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| ID | Type | Description | Link |
|---|---|---|---|
| R01FD003718 | U.S. FDA Grant/Contract | View source |
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| Name | Class |
|---|---|
| Dana-Farber Cancer Institute | OTHER |
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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)
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| New diagnosis of brain tumor | Experimental | In children with a new diagnosis of central nervous system tumor, a PET scan will be performed using [18F] FLT. |
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| Possible recurrent brain tumor | Experimental | In children in whom there is concern for recurrent central nervous system tumor, a PET scan will be performed using [18F] PET. |
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| Brain tumor response to chemotherapy | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [18F] FLT | Drug | [18F] FLT, intravenous, at a dose of 0.15 mCi/kg once before a PET scan |
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| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Frederick D Grant, MD | Children's Hospital, Boston, Harvard Medical School | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital, Boston | Boston | Massachusetts | 02115 | United States |
No current plans to share individual participant data
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Participants were assigned to one of three arms, depending on clinical presentation: 1) Clinical concern for new brain tumor, 2) Clinical concern for recurrent brain tumor, or 3) Planned initiation of new chemotherapy for a known brain tumor
Potential participants were identified by clinicians participating in their care.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. [18F] FLT: [18F] FLT, intravenous, at a dose of 0.15 mCi/kg once before a PET scan |
| FG001 | 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. [18F] FLT: [18F] FLT, intravenous, at a dose of 0.15 mCi/kg once before a PET scan |
| FG002 | 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. [18F] FLT: [18F] FLT, intravenous, at a dose of 0.15 mCi/kg once before a PET scan |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. [18F] FLT: [18F] FLT, intravenous, at a dose of 0.15 milliCurie (mCi)/kg once before a PET scan |
| BG001 | Possible Recurrent Brain Tumor |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | [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. | Participants were evaluable if brain tumor surgery was performed within 30 days of the FLT-PET scan, if surgical pathology confirmed the diagnosis of brain tumor, and the results of tissue immunohistology were available. On the brain PET scan, tumor uptake of FLT was assessed by SUVmax, the standard clinical measure of tracer uptake, and tumor proliferation was assessed as the fraction of cells with positive MIB immunostaining | Posted | Mean | Full Range | SUV max | on average 1 week |
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1 week
Systemic: Complete blood count and renal/liver labs before and after each FLT-PET. One week after FLT-PET, medical record review for adverse events.
Non-systemic: Referring clinicians inform study team of severe adverse events. Review: Adverse events reported to the Institutional Review Board (IRB) using current institutional procedures. Two severe adverse events reviewed by the IRB were judged to be consistent with the underlying brain tumor and associated therapy, and not due to FLT-PET.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. [18F] FLT: [18F] FLT, intravenous, at a dose of 0.15 mCi/kg once before a PET scan |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| intracranial tumor hemorrhage | Nervous system disorders | SNOMEDCT NCIThesauru | Non-systematic Assessment | intracranial tumor hemorrhage |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| urticarial rash | Skin and subcutaneous tissue disorders | SNOMEDCT NCIThesauru | Non-systematic Assessment | urticaria |
Arm 3: Despite much recruitment effort, 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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Frederick Grant | Children's Hospital of Philadelphia | 267-600-1542 | grantf@chop.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 1, 2019 | Feb 5, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C002854 | alovudine |
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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 |
| Surgical pathology did not confirm evaluable brain tumor |
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| MIB immunopathology results not available |
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| PET data failure |
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| Withdrawal by Subject |
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In children in whom there is concern for recurrent central nervous system tumor, a PET scan will be performed using [18F] PET. [18F] FLT: [18F] FLT, intravenous, at a dose of 0.15 mCi/kg once before a PET scan |
| BG002 | 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. [18F] FLT: [18F] FLT, intravenous, at a dose of 0.15 mCi/kg once before a PET scan |
| BG003 | Total | Total of all reporting groups |
| Participants |
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| Sex/Gender, Customized | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Brain Tumor classification | derived from major categories from: World Health Organization (WHO) Classification of Brain Tumors, 5th edition (2021) | Count of Participants | Participants |
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| OG000 |
| 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. [18F] FLT: [18F] FLT, intravenous, at a dose of 0.15 mCi/kg once before a PET scan |
| OG001 | 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. [18F] FLT: [18F] FLT, intravenous, at a dose of 0.15 mCi/kg once before a PET scan |
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|
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| Primary | MIB Positive (Percent) | On pathological specimens, tumor proliferation was assessed as the fraction of cells with positive MIB immunostaining | Participants in Arm 3 (Brain tumor response to chemotherapy) were not expected to undergo surgery during their chemotherapy. Therefore, they did have FLT-PET, but no assessment for tumor proliferation (percent MIB positive) was performed. | Posted | Mean | Full Range | percent positive cells | 30 days |
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| Secondary | Biodistribution of [18F]FLT | The distribution, localization, and kinetics of localization of [18F] FLT will be assessed by FLT-PET in 12 subjects. | Saved PET scan data has not been retrievable or usable due to 1) storage/format incompatibility among PET cameras from different vendors, 2) lack of interoperablity among different generations of cameras from the same vendor, and 3) backup data in institutional radiology archiving systems is not universally available for retrieval for quantitative image analysis. To date, working with camera vendors and software developers has been unsuccessful in overcoming this problem. | Posted | 6 hours |
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| Secondary | 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. | Despite much effort and working with referring physicians at multiple hospitals, enrollment in this arm remained low and participant completion of the entire protocol was low. As 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. Due to the small number of participants completing the protocol, FLT uptake was assessed, but clinical outcome was not evaluated. | Posted | Mean | Full Range | SUV max | 3 months |
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| 0 |
| 16 |
| 0 |
| 16 |
| 1 |
| 16 |
| EG001 | 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. [18F] FLT: [18F] FLT, intravenous, at a dose of 0.15 mCi/kg once before a PET scan | 0 | 28 | 2 | 28 | 3 | 28 |
| EG002 | 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. [18F] FLT: [18F] FLT, intravenous, at a dose of 0.15 mCi/kg once before a PET scan | 0 | 6 | 0 | 6 | 0 | 6 |
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| reversible posterior leukoencephalopathy sydrome | Nervous system disorders | SNOMEDCT NCIThesauru | Systematic Assessment |
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| anemia | Blood and lymphatic system disorders | SNOMEDCT NCIThesauru | Systematic Assessment |
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| lymphopenia | Blood and lymphatic system disorders | SNOMEDCT NCIThesauru | Systematic Assessment |
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| D001927 |
| Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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