18F-FLT Positron Emission Tomography and Diffusion-Weighted Magnetic Resonance Imaging in Planning Surgery and Radiation Therapy and Measuring Response in Patients With Newly Diagnosed Ewing Sarcoma

NCT01825902 | Completed Early Phase 1 DMC

• 2 other identifiers: MC1279NCI-2013-00707
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot trial studies fluorine F 18 fluorothymidine (18F-FLT) positron emission tomography and diffusion-weighted magnetic resonance imaging in planing surgery and radiation therapy and measuring response in patients with newly diagnosed Ewing sarcoma. Comparing results of diagnostic procedures done before and after treatment may help doctors predict a patient's response and help plan the best treatment.

Conditions

Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Ewing Sarcoma of Bone; Extraosseous Ewing Sarcoma; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor

Outcome Measures

Primary Outcomes (7)

• 18F-FLT PET activity

  The primary measure of the samples will be % of viable malignant cells remaining. To examine the correlation of 18F-FLT PET, 18F-FDG PET, and ADC signals in areas of concordance and discordance with standard MR imaging as it impacts differentiation of viable and necrotic tumor extent, sensitivity/specificity and positive/negative predictive values will be estimated. Findings will be summarized using point-estimates and corresponding 95% confidence intervals as appropriate. Differences in sensitivity and specificity will be evaluated using McNemar's test.

  At the time of surgical resection

• ADC values from DW-MRI

  The primary measure of the samples will be % of viable malignant cells remaining. To examine the correlation of 18F-FLT PET, 18F-FDG PET, and ADC signals in areas of concordance and discordance with standard MR imaging as it impacts differentiation of viable and necrotic tumor extent, sensitivity/specificity and positive/negative predictive values will be estimated. Findings will be summarized using point-estimates and corresponding 95% confidence intervals as appropriate. Differences in sensitivity and specificity will be evaluated using McNemar's test.

  At the time of surgical resection

• 18F-FDG PET activity

  The primary measure of the samples will be % of viable malignant cells remaining. To examine the correlation of 18F-FLT PET, 18F-FDG PET, and ADC signals in areas of concordance and discordance with standard MR imaging as it impacts differentiation of viable and necrotic tumor extent, sensitivity/specificity and positive/negative predictive values will be estimated. Findings will be summarized using point-estimates and corresponding 95% confidence intervals as appropriate. Differences in sensitivity and specificity will be evaluated using McNemar's test.

  At the time of surgical resection

• MRI contrast enhancement

  The primary measure of the samples will be % of viable malignant cells remaining. To examine the correlation of 18F-FLT PET, 18F-FDG PET, and ADC signals in areas of concordance and discordance with standard MR imaging as it impacts differentiation of viable and necrotic tumor extent, sensitivity/specificity and positive/negative predictive values will be estimated. Findings will be summarized using point-estimates and corresponding 95% confidence intervals as appropriate. Differences in sensitivity and specificity will be evaluated using McNemar's test.

  At the time of surgical resection

• Pathologic response

  The primary measure of the samples will be % of viable malignant cells remaining. To examine the correlation of 18F-FLT PET, 18F-FDG PET, and ADC signals in areas of concordance and discordance with standard MR imaging as it impacts differentiation of viable and necrotic tumor extent, sensitivity/specificity and positive/negative predictive values will be estimated. Findings will be summarized using point-estimates and corresponding 95% confidence intervals as appropriate. Differences in sensitivity and specificity will be evaluated using McNemar's test.

  At the time of surgical resection

• 18F-FLT PET and DW-MRI in predicting local control, event-free survival, and overall survival, measured by therapy-induced changes in the scans

  The prognostic ability of 18F-FLT PET and DW-MRI imaging will be evaluated by correlating changes in 18F-FLT uptake and ADC as treatment response both after chemotherapy (but prior to RT) and after RT with local control and survival outcomes, with the intent of establishing predictive thresholds. The results will be compared to standard prognostic factors such as change in tumor size and histopathology.

  Up to 5 years

• Radiotherapy target volume delineation with pre- and post-chemotherapy 18F-FLT PET and DW-MRI

  PET images and DW-MRI ADC maps co-registered and regions of concordance and discordance quantified for each modality as compared to pre-chemotherapy conventional MRI. The concordance correlation coefficient will be used to measure agreement between volumes generated at different times, with different modalities, and by different individuals. The measured variability associated with contrast-enhanced MRI will serve as the standard for comparison. The mean and standard deviation of volumes and their discordances will be calculated as a measure of the potential treatment impact of each modality.

  Up to 5 years

Secondary Outcomes (6)

• Imaging thresholds

  Up to 1 week after completion of chemotherapy and radiation therapy

• Efficacy of advanced imaging in accurately guiding biopsy, measured by differences in determining target location by contrast enhancement or 18F-FLT PET and DW-MRI

  At the time of surgery/biopsy

• Accuracy in distinguishing between necrosis and non-specific inflammation immediately following treatment

  Up to 5 years

• Reduction in acute side effects based on modified RT treatment volumes with pre- and post-chemotherapy 18F-FLT PET and DW-MRI as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  Within 7 days after completion of RT

• Reduction in late side effects based on modified RT treatment volumes with pre- and post-chemotherapy 18F-FLT PET and DW-MRI as assessed by the NCI CTCAE 4.0 version

  Up to 5 years

Study Arms (1)

Diagnostic (18F-FLT PET, 18F-FDG PET, DW-MRI)

EXPERIMENTAL

Patients undergo 18F-FLT PET, 18F-FDGPET, and DW-MRI the week prior to induction therapy, within one week after the completion of induction therapy, the week prior to RT (for patients that received surgery), and within 1 week of completion of RT.

Drug: fluorine F 18 fluorothymidine; Radiation: fludeoxyglucose F 18; Procedure: positron emission tomography; Procedure: diffusion-weighted magnetic resonance imaging; Other: laboratory biomarker analysis

Interventions

fluorine F 18 fluorothymidine DRUG

Undergo 18F-FLT PET

Also known as: 18F-FLT, 3'-deoxy-3'-[18F]fluorothymidine, fluorothymidine F-18

Diagnostic (18F-FLT PET, 18F-FDG PET, DW-MRI)

fludeoxyglucose F 18 RADIATION

Undergo 18F-FDG PET

Also known as: 18FDG, FDG

Diagnostic (18F-FLT PET, 18F-FDG PET, DW-MRI)

positron emission tomography PROCEDURE

Undergo 18F-FLT PET and 18F-FDG PET

Also known as: FDG-PET, PET, PET scan, tomography, emission computed

Diagnostic (18F-FLT PET, 18F-FDG PET, DW-MRI)

diffusion-weighted magnetic resonance imaging PROCEDURE

Undergo DW-MRI

Also known as: diffusion-weighted MRI

Diagnostic (18F-FLT PET, 18F-FDG PET, DW-MRI)

laboratory biomarker analysis OTHER

Correlative studies

Diagnostic (18F-FLT PET, 18F-FDG PET, DW-MRI)

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological confirmation of newly diagnosed localized or newly diagnosed with metastatic Ewing sarcoma (ES) or primitive neuroectodermal tumor (PNET) of bone or soft tissue
• Planning to receive definitive RT or surgery with or without adjuvant RT
• Willing to sign release of information for any follow-up records
• Provide informed written consent if \>= 18 years; if \< 18 years, provide informed written assent and parent or legal guardian provide informed written consent
• Patients must have measurable disease
• Willingness to participate in mandatory imaging studies
• Willingness to provide mandatory pathology samples for correlative research

You may not qualify if:

• Unable to undergo MRI scans with contrast (e.g. cardiac pacemaker, defibrillator, kidney failure)
• Unable to undergo 18F-FLT PET scan
• Any of the following:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Neuroectodermal Tumors, Primitive, Peripheral

Interventions

alovudine; Fluorodeoxyglucose F18; Magnetic Resonance Spectroscopy; 2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Deoxyglucose; Deoxy Sugars; Carbohydrates; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Nadia N. Laack, M.D.

  Mayo Clinic

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2013
• First Posted: April 8, 2013
• Study Start: March 1, 2013
• Primary Completion: January 1, 2014
• Study Completion: November 23, 2015
• Last Updated: November 20, 2017

Record last verified: 2016-03

Locations

US (1)