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F-18 Fluorothymidine PET Imaging for Early Evaluation of Response to Therapy in Head & Neck Cancer Patients

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00721799
First Posted: July 24, 2008
Last Update Posted: October 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Cancer Institute (NCI)
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Yusuf Menda, University of Iowa
  Purpose

This is an imaging protocol only, not a therapeutic study.

The primary goal of the proposed study is to examine the utility of a new imaging study, Positron Emission Tomography with F-18 Fluorothymidine (FLT PET), in the early treatment evaluation of head and neck cancer. FLT uptake in the tumor correlates with the rate of cell proliferation. It is therefore hoped that changes in tumor FLT uptake after therapy will reflect change in the number of actively dividing tumor cells and will provide early assessment of treatment response.

Research subjects will undergo one PET scan with FLT. The scan is done prior to any therapeutic intervention (radiation or chemotherapy) can be obtained up to 30 days prior to the start of therapy. The uptake of FLT in the tumor will be analyzed to see if it can be used as a predictor of treatment efficacy and/or outcome.

There is an optional biopsy component to this study. Should the attending physicians (primarily the otolaryngologists) believe that the subject can safely undergo an outpatient biopsy, and the subject agrees, a biopsy is performed. The biopsy will be done within 30 days prior to treatment, similar to FLT PET scans. Tissue from the biopsy will be analyzed for markers of cellular proliferation and these markers will be correlated with the findings of FLT PET scan.

There will be a 2-year clinical follow-up to assess for treatment outcomes, local control, and overall survival.


Condition Intervention Phase
Mouth Neoplasms Oropharyngeal Neoplasms Laryngeal Neoplasms Head and Neck Neoplasms Drug: 18F-Fluorothymidine PET scan Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: F-18 Fluorothymidine (FLT) PET Imaging for Early Evaluation of Response to Chemoradiation Therapy in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC)

Resource links provided by NLM:


Further study details as provided by Yusuf Menda, University of Iowa:

Primary Outcome Measures:
  • Efficacy of Mean Pre-therapy FLT Uptake (SUVmean) in Predicting Progression Free Survival (PFS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Progression free survival is defined as the span of time from day 1 of therapy to date of disease recurrence (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 27 subjects analyzed.

  • Efficacy of Maximum Pre-therapy FLT Uptake (SUVmax) in Predicting Progression Free Survival (PFS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Progression free survival is defined as the span of time from day 1 of therapy to date of disease recurrence (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 27 subjects analyzed.

  • Efficacy of Pre-therapy Metabolic Tumor Volume in Predicting Progression Free Survival (PFS) [ Time Frame: 36 months ]
    Metabolic tumor volume using the FLT PET tracer. Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Progression free survival is defined as the span of time from day 1 of therapy to date of disease recurrence (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 27 subjects analyzed.

  • Efficacy of FLT Flux (K-FLT) Pre-therapy in Predicting Progression Free Survival (PFS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Progression free survival is defined as the span of time from day 1 of therapy to date of disease recurrence (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 27 subjects analyzed. FLT uptake in the tumor is a dynamic process that involves facilitated diffusion in and out of the cell and molecular changes in FLT. The rate, measured in mL/g/min, is a composite of the rate of transport of FLT from blood into the tissue and the transfer from tissue back into the blood, as well as the rate of molecular change of FLT.

  • Efficacy of the Patlak Influx Rate Constant for FLT (K-Patlak) Pre-therapy in Predicting Progression Free Survival (PFS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Progression free survival is defined as the span of time from day 1 of therapy to date of disease recurrence (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 27 subjects analyzed. The Patlak influx rate, measured in l /min, is the rate of transport of FLT from blood into the tissue as well as the rate of molecular change of FLT, using a Patlak analysis.

  • Efficacy of Pretherapy Total Lesion Proliferation in Predicting Progression Free Survival (PFS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Progression free survival is defined as the span of time from day 1 of therapy to date of disease recurrence (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 27 subjects analyzed.

  • Efficacy of Mean Mid-therapy FLT Uptake (SUVmean) in Predicting Progression Free Survival (PFS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Progression free survival is defined as the span of time from day 1 of therapy to date of disease recurrence (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 25 subjects analyzed.

  • Efficacy of Maximum Mid-therapy FLT Uptake (SUVmax) in Predicting Progression Free Survival (PFS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Progression free survival is defined as the span of time from day 1 of therapy to date of disease recurrence (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 25 subjects analyzed.

  • Efficacy of FLT Flux (K-FLT) Mid-therapy in Predicting Progression Free Survival (PFS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Progression free survival is defined as the span of time from day 1 of therapy to date of disease recurrence (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 25 subjects analyzed. FLT uptake in the tumor is a dynamic process that involves facilitated diffusion in and out of the cell and molecular changes in FLT. The rate, measured in mL/g/min, is a composite of the rate of transport of FLT from blood into the tissue and the transfer from tissue back into the blood, as well as the rate of molecular change of FLT.

  • Efficacy of the Patlak Influx Rate Constant for FLT (K-Patlak) Mid-therapy in Predicting Progression Free Survival (PFS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Progression free survival is defined as the span of time from day 1 of therapy to date of disease recurrence (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 25 subjects analyzed. The Patlak influx rate, measured in l /min, is the rate of transport of FLT from blood into the tissue as well as the rate of molecular change of FLT, using a Patlak analysis.

  • Efficacy of Mid-therapy Total Lesion Proliferation in Predicting Progression Free Survival (PFS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Progression free survival is defined as the span of time from day 1 of therapy to date of disease recurrence (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 25 subjects analyzed.

  • Efficacy of Percent Change in Mean FLT Uptake (SUVmean) Between Scan 1 & 2 in Predicting Progression Free Survival (PFS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Progression free survival is defined as the span of time from day 1 of therapy to date of disease recurrence (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 25 subjects analyzed.

  • Efficacy of Percent Change in Maximum FLT Uptake (SUVmax) Between Scans 1 & 2 in Predicting Progression Free Survival (PFS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Progression free survival is defined as the span of time from day 1 of therapy to date of disease recurrence (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 25 subjects analyzed.

  • Efficacy of Percent Change in FLT Flux (K-FLT) Between Scans 1 & 2 in Predicting Progression Free Survival (PFS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Progression free survival is defined as the span of time from day 1 of therapy to date of disease recurrence (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 25 subjects analyzed.

  • Efficacy of Percent Change the Patlak Influx Rate Constant for FLT (K-Patlak) Between Scans 1 & 2 in Predicting Progression Free Survival (PFS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Progression free survival is defined as the span of time from day 1 of therapy to date of disease recurrence (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 25 subjects analyzed.

  • Efficacy of Percent Change in the Total Lesion Proliferation Between Scans 1 & 2 in Predicting Progression Free Survival (PFS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Progression free survival is defined as the span of time from day 1 of therapy to date of disease recurrence (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 25 subjects analyzed.

  • Efficacy of Mean Pre-therapy FLT Uptake (SUVmean) in Predicting Overall Survival (OS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Overall survival is defined as the span of time from day 1 of therapy to date of death from any cause (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 27 subjects analyzed.

  • Efficacy of Maximum Pre-therapy FLT Uptake (SUVmax) in Predicting Overall Survival (OS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Progression free survival is defined as the span of time from day 1 of therapy to date of death from any cause (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 27 subjects analyzed.

  • Efficacy of Pre-therapy Metabolic Tumor Volume in Predicting Overall Survival (OS) [ Time Frame: 36 months ]
    Metabolic tumor volume using the FLT PET tracer. Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Overall survival is defined as the span of time from day 1 of therapy to date of death from any cause (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 27 subjects analyzed.

  • Efficacy of FLT Flux (K-FLT) Pre-therapy in Predicting Overall Survival (OS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Overall survival is defined as the span of time from day 1 of therapy to date of death from any cause (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 27 subjects analyzed. FLT uptake in the tumor is a dynamic process that involves facilitated diffusion in and out of the cell and molecular changes in FLT. The rate K-FLT, measured in mL/g/min, is a composite of the rate of transport of FLT from blood into the tissue and the transfer from tissue back into the blood, as well as the rate of molecular change of FLT.

  • Efficacy of the Patlak Influx Rate Constant for FLT (K-Patlak) Pre-therapy in Predicting Overall Survival (OS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Overall survival is defined as the span of time from day 1 of therapy to date of death from any cause (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 27 subjects analyzed. The Patlak influx rate, measured in l /min, is the rate of transport of FLT from blood into the tissue as well as the rate of molecular change of FLT, using a Patlak analysis.

  • Efficacy of Pretherapy Total Lesion Proliferation in Predicting Overall Survival (OS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Overall survival is defined as the span of time from day 1 of therapy to date of death from any cause (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 27 subjects analyzed.

  • Efficacy of Mean Mid-therapy FLT Uptake (SUVmean) in Predicting Overall Survival (OS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Overall survival is defined as the span of time from day 1 of therapy to date of death from any cause (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 25 subjects analyzed.

  • Efficacy of Maximum Mid-therapy FLT Uptake (SUVmax) in Predicting Overall Survival (OS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Overall survival is defined as the span of time from day 1 of therapy to date of death from any cause (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 25 subjects analyzed.

  • Efficacy of FLT Flux (K-FLT) Mid-therapy in Predicting Overall Survival (OS). [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat).Overall survival is defined as the span of time from day 1 of therapy to date of death from any cause (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 25 subjects analyzed. FLT uptake in the tumor is a dynamic process that involves facilitated diffusion in and out of the cell and molecular changes in FLT. The rate K-FLT, measured in mL/g/min, is a composite of the rate of transport of FLT from blood into the tissue and the transfer from tissue back into the blood, as well as the rate of molecular change of FLT.

  • Efficacy of the Patlak Influx Rate Constant for FLT (K-Patlak) Mid-therapy in Predicting Overall Survival (OS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Overall survival is defined as the span of time from day 1 of therapy to date of death from any cause (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 25 subjects analyzed. The Patlak influx rate, measured in l /min, is the rate of transport of FLT from blood into the tissue as well as the rate of molecular change of FLT, using a Patlak analysis.

  • Efficacy of Mid-therapy Total Lesion Proliferation in Predicting Overall Survival (OS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Overall survival is defined as the span of time from day 1 of therapy to date of death from any cause (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 25 subjects analyzed.

  • Efficacy of Percent Change in Mean FLT Uptake (SUVmean) in Predicting Overall Survival (OS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Overall survival is defined as the span of time from day 1 of therapy to date of death from any cause (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 25 subjects analyzed.

  • Efficacy of Percent Change in Maximum FLT Uptake (SUVmax) in Predicting Overall Survival (OS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Overall survival is defined as the span of time from day 1 of therapy to date of death from any cause (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 25 subjects analyzed.

  • Efficacy of Percent Change in FLT Flux (K-FLT) in Predicting Overall Survival (OS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Overall survival is defined as the span of time from day 1 of therapy to date of death from any cause (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 25 subjects analyzed.

  • Efficacy of Percent Change the Patlak Influx Rate Constant for FLT (K-Patlak) in Predicting Overall Survival (OS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Overall survival is defined as the span of time from day 1 of therapy to date of death from any cause (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 25 subjects analyzed.

  • Efficacy of Percent Change in the Total Lesion Proliferation in Predicting Overall Survival (OS) [ Time Frame: 36 months ]
    Prediction efficacy is estimated using a hazard ratio (HR) and C-statistic (C-stat). Overall survival is defined as the span of time from day 1 of therapy to date of death from any cause (measured in months). Results are pooled with subjects from a pilot RDRC study for a total of 25 subjects analyzed.


Enrollment: 33
Actual Study Start Date: March 2008
Estimated Study Completion Date: June 2020
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FLT PET scan

Subjects receive 2 18F-Fluorothymidine PET scans

  • Scan 1 at baseline (within 30 days prior to the start of chemotherapy and radiation therapy)
  • Scan 2 between fraction 5 and 6 of radiation therapy (after 10 Gray of radiation)
Drug: 18F-Fluorothymidine PET scan
18F-Fluorothymidine (0.04 - 0.08 mCi / kg to a maximum dose of 5 mCi) administered once intravenously for a positron emission tomography (PET) scan.
Other Names:
  • FLT
  • FLT PET scan

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ability to understand and willingness to sign a written informed consent document.
  • Subject must have histologically confirmed squamous cell carcinoma of the head and neck.
  • Subject must be scheduled to receive combined chemo-radiotherapy treatment for their standard cancer care. Treatment decisions will be made by the treating otolaryngologist, radiation, and medical oncologists.
  • Male or females ≥ 18 years of age. Squamous cell cancer of the head and neck is exceedingly rare in children and not generally applicable to the pediatric population.
  • Karnofsky greater than or equal to 60% at time of screening.
  • Life expectancy of greater than 6 months.
  • Subject must have normal organ and marrow function (as defined below) within 30 days of study enrollment:
  • leukocytes ≥ 3,000/μL
  • absolute neutrophil count ≥1,500/μL
  • platelets ≥ 100,000/μL
  • total bilirubin ≤ 1.0 mg/dl*
  • Either AST OR ALT ≤ 2.5 X institutional upper limit of normal
  • creatinine ≤ 1.5 x institutional upper limit of normal
  • PT and PTT (if biopsy is to be performed) < 2.0 X upper normal limits
  • The effects of FLT on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A screening urine hCG will be administered in the Nuclear Medicine to women of childbearing potential before each FLT scan and pregnant women will not be accepted as subjects in this study.

Exclusion Criteria:

  • Subjects who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
  • Subject may not be receiving any other investigational agents.
  • Subject with a Karnofsky score of below 60.
  • Pregnant women are excluded from this study. FLT PET has potential for teratogenic effects. Because there are potentially unknown risks for adverse events in nursing infants secondary to treatment of the mother with FLT, breastfeeding should be discontinued if the mother is imaged with FLT and may not resume for 48 hours after the FLT imaging.
  • Subjects taking nucleoside analog medications such as those used as antiretroviral agents.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00721799


Locations
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
Sponsors and Collaborators
University of Iowa
National Cancer Institute (NCI)
National Institutes of Health (NIH)
Investigators
Principal Investigator: Yusuf Menda, M.D. The University of Iowa
Principal Investigator: John M. Buatti, M.D. The University of Iowa
  More Information

Additional Information:
Publications:
Responsible Party: Yusuf Menda, Associate Professor, Radiology-Nuclear Medicine, University of Iowa
ClinicalTrials.gov Identifier: NCT00721799     History of Changes
Other Study ID Numbers: 200801758
1R21CA130281 ( U.S. NIH Grant/Contract )
First Submitted: June 10, 2008
First Posted: July 24, 2008
Results First Submitted: March 29, 2017
Results First Posted: October 3, 2017
Last Update Posted: October 3, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Data will be shared through clinicaltrials.gov and in provision with the filed data sharing plan for the grant. Consent was not obtained from participants to share individual patient data.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Yusuf Menda, University of Iowa:
Positron-Emission Tomography
radiation therapy
cisplatin
chemotherapy
FLT

Additional relevant MeSH terms:
Neoplasms
Head and Neck Neoplasms
Laryngeal Neoplasms
Oropharyngeal Neoplasms
Mouth Neoplasms
Neoplasms by Site
Otorhinolaryngologic Neoplasms
Laryngeal Diseases
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Otorhinolaryngologic Diseases
Pharyngeal Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Mouth Diseases