Clinical Research Directory

Rare CNS Tumors Outcomes &Risk

Background: Primary tumors of the brain and spine are those that start in the brain or spine. These tumors are rare, accounting for \<2% of all cancers diagnosed in the United States. Some of these tumors occur in less than 2,000 people per year. Researchers want to study a large group of people with this kind of tumor. They want to learn more about the tumors, including the risk factors related to how they develop in adults. Objective: To collect health and gene data to learn about what changes are associated with a rare CNS Tumors, to eventually screen for these changes or target the genes in treatment. Eligibility: Adult participants \>= 18 years of age who self- identify as being diagnosed with one of 12 rare CNS tumors, including: Atypical teratoid rhabdoid tumor (ATRT); Brainstem and midline gliomas; Choroid plexus tumors; Ependymoma; High grade meningioma; Gliomatosis cerebri; Medulloblastoma; Oligodendroglioma / Anaplastic oligodendroglioma; Pineal region tumors; Pleomorphic xanthroastrocytoma / Anaplastic pleomorphic xanthroastrocytoma; PNET (Supratentorial embryonal tumor); Primary CNS sarcoma / Secondary CNS sarcoma (Gliosarcoma). Design: Participants will be invited to participate through an ad on the CERN Foundation website (ependymoma), information on the Neuro-Oncology Branch website and other identified advocacy and social media sites and direct mailer to those who have already participated in the EO projects. (Registered Trademark) * Interested participants will complete an enrollment form that will be sent to the study coordinator. * The coordinator will then send the participant a consent form and schedule a time for phone consent. * Participants will complete the Rare CNS tumors Outcomes Survey and once completed, the Rare CNS tumors Risk survey. (Registered Trademark) * The questions on the Outcomes Survey will include treatment history, symptoms social and clinical information and it should take about 25-35 minutes. The Risk survey will cover their demographic information, personal medical history, family medical history and environmental exposures. This should take about 52 minutes. * Participants who have physical problems can have help with the surveys and forms. * Once the surveys are completed, participants will be mailed a kit to collect saliva for germline DNA. Participants will ship the sample to the study team in a prepaid envelope * If the sample is not sufficient, participants will be contacted to give provide an additional sample.

Exploratory Study of Effects of Radiation Therapy in Pediatric Patients With Central Nervous System Tumors

This study will analyze the effects of radiation given to children who have tumors of the central nervous system (CNS). Researchers want to learn more about changes in the quality of life that patients may experience as a result of radiation. Patients ages 21 and younger who have a primary CNS tumor and who have not received radiation previously may be eligible for this study. They will have a medical history and physical examination. Collection of blood (about 2-1/2 tablespoons) and urine will be done, as well as a pregnancy test. Patients will complete neuropsychological tests, which provide information about their changes in functioning over time. An expert in psychology will give a number of tests, and the patient's parents or guardian will be asked to complete a questionnaire about the patient's behavior. Also, patients will be given a quality of life questionnaire to complete and vision and hearing tests. The radiation itself is prescribed by patients' doctors and is not part of this study. Magnetic resonance imaging (MRI) will give researchers information about the tumor and brain, through several scanning sequences . MRI uses a strong magnetic field and radio waves to obtain images of body organs and tissues. Patients will lie on a table that slides into the enclosed tunnel of the scanner. They will need to lie still, and medication may be given to help them to do that. They may be in the scanner for up to 2 hours. As the scanner takes pictures, patients will hear knocking or beeping sounds, and they will wear earplugs to reduce the noise. A contrast agent will be administered, to allow images be seen more clearly. Blood and urine tests will be conducted after the first dose of radiation. MRI scans will be done 2 weeks after patients finish radiation therapy and again at 6 to 8 weeks, 6 months, 12 months, and yearly. Also at those follow-up periods, patients will undergo similar procedures as previously, including blood and urine tests and neuropsychological testing. Patients can remain in this study for 5 years. ...

Reduced Craniospinal Radiation Therapy and Chemotherapy in Treating Younger Patients With Newly Diagnosed WNT-Driven Medulloblastoma

This phase II trial studies how well reduced doses of radiation therapy to the brain and spine (craniospinal) and chemotherapy work in treating patients with newly diagnosed type of brain tumor called WNT)/Wingless (WNT)-driven medulloblastoma. Recent studies using chemotherapy and radiation therapy have been shown to be effective in treating patients with WNT-driven medulloblastoma. However, there is a concern about the late side effects of treatment, such as learning difficulties, lower amounts of hormones, or other problems in performing daily activities. Radiotherapy uses high-energy radiation from x-rays to kill cancer cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, vincristine sulfate, cyclophosphamide and lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving reduced craniospinal radiation therapy and chemotherapy may kill tumor cells and may also reduce the late side effects of treatment.

Safety and Efficacy of Vertebral Body-Sparing Craniospinal Irradiation With Proton Therapy in Pediatric Tumors

his is a single-center, prospective observational study in children and adolescents with central nervous system tumors who need whole-brain and whole-spine radiation therapy (craniospinal irradiation, CSI). The study uses proton therapy with a special vertebral body-sparing (VBS) technique to protect the front and center of the vertebrae, which helps preserve bone marrow function and growth. The main goals are to find safe dose limits for the vertebrae and check how often severe side effects occur. The study will also look at bone marrow preservation, spinal deformity, tumor control, survival, chemotherapy completion, neurocognitive function, quality of life, and growth and development for up to 5 years after treatment.

PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications

Background: About 90,000 new cases of brain and spinal cord tumors are diagnosed annually in the United States. Most of these tumors are benign; however, about 30% are malignant, and 35% of people with malignant tumors in the brain and spinal cord will die within 5 years. Many of these people have changes in certain genes (MYC or MYCN) that drive the development of their cancers. Objective: To test a study drug (PLX038) in people with tumors of the brain or spinal cord. Eligibility: People aged 18 years or older with a tumor of the brain or spinal cord. Some participants must also have tumors with changes in the MYC or MYCN genes. Design: Participants will be screened. They will have a physical exam and blood tests. They will have imaging scans and a test of their heart function. They may need to have a biopsy: A sample of tissue will be removed from their tumor. PLX038 is given through a tube attached to a needle inserted into a vein in the arm. All participants will receive PLX038 on the first day of each 21-day treatment cycle. They will take a second drug 3 days later to help reduce the risk of infection; for this drug, participants will be shown how to inject themselves under the skin at home. Blood tests, imaging scans, and other tests will be repeated during study visits. Hair samples will also be collected during these visits. Some participants may have an additional biopsy. Study treatment will continue up to 7 months. Follow-up visits will continue every few months for up to 5 years.

DOTATOC PET/CT for Imaging NET Patients

Neuroendocrine tumours (NETs) are generally slow growing, but some can be aggressive and resistant to treatment. Compared to healthy cells, the surface of these tumor cells has a greater number of special molecules called somatostatin receptors (SSTR). Somatostatin receptor scintigraphy and conventional imaging are used to detect NETs. This study proposes 68Gallium(68Ga)-DOTATOC positron emission tomography/computed tomography (PET/CT) is superior to current imaging techniques. The goal is to evaluate the safety and sensitivity of 68Ga-DOTATOC PET/CT at detecting NETs and other tumors with over-expression of somatostatin receptors.

Flavored, Oral Irinotecan VAL-413 (Orotecan®) Given With Temozolomide for Treatment of Recurrent Pediatric Solid Tumors

A pilot pharmacokinetic trial to determine the safety and efficacy of a flavored, orally administered irinotecan VAL-413 (Orotecan®) given with temozolomide for treatment of recurrent pediatric solid tumors including but not limited to neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, hepatoblastoma and medulloblastoma

Pharmacoscopy for Patients With Refractory Primary Brain Tumors

Advanced technology of ex vivo drug profiling referred to as pharmacoscopy may allow to identify novel drugs for the treatment of glioblastoma and other refractory brain tumors at an individual patient level. This personalized therapeutic approach was developed and validated in pre-clinical glioma models. With the current research proposal, we seek to establish feasibility for a clinical interventional trial for patients with refractory primary brain tumors that is based on pharmacoscopy-guided selection of treatment. The study is supported by an unrestricted grant from Anti Cancer Fund.

Loc3CAR: Locoregional Delivery of B7-H3-CAR T Cells for Pediatric Patients With Primary CNS Tumors

Loc3CAR is a Phase I clinical trial evaluating the use of autologous B7-H3-CAR T cells for participants ≤ 21 years old with primary CNS neoplasms. B7-H3-CAR T cells will be locoregionally administered via a CNS reservoir catheter. Study participants will be divided into two cohorts: cohort A with B7-H3-positive relapsed/refractory non-brainstem primary CNS tumors, and cohort B with diffuse midline gliomas (DMG). Participants will receive four (4) B7-H3-CAR T cell infusions over a 4 week period. The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give patients with primary brain tumors. Primary objectives * To determine the safety, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the locoregional delivery of autologous B7-H3-CAR T cells in patients ≤ 21 years of age with recurrent/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B). Secondary objectives * To assess the efficacy, defined as sustained objective response, a partial response (PR) or complete response (CR) observed anytime on active treatment with B7-H3-CAR T cells in patients with relapsed/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B). * To characterize and monitor neurologic toxicities in patients while on study (Cohort A and B).

DFMO as Maintenance Therapy for Molecular High/Very High Risk and Relapsed Medulloblastoma

Difluoromethylornithine (DFMO) will be used in an open label, multicenter, study as Maintenance Therapy for Molecular High Risk/Very High Risk and Relapsed/Refractory Medulloblastoma.

Quantitative Assessment of Radiation-induced Neuroinflammation - A Proof of Principle Study

QARIN 1 is a study of \[18F\]DPA-714 Translocation Protein (TSPO) Positron Emission Tomography (PET) for longitudinal, quantitative assessment of brain neuroinflammation following whole brain radiation therapy. This TSPO PET, uses a radioactive tracer. An optional MRI (magnetic resonance imaging) will also be performed to monitor brain microstructure damages induced by neuroinflammation. Primary Objectives * Assessment of temporal and regional variability of uptake of translocator protein (TSPO) positron emission tomography (PET) tracer. * Regional variability will be assessed in medial temporal lobe, frontal lobe, and in white matter * Temporal variability will be assessed by scanning each subject four-times: at baseline (before or within 2 weeks of start of radiation therapy), before start of chemotherapy, at 1 year from the initiation of the radiation therapy, and at 1.5-2 years from the initiation of the radiation therapy * Correlation of radiation dose in specific brain regions with radiation induced neuroinflammation as measured by uptake of TSPO PET tracer. Exploratory Objectives * Assessment of radiation-induced brain microstructure injuries (RIBMI) in specific brain regions (medial temporal lobe, frontal lobe, and in white matter) using advanced magnetic resonance imaging (MRI) techniques. * Association of radiation dose with MRI measures of RIBMI in these specific brain regions. * Association of PET measures of RIN with MRI measures of RIBMI. * Association of PET measure of RIN and MRI measures of RIBMI in specific regions of interest (ROI) with specific domain of neuro-cognition. For example, to investigate whether PET measure of RIN and MRI measures of RIBMI in hippocampal ROI have strongest association with episodic memory; whether frontal lobe cortical ROI are associated with attention and executive function. * Association of a novel MRI based technique for assessment of RIN with TSPO PET. * Association of the PET and MRI measure of neuroinflammation within 2- years of completion of radiation with delayed cognitive outcome that will be measured at 3, 4 and 5 years from the completion of radiation

CSIMEMPHIS: Long-term Follow-up of Medulloblastoma Survivors That Received Craniospinal Irradiation

The study is being done to learn more about the long-term health and well-being of participants treated for medulloblastoma. The study is to decide which evaluations focusing on therapy-related lasting effects (or toxicities) should be considered. Medulloblastoma outcomes have improved with contemporary therapies including modern neurosurgical techniques and risk-adapted radiotherapy and chemotherapy regimens. However, survivors remain at risk for long-term health problems such as neurocognitive deficits, hearing loss, impaired cardiorespiratory fitness and physical performance, cardiac and neuroendocrine dysfunction, musculoskeletal conditions, and infertility.

Methionine PET/CT Studies In Patients With Cancer

The purpose of this study is to test the usefulness of imaging with radiolabeled methionine in the evaluation of children and young adults with tumor(s). Methionine is a naturally occurring essential amino acid. It is crucial for the formation of proteins. When labeled with carbon-11 (C-11), a radioactive isotope of the naturally occurring carbon-12, the distribution of methionine can be determined noninvasively using a PET (positron emission tomography) camera. C-11 methionine (MET) has been shown valuable in the monitoring of a large number of neoplasms. Since C-11 has a short half life (20 minutes), MET must be produced in a facility very close to its intended use. Thus, it is not widely available and is produced only at select institutions with access to a cyclotron and PET chemistry facility. With the new availability of short lived tracers produced by its PET chemistry unit, St. Jude Children's Research Hospital (St. Jude) is one of only a few facilities with the capabilities and interests to evaluate the utility of PET scanning in the detection of tumors, evaluation of response to therapy, and distinction of residual tumor from scar tissue in patients who have completed therapy. The investigators propose to examine the biodistribution of MET in patients with malignant solid neoplasms, with emphasis on central nervous system (CNS) tumors and sarcomas. This project introduces a new diagnostic test for the noninvasive evaluation of neoplasms in pediatric oncology. Although not the primary purpose of this proposal, the investigators anticipate that MET studies will provide useful clinical information for the management of patients with malignant neoplasms.

Individualized Treatment Plan in Children and Young Adults With Relapsed Medulloblastoma and Ependymoma

The current study will use a new treatment approach based on the molecular characteristics of each participant's tumor. The study will test the feasibility in the pilot phase of performing real-time drug screening on tissue taken during surgery in patients with relapsed medulloblastoma or ependymoma and of having a specialized tumor board assign a treatment plan based on the results of this screening and genomic sequencing. The aim of this trial is to allow every child and young adult with relapsed medulloblastoma and ependymoma to receive the most effective and least toxic therapies currently available and will pave the way for improved understanding and treatment of these tumors in the future. Moreover, if successful, it could serve as a paradigm for personalized medicine programs for other types of cancer.

Study in Children and Adolescents of 177Lu-DOTATATE (Lutathera®) Combined With the PARP Inhibitor Olaparib for the Treatment of Recurrent or Relapsed Solid Tumours Expressing Somatostatin Receptor (SSTR) (LuPARPed).

Study in children and adolescents of 177Lu DOTATATE (Lutathera®) combined with the PARP inhibitor olaparib for treatment of recurrent or relapsed solid tumours expressing somatostatin receptors (SSTR) (LuPARPed)

Lutathera for Treatment of Recurrent or Progressive High-Grade CNS Tumors

This study will evaluate the safety and efficacy of Lutathera (177Lu-DOTATATE) in patients with progressive or recurrent High-Grade Central Nervous System (CNS) tumors and meningiomas that demonstrate uptake on DOTATATE PET. The drug will be given intravenously once every 8 weeks for a total of up to 4 doses over 8 months in patients aged 4 to \<12 years (Phase I) or 12 to \</=39 years (Phase II) to test its safety and efficacy, respectively. Funding Source - FDA OOPD (grant number FD-R-0532-01)

my.naviGATE: A Guide to After-Treatment Effects for Adolescents and Young Adults

This study aims to design and test a novel, personalized digital intervention-my.naviGATE-for adolescent and young adults (AYA) with cancer. my.naviGATE is a mobile app that provides personalized survivorship education, access to virtual peer navigation, and responsive participant-reported outcomes (PROs).

A Pilot Study of SurVaxM in Children Progressive or Relapsed Medulloblastoma, High Grade Glioma, Ependymoma and Newly Diagnosed Diffuse Intrinsic Pontine Glioma

Patients will receive a vaccine called SurVaxM on this study. While vaccines are usually thought of as ways to prevent diseases, vaccines can also be used to treat cancer. SurVaxM is designed to tell the body's immune system to look for tumor cells that express a protein called survivin and destroy them. The survivin protein can be found on up to 95% of glioblastomas and other types of cancer but is not found in normal cells. If the body's immune system knows to destroy cells that express survivin, it may help to control tumor growth and recurrence. SurVaxM will be mixed with Montanide ISA 51 before it is given. Montanide ISA 51 is an ingredient that helps create a stronger immune response in people, which helps the vaccine work better. This study has two phases: Priming and Maintenance. During the Priming Phase, patients will get one dose of SurVaxM combined with Montanide ISA 51 through a subcutaneous injection (a shot under the skin) at the start of the study and every 2 weeks for 6 weeks (for a total of 4 doses). At the same time that patients get the SurVaxM/Montanide ISA 51 injection, they will also get a second subcutaneous injection of a medicine called sargramostim. Sargramostim is given close to the SurVaxM//Montanide ISA 51 injection and works to stimulate the immune system to help the SurVaxM/Montanide ISA 51 work more effectively. If a patient completes the Priming Phase without severe side effects and his or her disease stays the same or improves, he or she can continue to the Maintenance Phase. During the Maintenance Phase, the patient will get a SurVaxM/Montanide ISA 51 dose along with a sargramostim dose about every 8 weeks for up to two years. After a patient finishes the study treatment, the doctor and study team will continue to follow his/her condition and watch for side effects up to 3 years following the last dose of SurVaxM/Montanide ISA 51. Patients will be seen in clinic every 3 months during the follow-up period.

PEP-CMV + Nivolumab for Newly Diagnosed Diffuse Midline Glioma/High-grade Glioma and Recurrent Diffuse Midline Glioma/High-grade Glioma, Medulloblastoma, and Ependymoma

This is a multisite, phase I/II clinical trial in children and young adults with newly-diagnosed high-grade glioma (HGG), diffuse midline glioma (DMG) and recurrent HGG/DMG, Medulloblastoma (MB), or ependymoma (EPN) to determine the safety, immunogenicity, and efficacy of a CMV-directed peptide vaccine plus checkpoint blockade.

Brain Tumor-Specific Immune Cells (IL13Ralpha2-CAR T Cells) for the Treatment of Leptomeningeal Glioblastoma, Ependymoma, or Medulloblastoma

This phase I trial investigates the side effects of brain tumor-specific immune cells (IL13Ralpha2-CAR T cells) in treating patients with leptomeningeal disease from glioblastoma, ependymoma, or medulloblastoma. Immune cells are part of the immune system and help the body fight infections and other diseases. Immune cells can be engineered to destroy brain tumor cells in the laboratory. IL13Ralpha2-CAR T cells is brain tumor specific and can enter and express its genes in immune cells. Giving IL13Ralpha2-CAR T cells may better recognize and destroy brain tumor cells in patients with leptomeningeal disease from glioblastoma, ependymoma or medulloblastoma.

Digoxin Medulloblastoma Study

The purpose of this study is to evaluate the efficacy of digoxin in treating relapsed non-SHH, non-WNT medulloblastoma in pediatric and young adult patients.

Phase I Study of APX005M in Pediatric Central Nervous System Tumors

This phase I trial studies the side effects and best dose of APX005M in treating younger patients with primary malignant central nervous system tumor that is growing, spreading, or getting worse (progressive), or newly diagnosed diffuse intrinsic pontine glioma. APX005M can trigger activation of B cells, monocytes, and dendritic cells and stimulate cytokine release from lymphocytes and monocytes. APX005M can mediate a direct cytotoxic effect on CD40+ tumor cells.

HeadStart4: Newly Diagnosed Children (<10 y/o) With Medulloblastoma and Other CNS Embryonal Tumors

This is a prospective randomized clinical trial, to determine whether dose-intensive tandem Consolidation, in a randomized comparison with single cycle Consolidation, provides an event-free survival (EFS) and overall survival (OS). The study population will be high-risk patients (non-Wnt and non-Shh sub-groups) with medulloblastoma, and for all patients with central nervous system (CNS) embryonal tumors completing "Head Start 4" Induction. This study will further determine whether the additional labor intensity (duration of hospitalizations and short-term and long-term morbidities) associated with the tandem treatment is justified by the improvement in outcome. It is expected that the tandem (3 cycles) Consolidation regimen will produce a superior outcome compared to the single cycle Consolidation, given the substantially higher dose intensity of the tandem regimen, without significant addition of either short-term or long-term morbidities.

Molecular and Clinical Risk-Directed Therapy for Infants and Young Children With Newly Diagnosed Medulloblastoma

This is a multi-center, multinational phase 2 trial that aims to explore the use of molecular and clinical risk-directed therapy in treatment of children 0-4.99 years of age with newly diagnosed medulloblastoma.