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

Mayo Clinic

Status and phase: Completed; Early Phase 1

Conditions: Head and Neck Cancer

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00757549

P30CA015083 (U.S. NIH Grant/Contract)

NCI-2009-01193 (Registry Identifier)

08-002166 (Other Identifier)

MC057M (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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)