FLT-PET Imaging of Brain Tumors in Children

Phase 2

Completed

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:

1. Children with a new diagnosis of central nervous system tumor.

2. Children in whom conventional imaging has raised concern for possible recurrence of a central nervous system tumor.

3. 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
New diagnosis of brain tumor	[18F] FLT	In children with a new diagnosis of central nervous system tumor, a PET scan will be performed using \[18F\] FLT.
Possible recurrent brain tumor	[18F] FLT	In children in whom there is concern for recurrent central nervous system tumor, a PET scan will be performed using \[18F\] PET.
Brain tumor response to chemotherapy	[18F] FLT	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.

Primary Outcome Measures

Name	Time	Method
MIB Positive (Percent)	30 days	On pathological specimens, tumor proliferation was assessed as the fraction of cells with positive MIB immunostaining
[18F] Fluorothymidine ([18F]-FLT) Uptake as a Marker of Cellular Proliferation	on average 1 week	\[18F\] FLT uptake, as determined by pre-operative positron emission tomography (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.

Secondary Outcome Measures

Name	Time	Method
Biodistribution of [18F]FLT	6 hours	The distribution, localization, and kinetics of localization of \[18F\] FLT will be assessed by FLT-PET in 12 subjects.
Preliminary Evaluation of Clinical Utility of [18F] FLT PET	3 months	In individuals with a diagnosed primary brain tumor in whom therapy will include chemotherapy,.\[18F\] FLT uptake, as determined by positron emission tomography (PET) imaging, will assessed before and after two cycles of chemotherapy. Response will be determined by comparing the FL uptake before and after therapy.