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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00757549
First received: September 22, 2008
Last updated: March 20, 2014
Last verified: March 2014
  Purpose

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 phase II 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.


Condition Intervention Phase
Head and Neck Cancer
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
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Diagnostic
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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: September 2008
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00757549

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Jann N. Sarkaria, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Jann N. Sarkaria, M.D., Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier: NCT00757549     History of Changes
Other Study ID Numbers: MC057M, P30CA015083, MC057M, 08-002166, NCI-2009-01193
Study First Received: September 22, 2008
Last Updated: March 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
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

Additional relevant MeSH terms:
Head and Neck Neoplasms
Oropharyngeal Neoplasms
Neoplasms by Site
Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Cetuximab
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 23, 2014