FLT-PET Imaging of Brain Tumors in Children

• ClinicalTrials.gov Identifier: NCT01244737
• Recruitment Status: Active, not recruiting
• First Posted: November 19, 2010
• Last Update Posted: August 19, 2021
• Sponsor: Frederick Daniel Grant
• Collaborator: Dana-Farber Cancer Institute
• Information provided by (Responsible Party): Frederick Daniel Grant, Boston Children's Hospital

Study Description

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)

Condition or disease	Intervention/treatment	Phase
Brain Neoplasms	Drug: [18F] FLT	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 52 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Diagnostic
• Official Title: Phase 2 Study of [18F]FLT for PET Imaging of Brain Tumors in Children
• Actual Study Start Date: October 2010
• Actual Primary Completion Date: August 31, 2019
• Estimated Study Completion Date: February 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. [18F] FLT uptake as a marker of cellular proliferation [ Time Frame: on average 1 week ]
   [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.

Secondary Outcome Measures :

1. Biodistribution of [18F]FLT [ Time Frame: 6 hours ]
   The distribution, localization, and kinetics of localization of [18F] FLT will be assessed by FLT-PET in 12 subjects.
2. Preliminary evaluation of clinical utility of [18F] FLT PET [ Time Frame: up to 2 years after enrollment ]
   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.

Eligibility Criteria

• Ages Eligible for Study: up to 21 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Massachusetts

Children's Hospital, Boston

Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Frederick Daniel Grant

Dana-Farber Cancer Institute

Investigators

• Principal Investigator: Frederick D Grant, MD; Children's Hospital, Boston, Harvard Medical School

More Information

• Responsible Party: Frederick Daniel Grant, Assistant Professor in Radiology, Boston Children's Hospital
• ClinicalTrials.gov Identifier: NCT01244737
• Other Study ID Numbers: IND 104365; R01FD003718 ( U.S. FDA Grant/Contract )
• First Posted: November 19, 2010
• Last Update Posted: August 19, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: No current plans to share individual participant data

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Frederick Daniel Grant, Boston Children's Hospital:

Brain neoplasms; Children; Positron-Emission Tomography; 18F-FLT

Additional relevant MeSH terms:

Brain Neoplasms; Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases