Clinical trial NCT01825902: 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
Official title: A Pilot Study of the Utility of 18F-FLT-PET and Diffusion-Weighted MRI for Surgical Planning, Radiotherapy Target Delineation, and Treatment Response Evaluation in Ewing Sarcoma Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
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
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2013-04-08
Enrollment: 1
Sex: ALL
Minimum age (years): 7
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Detailed description: PRIMARY OBJECTIVES:

I. Establish correlation between 18F-FLT positron emission tomography (PET) activity, apparent diffusion coefficients (ADC) values from diffusion-weighted magnetic resonance imaging (DW-MRI), fludeoxyglucose F 18 (18F-FDG) PET activity, magnetic resonance imaging (MRI) contrast enhancement, and pathologic response for Ewing sarcoma.

II. Assess the efficacy of detecting therapy induced changes in 18F-FLT PET uptake and ADC from DW-MRI for more accurately predicting local control, event-free survival, and overall survival as compared to standard prognostic factors (e.g. change in tumor size).

III. Compare radiotherapy target volume delineation with pre- and post-chemotherapy 18F-FLT PET and DW-MRI information to delineation with pre-chemotherapy conventional MRI to determine role of advanced imaging in radiotherapy treatment planning for Ewing sarcoma.

SECONDARY OBJECTIVES:

I. Establish correlation between 18F-FLT PET activity, ADC values from DW-MRI, 18F-FDG PET activity, MRI contrast enhancement, and biomolecular assays for Ewing sarcoma.

II. Determine imaging thresholds to discriminate between viable and necrotic tumor, as established through pathologic correlations.

III. Assess efficacy of advanced imaging for more accurately guiding biopsy targeting by comparing planned targeting with standard (MRI contrast enhancement) vs. advanced imaging (18F -FLT PET and DW-MRI).

IV. Compare post-treatment response assessment with 18F-FLT PET and DW-MRI vs. 18F-FDG PET to determine whether 18F-FLT PET and ADC information is more accurate than 18F-FDG PET for distinguishing between necrosis and non-specific inflammation immediately following treatment.

V. Estimate potential reduction in acute and late side effects based on modified radiation therapy (RT) treatment volumes with pre- and post-chemotherapy 18F-FLT PET and DW-MRI information as compared to volumes delineated with pre-chemotherapy conventional MRI.

VI. Evaluate automatic image segmentation techniques for 18F-FLT PET and DW-MRI, comparing against biopsy determined imaging thresholds and expert Nuclear Medicine and MR Radiologist contours.

OUTLINE:

Patients undergo 18F-FLT PET, 18F-FDG PET, 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.

After completion of study intervention, patients are followed up every 3 months for 1 year and then every 6 months for up to 4 years.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: 18F-FLT PET activity
timeFrame: At the time of surgical resection
measure: ADC values from DW-MRI
timeFrame: At the time of surgical resection
measure: 18F-FDG PET activity
timeFrame: At the time of surgical resection
measure: MRI contrast enhancement
timeFrame: At the time of surgical resection
measure: Pathologic response
timeFrame: At the time of surgical resection
measure: 18F-FLT PET and DW-MRI in predicting local control, event-free survival, and overall survival, measured by therapy-induced changes in the scans
timeFrame: Up to 5 years
measure: Radiotherapy target volume delineation with pre- and post-chemotherapy 18F-FLT PET and DW-MRI
timeFrame: Up to 5 years
Secondary outcomes:
measure: Imaging thresholds
timeFrame: Up to 1 week after completion of chemotherapy and radiation therapy
measure: 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
timeFrame: At the time of surgery/biopsy
measure: Accuracy in distinguishing between necrosis and non-specific inflammation immediately following treatment
timeFrame: Up to 5 years
measure: 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
timeFrame: Within 7 days after completion of RT
measure: 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
timeFrame: Up to 5 years
measure: Automatic image segmentation techniques for 18F-FLT PET and DW-MRI
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Nadia N. Laack, M.D.
role: STUDY_CHAIR
References: