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

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.