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

NCT00721799 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2008017581R21CA130281
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mouth Neoplasms; Oropharyngeal Neoplasms; Laryngeal Neoplasms; Head and Neck Neoplasms

Keywords

Positron-Emission Tomography; radiation therapy; cisplatin; chemotherapy; FLT

Outcome Measures

Primary Outcomes (32)

• Efficacy of Mean Pre-therapy FLT Uptake (SUVmean) in Predicting Progression Free Survival (PFS)

  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.

  36 months

• Efficacy of Maximum Pre-therapy FLT Uptake (SUVmax) in Predicting Progression Free Survival (PFS)

  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.

  36 months

• Efficacy of Pre-therapy Metabolic Tumor Volume in Predicting Progression Free Survival (PFS)

  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.

  36 months

• Efficacy of FLT Flux (K-FLT) Pre-therapy in Predicting Progression Free Survival (PFS)

  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.

  36 months

• Efficacy of the Patlak Influx Rate Constant for FLT (K-Patlak) Pre-therapy in Predicting Progression Free Survival (PFS)

  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.

  36 months

• Efficacy of Pretherapy Total Lesion Proliferation in Predicting Progression Free Survival (PFS)

  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.

  36 months

• Efficacy of Mean Mid-therapy FLT Uptake (SUVmean) in Predicting Progression Free Survival (PFS)

  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.

  36 months

• Efficacy of Maximum Mid-therapy FLT Uptake (SUVmax) in Predicting Progression Free Survival (PFS)

  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.

  36 months

• Efficacy of FLT Flux (K-FLT) Mid-therapy in Predicting Progression Free Survival (PFS)

  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.

  36 months

• Efficacy of the Patlak Influx Rate Constant for FLT (K-Patlak) Mid-therapy in Predicting Progression Free Survival (PFS)

  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.

  36 months

• Efficacy of Mid-therapy Total Lesion Proliferation in Predicting Progression Free Survival (PFS)

  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.

  36 months

• Efficacy of Percent Change in Mean FLT Uptake (SUVmean) Between Scan 1 & 2 in Predicting Progression Free Survival (PFS)

  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.

  36 months

• Efficacy of Percent Change in Maximum FLT Uptake (SUVmax) Between Scans 1 & 2 in Predicting Progression Free Survival (PFS)

  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.

  36 months

• Efficacy of Percent Change in FLT Flux (K-FLT) Between Scans 1 & 2 in Predicting Progression Free Survival (PFS)

  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.

  36 months

• Efficacy of Percent Change the Patlak Influx Rate Constant for FLT (K-Patlak) Between Scans 1 & 2 in Predicting Progression Free Survival (PFS)

  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.

  36 months

• Efficacy of Percent Change in the Total Lesion Proliferation Between Scans 1 & 2 in Predicting Progression Free Survival (PFS)

  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.

  36 months

• Efficacy of Mean Pre-therapy FLT Uptake (SUVmean) in Predicting Overall Survival (OS)

  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.

  36 months

• Efficacy of Maximum Pre-therapy FLT Uptake (SUVmax) in Predicting Overall Survival (OS)

  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.

  36 months

• Efficacy of Pre-therapy Metabolic Tumor Volume in Predicting Overall Survival (OS)

  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.

  36 months

• Efficacy of FLT Flux (K-FLT) Pre-therapy in Predicting Overall Survival (OS)

  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.

  36 months

• Efficacy of the Patlak Influx Rate Constant for FLT (K-Patlak) Pre-therapy in Predicting Overall Survival (OS)

  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.

  36 months

• Efficacy of Pretherapy Total Lesion Proliferation in Predicting Overall Survival (OS)

  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.

  36 months

• Efficacy of Mean Mid-therapy FLT Uptake (SUVmean) in Predicting Overall Survival (OS)

  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.

  36 months

• Efficacy of Maximum Mid-therapy FLT Uptake (SUVmax) in Predicting Overall Survival (OS)

  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.

  36 months

• Efficacy of FLT Flux (K-FLT) Mid-therapy in Predicting Overall Survival (OS).

  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.

  36 months

• Efficacy of the Patlak Influx Rate Constant for FLT (K-Patlak) Mid-therapy in Predicting Overall Survival (OS)

  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.

  36 months

• Efficacy of Mid-therapy Total Lesion Proliferation in Predicting Overall Survival (OS)

  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.

  36 months

• Efficacy of Percent Change in Mean FLT Uptake (SUVmean) in Predicting Overall Survival (OS)

  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.

  36 months

• Efficacy of Percent Change in Maximum FLT Uptake (SUVmax) in Predicting Overall Survival (OS)

  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.

  36 months

• Efficacy of Percent Change in FLT Flux (K-FLT) in Predicting Overall Survival (OS)

  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.

  36 months

• Efficacy of Percent Change the Patlak Influx Rate Constant for FLT (K-Patlak) in Predicting Overall Survival (OS)

  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.

  36 months

• Efficacy of Percent Change in the Total Lesion Proliferation in Predicting Overall Survival (OS)

  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.

  36 months

Study Arms (1)

FLT PET scan

EXPERIMENTAL

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

Interventions

18F-Fluorothymidine PET scan DRUG

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.

Also known as: FLT, FLT PET scan

FLT PET scan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Iowa: lead
• National Cancer Institute (NCI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Related Publications (3)

• Menda Y, Boles Ponto LL, Dornfeld KJ, Tewson TJ, Watkins GL, Schultz MK, Sunderland JJ, Graham MM, Buatti JM. Kinetic analysis of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) in head and neck cancer patients before and early after initiation of chemoradiation therapy. J Nucl Med. 2009 Jul;50(7):1028-35. doi: 10.2967/jnumed.108.058495. Epub 2009 Jun 12.

  PMID: 19525472 RESULT

• Menda Y, Ponto LL, Dornfeld KJ, Tewson TJ, Watkins GL, Gupta AK, Anderson C, McGuire S, Schultz MK, Sunderland JJ, Graham MM, Buatti JM. Investigation of the pharmacokinetics of 3'-deoxy-3'-[18F]fluorothymidine uptake in the bone marrow before and early after initiation of chemoradiation therapy in head and neck cancer. Nucl Med Biol. 2010 May;37(4):433-8. doi: 10.1016/j.nucmedbio.2010.02.005.

  PMID: 20447554 RESULT

• Juweid ME, Thomas D, Menda Y, Tewson T, Graham MM, Herrmann K, Buck AK, Fayad L. PET/CT with 18F-FLT is unlikely to cause significant hepatorenal or hematologic toxicity. J Nucl Med. 2010 May;51(5):824-5. doi: 10.2967/jnumed.110.075945. No abstract available.

  PMID: 20439512 RESULT

Related Links

• The Holden Comprehensive Cancer Center

MeSH Terms

Conditions

Mouth Neoplasms; Oropharyngeal Neoplasms; Laryngeal Neoplasms; Head and Neck Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Otorhinolaryngologic Diseases; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms

Limitations and Caveats

* HPV (human papilloma virus) status of tumors not available. * Therapy heterogeneity in the therapy; radiotherapy fairly consistent but chemotherapy regimens varied. * Small sample size is limiting.

Results Point of Contact

• Title: Yusuf Menda, MD
• Organization: The University of Iowa Department of Radiology

yusuf-menda@uiowa.edu

319-356-3214

Study Officials

• Yusuf Menda, M.D.

  University of Iowa

  PRINCIPAL INVESTIGATOR

• John M. Buatti, M.D.

  University of Iowa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Radiology-Nuclear Medicine

Study Record Dates

• First Submitted: June 10, 2008
• First Posted: July 24, 2008
• Study Start: March 1, 2008
• Primary Completion: December 31, 2014
• Study Completion: December 31, 2014
• Last Updated: August 6, 2019
• Results First Posted: October 3, 2017

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)