Expired Study
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Iowa City, Iowa 52242


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.


Study summary:

There are approximately 40,000 new cases of head and neck cancer each year in the United States. Approximately two thirds of these patients present with locally advanced disease with either large disease at the primary site and/or spread to regional lymph node levels. Treatment options include surgery, radiotherapy, and chemotherapy, usually applied in combination for advanced disease. Despite aggressive treatment, the 5-year survival for locally advanced disease remains poor (overall, approximately 50%). To increase the efficacy of locoregional therapy, different treatment maneuvers are used including increased radiation dose, concurrent use of chemotherapy and radiation therapy and high dose intra-arterial chemotherapy. Unfortunately, the increased intensity of combined treatment also leads to greater treatment related morbidity and mortality. It is currently difficult to predict who will benefit from intensive chemoradiotherapy and who would be most effectively treated with other combinations such as surgery and postoperative radiotherapy. It is predictable that the most immediate signal of a successful antitumor therapeutic regime will be a decrease in cellular proliferation in the tumor. Therefore, a tracer, which is taken up into and retained in cells as a function of their proliferative activity, should provide rapid information as to the effectiveness of the treatment. FLT is an ideal tracer in this setting as its uptake is a function of thymidine kinase activity. Thymidine kinase activity is an established marker of cellular proliferation. FLT can be imaged with a PET scanner and the FLT uptake in the tumor can be reliably quantified. Preliminary studies including at our institution also confirm accumulation of FLT in untreated head and neck cancers. The objective of our study is to evaluate the utility of FLT PET imaging in predicting the outcome of treatment in terms of locoregional control and disease-free survival in patients (i.e., progression free survival) with head and neck cancer as well as overall survival.


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.


Study is Available At:


Original ID:

200801758


NCT ID:

NCT00721799


Secondary ID:

1R21CA130281


Study Acronym:


Brief Title:

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


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)


Overall Status:

Completed


Study Phase:

Phase 2


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

University of Iowa


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

33


Enrollment Type:

Actual


Overall Contact Information

Official Name:Yusuf Menda, M.D.
Principal Investigator
University of Iowa

Study Dates

Start Date:March 1, 2008
Completion Date:December 31, 2014
Completion Type:Actual
Primary Completion Date:December 31, 2014
Primary Completion Type:Actual
Verification Date:July 2019
Last Changed Date:July 23, 2019
First Received Date:June 10, 2008
First Results Date:March 29, 2017

Study Outcomes

Outcome Type:Primary Outcome
Measure:Efficacy of Mean Pre-therapy FLT Uptake (SUVmean) in Predicting Progression Free Survival (PFS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Maximum Pre-therapy FLT Uptake (SUVmax) in Predicting Progression Free Survival (PFS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Pre-therapy Metabolic Tumor Volume in Predicting Progression Free Survival (PFS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of FLT Flux (K-FLT) Pre-therapy in Predicting Progression Free Survival (PFS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of the Patlak Influx Rate Constant for FLT (K-Patlak) Pre-therapy in Predicting Progression Free Survival (PFS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Pretherapy Total Lesion Proliferation in Predicting Progression Free Survival (PFS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Mean Mid-therapy FLT Uptake (SUVmean) in Predicting Progression Free Survival (PFS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Percent Change in the Total Lesion Proliferation in Predicting Overall Survival (OS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Percent Change the Patlak Influx Rate Constant for FLT (K-Patlak) in Predicting Overall Survival (OS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Percent Change in FLT Flux (K-FLT) in Predicting Overall Survival (OS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Percent Change in Maximum FLT Uptake (SUVmax) in Predicting Overall Survival (OS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Percent Change in Mean FLT Uptake (SUVmean) in Predicting Overall Survival (OS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Mid-therapy Total Lesion Proliferation in Predicting Overall Survival (OS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of the Patlak Influx Rate Constant for FLT (K-Patlak) Mid-therapy in Predicting Overall Survival (OS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of FLT Flux (K-FLT) Mid-therapy in Predicting Overall Survival (OS).
Time Frame:36 months
Safety Issues:False
Description: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 R
Outcome Type:Primary Outcome
Measure:Efficacy of Maximum Mid-therapy FLT Uptake (SUVmax) in Predicting Overall Survival (OS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Mean Mid-therapy FLT Uptake (SUVmean) in Predicting Overall Survival (OS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Pretherapy Total Lesion Proliferation in Predicting Overall Survival (OS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of the Patlak Influx Rate Constant for FLT (K-Patlak) Pre-therapy in Predicting Overall Survival (OS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of FLT Flux (K-FLT) Pre-therapy in Predicting Overall Survival (OS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Pre-therapy Metabolic Tumor Volume in Predicting Overall Survival (OS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Maximum Pre-therapy FLT Uptake (SUVmax) in Predicting Overall Survival (OS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Mean Pre-therapy FLT Uptake (SUVmean) in Predicting Overall Survival (OS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Percent Change in the Total Lesion Proliferation Between Scans 1 & 2 in Predicting Progression Free Survival (PFS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure: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
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Percent Change in FLT Flux (K-FLT) Between Scans 1 & 2 in Predicting Progression Free Survival (PFS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Percent Change in Maximum FLT Uptake (SUVmax) Between Scans 1 & 2 in Predicting Progression Free Survival (PFS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Percent Change in Mean FLT Uptake (SUVmean) Between Scan 1 & 2 in Predicting Progression Free Survival (PFS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Mid-therapy Total Lesion Proliferation in Predicting Progression Free Survival (PFS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of the Patlak Influx Rate Constant for FLT (K-Patlak) Mid-therapy in Predicting Progression Free Survival (PFS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of FLT Flux (K-FLT) Mid-therapy in Predicting Progression Free Survival (PFS)
Time Frame:36 months
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Efficacy of Maximum Mid-therapy FLT Uptake (SUVmax) in Predicting Progression Free Survival (PFS)
Time Frame:36 months
Safety Issues:False
Description: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

Study Interventions

Intervention Type:Drug
Name:18F-Fluorothymidine PET scan
Description: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.
Arm Name:FLT PET scan
Other Name:FLT

Study Arms

Study Arm Type:Experimental
Arm Name:FLT PET scan
Description: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)

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:University of Iowa
Agency Class:NIH
Agency Type:Collaborator
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Results Reference
Citation: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.
PMID:20439512
Reference Type:Results Reference
Citation: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
Reference Type:Results Reference
Citation: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

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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