Neoplasms

All Conditions

Symptoms and General Pathology

Rare Diseases

Glioma

Disease Progression

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Single intravenous administration of 18F fluciclovine for PET-MRI Scan

18F-Fluciclovine will be injected via IV prior to Positron emission tomography (PET)-Magnetic resonance imaging (MRI)

18F-Fluciclovine PET-MRI

Ali Nabavizadeh

Hannah Anderson

Ali Nabavizadeh, MD

The purpose of this study is to see if 18F-fluciclovine (Axumin®) PET imaging is useful and safe in the management of children with High Grade Gliomas. Investigators seek to determine if this imaging will help doctors tell the difference between tumor growth (progression) and other tumor changes that can occur after treatment.

Following radiation and immunotherapy, many pediatric participants with high-grade gliomas (HGG), including diffuse midline glioma (DMG), demonstrate radiographic findings suspicious of disease progression. Differentiating post-treatment changes from true tumor progression is paramount to clinical decision-making, as true tumor progression may warrant a change in treatment, while post-treatment changes are typically not an indication to change treatment. Unfortunately, conventional MRI cannot reliably distinguish between true progression and post-treatment changes. Therefore, finding a physiological correlate to delineate true progression from pseudo-progression is critical.

The overall objective of this current application is to evaluate 18F-fluciclovine PET imaging as a diagnostic biomarker for tumor progression compared to post-treatment changes in pediatric HGG. The long-term goal of this research is to accurately differentiate tumor progression from post-treatment changes in pediatric HGG using 18F-fluciclovine PET imaging.

18F-Fluciclovine PET-MRI in High-grade Glioma

Evaluation of 18F-Fluciclovine PET-MRI to Differentiate Tumor Progression From Post-treatment Changes in Pediatric High-grade Glioma (HGG)

Comparison of Standardized uptake value (SUV) max, SUV peak, and uptake kinetics post radiation between participants who experience true progression versus those who experience pseudoprogression as confirmed by routine imaging.

Evaluation of SUV uptake post radiation in participants with planned biopsy or resection who experience true progression versus those who experience pseudoprogression as confirmed by histopathology.

The Safety profile of 18F-Fluciclovine PET in pediatric HGG participants will be assessed based on CTCAE 5.0 toxicity experienced after administration of 18F-Fluciclovine

Blue Earth Diagnostics

Dragon Master Foundation

Children's Hospital of Philadelphia

18F-Fluciclovine will be injected via IV prior to PET-MRI imaging

18F-Fluciclovine

The purpose of this study is to see if 18F-Fluciclovine (Axumin®) is useful and safe in the management of children with Low Grade Gliomas (LGG). Imaging with 18F-Fluciclovine PET-MRI will be performed prior to initiation of therapy for LGG, and then 3 months, and 1 year after starting therapy. Changes in 18F-Fluciclovine uptake will be compared to changes in MRI measurements at 3 months and 1 year as compared to baseline.

Evaluation of 18F-Fluciclovine Positron Emission Tomography - Magnetic Resonance Imaging (PET-MRI) in LGG

Evaluation of 18F-Fluciclovine PET-MRI as a Biomarker of Response in Pediatric and Young Adult Patients With Low Grade Gliomas (LGG)

Determine if Baseline PET uptake as predictors of treatment response

Identify changes in PET metrics at the time of progression

To identify change in the standardized uptake value (SUV) parameters (SUVmax, SUVpeak) for the 18F-Fluciclovine PET scan

Calculate the change in tumor measurement on MRI

The Safety profile of 18F-Fluciclovine PET in pediatric LGG participants will be accessed by the CTCAE 5.0 toxicity experienced after administration of 18F-Fluciclovine

Nervous System Diseases

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

This is a device feasibility study, therefore participants will only be enrolled into the investigational arm and will receive the RNS System Implantation.

Following resection consistent with SoC, if there is evidence of residual tumor which cannot be resected due to invasion of hand-M1 but which is small enough to be covered by two four-electrode strips, these strips will be placed on the functional cortex of interest and secured to the dura. The location of the leads will be registered into the navigation software (either Medtronic Stealth or Brainlab). The dura will then be closed as watertight as possible, and the RNS System will be incorporated into the craniotomy on closure Prior to closure, four bone screws will be placed and registered to the intraoperative navigation system as internal fiducials to be retrieved for future procedures.

RNS System Implantation

Sarah Cornell

Max Krucoff, MD

This study uses a cranial implant to deliver cortical stimulation that, when paired with physiotherapy, will remap the brain so that critical brain functions can be protected during brain tumor surgery. This pilot study will provide initial evidence for the safety and feasibility of such a protocol which will lead to future pivotal trials that could radically change eloquent area brain surgery. For patients with otherwise incompletely resectable brain tumors, this could mean a longer life expectancy and a better quality of life.

Study Protocol: Participants will undergo a standard-of-care craniotomy for resection of low-grade glioma. If part of the lesion cannot be removed due to involvement of functional cortex, RNS (Responsive Neurostimulation System \[RNS; NeuroPace, Inc.\]) electrodes will be implanted over the tumor-invaded area(s) in five participants. Stimulation will then be optimized for each individual to disrupt the function of the invaded cortical node (e.g., hand motor area -\> hand dysfunction) (Aim 1). Over the next two months, outpatient physiotherapy will work to overcome the stim-induced deficits through gradual increases in stimulation amplitude as other, non-stimulated brain regions begin to assume its function (Aim 2). Once complete, participants will return to the OR for device explantation, repeated intraoperative mapping, and extended resection (if safe) (Aim 3).

Aim 1: Optimize stimulation to maximize stim-induced deficits and minimize side effects Rationale: To induce plasticity, stimulation parameters must be individually tuned to maximize effect and minimize side effects. Approach: After device implantation and prior to hospital discharge, stimulus settings (frequency, pulse-width, and amplitude) will be optimized to the relevant clinical response while minimizing adverse effects (e.g., focal tonus, myoclonus, or seizures) while still in the safe, inpatient setting. Outcomes: Primary Endpoints: 1) stim-induced focal clinical deficit as measured on the relevant clinical scale (e.g., manual motor score \[0-5\], picture naming \[x/10\]), repetition \[x/3\]); 2) stim-induced side effects (e.g., seizures).

Aim 2: Evaluate extent of remapping and safety of outpatient stimulation-physiotherapy protocol. Rationale: The ability to deliver chronic, outpatient stimulation is vital for practical clinical translation, yet neither its safety nor efficacy has been demonstrated. Approach: After Aim 1, a physiotherapist will assign a personalized, outpatient therapy regimen aimed at overcoming stim-induced deficits. Participants will have daily virtual sessions and return to clinic 2x/week for amplitude increases to re-induce deficits that therapy has overcome. This will continue until stimulation no longer can induce a deficit, suggesting successful functional remapping and enabling a return to the OR for further resection. Outcomes: Primary Endpoints: 1) absence of stim-related ER visits, readmissions, or serious adverse events (safety), 2) changes in intraop stimulation maps from surgery 1 to surgery 2 (induced remapping).

Aim 3: Evaluate ability to extend surgical resections and associated neurological outcomes. Rationale: Any change in functional boundaries will only be useful if it results in a safe, extended resection. Approach: Each surgery will proceed with standard-of-care intraoperative functional mapping techniques and decision making. Neurological examinations will be performed preoperatively, daily while inpatient, then again at 2-weeks and 3-months postoperatively. Extent of resection will be evaluated as 3D residual tumor volume on postoperative MRI. Outcomes: Primary Endpoint: 1) Change in residual tumor volume after second versus first resection, 2) new neurological deficits 3-months after second resection compared to before second resection. Secondary Endpoint: 1) New, temporary neurological deficits after the second surgery

A Study Using Brain Stimulation and Behavioral Therapy to Increase Extent of Resection in Low-Grade Gliomas

Inducing Functional Plasticity in Glioma-Involved Functional Cortex With Deficit-Inducing Cortical Stimulation and Targeted Behavioral Therapy to Increase Extent of Resection

Calculated as: Tumor volume after second surgery - tumor volume before second surgery. Determination of volumes will be made by an attending radiologist without knowledge of clinical outcome. Manual segmentation will be performed to measure tumor volumes based on fluid-attenuated inversion recovery (FLAIR) axial slices.

Calculated as manual muscle score (MMS) before stimulation - MMS after stimulation.

MMS is a zero-to-five scale assessed as the following:

5 - normal strength 4 - give away weakness 3 - movement against gravity 2 - movement in anti-gravity position

1 - muscle twitch 0 - no movement

3a. Calculated as picture naming score (x/10) before stimulation minus after stimulation.

3b. Calculated as sentence repitition score (x/3) before stimulation minus after stimulation.

Reported as number of unintended stimulation effects, such as myoclonus, tonus, seizures, or unpleasant sensations

Reported as number of stimulation- or physiotherapy related ER visits, readmissions, or serious adverse events

This outcome will be reported as a descriptive variable, calculated as changes in the intraoperative stimulation map obtained during surgery 2 compared to surgery 1

Any new, permanent neurological deficits resulting from the second surgery

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
18F-Fluciclovine PET-MRI in High-grade Glioma	NCT05553041	Glioma High Grade Glio... Glioma, Maligna... Glioma Intracra... Diffuse Glioma	18F-Fluciclovin...	1 Year - 21 Years	Children's Hospital of Philadelphia
Evaluation of 18F-Fluciclovine Positron Emission Tomography - Magnetic Resonance Imaging (PET-MRI) in LGG	NCT05555550	Glioma Low-grade Gliom... Low Grade Gliom... Glioma, Maligna... Glioma Intracra...	18F-Fluciclovin...	1 Year - 21 Years	Children's Hospital of Philadelphia
18F-Fluciclovine PET-MRI in High-grade Glioma	NCT05553041	Glioma High Grade Glio... Glioma, Maligna... Glioma Intracra... Diffuse Glioma	18F-Fluciclovin...	1 Year - 21 Years	Children's Hospital of Philadelphia
A Study Using Brain Stimulation and Behavioral Therapy to Increase Extent of Resection in Low-Grade Gliomas	NCT04745156	Glioma Glioma Intracra... Gliomas Benign Brain Tumor Brain Cancer Motor Cortex; L...	RNS System Impl...	18 Years - 65 Years	Medical College of Wisconsin

Spots Global Cancer Trial Database for glioma intracranial