3'-Deoxy-3'-[18F] Fluorothymidine and Fludeoxyglucose F 18 PET Scans in Evaluating Response to Cetuximab, Cisplatin, and Radiation Therapy in Patients With Advanced Cancer of the Oropharynx, Larynx, or Hypopharynx

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Diagnostic procedures, such as 3'-deoxy-3'-[18F] fluorothymidine (FLT) and fludeoxyglucose F 18 (FDG) PET scans, may help doctors predict a patient's response to treatment and help plan the best treatment. PURPOSE: This pilot trial is studying FLT and FDG PET scans to see how well they evaluate response to cetuximab, cisplatin, and radiation therapy in patients with advanced cancer of the oropharynx, larynx, or hypopharynx.

Detailed Description
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
Head and Neck Cancer

Intervention / Treatment
-----------------
* Biological: cetuximab
* Drug: cisplatin
* Genetic: TdT-mediated dUTP nick end labeling assay
* Other: 3'-deoxy-3'-[18F]fluorothymidine
* Other: immunohistochemistry staining method
* Other: laboratory biomarker analysis
* Radiation: fludeoxyglucose F 18
* Radiation: radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed squamous cell carcinoma of the oropharynx, larynx, or hypopharynx Advanced disease Requires chemoradiotherapy PATIENT CHARACTERISTICS: ECOG performance status 0-1 Life expectancy ≥ 16 weeks Weight loss ≤ 10% within the past 3 months Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception ANC ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Total bilirubin ≤ 1.5 times upper limit of normal (ULN) AST ≤ 3 times ULN Hemoglobin ≥ 8 g/dL Creatinine clearance ≥ 40 mL/min No peripheral neuropathy ≥ grade 2 No NYHA class III-IV heart disease No uncontrolled infection No poorly controlled diabetes that would limit the ability to obtain reliable fludeoxyglucose F 18 PET scan results No other severe underlying disease that, in the judgment of the investigator, would preclude study participation PRIOR CONCURRENT THERAPY: More than 2 weeks since prior major surgery and recovered No prior radiotherapy to the planned treatment field No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: cetuximab|nan|
|Drug: cisplatin|nan|
|Genetic: TdT-mediated dUTP nick end labeling assay|nan|
|Other: 3'-deoxy-3'-[18F]fluorothymidine|nan|
|Other: immunohistochemistry staining method|nan|
|Other: laboratory biomarker analysis|nan|
|Radiation: fludeoxyglucose F 18|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in the standard uptake value levels calculated for the identified volumes of interest for FLT and FDG PET scans from baseline to after 2 weeks of cetuximab therapy and from baseline to after 20-30 Gy of radiotherapy |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantified change values (after cetuximab therapy and after 20-30 Gy of radiotherapy) for the FLT and FDG PET scan-based topographic profiles created using the ImQuant software package |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the larynx, recurrent squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the oropharynx