Clinical Research Directory

Mirdametinib to Reduce the Size of Large/Giant Congenital Melanocytic Nevi in Children, Adolescents and Young Adults

Background: Large and giant congenital melanocytic nevi (LGCMN) are dark birthmarks (moles). They can grow to 8 inches or more across. People with LGCMN have an increased risk of getting skin cancer or problems with the nervous system. Researchers want to find out if a drug approved for a different use (mirdametinib) can shrink the size of LGCMN. Objective: To test mirdametinib in people with LGCMN. Eligibility: People aged 3 to 40 years with LGCMN. Design: Participants will be screened. Their LGCMN sites will be measured and photographed. They will have blood tests, an eye exam, and tests of their heart function. They will also have: * An exam of their nervous system: Their muscle strength, ability to feel and touch, balance, alertness, and other skills will be tested. * Magnetic resonance imaging (MRI) scan: They will lie on a bed that slides into a tube; the scan will use large magnets to create images of their brain and spinal cord. * Skin biopsy: A small sample of their skin may be taken. * VECTRA scan: This is a 3-dimensional imaging system that takes pictures of all of the skin all at once. Mirdametinib will be either pills or capsules that are taken by mouth. Participants will take the drug in 4-week cycles. They will take the pills 2 times a day for 3 weeks with 1 week off. Participants may continue taking the drug for 2 years. They will have clinic visits 12 times while taking the drug. Imaging scans and other tests will be repeated. Participants will continue to have checkups every 6 months for 3 more years.

A Study of SRN-101 Gene Therapy in Adults With Recurrent High-Grade Glioma (ALERT-1)

ALERT-1 is a Phase 1/2 study evaluating the safety and preliminary anti-tumor activity of SRN-101, an investigational gene therapy, in adults with recurrent high-grade glioma. High-grade glioma is a type of brain cancer. This study is for adults whose cancer has returned for the first time and for whom surgical removal of the tumor is not planned. SRN-101 uses an adeno-associated virus (AAV) to deliver a gene for human interferon beta, a protein within the tumor. The safety and effectiveness of SRN-101 in this setting have not been established. Each participant will receive one infusion of SRN-101 directly into the brain tumor during an MRI-guided procedure. The study will first evaluate different dose levels and then evaluate a selected dose in additional participants. Participants will have MRI scans, blood tests and other health assessments, and follow-up visits to assess safety and changes in their cancer.

Implantable Microdevice In Primary Brain Tumors

This pilot study will assess the safety and feasibility of using an implantable microdevice to measure local intratumor response to chemotherapy and other clinically relevant drugs in malignant brain tumors. * The device involved in this study is called a microdevice. * The drugs used in this study will only include drugs already used systemically for the treatment of gliomas.

Hypofractionation Trial of Re-irradiation in Good Prognosis Recurrent Glioblastoma

Background: Glioblastoma (GBM) is a cancer of the brain. Current survival rates for people with GBM are poor; survival ranges from 5.2 months to 39 months. Most tumors come back within months or years after treatment, and when they do, they are worse: Overall survival drops to less than 10 months. No standard treatment exists for people whose GBM has returned after radiation therapy. Objective: To find a safe schedule for using radiation to treat GBM tumors that returned after initial radiation treatment. Eligibility: People aged 18 years and older with grade 4 GBM that returned after initial radiation treatment. Design: Participants will be screened. They will have a physical exam with blood tests. A sample of tumor tissue may be collected. Participants will undergo re-irradiation planning: They will wear a plastic mask over their head during imaging scans. These scans will pinpoint the exact location of the tumor. This spot will be the target of the radiation treatments. Participants will undergo radiation treatment 4 times per week. Some people will have this treatment for 3 weeks, some for 2 weeks, and some for 1 week. Blood tests and other exams will be repeated at each visit. Participants will complete questionnaires about their physical and mental health. They will answer these questions before starting radiation treatment; once a week during treatment; and at intervals for up to 3 years after treatment ends. Participants will have follow-up visits 1 month after treatment and then every 2 months for 6 months. Follow-up clinic visits will continue up to 3 years. Follow-ups by phone or email will continue an additional 2 years.

Proton Therapy Research Infrastructure- ProTRAIT- Neuro-oncology

The first proton therapy treatments in the Netherlands have taken place in 2018. Due to the physical properties of protons, proton therapy has tremendous potential to reduce the radiation dose to the healthy, tumour-surrounding tissues. In turn, this leads to less radiation-induced complications, and a decrease in the formation of secondary tumours. The Netherlands has spearheaded the development of the model-based approach (MBA) for the selection of patients for proton therapy when applied to prevent radiation-induced complications. In MBA, a pre-treatment in-silico planning study is done, comparing proton and photon treatment plans in each individual patient, to determine (1) whether there is a significant difference in dose in the relevant organs at risk (ΔDose), and (2) whether this dose difference translates into an expected clinical benefit in terms of NormalTissue Complication Probabilities (ΔNTCP). To translate ΔDose into ΔNTCP, NTCP-models are used, which are prediction models describing the relation between dose parameters and the likelihood of radiation-induced complications. The Dutch Society for Radiotherapy and Oncology (NVRO) setup the selection criteria for proton therapy in 2015, taking into account toxicity and NTCP. However, NTCP-models can be affected by changes in the irradiation technique. Therefore, it is paramount to continuously update and validate these NTCP-models in subsequent patient cohorts treated with new techniques. In ProTRAIT, a Findable, Accessible, Interoperable and Reusable (FAIR)data infrastructure for both clinical and 3D image and 3D dose information has been developed and deployed for proton therapy in the Netherlands. It allows for a prospective, standardized, multi-centric data from all Dutch proton and a representative group of photon therapy patients.

Pre-Radiation Chemotherapy for Newly Diagnosed High-Grade Glioma.

Better treatments are needed for high-grade gliomas (HGG), and new ways of treating this disease should be tested. The investigators want to see if giving medicine before radiation works well. After radiation, MRI scans can be harder to understand because radiation changes how the brain looks on the scan. If new medicines are given before radiation, the scans are easier to read. First, the investigators need to find out if giving chemotherapy early works using a drug we already know can treat gliomas. The investigators will start with temozolomide, which is the only chemotherapy approved by the FDA for HGG. If this approach is successful, the investigators can then test new drugs using this screening method.

Phase II Elderly/Frail Pts With Newly Diagnosed or Recurrent Malignant Glioma Treated With Cesium-131 GammaTile®

This is a phase 2, open-label clinical trial determining feasibility, safety, and tolerability of GammaTile® in elderly or frail subjects with newly diagnosed or recurrent malignant gliomas.

Insights Into the Pathophysiology of Neurovascular Uncoupling in Patients With Brain Lesions.

Neurovascular uncoupling (NVU) represents a major source of potential bias for the identification of eloquent brain regions through activation procedures in blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). Same region shows proper pattern in glucose metabolism in victiny of brain lesions, investigated with positron emitted tomography with radiolabeled glucose (PET-FDG) This research project aims at investigating the mechanisms of NVU by using a multimodal noninvasive imaging approach in neurosurgical patients.

FearLess in NeuroOncology

The overarching goal of this project is to assess the feasibility, acceptability, and appropriateness of recruitment methods, target population, and a waitlist design to finalize the protocol of FearLess in primary malignant brain tumor patients and caregivers

HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors

This study is a clinical trial to determine the safety of inoculating G207 (an experimental virus therapy) into a recurrent or refractory cerebellar brain tumor. The safety of combining G207 with a single low dose of radiation, designed to enhance virus replication, tumor cell killing, and an anti-tumor immune response, will also be tested. Funding Source- FDA OOPD

Study of Olutasidenib and Temozolomide in HGG

The goal of this study is to determine the efficacy of the study drug olutasidenib to treat newly diagnosed pediatric and young adult patients with a high-grade glioma (HGG) harboring an IDH1 mutation. The main question the study aims to answer is whether the combination of olutasidenib and temozolomide (TMZ) can prolong the life of patients diagnosed with an IDH-mutant HGG.

Pediatric Long-Term Follow-up and Rollover Study

A roll-over study to assess long-term effect in pediatric patients treated with dabrafenib and/or trametinib.

Mycophenolate Mofetil in Combination With Standard of Care for the Treatment of Glioblastoma

This phase I/Ib trial tests the safety, side effects, and best dose of mycophenolate mofetil in combination with temozolomide and/or radiation therapy (standard of care) in treating patients with glioblastoma. Mycophenolate mofetil is an immunosuppressant drug that is typically used to prevent organ rejection in transplant recipients. However, mycophenolate mofetil may also help chemotherapy with temozolomide work better by making tumor cells more sensitive to the drug. The purpose of this trial is to determine if mycophenolate mofetil combined with temozolomide can stop glioblastoma.

Adaptive Radiotherapy and MRIs Based on Patients With Newly Diagnosed High-Grade Glioma

The purpose of this study is to find out if performing additional Magnetic Resonance Image (MRI) scans of the subjects' brain during each week of the radiation treatment of their high-grade glioma will help improve the radiation treatment.

A Phase IB 2 Dose Trial of IRS-1 HSV C134 (IND 17296) Administered Intratumorally in Patients With Recurrent Malignant Glioma

The purpose of this study is to determine how safe and how well-tolerated the experimental study drug, C134 is when administered twice into the brain where the tumor is located. This is a Phase IB 2 dosing study. All the patients who take part in this study will receive the same type of experimental treatment. There is no "placebo" in this study. The patient will receive the dose of C134 administered, which will be added in the tumor infiltrated tissue in the area of the resection cavity. Anywhere from 4-12 patients are expected to take part in the study; the final number will depend on the safety results.

Clinical Benefit of Using Molecular Profiling to Determine an Individualized Treatment Plan for Patients With High Grade Glioma

This is a 2 strata pilot trial within the Pacific Pediatric Neuro-Oncology Consortium (PNOC). The study will use a new treatment approach based on each patient's tumor gene expression, whole-exome sequencing (WES), targeted panel profile (UCSF 500 gene panel), and RNA-Seq. The current study will test the efficacy of such an approach in children with High-grade gliomas HGG.

Social Determinants of Health in Glioblastoma Population

The overall aim of this study is to prospectively characterize social health disparities in a cross-sectional cohort of glioma patients with attention to exploring and thematically categorizing the patient-specific and community-level factors. This will be conducted in two parts.

Ketoconazole Before Surgery in Treating Patients With Recurrent Glioma or Breast Cancer Brain Metastases

This trial studies the side effects and how well ketoconazole works before surgery in treating patients with glioma that has come back or breast cancer that has spread to the brain. Ketoconazole is an antifungal drug that may be able to block a protein, tGLI1 and may help to treat brain tumors.

GliomaAI-Astro4: MRI-Based Detection of IDH Mutant Astrocytoma Grade 4

The goal of this observational study is to learn whether an artificial intelligence system called GliomaAI-Astro4 can help detect a specific molecular type of brain tumour called IDH mutant Astrocytoma Grade 4 using routine MRI scans. The study uses previously collected and fully anonymised MRI data from 1,372 patients from 13 institutions in the Cancer Imaging Archive (TCIA). The main questions it aims to answer are: * How accurately can GliomaAI-Astro4 identify IDH mutant Astrocytoma Grade 4 from MRI scans? * How well does the system perform across data from different hospitals and patient groups? Researchers will use existing MRI scans and clinical information to train and test the AI system. No new scans, treatments, or hospital visits are required for participants, and all data used is fully anonymised and obtained from an existing research database. Participants will not be asked to do anything, as this study only uses previously collected imaging data.

GliomaAI-Astro23: MRI-Based Detection of IDH Mutant Astrocytoma (Grade 2 and 3)

The goal of this observational study is to learn whether an artificial intelligence system called GliomaAI-Astro23 can help detect a specific molecular type of brain tumour called IDH mutant Astrocytoma (grade 2 and 3) using routine MRI scans. The study uses previously collected and fully anonymised MRI data from 1,372 patients from 13 institutions in the Cancer Imaging Archive (TCIA). The main questions it aims to answer are: * How accurately can GliomaAI-Astro23 identify IDH mutant Astrocytoma (grade 2 and 3) from MRI scans? * How well does the system perform across data from different hospitals and patient groups? Researchers will use existing MRI scans and clinical information to train and test the AI system. No new scans, treatments, or hospital visits are required for participants, and all data used is fully anonymised and obtained from an existing research database. Participants will not be asked to do anything, as this study only uses previously collected imaging data.

Astrocytoma / Desmoplastic Gamliogliomes (DIA / DIG) - Study of the French Cohort of the Last 20 Years : Clinical, Anatomopathological, Molecular and Radiological Charactersics

Astrocytomas / infantile desmoplastic gangliogliomas (DIA / DIG) are rare brain tumors usually affecting infants. They represent about 0.5% of all pediatric brain tumors. DIA / DIG occurs mainly in the first 2 years of life, with a sex ratio M / F of 1.7 to 1. From a histological point of view, DIA / DIG are neuroepithelial tumors. These tumors may have a purely astrocytic differentiation (DIA) or be composed of tumor cells with astrocytic and neuronal differentiation (DIG). The desmoplastic component is usually adjacent to the meninges and is defined by the increase or modification of connective tissues related to the presence of neoplastic cells with the formation of a collagen-rich extracellular matrix. Due to their benign biological behavior and favorable clinical course, they are classified in benign tumors, ie grade I according to the WHO classification. However, all tumors called DIA / DIG do not behave in a benign manner. Cases of metastatic cerebrospinal and malignant disorders have been described. It appears that about 40% of DIG cases require additional medical treatment such as chemotherapy, radiotherapy and / or new surgery, and 15% of infants and children with GIDD die from the disease. It is possible that what is grouped within the DIA / DIG is a heterogeneous group of tumors, evolution and prognosis very variable. The cytogenetic knowledge of DIA / DIG is very limited and is only available on small numbers of cases. Cytogenetic analyzes of several cases of DIG showed normal karyotypes. More recently, a CGH-Array study of 3 cases of DIA / DIG did not find any significant chromosomal gains or losses. It has been shown, however, that a mutation involving BRAF (BRAF rearrangement or BRAF V600E mutations) was a recurrent element in low grade gliomas, particularly in pediatric patients. It is also suggested that deregulation of BRAF activity in some DIA / DIG may indicate the importance of the MAPK (mitogen-activated protein kinase) pathway in signaling pathways for DIA / DIG development. However, data on the link between the BRAF gene and DIA / DIG remains very limited. Thus, further studies are needed to study the other members of the MAPK pathway in DIA / DIG (eg PI3K / AKT / mTOR). This could provide new therapeutic possibilities involving targeted therapies specific to the MAPK signaling pathway. It appears that DIA / DIG does not all behave in a benign manner and some would undergo a malignant transformation that could be due to chromosomal alterations such as, for example, TP53, PI3K. In addition, because of the limited number of cases, it would be interesting to study the characteristics of patients with DIA / DIG in order to study their characteristics and whether there are clinical, pathological, cytogenetic and / Molecular forms between benign and malignant forms.

First-in Cancer-Type Phase I Study of FT536 for Recurrent WHO Grade 4 Astrocytoma

This is a single center, first-in cancer-type phase I clinical trial of FT536 for adult patients with recurrent WHO Grade 4 astrocytoma, irrespective of IDH-mutational status, for which a standard of care repeat craniotomy for gross tumor resection at time of first or second recurrence is achievable. Per this treatment schema, FT536 will be administered once intratumorally

Investigational Imaging Technique During Brain Surgery

This early phase I trial tests the safety and reliability of an investigational imaging technique called quantitative oblique back illumination microscopy (qOBM) during brain surgery for detecting brain tumors and brain tumor margins in patients with glioblastoma, astrocytoma, or oligodendroglioma. Surgical margins refer to the edge or border of the tissue removed in cancer surgery. qOBM may be able to assess and reveal brain tumor surgical margins in a more safe and reliable manner.

Tuvusertib in Astrocytoma With ATRX Mutation

The TUVASTRAT study is a phase 2, non-randomized, two.cohort, CRS clinical trial of tuvusertib in patients with first recurrence of IDH1/2-mutated, ATRX-mutated and p53-mutated astrocytoma (Grade 2-4 from WHO classification). The mutational status of IDH (required for diagnosis) is also required. CDKN2A and ATRX will be also determined locally as per standard of care. All enrolled patients should have received first-line chemotherapy and have reported a contrast enhanced PD. Eligible patients are enrolled in two cohorts depending on their eligibility to undergo rescue surgery: * Cohort A: First recurrence of IDH1/2-mutated, ATRX-mutated astrocytoma NOT eligible for rescue surgery. * Cohort B: First recurrence of IDH1/2-mutated, ATRX-mutated astrocytoma candidates to rescue surgery. The primary hypothesis is that treatment with tuvusertib, an ATR inhibitor, will improve the efficacy outcomes and increase the 6-months PFS rate from 45% reported by the standard therapies up to 65% in patients with recurrent IDH-mutated astrocytomas with ATRX mutation. Clinic visits will occur every 3 weeks ±3 days. Tumor assessments by MRI according to RANO 2.0 criteria will be performed at baseline, and every 12 weeks +/-2 weeks (Q12W) until PD, patient withdrawal, start of new treatment line or death. This schedule must be maintained regardless of any delays in dosing. After the first suspect of progression, we recommend a second MRI at 4-8 weeks to confirm the progression, except if there is clinical progression. The MRI imaging will be assessed by PI and central radiologists. The trial includes the assessment of safety (AEs, comorbidities) throughout the study period at every visit, the collection of health-related patient reported outcomes through validated questionnaires at baseline, coincident with the tumor assessments and at the safety visit. Neurologic / neurocognitive status will be assessed through validated tests administered by the physicians. Additionally, ATRX, IDH, P53 and CDK2A mutations will be centrally reviewed in tumor biopsies or archival tumor tissue obtained as close as possible to the baseline. PKs will be determined in sparse peripheral blood samples during the treatment phase. The study includes a data safety monitoring committee (DSMC) to regularly review safety and efficacy. The DSMC will review efficacy and safety at least yearly and more frequently if deemed necessary.