosis (TUNEL assay and caspase-3 by IHC)
signaling pathway (expression of EGFR, AKT, and MAPK by IHC), molecules affecting FDG uptake
(expression of GLUT1, GLUT3, and hexokinase by IHC), and thymidine kinase 1 activity or
expression.

After completion of study treatment, patients are followed every 3 months for up to 5 years.