FLT-PET Imaging of Brain Tumors in Children

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

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)

Study Overview

• Status: Completed
• Conditions: Brain Neoplasms
• Intervention / Treatment: Drug: [18F] FLT

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Children's Hospital, Boston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: New diagnosis of brain tumor; In children with a new diagnosis of central nervous system tumor, a PET scan will be performed using [18F] FLT.	Drug: [18F] FLT; [18F] FLT, intravenous, at a dose of 0.15 mCi/kg once before a PET scan; Other Names: 3'-deoxy-3'-[F-18] fluorothymidine; [18F] fluorothymidine
Experimental: Possible recurrent brain tumor; 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; [18F] FLT, intravenous, at a dose of 0.15 mCi/kg once before a PET scan; Other Names: 3'-deoxy-3'-[F-18] fluorothymidine; [18F] fluorothymidine
Experimental: Brain tumor response to chemotherapy; 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; [18F] FLT, intravenous, at a dose of 0.15 mCi/kg once before a PET scan; Other Names: 3'-deoxy-3'-[F-18] fluorothymidine; [18F] fluorothymidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[18F] Fluorothymidine ([18F]-FLT) Uptake as a Marker of Cellular Proliferation	[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.	on average 1 week
MIB Positive (Percent)	On pathological specimens, tumor proliferation was assessed as the fraction of cells with positive MIB immunostaining	30 days

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 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.	3 months

Collaborators and Investigators

• Sponsor: Frederick Daniel Grant
• Collaborators: Dana-Farber Cancer Institute
• Investigators: Principal Investigator: Frederick D Grant, MD, Children's Hospital, Boston, Harvard Medical School

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2010
• Primary Completion (Actual): February 5, 2023
• Study Completion (Actual): February 5, 2023

Study Registration Dates

• First Submitted: October 29, 2010
• First Submitted That Met QC Criteria: November 18, 2010
• First Posted (Estimated): November 19, 2010

Study Record Updates

• Last Update Posted (Actual): July 11, 2024
• Last Update Submitted That Met QC Criteria: June 15, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Children; Positron-Emission Tomography; Brain neoplasms; 18F-FLT
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Neoplasms
• Other Study ID Numbers: IND 104365; R01FD003718 (U.S. FDA Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No current plans to share individual participant data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No