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
Condition: Head and Neck Cancer
MeSH terms: Head and Neck Neoplasms
Study type: Interventional
Phase: Early Phase 1

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.
    

Intervention name(s): cetuximab; cisplatin; TdT-mediated dUTP nick end labeling assay; 3'-deoxy-3'-[18F]fluorothymidine; immunohistochemistry staining method; laboratory biomarker analysis; fludeoxyglucose F 18; radiation therapy
Intervention type(s): Biological; Drug; Genetic; Other; Other; Other; Radiation; Radiation
Intervention MeSH terms: Cetuximab; Fluorodeoxyglucose F18
Primary purpose: Diagnostic
Keywords: 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