Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Nervous System Diseases

Rare Diseases

Recurrence

Melanoma

Brain Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroendocrine Tumor

Neuroepithelioma

This is a two-year microdosing study that will enroll 5 metastatic melanoma patients and 18 malignant brain tumor patients (surgical (n=13) and non-surgical candidates (n=5)). We have already accrued 5 melanoma patients and expect to accrue brain tumor patients within a 1 year period.

Five (5) patients with newly diagnosed or recurrent melanoma, and 18 malignant brain tumor patients (surgical (n=13) or non-surgical candidates (n=5)). Patients with either primary or metastatic brain tumors, will be i.v. injected with approximately 5 mCi (3.4-6.7 nanomoles) of 124I-cRGDY-PEG-dots (specific activity range 750.0 - 1450 mCi/mol) and undergo the microdosing study for purposes of collecting pharmacokinetic and dosimetry data. All studies will be performed using a dedicated scanner, which integrates a dedicated PET scanner and a spiral CT with proprietary fusion software.

PET scan with 124I-cRGDY-PEG-dots

Hilda Stambuk, MD

Current tests to detect cancer, including CAT scans and MRI scans, are limited. PET scans use special dyes that are injected into a vein and can better localize possible cancer. The investigators have developed a new particle that can carry a radioactive dye to a very specific area of the tumor. When using a PET scan the radioactive dye can be viewed in areas of possible disease. This particle has been studied in mice and was safe.

The particles will not treat the cancer and any images or information found during this study will not be used for your treatment. The information collected may be used to guide the design of future studies to detect and/or treat tumors.

PET Imaging of Patients With Melanoma and Malignant Brain Tumors Using an 124I-labeled cRGDY Silica Nanomolecular Particle Tracer: A Microdosing Study

in a limited number of human melanoma and brain tumor patients to characterize biodistribution, pharmacokinetics, and metabolic stability.

studies have demonstrated that a dose 100 times the proposed human dose equivalent did not induce adverse effects

Memorial Sloan Kettering Cancer Center

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neoplasms, Glandular and Epithelial

Daniel Marcus, PhD

The goal of this study is to create a comprehensive database of Magnetic Resonance Imaging (MRI) and of pathology for patients with brain tumors. Both standard, advanced, and research MRI components may be included, these will be analyzed in comparison with pathology results if/when a biopsy is obtained, and also used to predict/evaluate responses to therapy. This study will create a database of de-identified MRI images which include these techniques so that brain tumors can be studied over time (longitudinally) in an organized manner.

Glioblastoma (GBM) is the most common primary malignant neoplasm of the adult brain. Even after multimodal therapy, treatment outcomes remain poor, with a median survival of approximately one year. A central challenge facing investigators in the modern era is how to resolve the heterogeneity inherent in GBM pathology using technology and how to identify individual genetic or molecular markers that indicate how treatment can be individualized to improve outcomes with an emphasis on using this heterogeneity to improve patient care. With advances in imaging and the potential for genetic sequence analysis, increasingly clinicians and researchers have focused on specific clinical, imaging, and genetic biomarkers to allow the personalization of brain tumor treatment in an attempt to improve the limitations we have faced in extending patient survival from this devastating disease. Specific methodologies have been developed to allow genetic microarray analysis of patient's tumor tissue, and this type of research is ongoing at one of our participating institutions, Swedish Medical Center. In addition, centers such as Washington University School of Medicine in St. Louis, Missouri have extensive experience pursuing advanced imaging biomarkers and their applications to clinical neuro-oncology research.

Of importance, however, although clinicians and researchers have come to recognize that in-vivo imaging technologies may have as much if not more relevance than genetic biomarkers in the personalization of brain tumor treatment, clinical trials attempting to validate these biomarkers and correlate them with particular outcomes have been limited by a lack of technology infrastructure that would allow multi-site image acquisition, processing, data analysis, subsequent correlation with clinical and genetic data, and ultimately sharing of anonymized data with other researchers from a central archiving site. BIRN infrastructure will integrate neuroimaging, genetic microarray, and clinical data with a focus on integrating imaging biomarkers into prospective clinical research in patients with malignant brain tumors.

In this project, a consortium of neuro-oncology research centers will be federated to obtain a unified set of clinical, genetic, and imaging data. In the initial phase, 100 patients with malignant brain tumors at two participating sites will be studied. Our ultimate goal will be to use the developed protocols and informatics infrastructure to expand the consortium to include a large number neuro-oncology clinical sites suitable for executing large scale clinical trials that will facilitate the generation of data to identify which imaging biomarkers are relevant for the personalization of brain tumor treatment and ultimately improvement of outcomes for patients with this devastating disease.

BIRN (Biomedical Informatics Research Network) Resources Facilitate the Personalization of Malignant Brain Tumor

BIRN (Biomedical Informatics Research Network)Resources Facilitate the Personalization of Malignant Brain Tumor

National Institute of Neurological Disorders and Stroke (NINDS)

Washington University School of Medicine

Neuralgia

Movement Disorders

Pain

Non-invasive brain intervention using MR-guided focused ultrasound

Non-invasive intervention with focused ultrasound (ExAblate 4000)

Javier - Fandino, MD

Ernst - Martin, MD

Focused Ultrasound Focused ultrasound is an attractive method for non-invasive thermal ablation of soft tissue tumors. Treatment begins by acquiring a series of MR images of the target organ. The physician then identifies a target volume in the MR images and delineates the treatment contours on the images. Therapy planning software calculates the parameters required to effectively treat the defined target volume. During the treatment an ultrasound transducer generates and focuses ultrasound energy to a focal point, called a sonication. The sonication raises the tissue temperature within a well-defined region to a degree, which causes thermal coagulation. MR images acquired during sonication provide a quantitative, real-time temperature map of the target area to confirm the location of the sonication and the size of the coagulated region. The sonication process is repeated at multiple adjacent points to cover the entire prescribed treatment volume.

Magnetic Resonance (MR) Guided Focused Ultrasound in the Treatment of Brain Tumors

MR-guided Ultrasound-Neurosurgery for the Treatment of Malignant Brain Tumors

Size of lesion in the tumor tissue for each sonication as a function of applied energy/temperature.

Number of Participants with Adverse Events as a Measure of Safety and Tolerability.

University Children's Hospital, Zurich

Diffuse Intrinsic Pontine Glioma

Brain Stem Neoplasms

Infratentorial Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Mitogens

Crenolanib

The patients are newly diagnosed Diffuse Intrinsic Pontine Glioma patients. Patients may take crenolanib as an intact tablet or crushed in apple sauce/juice. Currently accruing to dose level 3 (170 mg/m\^2).

The patients are recurrent, refractory or progressive high-grade glioma including Diffuse Intrinsic Pontine Glioma patients. Patients may take crenolanib as an intact tablet or crushed in apple sauce/juice. Currently accruing to dose level 4 (220 mg/m\^2).

Crenolanib orally administered as whole or crushed tablets once per day with concurrent Radiation Therapy. Crenolanib will continue at the same dose level post Radiation Therapy

Alberto Broniscer, MD

This is a Phase I clinical trial evaluating crenolanib (CP-868,596), an inhibitor of Platelet Derived Growth Factor Receptor (PDGFR)-kinase in children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG) (Stratum A) or in recurrent, progressive or refractory High Grade Glioma (HGG) including DIPG (Stratum B). This study drug targets the most commonly amplified region of genome found in DIPG and pediatric high grade glioma (HGG) which encodes for the PDGF receptor kinase. An oral investigational agent crenolanib will be administered daily during and after local radiation therapy (RT) in Diffuse Intrinsic Pontine Glioma DIPG (Stratum A), or daily for children with recurrent/refractory HGG (Stratum B).

Primary Objectives:

* To estimate the maximum tolerated dose (MTD) of crenolanib administered concurrently with RT in pediatric research participants with DIPG
* To estimate the MTD of crenolanib in children and young adults with recurrent/refractory HGG including DIPG
* To characterize the pharmacokinetics of crenolanib in pediatric patients and relate drug disposition to toxicity

Exploratory Secondary Objectives:

* To characterize toxicities and/or adverse events associated with the chronic use of crenolanib
* To evaluate the association between specific polymorphisms of drug metabolizing enzymes and the pharmacokinetics of crenolanib
* To evaluate changes in phosphorylation of targets of PDGF pathway activation in peripheral blood mononuclear cells and investigate the possible relationship between these changes, plasma drug levels of crenolanib and outcome measures
* To evaluate PDGFR, genotype, protein expression and DNA amplification in tumor tissue where available
* To investigate whether magnetic resonance imaging (MRI) techniques that reflect tumor pathophysiology (metabolism, oxygenation, perfusion and vessel wall integrity) are correlated with clinical response
* To characterize the neural tract involvement and tumor progression routes of pediatric brainstem glioma based upon anatomical magnetic resonance imaging and diffusion tensor imaging
* To assess the pattern of failure in radiation therapy in Stratum A participants.
* To describe the research participants' and parents' perspective of symptoms and the quality of life of children enrolled on this phase I trial
* To describe the quality of life and the impact of self-care activities of parents of pediatric research participants enrolled on this phase I trial
* To assess the impact of therapeutic alliance and social support on peace of mind, hope, anxiety/depression and quality of life among parents of pediatric research participants enrolled on this phase I trial

Stratum A- Appropriate dose RT will be administered in 30-33 fractions over approximately 6 weeks for Stratum A patients. Treatment with crenolanib will start on the same day as RT and continue daily during and after Radiation Therapy for a maximum treatment duration of 2 years. We plan to treat a maximum of 5 cohorts of research participants (dosage levels 0, 1, 2, 3, and 4) with escalating doses of crenolanib. A cycle is defined as 28 days and the first 8 weeks of therapy will constitute the dose-limiting toxicity (DLT)-evaluation period.

Stratum B - Crenolanib will be administered orally on a daily basis continuously for 28 days, which defines one cycle. The maximum treatment duration will be 2 years. We plan to treat a maximum of 5 cohorts of research participants (dosage levels 0, 1, 2, 3, and 4) with escalating doses of crenolanib. Dose escalation will be independent of Stratum A escalation. The DLT evaluation period will be four weeks.

PDGFR Inhibitor Crenolanib in Children/Young Adults With Diffuse Intrinsic Pontine Glioma or Recurrent High-Grade Glioma

Platelet Derived Growth Factor Receptor (PDGFR) Inhibitor Crenolanib in Children and Young Adults With Newly Diagnosed Diffuse Intrinsic Pontine Glioma or Recurrent High-Grade Glioma Including Diffuse Intrinsic Pontine Glioma

Individual pharmacokinetic parameters will be estimated using nonlinear mixed effects modeling methods (NONMEM) to estimate both the inter- and intra-subject variability.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
PET Imaging of Patients With Melanoma and Malignant Brain Tumors Using an 124I-labeled cRGDY Silica Nanomolecular Particle Tracer: A Microdosing Study	NCT01266096	Newly Diagnosed... Malignant Brain...	PET scan with 1...	18 Years -	Memorial Sloan Kettering Cancer Center
BIRN (Biomedical Informatics Research Network) Resources Facilitate the Personalization of Malignant Brain Tumor	NCT01124461	GLIOBLASTOMA MU... Brain Neoplasm		18 Years - 70 Years	Washington University School of Medicine
Magnetic Resonance (MR) Guided Focused Ultrasound in the Treatment of Brain Tumors	NCT01698437	Malignant Brain...	Non-invasive in...	18 Years -	University Children's Hospital, Zurich
Magnetic Resonance (MR) Guided Focused Ultrasound in the Treatment of Brain Tumors	NCT01698437	Malignant Brain...	Non-invasive in...	18 Years -	University Children's Hospital, Zurich
PDGFR Inhibitor Crenolanib in Children/Young Adults With Diffuse Intrinsic Pontine Glioma or Recurrent High-Grade Glioma	NCT01393912	Diffuse Intrins... Progressive or ...	Crenolanib	18 Months - 21 Years	St. Jude Children's Research Hospital
PET Imaging of Patients With Melanoma and Malignant Brain Tumors Using an 124I-labeled cRGDY Silica Nanomolecular Particle Tracer: A Microdosing Study	NCT01266096	Newly Diagnosed... Malignant Brain...	PET scan with 1...	18 Years -	Memorial Sloan Kettering Cancer Center

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