FLT-PET Imaging of Brain Tumors in Children

Study Overview
=================
Brief Summary
-----------------
Brain tumors are the leading cause of death from solid tumors in children. Tumor imaging is important in the management of these tumors, but current imaging methods have limitations in providing the necessary information for optimal treatment of these patients. The goal of this study is to evaluate the potential utility of positron emission tomography (PET) with 3'-deoxy-3'-[F-18] fluorothymidine (18F-FLT) in the medical management of brain tumors in children. Funding source - FDA Office of Orphan Product Development (OOPD)

Detailed Description
-----------------
Although pediatric central nervous system tumors are rare, they are a significant contributor to morbidity and mortality in children. Tumor staging, detecting recurrent tumor, and assessing the response to therapy are critical in the treatment of brain tumors, but current imaging methods have major limitations in providing such information. The objective of this study is to validate 3'-deoxy-3'-[F-18] fluorothymidine (18F-FLT) as a measure of tumor proliferation and to demonstrate the utility of 18F-FLT as a PET imaging agent in children with central nervous system tumors. The proposed studies will evaluate 18F-FLT PET in three groups: Children with a new diagnosis of central nervous system tumor. Children in whom conventional imaging has raised concern for possible recurrence of a central nervous system tumor. Children receiving post-operative chemotherapy for a central nervous system tumor. In these three groups, correlation of 18F-FLT uptake with tumor histopathology and patient outcome will be used to assess the utility of 18F-FLT for grading tumors at diagnosis, for accurate identification of tumor recurrence, and for early assessment of the response to chemotherapy.

Official Title
-----------------
Phase 2 Study of [18F]FLT for PET Imaging of Brain Tumors in Children

Conditions
-----------------
Brain Neoplasms

Intervention / Treatment
-----------------
* Drug: [18F] FLT


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: age 21 years or less capable of achieving imaging without need for sedation or anesthesia (typically age 8 years or greater, but there is no lower limit for age for eligibility) Karnofsky Performance Status of 50 or greater in subjects age 12 years or greater, for age less than 12 years a Lansky play scale of 50% or greater Patients receiving steroids and/or anti-seizure medications are eligible Exclusion Criteria: clinically active infection pregnancy or breast-feeding serious intercurrent medical illness require emergency surgical intervention that would be inappropriately delayed by FLT-PET imaging

Ages Eligible for Study
-----------------
Maximum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: New diagnosis of brain tumor<br>In children with a new diagnosis of central nervous system tumor, a PET scan will be performed using [18F] FLT. | Drug: [18F] FLT<br>* [18F] FLT, intravenous, at a dose of 0.15 mCi/kg once before a PET scan<br>* Other names: [18F] fluorothymidine;|
| Experimental: Possible recurrent brain tumor<br>In children in whom there is concern for recurrent central nervous system tumor, a PET scan will be performed using [18F] PET. | Drug: [18F] FLT<br>* [18F] FLT, intravenous, at a dose of 0.15 mCi/kg once before a PET scan<br>* Other names: [18F] fluorothymidine;|
| Experimental: Brain tumor response to chemotherapy<br>In children with a newly diagnosed central nervous system tumor who will be treated with post-operative chemotherapy, a PET scan will be performed using [18F] FLT before the start and after two cycles of chemotherapy. Despite much effort and working with referring physicians at multiple hospitals, enrollment in this arm remained low, and it seemed unlikely that meaningful enrollment would be accomplished. A revised study plan was submitted to the granting agency and FDA, and this arm was closed to further enrollment. | Drug: [18F] FLT<br>* [18F] FLT, intravenous, at a dose of 0.15 mCi/kg once before a PET scan<br>* Other names: [18F] fluorothymidine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| [18F] FLT uptake as a marker of cellular proliferation | [18F] FLT uptake, as determined by pre-operative FLT-PET imaging, will be compared to histological markers of cellular proliferation in the resected brain tumor. This will be performed in three groups of subjects (3 arms): (1)children with newly diagnosed central nervous system tumors, (2) children in whom there is concern for recurrence of central nervous system tumor,(3) children with central nervous system tumors that are treated with post-operative chemotherapy. | on average 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biodistribution of [18F]FLT | The distribution, localization, and kinetics of localization of [18F] FLT will be assessed by FLT-PET in 12 subjects. | 6 hours | 
| Preliminary evaluation of clinical utility of [18F] FLT PET | In subjects in Arm 3 (receiving chemotherapy), clinical data (date of recurrence and/or death) will be collected for up to 2 years to determine if [18F] FLT uptake after chemotherapy predicts clinical outcome. | up to 2 years after enrollment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Brain neoplasms, Children, Positron-Emission Tomography, 18F-FLT