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69 Study Matches
Optical Coherence Tomography Angiography in Neurological Disease
Optical Coherence Tomography Angiography (OCTA) is a non-invasive tool that images the neurovascular structures of the eye by using near-infrared light. Previous literature has demonstrated the potential of OCTA as a screening tool in stroke, but its utility in other neurological illness such as intracranial hemorrhage is unclear. Hence, this pilot study will gather preliminary data to support future grant applications to investigate this area more fully by recruiting patients with neurological illness and healthy controls and comparing their OCTA imaging parameters.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Emily.Melikman@UTSouthwestern.edu
Noah Jouett
ALL
18 Years to old
NCT06797765
STU-2024-0876
Inclusion Criteria:
* Age 18 years or older
* Patient admitted to the neuroscience intensive care unit with a diagnosis of: subarachnoid hemorrhage, intracerebral hemorrhage, intracranial aneurysm (ruptured or unruptured), intracranial vascular malformation, ischemic stroke, seizure disorder, intracranial infection, intracranial tumor(s), inflammatory demyelinating disease, traumatic brain injury and/or neuromuscular respiratory failure OR subjects from the community without major neurologic, cardiovascular, pulmonary or metabolic disease
Exclusion Criteria:
* Pregnancy
* Non-English speaking
* GCS motor score less than 6 (i.e. must be able to follow commands)
* Temporary or permanent physical limitation that renders the patient unable to sit up and look inside OCTA device DEVICE: OCTA
Octa, Stroke, Subarachnoid Hemorrhage, Intracerebral Hemorrhage, Brain and Nervous System
UT Southwestern
Treatment ResistAnt Depression Subcallosal CingulatE Network DBS (TRANSCEND) (TRANSCEND)
The goal of this clinical trial is to evaluate the effectiveness and safety of bilateral stimulation of the subcallosal cingulate white matter (SCCwm) using Deep Brain Stimulation (DBS) as an adjunctive treatment of non-psychotic unipolar Major Depressive Disorder (MDD) in adults.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Hila.AbushSegev@UTSouthwestern.edu
Kala Bailey
ALL
22 Years to 70 Years old
NA
NCT06423430
STU-2024-0461
*
• The patient must be diagnosed with non-psychotic unipolar Major Depressive Disorder.
• The patient must be in a major depressive episode for ≥12 months or have had at least 3 lifetime depressive episodes.
• The patient has tried and failed a minimum of four different types of antidepressant treatments as measured by a tool designed for this purpose.
• Depression medication and treatment regimen must be stable for a minimum of 4 weeks before the first baseline visit *
• Pregnant or those who plan to become pregnant during study
• Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that could limit participation in the study or interfere with adherence to the study protocol.
• Current or lifetime history of psychotic features in any Major Depressive Episode.
• Has an intracranial Central Nervous System disease that impairs motor, sensory or cognitive function or that requires intermittent or chronic medication.
• Significant acute suicide risk.
• Diagnosis of Substance Use Disorder or Alcohol Use Disorder without sustained remission (12 months or longer).
• Current and ongoing use of neurostimulation treatment that may interfere with DBS therapy/system.
• Treatment with another investigational device or investigational drugs.
Inclusion Criteria:
• The patient must be diagnosed with non-psychotic unipolar Major Depressive Disorder.
• The patient must be in a major depressive episode for ≥12 months or have had at least 3 lifetime depressive episodes.
• The patient has tried and failed a minimum of four different types of antidepressant treatments as measured by a tool designed for this purpose.
• Depression medication and treatment regimen must be stable for a minimum of 4 weeks before the first baseline visit *
Exclusion Criteria:
• Pregnant or those who plan to become pregnant during study
• Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that could limit participation in the study or interfere with adherence to the study protocol.
• Current or lifetime history of psychotic features in any Major Depressive Episode.
• Has an intracranial Central Nervous System disease that impairs motor, sensory or cognitive function or that requires intermittent or chronic medication.
• Significant acute suicide risk.
• Diagnosis of Substance Use Disorder or Alcohol Use Disorder without sustained remission (12 months or longer).
• Current and ongoing use of neurostimulation treatment that may interfere with DBS therapy/system.
• Treatment with another investigational device or investigational drugs.
DEVICE: Sham-stimulation, DEVICE: Active-stimulation
Treatment Resistant Depression, Psychiatric Disorders
DBS, Major Depressive Disorder, Bilateral Stimulation, Antidepressant Treatment, neurostimulation, ABT-CIP-10494
UT Southwestern
Study of the Clinical and Radiological Impact of Ravulizumab in People With Neuromyelitis Optica Spectrum Disorder (AMAZE)
This is an observational study to: * evaluate the on-treatment clinical performance of ravulizumab in relation to the pre-treatment time period (time period prior to exposure), * enhance knowledge regarding conventional MRI outcomes in people with NMOSD treated with ravulizumab, * identify factors suggestive of subclinical disease progression through conventional MRI sequences, * determine if treatment with ravulizumab, impacts longitudinal 3D conformational MRI measures at the dorsal medulla and other regions of the CNS, and * identify biomarkers (e.g., serum neurofilament light chain (sNfL), conventional and novel MRI markers, etc.) related to disease activity.
Call 214-648-5005
studyfinder@utsouthwestern.edu, JOSE.SANTOYO@UTSouthwestern.edu
Darin Okuda
ALL
18 Years to old
NCT06398158
STU-2023-0744
Inclusion Criteria:
• Signed informed consent available prior to conduct of any study associated activities
• Men and women \> 18 years of age
• Aquaporin-4 IgG positive people with neuromyelitis optica spectrum disorder treated with commercially available ravulizumab in a manner consistent with the approved indication
• Expanded Disability Status Scale score of \<7.0
Exclusion Criteria:
• Individuals who are intolerant to MRI
• Individuals previously exposed to eculizumab with treatment discontinuation due to lack of effective disease control (i.e., clinical relapse or demonstration of MRI advancement after 12 weeks of sustained treatment exposure)
• Unresolved meningococcal disease
• History of an active infection
• Existing participation in neuromyelitis optical spectrum disorder interventional clinical studies
• Pregnant or lactating women
DRUG: Ravulizumab
Neuromyelitis Optica, Brain and Nervous System
UT Southwestern
Dinutuximab With Chemotherapy, Surgery and Stem Cell Transplantation for the Treatment of Children With Newly Diagnosed High Risk Neuroblastoma
This phase III trial tests how well the addition of dinutuximab to Induction chemotherapy along with standard of care surgical resection of the primary tumor, radiation, stem cell transplantation, and immunotherapy works for treating children with newly diagnosed high-risk neuroblastoma. Dinutuximab is a monoclonal antibody that binds to a molecule called GD2, which is found on the surface of neuroblastoma cells, but is not present on many healthy or normal cells in the body. When dinutuximab binds to the neuroblastoma cells, it helps signal the immune system to kill the tumor cells. This helps the cells of the immune system kill the cancer cells, this is a type of immunotherapy. When chemotherapy and immunotherapy are given together, during the same treatment cycle, it is called chemoimmunotherapy. This clinical trial randomly assigns patients to receive either standard chemotherapy and surgery or chemoimmunotherapy (chemotherapy plus dinutuximab) and surgery during Induction therapy. Chemotherapy drugs administered during Induction include, cyclophosphamide, topotecan, cisplatin, etoposide, vincristine, and doxorubicin. These drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing or by stopping them from spreading. Upon completion of 5 cycles of Induction therapy, a disease evaluation is completed to determine how well the treatment worked. If the tumor responds to therapy, patients receive a tandem transplantation with stem cell rescue. If the tumor has little improvement or worsens, patients receive chemoimmunotherapy on Extended Induction. During Extended Induction, dinutuximab is given with irinotecan, temozolomide. Patients with a good response to therapy move on to Consolidation therapy, when very high doses of chemotherapy are given at two separate points to kill any remaining cancer cells. Following, transplant, radiation therapy is given to the site where the cancer originated (primary site) and to any other areas that are still active at the end of Induction. The final stage of therapy is Post-Consolidation. During Post-Consolidation, dinutuximab is given with isotretinoin, with the goal of maintaining the response achieved with the previous therapy. Adding dinutuximab to Induction chemotherapy along with standard of care surgical resection of the primary tumor, radiation, stem cell transplantation, and immunotherapy may be better at treating children with newly diagnosed high-risk neuroblastoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
ALL
to 30 Years old
PHASE3
NCT06172296
STU-2024-0471
Inclusion Criteria:
* Patients must be enrolled on APEC14B1 and have consented to testing through the Molecular Characterization Initiative (MCI), prior to enrollment on ANBL2131
* ≤ 30 years at the time of initial diagnosis with high-risk disease
* \* Must have a diagnosis of neuroblastoma (NBL) or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamines
* Newly diagnosed, high risk neuroblastoma (HRNBL) defined as one of the following:
* Any age with International Neuroblastoma Risk Group (INRG) Stage L2, MS, or M and MYCN amplification
* Age ≥ 547 days and INRG stage M regardless of biologic features (clinical MYCN testing not required prior to enrollment)
* Any age initially diagnosed with INRG Stage L1 MYCN amplified NBL who have progressed to stage M without systemic chemotherapy
* Age ≥ 547 days of age initially diagnosed with INRG Stage L1, L2, or MS who have progressed to stage M without systemic chemotherapy (clinical MYCN testing not required prior to enrollment)
* Patients must have a body surface area (BSA) ≥ 0.25 m\^2
* No prior anti-cancer therapy except as outlined below:
* Patients initially recognized to have high-risk disease treated with topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing, and with consent
* Patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high-risk disease but subsequently found to meet the criteria
* Patients who received localized emergency radiation to sites of life threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis
* Human immunodeficiency virus (HIV) -infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* A serum creatinine based on age/sex as follows:
* 1 month to \< 6 months: Male 0.4 mg/dL and female 0.4mg/dL
* 6 months to \< 1 year: Male 0.5 mg/dL and female 0.5 mg/dL
* 1 to \< 2 years: Male 0.6 mg/dL and female 0.6 mg/dL
* 2 to \< 6 years: Male 0.8 mg/dL and female 0.8 mg/dL
* 6 to \< 10 years: Male 1 mg/dL and female 1 mg/dL
* 10 to \< 13 years: Male 1.2 mg/dL and female 1.2 mg/dL
* 13 to \< 16 years: Male 1.5 mg/dL and female 1.4 mg/dL
* ≥ 16 years: Male 1.7 mg/dL and female 1.4 mg/dL
* The threshold creatinine values were derived from the Schwartz formula for estimating glomerular filtration rate (GFR) utilizing child length and stature data published by the Centers for Disease Control (CDC)
* or a 24-hour urine creatinine clearance ≥ 70 mL/min/1.73 m\^2 or
* or a GFR ≥ 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method or direct small molecule clearance method (iothalamate or other molecule per institutional standard)
* Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
* Serum glutamic pyruvic transaminase (SGPT) (Alanine aminotransferase \[ALT\]) ≤ 10 x ULN\*
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* \* Shortening fraction of ≥ 27% by echocardiogram, or
* Ejection fraction of ≥ 50% by echocardiogram or radionuclide angiogram
* Ability to tolerate Peripheral Blood Stem Cell (PBSC) collection:
No known contraindication to PBSC collection. Examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
Exclusion Criteria:
* Patients who are 365-546 days of age with INRG Stage M and MYCN non-amplified NBL, irrespective of additional biologic features
* Patients ≥ 547 days of age with INRG Stage L2, MYCN non-amplified NBL, regardless of additional biologic features
* Patients with known bone marrow failure syndromes
* Patients on chronic immunosuppressive medications (e.g., tacrolimus, cyclosporine, corticosteroids) for reasons other than prevention/treatment of allergic reactions and adrenal replacement therapy are not eligible. Topical and inhaled corticosteroids are acceptable
* Patients with a primary immunodeficiency syndrome who require ongoing immune globulin replacement therapy
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required prior to enrollment for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, food and drug administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, BIOLOGICAL: Dinutuximab, DRUG: Doxorubicin, PROCEDURE: Echocardiography Test, DRUG: Etoposide, PROCEDURE: FDG-Positron Emission Tomography and Computed Tomography Scan, PROCEDURE: Hematopoietic Cell Transplantation, DRUG: Irinotecan, DRUG: Isotretinoin, PROCEDURE: Leukapheresis, PROCEDURE: Magnetic Resonance Imaging, DRUG: Melphalan, PROCEDURE: Multigated Acquisition Scan, RADIATION: Radiation Therapy, PROCEDURE: Radionuclide Imaging, OTHER: Survey Administration, DRUG: Temozolomide, DRUG: Thiotepa, DRUG: Topotecan, PROCEDURE: Tumor Resection, DRUG: Vincristine
Ganglioneuroblastoma, Nodular, Neuroblastoma, Brain and Nervous System
Children’s Health
A Study to Estimate How Often Post-stroke Spasticity Occurs and to Provide a Standard Guideline on the Best Way to Monitor Its Development (EPITOME)
This study will monitor patients during the first year following their stroke. Stroke is a very serious condition where there is a sudden interruption of blood flow in the brain. The main aim of the study will be to find out how many of those who experience their first-ever stroke then go on to develop spasticity that would benefit from treatment with medication. Spasticity is a common post-stroke condition that causes stiff or ridged muscles. The results of this study will provide a standard guideline on the best way to monitor the development of post-stroke spasticity.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Victoria.Castillo@UTSouthwestern.edu
Fatma Gul
ALL
18 Years to 90 Years old
NCT06055725
STU-2023-1049
Inclusion Criteria:
* Participant must be aged 18 to 90 years at the time of providing informed consent
* First-ever clinical stroke, defined according to World Health Organization criteria as rapidly developing clinical signs of focal (at times global) disturbance of cerebral function lasting more than 24 hours, within the past 4 weeks;
* Confirmed paresis of the arms and/or legs which does not resolve within 1 day, according to the NIHSS score (a score of \> 0 on Question 5 or 6 of the scale) between Day 3 and day 14 after the stroke
* Capable of giving informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol
Exclusion Criteria:
* Upper or lower extremity functional impairment prior to stroke per investigator judgement (e.g., modified Rankin Scale \>2);
* Presence of significant/major neurological impairment that might affect muscle tone (other than limb paresis);
* Severe multi-impairment or diminished physical condition before stroke that could have caused paresis/spasticity/motor deficit per investigator judgement;
* Life expectancy of less than 12 months as a result of severity of stroke or other illnesses (e.g. cardiac disease, malignancy, etc.)
* Participation in any interventional study Spasticity as Sequela of Stroke
UT Southwestern
Transcutaneous Auricular Neurostimulation After Lumbar Fusion Surgery
The purpose of this study, entitled "Delivering Transcutaneous Auricular Neurostimulation as an Adjunct Non-Opioid Pain Management Therapy for Patients Undergoing Lumbar Fusion Surgery", is to demonstrate whether transcutaneous auricular neurostimulation (tAN) can non-invasively reduce the perception of pain in patients undergoing lumbar fusion surgery. tAN is placed on and around the ear to non-invasively stimulate branches of the vagus and trigeminal nerves and modulate specific brain regions associated with pain.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Aisha.Qureshi@UTSouthwestern.edu
Alex Valadka
ALL
18 Years to 85 Years old
NA
NCT06100172
STU-2023-0197
Inclusion Criteria:
• Medically cleared to undergo a lumbar fusion surgery
• 18-85 years of age
• English Proficiency
• Participants must be able to provide informed consent and function at an intellectual level sufficient for study requirements
Exclusion Criteria:
• Current evidence of an uncontrolled and/or clinically significant medical condition
• History of bleeding disorders or coagulopathy
• History of seizures or epilepsy
• History of neurological diseases or traumatic brain injury
• Use of illegal recreational drugs
• Presence of devices, e.g. pacemakers, cochlear prosthesis, neuro-stimulators
• Use of acupuncture within 4 weeks of surgery
• Grossly abnormal external ear anatomy or active ear infection
• Women of childbearing potential, not using effective contraception per investigator judgment or not willing to comply with contraception for the duration of the study
• Females who are pregnant or lactating
• Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial
DEVICE: Sparrow Ascent Transcutaneous Auricular Neurostimulation (tAN), DEVICE: Sham Control Device
Pain, Postoperative, Opioid Use, Lumbar Spine Injury
Lumbar Fusion, Transcutaneous auricular neurostimulation (tAN)
UT Southwestern
A Dose Escalation and Dose Expansion Study of Intratumoral ONM-501 Alone and in Combination With Cemiplimab in Patients With Advanced Solid Tumors and Lymphomas. (ON-5001)
A phase 1, multicenter, open label, non-randomized dose escalation and dose expansion study to examine the maximum tolerated dose, (MTD), minimum effective dose (MED) and/or recommended dose for expansion (RDE) of intratumoral ONM-501 as monotherapy and in combination with a PD-1 checkpoint inhibitor in patients with advanced solid tumors and lymphomas.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Heather McArthur
ALL
18 Years and over
PHASE1
NCT06022029
STU-2023-0921
Inclusion Criteria:
• Ability to understand and willingness to sign written informed consent before performance of any study procedures
• Age ≥ 18 years
• Participants with solid tumors or lymphomas, confirmed by available histopathology records or current biopsy, that are advanced, nonresectable, or recurrent and progressing since last antitumor therapy, and for which no alternative standard therapy exists.
• Participants must have a minimum of one injectable and measurable lesion.
• Participants with prior Hepatitis B or C are eligible if they have adequate liver function
• Participants with human immunodeficiency virus (HIV) are eligible if on established HAART for a minimum of 4 weeks prior to enrollment, have an HIV viral load \<400 copies/mL, and have CD4+ T-cell (CD4+) counts ≥ 350 cells/uL
• Adequate bone marrow function:
• Adequate liver function
Exclusion Criteria:
Patients will be excluded from this study if they meet any of the following criteria (Part 1a and Part 1b).
• Other malignancy active within the previous 2 years except for basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast that has completed curative therapy.
• Major surgery within 4 weeks before the first dose of study drug.
• Brain metastases that are untreated or in the posterior fossa or involve the meninges. Participants with stable or previously treated progressing brain metastases (except in the posterior fossa or involving the meninges) may be permitted in a case-by-case basis at the Sponsor's discretion.
• Prolongation of corrected QT (QTc) interval to \>470 millisecond (ms) for males and females when electrolytes balance is normal.
• Females who are breastfeeding or pregnant at screening or baseline
• Females of childbearing potential that refuse to use a highly effective method of contraception.
• Has uncontrolled or poorly controlled hypertension as defined by a sustained BP \> 9. Has received prior investigational therapy within 5 half-lives of the agent or 4 weeks before the first administration of study drug, whichever is shorter.
• Has had any major cardiovascular event within 6 months prior to study drug 10. Has known hypersensitivity to any component in the formulation of ONM-501
• Has an active infection requiring systemic treatment
• Is participating in another therapeutic clinical trial Additional Exclusion Criteria for ONM-501 in Combination with cemiplimab (Part 1b)
• Has known hypersensitivity to any component in the formulation of cemiplimab
• Has any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (\>10 mg daily prednisone equivalent)
• Has a condition requiring systemic treatment with corticosteroids
DRUG: ONM-501, DRUG: Cemiplimab
Triple Negative Breast Cancer, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Lymphoma, Non-Hodgkin, Mantle Cell Lymphoma, Bladder Cancer, Uveal Melanoma, Recurrent, Cervix Cancer, Carcinoma In Situ, Head and Neck Squamous Cell Carcinoma, Skin Cancer, Metastatic Cancer, Tumor, Solid, Tumor Recurrence, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Hodgkins Lymphoma, Kaposis sarcoma, Kidney, Lung/Thoracic, Lymphoid Leukemia, Melanoma, skin, Multiple Myeloma, Mycosis Fungoides, Non-Hodgkins Lymphoma, Other Digestive Organ, Other Endocrine System, Other Skin, Rectum, Small Intestine, Soft Tissue, Stomach, Urinary Bladder
Solid tumors, Lymphoma, ONM-501, STING, Intra-tumoral, HNSCC, Breast Cancer, Melanoma, Skin Cancer, cemiplimab, Libtayo, DLBCL, bladder cancer, cervical cancer, metastases, immunotherapy, ICI, TNBC, Triple Negative, mTNBC, anti-PD-1 antibody, BRCA1, BRCA2, anti-PD-L1, uveal, NHL, Mantle Zone lymphoma, FL, stimulator of interferon genes
UT Southwestern
Emotional Cognition: Establishing Constructs and Neural-Behavioral Mechanisms in Older Adults with Depression (ENSURE)
This is a cross-sectional pilot study designed to establish hot and cold cognitive functions and underlying neurocircuitry in older adults with MDD. The investigators will study 120 participants aged 21-80 years old with MDD. All participants will undergo clinical and neurocognitive assessment, and Magnetoencephalography (MEG)/Magnetic resonance imaging (MRI) procedures at one time point. The investigators will also enroll 120 demographically matched comparable, never-depressed healthy participants (controls) to establish cognitive benchmarks. Healthy controls will complete clinical and neurocognitive measures at one time point. To attain a balanced sample of adults across the lifespan, the investigators will enroll participants such that each age epoch (e.g., 21-30, 31-40, etc.) has a total of ten subjects (n=10) in both the healthy control cohort and depressed cohort.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Aatika.Parwaiz@UTSouthwestern.edu
Shawn McClintock
ALL
21 Years to 80 Years old
NCT05966532
STU-2021-1131
Inclusion Criteria:
• Male and female participants
• Age between 21-80 years old
• DSM-5 diagnosis of major depressive disorder (MDD) based on Mini Neuropsychiatric Interview
• Inventory of Depressive Symptomatology-Clinician Rated version (IDS-C) total score \> 14
• Able to read, write, and comprehend English
• Provide informed consent; willing to comply with study protocol
Exclusion Criteria:
• History of bipolar disorder, schizophrenia, or schizoaffective disorder
• Presence of psychotic features
• Lifetime central nervous system (CNS) disease (including head injury with loss of consciousness \> 5 minutes)
• History of neurodevelopmental disorder (e.g., Autism spectrum disorder)
• History of medical conditions that can affect neurocognitive function as well as be confounded with age (e.g., thyroid disease, endocrine illnesses)
• Women who are pregnant
• Current use of medications with known impacts on neurocognitive function (e.g., acetylcholinesterase inhibitors, amphetamine, methylphenidate, vortioxetine, sedatives)
• Alcohol/substance use disorder within past 3 months
• DSM-5 diagnosis of major cognitive impairment
• Current sensory or physical impairment that interferes with testing.
• Contraindication to MRI and MEG (only for depressed participants) (e.g., any electronic / metallic implants near or within the head or body, claustrophobia)
BEHAVIORAL: Hot Cognitive Task, BEHAVIORAL: Cold cognitive tasks, OTHER: Structural magnetic resonance imaging (sMRI), OTHER: Magnetoencephalography imaging (MEG), BEHAVIORAL: four self-report forms per the requirement of the NIH Common Data Elements project, BEHAVIORAL: Four self-report measures to assess interpersonal functioning, BEHAVIORAL: Clinical assessments, OTHER: ATHF
Major Depressive Disorder (MDD), Healthy Adult Volunteer, Brain and Nervous System
Emotional Cognition
UT Southwestern
Sonocloud-9 in Association With Carboplatin Versus Standard-of-Care Chemotherapies (CCNU or TMZ) in Recurrent GBM (SONOBIRD)
The brain is protected from any toxic or inflammatory molecule by the blood-brain barrier (BBB). This physical barrier is located at the level of the blood vessel walls. Because of these barrier properties, the blood vessels are also impermeable to the passage of therapeutic molecules from the blood to the brain. The development of effective treatments against glioblastoma is thus limited due to the BBB that prevents most drugs injected in the bloodstream from getting into brain tissue where the tumour is seated. The SonoCloud-9 (SC9) is an investigational device using ultrasound technology and specially developed to open the BBB in the area of and surrounding the tumour. The transient opening of the BBB allows more drugs to reach the brain tumour tissue. Carboplatin is a chemotherapy that is approved to treat different cancer types alone or in combination with other drugs, and has been used in the treatment of glioblastoma. Despite its proven efficacy in the laboratory on glioblastoma cells, carboplatin does not readily cross the BBB in humans. A clinical trial has shown that in combination with the SonoCloud-9, more carboplatin can reach the brain tumour tissue. The objective of the proposed trial is to show that the association - carboplatin with the SonoCloud-9 - will increase efficacy of the drug in patients with recurrent glioblastoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Toral Patel
ALL
18 Years to old
PHASE3
NCT05902169
STU-2023-1253
Inclusion Criteria:
• Histologically proven glioblastoma (WHO criteria 2021), absence of IDH mutation demonstrated by negative IDH1 R132H staining on Immunohistochemistry.
• Patient must have received prior first line therapy that must have contained both:
• Prior surgery or biopsy and standard fractionated radiotherapy (1.8-2 Gy/fraction, \>56 Gy\<66 Gy) or hypofractionated radiotherapy (15 x 2.66 Gy or similar regimen)
• One line of maintenance chemotherapy and/or immune- or biological therapy, (with or without Tumor-Treating Fields)
• First, unequivocal disease progression with
• measurable tumor (\>100 mm2 or 1 cm3, based on RANO criteria) documented (e.g., increase of 25% in tumor diameter) on MRI performed within 14 days of inclusion and,
• interval of a minimum of 12 weeks since the completion of prior radiotherapy, unless there is a new lesion outside the radiation field or unequivocal evidence of viable tumor on histopathological sampling
• Patient is candidate for craniotomy and at least 50% resection of enhancing region
• Maximal enhancing tumor diameter prior to inclusion ≤ 5 cm on T1w. (In case of planned lobectomy, post operative peritumoral brain or residual size ≤5 cm)
• WHO performance status ≤ 2 (equivalent to Karnofsky Performance Status (KPS) ≥ 70)
• Age ≥ 18 years
• Participant must be recovered from acute toxic effects (\
• ≥ 6 weeks of prior bevacizumab
• Adequate hematologic, hepatic, and renal laboratory values within 14 days of inclusion i.e.:
• Hemoglobin ≥ 10 g/dL, platelets ≥ 100,000/mm3, neutrophils ≥ 1500/mm3.
• Liver function test with ≤ grade 1 alterations, except if due to antiepileptic drug therapy or isolated increased bilirubin due to Gilbert syndrome
• Estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m2 using Cockcroft Gault formula
• Patient able to understand clinical trial information and willing to provide signed and informed consent
• Patient of childbearing potential must have a negative pregnancy test within 14 days of inclusion and must agree to use a medically-acceptable method of birth control during the treatment period and, if randomized in the experimental arm, for at least 1 month after the last cycle of carboplatin
• A male patient must agree to use condoms during the treatment period and, if randomized in the experimental arm, for at least 3 months after the last cycle of carboplatin; the patient must also refrain from donating sperm during this period.
• Patient must be a beneficiary of a health plan that covers routine patient care costs. Patient must be a beneficiary of or affiliated with a social security scheme (according to country-specific requirements) Non-
Inclusion Criteria:
• Multifocal enhancing tumor on T1w (unless all localized in a 5 cm diameter area)
• Posterior fossa tumor
• Known BRAF/ NTKR mutated patients
• Patient at risk of surgery site infection (e.g., 2 or more previous craniotomies/neurosurgery within the last 3 months, poor skin condition, and/or previously infected surgical field, or any other condition that is of increased infectious risk in the opinion of the neurosurgeon)
• Patient treated at high, stable -or average- dose of corticosteroids (≥ 6 mg/day dexamethasone or equivalent) in the 7 days prior to inclusion. Patients on dexamethasone for reasons other than mass effect may still be enrolled.
• Contra-indication to carboplatin, CCNU or TMZ
• Known history of hypersensitivity reactions to perflutren lipid microsphere components or to any of the inactive ingredients in ultrasound resonator
• Patient has received bevacizumab for other reasons (such as tumor progression) than treating edema
• Peripheral neuropathy or neuropathy ≥ grade 2
• Uncontrolled epilepsy or evidence of intracranial pressure
• Patient with known intracranial aneurism or having presented intra-tumor significant spontaneous hemorrhage
• Patient with unremovable coils, clips, shunts, intravascular stents, and/or wafer, or reservoirs
• Patient with medical need to be on continued anti-platelet aggregation therapy and/or anticoagulation. Patients for whom anticoagulation/platelet aggregation can be temporarily interrupted may be eligible after discussion and prior authorization by the sponsor.
• Patient receiving enzyme-inducing antiepileptic drugs (namely phenytoin, carbamazepine and derivatives, phenobarbital), unless switched on another antiepileptic regimen
• History of other malignancy within 3 years prior to study start with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma, non-melanomatous skin cancer or carcinoma in situ of the uterine cervix
• Patient with known or suspected active or chronic infections
• Patient with known significant cardiac disease, known to have right-to-left shunts, severe pulmonary hypertension (pulmonary artery pressure \> 90 mm Hg), uncontrolled systemic hypertension, or acute respiratory distress syndrome
• Known sensitivity/allergy to gadolinium, or other intravascular contrast agents
• Patient with impaired thermo-regulation or temperature sensation
• Pregnant, or breastfeeding patient
• Any other serious patient medical or psychological condition that may interfere with adequate and safe delivery of treatment and care (e.g., positive human immunodeficiency virus \[HIV\] status, potential blood-borne infections,...), circumstance (e.g., sinus opening during surgery), psychological, morphological characteristics (e.g., skin characteristics, bone thickness), or any pre-existing comorbidities that in the investigator's opinion may prevent the implantation of the device, may impair the ability of the patient to receive treatment with SonoCloud-9 or may be confounding for evaluation of the clinical trial endpoints
• Patients under guardianship, curatorship, under legal protection or deprived of liberty by an administrative or judicial decision Exclusion Criterion: Occurrence of any major medical illnesses or impairments that in the Investigator's opinion may hampered the ability of the patient to receive treatment with SonoCloud-9 or may be confounding for evaluation of the clinical endpoints.
DEVICE: SonoCloud-9 (SC9), DRUG: Carboplatin, DRUG: Lomustine, DRUG: Temozolomide
Glioblastoma, Recurrent Glioblastoma, GBM, Brain and Nervous System
carboplatin, SonoCloud, blood-brain barrier, Low Intensity Pulsed Ultrasound (LIPU)
UT Southwestern
A Study of Revumenib in Combination With Chemotherapy for Patients Diagnosed With Relapsed or Refractory Leukemia
This phase II trial tests the safety and best dose of revumenib in combination with chemotherapy, and evaluates whether this treatment improves the outcome in infants and young children who have leukemia that has come back (relapsed) or does not respond to treatment (refractory) and is associated with a KMT2A (MLL) gene rearrangement (KMT2A-R). Leukemia is a cancer of the white blood cells, where too many underdeveloped (abnormal) white blood cells, called "blasts", are found in the bone marrow, which is the soft, spongy center of the bones that produces the three major blood cells: white blood cells to fight infection; red blood cells that carry oxygen; and platelets that help blood clot and stop bleeding. The blasts crowd out the normal blood cells in the bone marrow and spread to the blood. They can also spread to the brain, spinal cord, and/or other organs of the body. The leukemia cells of some children have a genetic change in which a gene (KMT2A) is broken and combined with other genes that typically do not interact with one another; this is called "rearranged". This genetic rearrangement alters how other genes are turned on or off in the cell, turning on genes that drive the development of leukemia. Patients with KMT2A rearrangement have higher risk for cancer coming back after treatment. Revumenib is an oral medicine that directly targets the changes that occur in a cell with a KMT2A rearrangement and has been shown to specifically kill these leukemia cells in preclinical laboratory settings and in animals. Drugs used in chemotherapy, such as vincristine, prednisone, asparaginase, fludarabine and cytarabine work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial is being done to find out if the combination of revumenib and chemotherapy would be safe and/or effective in treating infants and young children with relapsed or refractory KMT2A-R leukemia.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Caroline Smith
ALL
1 Month to 6 Years old
PHASE2
NCT05761171
STU-2023-1226
Inclusion Criteria:
* Patients must be 1 month to \< 6 years old at the time of study enrollment and must have had initial diagnosis of leukemia at \< 2 years old.
* Patients must have KMT2A-rearranged acute lymphoblastic leukemia (ALL), acute leukemia of ambiguous lineage (ALAL), or mixed phenotype acute leukemia (MPAL), which is determined to be refractory or in first marrow relapse. All patients must undergo cytogenetics and fluorescence in situ hybridization (FISH) testing of a relapsed/refractory blast sample at a Children's Oncology Group (COG)-approved laboratory for KMT2A-R status determination and the presence of a KMT2A- rearrangement must be confirmed by central review. Cytogenetics results must be submitted for central review by Day 10 of protocol therapy, for confirmation of KMT2A-R status. Patients enrolled with refractory disease may utilize initial diagnostic cytogenetics for eligibility and submission for central review if testing was performed at a COG approved laboratory. Patients will be eligible to remain on protocol therapy if KMT2A-R is confirmed by central review. Additional methods of assessing for KMT2A-R may be considered if FISH does not detect the rearrangement.
* Disease status at time of enrollment must be one of the following:
* First relapse (untreated): Any recurrence of marrow disease, with or without other extramedullary sites(s), at any point after achieving remission ("remission-1", per definition below) and meeting one of the below criteria. Patients must not have received any disease-directed therapy for the marrow relapse prior to enrollment, other than permitted cytoreduction.
* Relapse M1: M1 morphology (\< 5% blasts) + at least 2 confirmatory tests showing \>= 1% blasts (testing includes flow, cytogenetics, polymerase chain reaction \[PCR\]/next-generation sequencing \[NGS\] of immunoglobulin \[Ig\]/T-cell receptor \[TCR\] rearrangement, and/or PCR or NGS of fusion gene identical to diagnosis), OR
* Relapse M2: M2 morphology (5-25% blasts) + 1 confirmatory test showing \> 1% blasts, OR
* Relapse M3: M3 morphology (\> 25% blasts)
* Primary refractory, or failure to achieve remission-1: remission-1 is defined as \< 1% marrow blasts by flow MRD and resolution of extramedullary disease following at least 2 courses of frontline chemotherapy. Patients who receive 2 courses of chemotherapy and 1 course of blinatumomab are also eligible, but no further treatment attempts beyond that are permitted
* Central nervous system (CNS) disease: Patients must have CNS1 or CNS2 status and no clinical signs or neurologic symptoms suggestive of CNS leukemia, such as cranial palsy.
* Patients with CNS3 disease may receive antecedent intrathecal chemotherapy to achieve CNS1 or CNS2 status prior to enrollment.
* Patients with a history of CNS chloromatous disease are required to have no radiographic evidence of CNS disease prior to enrollment.
* White blood cell (WBC) must be \< 50,000/uL at the time of study enrollment. Patients can receive cytoreduction with hydroxyurea and/or corticosteroids for up to 7 days prior to enrollment.
* Patients \>= 12 months of age must have a performance status by Lansky Scale of \>= 50%.
* Patients must be able to take enteral medications. Acceptable routes of administration for revumenib (SNDX-5613) include: oral (PO), nasogastric (NG) tube, nasojejunal (NJ) tube, nasoduodenal (ND), and gastrostomy tube (G-tube).
* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive:
* \>= 14 days must have elapsed after the completion of other cytotoxic therapy, including patients who relapse during pre-Maintenance upfront therapy, with these specific exceptions: cytoreduction with hydroxyurea and/or corticosteroids, and intrathecal chemotherapy, which have no required washout periods. For patients who relapse during upfront Maintenance therapy, \>= 7 days must have elapsed after the last dose of chemotherapy. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy.
* NOTE: Cytoreduction with hydroxyurea and/or corticosteroids is permitted prior to enrollment for patients with WBC \>= 50,000/uL, and by provider discretion regardless of WBC, to reduce potential risk of differentiation syndrome with revumenib initiation. Hydroxyurea and/or corticosteroids may be given for up to 7 days, with no wash-out required.
* NOTE: No waiting period is required for patients having received intrathecal cytarabine, methotrexate, and/or hydrocortisone. Intrathecal chemotherapy that is given up to 7 days prior to the initiation of protocol therapy counts as protocol therapy and not prior anti-cancer therapy. Intrathecal chemotherapy given \> 7 days prior does not count as protocol therapy.
* NOTE: Prior exposure to fludarabine and cytarabine (FLA) is permitted.
* Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent.
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1. There is an exception for blinatumomab infusions, for which patients must have been off for at least 3 days and all drug related toxicity must have resolved to grade 2 or lower as outlined in the inclusion/exclusion criteria.
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or \>= 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator.
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon, or cytokines
* Stem cell infusions (with or without total body irradiation (TBI):
* Allogeneic (non-autologous) bone marrow or stem cell transplant, or stem cell boost: \>= 84 days after infusion
* Donor leukocyte infusion: \>= 28 days
* Cellular therapy: \>= 28 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.)
* Radiation therapy (XRT)/external beam irradiation including protons: \>= 14 days after local XRT; \>= 84 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow radiation.
* A creatinine based on age as follows:
* Age 1 month to \< 6 months: maximum creatinine 0.4 mg/dL
* Age 6 months to \< 1 year: maximum creatinine 0.5 mg/dL
* Age 1 to \< 2 years: maximum creatinine 0.6 mg/dL
* Age 2 to \< 6 years: maximum creatinine 0.8 mg/dL OR
* a 24-hour urine creatinine clearance \>= 70 mL/min/1.73 m\^2 OR
* a glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard).
* NOTE: Estimated GFR (eGFR) from creatinine, cystatin C or other estimates are not acceptable for determining eligibility.
* A direct bilirubin =\< 1.5 x upper limit of normal (ULN) for age, unless disease related
* Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (3 x ULN) unless disease related.
* Note: For the purpose of eligibility, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by radionuclide angiogram.
* Corrected QT interval using Fridericia formula (QTcF) of \< 450 msec (using the average of triplicate measurements)
* NOTE: There are no specific electrolyte parameters for eligibility. However, it should be noted that, to limit QTc prolongation risk, patients must maintain adequate potassium and magnesium levels to initiate and continue revumenib (SNDX-5613) on protocol therapy.
* Patients must be able to comply with the safety monitoring requirements of the study, in the opinion of the treating investigator.
Exclusion Criteria:
* Patients with isolated extramedullary leukemia.
* Patients diagnosed with Down syndrome.
* Patients known to have one of the following syndromes:
* Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndrome.
* Patients with a secondary KMT2A-R leukemia that developed after treatment of prior malignancy with cytotoxic chemotherapy.
* Patients with a history of congenital prolonged QT syndrome, congestive heart failure or uncontrolled arrhythmia in the past 6 months prior to study enrollment.
* Patients with an active, uncontrolled infection, further defined below:
* Positive bacterial blood culture within 48 hours of study enrollment
* Fever above 38.2 degrees Celsius (C) within 48 hours of study enrollment with clinical signs of infection. Fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability
* A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection
* Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved. For patients with Clostridium (C.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline
* Active viral or protozoal infection requiring IV treatment
* Human immunodeficiency virus (HIV)-infected patients are eligible if on effective anti-retroviral therapy that does not interact with planned study agents and with undetectable viral load within 6 months of enrollment.
* Patients with active acute graft-versus-host disease (GVHD) \> grade 0 (unless skin only), or chronic GVHD \> mild (unless skin only) are not eligible. Patients with acute or chronic skin GVHD that is =\< grade 1, or chronic skin GVHD that is graded as mild are eligible.
* Patients who have received a prior solid organ transplantation.
* Patients with known Charcot-Marie-Tooth disease, if treating on Regimen A (with vincristine).
* CYP3A4 Inhibitors or Inducers: Patients who require concomitant therapy with strong CYP3A4 inhibitors or moderate or strong CYP3A4 inducers, as these are prohibited during the chemotherapy combination cycles. These agents should be discontinued at least 5 half-lives prior to starting protocol therapy. Concomitant use of strong CYP3A4 inhibitor -azole antifungals are permitted during the revumenib (SNDX-5613) monotherapy cycles, with appropriate revumenib (SNDX-5613) dose modification
* P-glycoprotein (P-gp) inhibitors or inducers: Vincristine is a substrate for P-gp. Concomitant use of P-gp inhibitors or inducers with vincristine (patients receiving Regimen A Cycle 1) should be avoided.
* Investigational drugs: Patients who are currently receiving another investigational drug.
* Anti-cancer agents: Patients who are currently receiving other anti-cancer agents (exceptions: hydroxyurea and corticosteroids, which may be used as cytoreduction prior to enrollment).
* Anti-GVHD agents: Patients who are receiving cyclosporine, tacrolimus, or other systemic agents to treat graft-versus-host disease post bone marrow transplant. Patients should discontinue anti-GVHD agents \> 7 days prior to enrollment and have no evidence of worsening GVHD. Topical steroids are permitted.
* Patients who have previously been treated with revumenib (SNDX-5613). Prior exposure to other menin inhibitors is permitted.
* All patients and/or their parents or legal guardians must sign a written informed consent.
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met. PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, DRUG: Calaspargase Pegol, DRUG: Cytarabine, PROCEDURE: Echocardiography, DRUG: Fludarabine Phosphate, DRUG: Hydrocortisone Sodium Succinate, PROCEDURE: Lumbar Puncture, DRUG: Methotrexate, PROCEDURE: Multigated Acquisition Scan, DRUG: Prednisolone, DRUG: Prednisone, DRUG: Revumenib, DRUG: Vincristine Sulfate
Recurrent Acute Leukemia of Ambiguous Lineage, Recurrent Acute Lymphoblastic Leukemia, Recurrent Acute Myeloid Leukemia Due to Lineage Switch From Acute Leukemia of Ambiguous Lineage, Recurrent Acute Myeloid Leukemia Due to Lineage Switch From B Acute Lymphoblastic Leukemia, KMT2A-Rearranged, Recurrent Acute Myeloid Leukemia Due to Lineage Switch From Mixed Phenotype Acute Leukemia, Recurrent Mixed Phenotype Acute Leukemia, Refractory Acute Leukemia of Ambiguous Lineage, Refractory Acute Lymphoblastic Leukemia, Refractory Acute Myeloid Leukemia Due to Lineage Switch From Acute Leukemia of Ambiguous Lineage, Refractory Acute Myeloid Leukemia Due to Lineage Switch From B Acute Lymphoblastic Leukemia, KMT2A-Rearranged, Refractory Acute Myeloid Leukemia Due to Lineage Switch From Mixed Phenotype Acute Leukemia, Refractory Mixed Phenotype Acute Leukemia, Leukemia, Not Otherwise Specified, Leukemia, Other
Children’s Health
Alzheimer's Disease Neuroimaging Initiative 4 (ADNI4)
Since its launch in 2004, the overarching aim of the Alzheimer's Disease Neuroimaging Initiative (ADNI) Study has been to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI4 continues the previously funded ADNI1, ADNI-GO, ADNI2, and ADNI3 studies that have combined public/private collaborations between academia and industry to determine the relationships between the clinical, cognitive, imaging, genetic and biochemical biomarker characteristics of the entire spectrum of AD.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Gisella.Rodriguez-Larrain@UTSouthwestern.edu
Trung Nguyen
ALL
55 Years to 90 Years old
NCT05617014
STU-2023-0505
Inclusion Criteria for Newly Enrolled Participants, CN Cohort:
• Participant may or may not have a significant subjective memory concern as reported by participant, study partner, or clinician.
• Normal memory function documented by scoring above demographically-adjusted cutoffs on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (the maximum score is 25):
• ≥9 for 16 or more years of education
• ≥ 5 for 8-15 years of education
• ≥ 3 for 0-7 years of education
• Note: cut-offs may be modified over time as the field evolves in this area
• Mini-Mental State Exam score between 24 and 30 (inclusive) (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director and/or Clinical Core)
• Clinical Dementia Rating = 0. Memory Box score must be 0.
• Cognitively normal, based on an absence of significant impairment in cognitive functions or activities of daily living.
• Stability of Permitted Medications for 4 weeks. In particular, participants may:
• Take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 years)
• Estrogen replacement therapy is permissible
• Gingko biloba is permissible, but discouraged
• Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening. Inclusion Criteria for Newly Enrolled Participants, MCI Cohort
• Participant must have a subjective memory concern as reported by participant, study partner, or clinician.
• Abnormal memory function documented by scoring within the demographically- adjusted ranges on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (the maximum score is 25):
• ≤11 for 16 or more years of education
• ≤9 for 8-15 years of education
• ≤6 for 0-7 years of education.
• Note: cut-offs may be modified over time as the field evolves in this area.
• Mini-Mental State Exam score between 24 and 30 (inclusive) (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director and/or Clinical Core)
• Clinical Dementia Rating = 0.5. Memory Box score must be at least 0.5
• General cognition and functional performance sufficiently preserved such that a diagnosis of dementia cannot be made by the site physician at the time of the screening visit.
• Stability of Permitted Medications for 4 weeks. In particular, participants may:
• Take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 year)
• Estrogen replacement therapy is permissible
• Gingko biloba is permissible, but discouraged
• Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening
• Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screen
• Aducanumab and any other approved treatments for the neurobiology of AD if stable for 24 weeks prior to screen Inclusion Criteria for Newly Enrolled Participants, DEM Cohort
• Participant must have a subjective memory concern as reported by participant, study partner, or clinician.
• Abnormal memory function documented by scoring within the demographically- adjusted ranges on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (the maximum score is 25):
• ≤11 for 16 or more years of education
• ≤9 for 8-15 years of education
• ≤6 for 0-7 years of education.
• Note: cut-offs may be modified over time as the field evolves in this area.
• Mini-Mental State Exam score between 20 and 28 (inclusive) (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director and/or Clinical Core)
• Clinical Dementia Rating = 0.5 or 1.0.
• Meets the National Institute on Aging/Alzheimer's Association Diagnostic Guidelines for Dementia (2011)
• Stability of Permitted Medications for 4 weeks. In particular, participants may:
• Take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 year)
• Estrogen replacement therapy is permissible
• Gingko biloba is permissible, but discouraged
• Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening
• Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screen
• Aducanumab and any other approved treatments for the neurobiology of AD if stable for 24 weeks prior to screen Inclusion Criteria for Newly Enrolled Participants, All Cohorts
• Geriatric Depression Scale score less than 10.
• Age between 55-90 years (inclusive).
• Study partner who has frequent contact with the participant (i.e., minimum average of 2 hours per week) and may be able to accompany the participant to clinic visits or provide information remotely (e.g. over the phone).
• Visual and auditory acuity adequate for neuropsychological testing.
• Good general health with no diseases expected to interfere with the study.
• Participant is not pregnant, lactating, or of childbearing potential (i.e., women must be two years post-menopausal or surgically sterile).
• Willing and able to participate in a longitudinal imaging study.
• Must be literate and speak English or Spanish fluently.
• Agrees to collection of blood for GWAS, APOE testing, DNA and RNA testing
• Agrees to collection of blood for biomarker testing.
• The Administrative Core, described in section 9.1.1, will collaborate with leadership from all Cores to review the blood biomarker data from the remote blood cohort and select participants to join the in-clinic cohort. See ADNI4: Remote protocol.
• Agrees to participate in the ADNI study which includes cognitive evaluation, MRI and PET scans.
• Flexibility can be made to all criteria for those with at least 8 years in a low socio-economic status (SES) neighborhood. Inclusion Criteria for Rollover Participants, All Cohorts The following additional inclusion criteria apply to all diagnostic categories for rollover participants only:
• Must have been enrolled and followed in one of the following previous ADNI studies: ADNIGO, ADNI2, ADNI3 for at least one year.
• Willing and able to continue to participant in an ongoing longitudinal study. A reduced battery of tests is allowable.
• Study partner may be available who has frequent contact with the participant (i.e., minimum average of 2 hours per week), and may be able to accompany the participant to clinic visits or provide information remotely (e.g. over the phone). Exclusion Criteria for Newly Enrolled Participants, CN Cohort:
• Any significant neurologic disease, such as Parkinson's disease, vascular cognitive impairment/dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities Exclusion Criteria for Newly Enrolled Participants, MCI and DEM Cohorts:
• Any significant neurologic disease other than suspected Alzheimer's disease, such as Parkinson's disease (Parkinsonian symptoms complicating MCI/AD are acceptable), vascular cognitive impairment dementia (multiple lacunes less than or equal to 1.5 cm and/or extensive white matter changes are acceptable), Huntington's disease, normal pressure hydrocephalus, brain tumor (clinically insignificant meningioma acceptable), progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities. Exclusion Criteria for Newly Enrolled Participants, All Cohorts: Additional exclusion criteria apply to all diagnostic categories for newly enrolled participants:
• Screening/Baseline MRI brain scan with evidence of infection, or other clinically significant focal lesions. Participants with cortical strokes, not large enough to distort anatomy, multiple lacunar infarctions or extensive white matter disease are allowed.
• Screening/Baseline MRI brain scan with evidence of large structural abnormalities that would corrupt image analytical pipelines - e.g. large hemispheric infarcts, large areas of encephalomalacia, large arachnoid cysts
• Unable to complete MRIs for any reason (e.g. pacemaker or other implanted metal devices, severe claustrophobia, anxiety which prevents MRI scans, too large to fit, etc.).
• Current major depression, bipolar disorder as described in DMS-IV within the past 1 year. Psychotic features, agitation or behavioral problems within the last 3 months which could lead to difficulty complying with the protocol.
• Currently treated with medication for obsessive-compulsive disorder or attention deficit disorder.
• History of schizophrenia (DSM-5 criteria).
• History of alcohol or substance disorder within the past 2 years (DSM-5 criteria).
• Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol.
• Clinically significant abnormalities in B12, or thyroid function tests that might interfere with the study. A low B12 is exclusionary, unless follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is not physiologically significant.
• Residence in skilled nursing facility
• Current use of specific psychoactive medications (e.g. certain antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.), at the discretion of the clinician.
• Current use of any other exclusionary medications.
• Investigational agents are prohibited for five half-lives or one month, whichever time period is longer, prior to entry and for the duration of the trial.
• Participation in clinical studies involving neuropsychological measures being collected more than once time per year.
• Female that is pregnant, lactating, or of childbearing potential.
• Flexibility can be made to all criteria for those with at least 8 years in a low socio-economic status (SES) neighborhood.
• Participant may or may not have a significant subjective memory concern as reported by participant, study partner, or clinician.
• Normal memory function documented by scoring above demographically-adjusted cutoffs on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (the maximum score is 25):
• ≥9 for 16 or more years of education
• ≥ 5 for 8-15 years of education
• ≥ 3 for 0-7 years of education
• Note: cut-offs may be modified over time as the field evolves in this area
• Mini-Mental State Exam score between 24 and 30 (inclusive) (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director and/or Clinical Core)
• Clinical Dementia Rating = 0. Memory Box score must be 0.
• Cognitively normal, based on an absence of significant impairment in cognitive functions or activities of daily living.
• Stability of Permitted Medications for 4 weeks. In particular, participants may:
• Take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 years)
• Estrogen replacement therapy is permissible
• Gingko biloba is permissible, but discouraged
• Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening. Inclusion Criteria for Newly Enrolled Participants, MCI Cohort
• Participant must have a subjective memory concern as reported by participant, study partner, or clinician.
• Abnormal memory function documented by scoring within the demographically- adjusted ranges on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (the maximum score is 25):
• ≤11 for 16 or more years of education
• ≤9 for 8-15 years of education
• ≤6 for 0-7 years of education.
• Note: cut-offs may be modified over time as the field evolves in this area.
• Mini-Mental State Exam score between 24 and 30 (inclusive) (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director and/or Clinical Core)
• Clinical Dementia Rating = 0.5. Memory Box score must be at least 0.5
• General cognition and functional performance sufficiently preserved such that a diagnosis of dementia cannot be made by the site physician at the time of the screening visit.
• Stability of Permitted Medications for 4 weeks. In particular, participants may:
• Take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 year)
• Estrogen replacement therapy is permissible
• Gingko biloba is permissible, but discouraged
• Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening
• Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screen
• Aducanumab and any other approved treatments for the neurobiology of AD if stable for 24 weeks prior to screen Inclusion Criteria for Newly Enrolled Participants, DEM Cohort
• Participant must have a subjective memory concern as reported by participant, study partner, or clinician.
• Abnormal memory function documented by scoring within the demographically- adjusted ranges on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (the maximum score is 25):
• ≤11 for 16 or more years of education
• ≤9 for 8-15 years of education
• ≤6 for 0-7 years of education.
• Note: cut-offs may be modified over time as the field evolves in this area.
• Mini-Mental State Exam score between 20 and 28 (inclusive) (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director and/or Clinical Core)
• Clinical Dementia Rating = 0.5 or 1.0.
• Meets the National Institute on Aging/Alzheimer's Association Diagnostic Guidelines for Dementia (2011)
• Stability of Permitted Medications for 4 weeks. In particular, participants may:
• Take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 year)
• Estrogen replacement therapy is permissible
• Gingko biloba is permissible, but discouraged
• Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening
• Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screen
• Aducanumab and any other approved treatments for the neurobiology of AD if stable for 24 weeks prior to screen Inclusion Criteria for Newly Enrolled Participants, All Cohorts
• Geriatric Depression Scale score less than 10.
• Age between 55-90 years (inclusive).
• Study partner who has frequent contact with the participant (i.e., minimum average of 2 hours per week) and may be able to accompany the participant to clinic visits or provide information remotely (e.g. over the phone).
• Visual and auditory acuity adequate for neuropsychological testing.
• Good general health with no diseases expected to interfere with the study.
• Participant is not pregnant, lactating, or of childbearing potential (i.e., women must be two years post-menopausal or surgically sterile).
• Willing and able to participate in a longitudinal imaging study.
• Must be literate and speak English or Spanish fluently.
• Agrees to collection of blood for GWAS, APOE testing, DNA and RNA testing
• Agrees to collection of blood for biomarker testing.
• The Administrative Core, described in section 9.1.1, will collaborate with leadership from all Cores to review the blood biomarker data from the remote blood cohort and select participants to join the in-clinic cohort. See ADNI4: Remote protocol.
• Agrees to participate in the ADNI study which includes cognitive evaluation, MRI and PET scans.
• Flexibility can be made to all criteria for those with at least 8 years in a low socio-economic status (SES) neighborhood. Inclusion Criteria for Rollover Participants, All Cohorts The following additional inclusion criteria apply to all diagnostic categories for rollover participants only:
• Must have been enrolled and followed in one of the following previous ADNI studies: ADNIGO, ADNI2, ADNI3 for at least one year.
• Willing and able to continue to participant in an ongoing longitudinal study. A reduced battery of tests is allowable.
• Study partner may be available who has frequent contact with the participant (i.e., minimum average of 2 hours per week), and may be able to accompany the participant to clinic visits or provide information remotely (e.g. over the phone). Exclusion Criteria for Newly Enrolled Participants, CN Cohort:
• Any significant neurologic disease, such as Parkinson's disease, vascular cognitive impairment/dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities Exclusion Criteria for Newly Enrolled Participants, MCI and DEM Cohorts:
• Any significant neurologic disease other than suspected Alzheimer's disease, such as Parkinson's disease (Parkinsonian symptoms complicating MCI/AD are acceptable), vascular cognitive impairment dementia (multiple lacunes less than or equal to 1.5 cm and/or extensive white matter changes are acceptable), Huntington's disease, normal pressure hydrocephalus, brain tumor (clinically insignificant meningioma acceptable), progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities. Exclusion Criteria for Newly Enrolled Participants, All Cohorts: Additional exclusion criteria apply to all diagnostic categories for newly enrolled participants:
• Screening/Baseline MRI brain scan with evidence of infection, or other clinically significant focal lesions. Participants with cortical strokes, not large enough to distort anatomy, multiple lacunar infarctions or extensive white matter disease are allowed.
• Screening/Baseline MRI brain scan with evidence of large structural abnormalities that would corrupt image analytical pipelines - e.g. large hemispheric infarcts, large areas of encephalomalacia, large arachnoid cysts
• Unable to complete MRIs for any reason (e.g. pacemaker or other implanted metal devices, severe claustrophobia, anxiety which prevents MRI scans, too large to fit, etc.).
• Current major depression, bipolar disorder as described in DMS-IV within the past 1 year. Psychotic features, agitation or behavioral problems within the last 3 months which could lead to difficulty complying with the protocol.
• Currently treated with medication for obsessive-compulsive disorder or attention deficit disorder.
• History of schizophrenia (DSM-5 criteria).
• History of alcohol or substance disorder within the past 2 years (DSM-5 criteria).
• Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol.
• Clinically significant abnormalities in B12, or thyroid function tests that might interfere with the study. A low B12 is exclusionary, unless follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is not physiologically significant.
• Residence in skilled nursing facility
• Current use of specific psychoactive medications (e.g. certain antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.), at the discretion of the clinician.
• Current use of any other exclusionary medications.
• Investigational agents are prohibited for five half-lives or one month, whichever time period is longer, prior to entry and for the duration of the trial.
• Participation in clinical studies involving neuropsychological measures being collected more than once time per year.
• Female that is pregnant, lactating, or of childbearing potential.
• Flexibility can be made to all criteria for those with at least 8 years in a low socio-economic status (SES) neighborhood.
RADIATION: Neuraceq, RADIATION: Amyvid, RADIATION: Tauvid, RADIATION: MK-6240, RADIATION: NAV4694, RADIATION: PI-2620
Mild Cognitive Impairment, Alzheimer Disease, Dementia, Brain and Nervous System
amyloid, plaques, neuroimaging, biomarkers, cognition disorder, early detection, pre-dementia, dementia, Alzheimer's disease, tau, observational
UT Southwestern
Cognitive Outcomes of Brain Stimulation As a Later-in-Life Treatment (COBALT)
This is a pilot study being done to attempt to improve episodic memory problems in persons with mild cognitive impairment (MCI) or dementia. The pre-supplemental motor area (preSMA) and dorsal anterior cingulate cortex (dACC) have been shown to play a role in episodic memory and language retrieval. Prior studies have suggested that neurostimulation targeting this region can improve episodic memory and word recall. The purpose of this study is to examine the efficacy of high-definition transcranial direct current stimulation (HD-tDCS) to the preSMA/dACC region and its influence on word retrieval and other cognitive functions in patients with MCI or dementia. Entraining the preSMA/dACC circuit with 10 sessions of HD-tDCS will allow us to study whether neurostimulation may be an effective treatment.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Hannah.Cabrera@UTSouthwestern.edu
Christian LoBue
ALL
55 Years and over
NA
NCT05564715
STU-2022-0799
Inclusion Criteria:
Active diagnosis of mild cognitive impairment or dementia, Female and male subjects, All races/ethnicities, Age 55 years and older, Fluent in English,
Exclusion Criteria:
Lifetime history of major neurologic syndromes (e.g., epilepsy, brain tumor, etc), Substance use disorder within the past year, Has metal fragments in skull/head, Current vision or hearing impairment that interferes with testing, Current medication use known to alter HD-tDCS reactivity DEVICE: NeuroElectric StarStim, DEVICE: Sham Treatment
Mild Cognitive Impairment, Dementia, Amnestic Mild Cognitive Impairment - aMCI, Brain and Nervous System
UT Southwestern; Parkland Health & Hospital System
ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study) (ACTION)
This is a randomized, double-blind, placebo-controlled, parallel-group, international, Phase 3 study in patients with newly diagnosed H3 K27M-mutant diffuse glioma to assess whether treatment with ONC201 following frontline radiotherapy will extend overall survival and progression-free survival in this population. Eligible participants will have histologically diagnosed H3 K27M-mutant diffuse glioma and have completed standard frontline radiotherapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
ALL
Not specified
PHASE3
NCT05580562
STU-2023-0079
Inclusion Criteria:
• Able to understand the study procedures and agree to participate in the study by providing written informed consent (by participant or legally authorized representative), and assent when applicable.
• Body weight ≥ 10 kg at time of randomization.
• Histologically diagnosed H3 K27M-mutant diffuse glioma (new diagnosis). Detection of a missense K27M mutation in any histone H3-encoding gene detected by testing of tumor tissue (immunohistochemistry \[IHC\] or next-generation sequencing \[NGS\] in a Clinical Laboratory Improvement Amendments \[CLIA\]-certified or equivalent laboratory). \[Site to provide (as available): ≥ 10 unstained formalin-fixed paraffin-embedded (FFPE) slides from tumor tissue.\]
• At least one, high-quality, contrast-enhanced MRI of the brain obtained prior to starting radiotherapy for submission to sponsor's imaging vendor for central read. For participants who had a surgical resection, this scan must be post-resection; for participants who did not have a resection, this scan may be pre- or post-biopsy.
• At least one, high-quality, contrast-enhanced MRI of the brain obtained 2 to 6 weeks after completion of frontline radiotherapy. If unable to obtain contrast-enhanced imaging due to lack of venous access after multiple attempts, a patient may still be eligible after collection of a nonenhanced MRI of the brain. \[Site to also provide all available MRIs completed prior to initiating treatment with study intervention.\]
• Received frontline radiotherapy
• Initiated radiotherapy within 12 weeks from the initial diagnosis of H3 K27M-mutant diffuse glioma.
• Completed radiotherapy within 2 to 6 weeks prior to randomization
• Completed standard fractionated radiotherapy (eg. 54 to 60 Gy in 28 to 33 fractions given over approximately 6 weeks or hypofractionated radiotherapy (eg. 40 Gy in 15 fractions given over approximately 3 weeks).
• Karnofsky Performance Status or Lansky Performance Status ≥ 70 at time of randomization.
• Stable or decreasing dose of corticosteroids and anti-seizure medications for 7 days prior to randomization, if applicable. Stable steroid dose is defined as ≤ 2 mg/day increase (based on dexamethasone dose or equivalent dose of an alternative steroid).
Exclusion Criteria:
• Primary spinal tumor.
• Diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons.
• Evidence of leptomeningeal spread of disease or cerebrospinal fluid dissemination.
• Any known concurrent malignancy.
• New lesion(s) outside of the radiation field.
• Received whole-brain radiotherapy.
• Received proton therapy for glioma.
• Use of any of the following treatments within the specified time periods prior to randomization:
• ONC201 or ONC206 at any time.
• Systemic bevacizumab (includes biosimilars) at any time since the initial diagnosis of H3 K27M-mutant diffuse glioma.
• Temozolomide within past 3 weeks.
• Tumor treating fields at any time.
• DRD2 antagonist within past 2 weeks.
• Any investigational therapy within past 4 weeks.
• Strong CYP3A4 inhibitors within 3 days.
• Strong CYP3A4 inducers (includes enzyme-inducing antiepileptic drugs) within 2 weeks.
• Laboratory test results meeting any of the following parameters within 2 weeks prior to randomization:
• Absolute neutrophil count \< 1.0 × 109/L or platelets \< 75 × 109/L.
• Total bilirubin \> 1.5 × upper limit of normal (ULN) (participants with Gilbert's syndrome may be included with total bilirubin \> 1.5 × ULN if direct bilirubin is ≤ 1.5 × ULN).
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 × ULN.
• Creatinine clearance ≤ 60 mL/min as calculated by the Cockcroft Gault equation (or estimated glomerular filtration rate \< 60 mL/min/1.73 m2).
• QTc \> 480 msec (based on mean from triplicate electrocardiograms) during screening.
• Known hypersensitivity to any excipients used in the study intervention formulation.
• Pregnant, breastfeeding, or planning to become pregnant while receiving study intervention or within 3 months after the last dose. Participants of childbearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study intervention.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring systemic therapy or psychiatric illness/social situations that would limit compliance with study requirements.
• Any other condition (eg, medical, psychiatric, or social) that, in the opinion of the investigator, may interfere with participant safety or the ability to complete the study according to the protocol.
DRUG: Dordaviprone (ONC201), DRUG: Dordaviprone (ONC201) + Placebo, OTHER: Placebo
H3 K27M, Glioma, Brain and Nervous System
H3 K27M, H3 K28M, H3 K27-altered, histone, H3F3A, HIST1H3B, HIST1H3C, H3.1, H3.3, DMG, thalamus, thalamic, midline
Children’s Health
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.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
ALL
to 59 Months old
PHASE2
NCT05535166
STU-2023-0119
Inclusion Criteria - Screening Phase (All Patients)
* Participants with presumptive/suspected newly diagnosed medulloblastoma.
* Participant meets one of the following criteria at the time of screening:
* Age \< 36 months OR Age ≥ 36 months and \< 60 months with presumptive/suspected non-metastatic disease
* Participant must have adequate tumor tissue from primary tumor for central review of pathology and molecular classification by methylation and IHC
* Participant must be able to begin treatment as outlined in the protocol within 36 days of definitive surgery (day of surgery is Day 0). In case a second surgery is clinically indicated to remove the residual tumor prior to starting treatment, the second surgery will be considered as the definitive surgery (Day 0).
* Parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines.
Exclusion Criteria - Screening Phase
* Participants with other clinically significant medical disorders (i.e., serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with the study procedure.
Inclusion Criteria - Study Enrollment (All Patients)
* Participant must be \< 60 months of age at time of enrollment.
* Note: Each treatment stratum has additional specific age requirements
* Participant must have confirmation of newly diagnosed medulloblastoma per Central Review:
* Central review includes histopathology, IHC and St. Jude Clinical Genomic Methylation Profiling conducted on MLPNet. If tissue or the extracted DNA does not meet quality control criteria for methylation analysis or if methylation classifier is unable assign molecular group/subgroup within the assigned classifier (MLPNet) parameters, then IHC will be used to define molecular group of these cases. IHC cannot be used to determine molecular subgroup. Therefore, IHC defined SHH patients will be enrolled on Stratum S-1 under "SHH-NOS", and all NWNS and indeterminate molecular group will be enrolled on stratum N.
* Note: Diagnosis of medulloblastoma, as well as group and subgroup assignment, will be done by central pathology review at St. Jude only. No outside testing is allowed for trial enrollment.
* Participant must have disease staged by MRI of the brain and spine and by cytologic examination of CSF\* and be placed into the following categories:
* M0: no evidence of metastatic disease.
* must include a negative CSF cytology result
* M1: Tumor cells found in the CSF but no other evidence of metastasis
* M2: Intracranial tumor beyond the primary tumor site
* M3: Metastatic disease in the spine
* M4: Extraneural metastatic disease
* \*All participants are to undergo CSF cytologic examination regardless of presence or absence of gross metastatic disease unless procedure is medically contraindicated. CSF is to be obtained by lumbar puncture (LP) performed at least 10 days after surgery. If LP is medically contraindicated, ventricular CSF from a shunt or Ommaya reservoir may be used for staging but this is not the preferred option due to lower sensitivity. If LP is medically contraindicated and the patient doesn't have a shunt or reservoir for CSF sampling, the treating physician should reach out to PI or Co-PI regarding decision on enrollment to SJiMB21. The decision to enroll without CSF cytology will be made on case-by-case basis.
* Note: Participants who have M2 disease and positive CSF will be assigned to M3.
* Note: Participants will be assigned to the highest stage number for which they meet eligibility.
* Note: Treatment stratums may have additional stage requirements.
* Patient must have received no previous radiotherapy, chemotherapy, or other brain tumor-directed therapy other than corticosteroid therapy and surgery.
* Participant must have a Lansky performance score of \> 30 (except for patients with posterior fossa syndrome.
* Participant must have adequate organ function prior to study entry, as defined by:
* Absolute neutrophil counts (ANC) \>750/mm\^3
* Platelet count ≥ 50,000/mm\^3 without support of a platelet transfusion within 7 days
* Hemoglobin ≥8.0 g/dL (with or without support of a blood transfusion).
* Normal liver function as defined by Alanine aminotransferase (ALT) concentration ≤ 3 x 45 U/L and total bilirubin ≤ 3 x 1.0.
* Adequate renal function as defined by a serum creatinine concentration:
* Age - 0 to \<1year; Maximum Serum Creatinine (mg/dl) - Male 0.5; Female 0.5
* Age - 1 to \< 2years; Maximum Serum Creatinine (mg/dl) - Male 0.6; Female 0.6
* Age - 1 to \< 2yearsr; Maximum Serum Creatinine (mg/dl) - Male 0.8; Female 0.8
* Participant's parent or legal guardian has the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines.
Inclusion Criteria - Stratum S-2
* Participant must have confirmed diagnosis of the following medulloblastoma molecular group and subgroup per Central Review.
* Medulloblastoma SHH-2
* Participant must meet one of the following criteria at time of enrollment:
* Age \<36 months OR Age ≥ 36 months and \< 60 months with non-metastatic disease (M0) Inclusion Criteria - Stratum S-1
* Participant must have confirmed diagnosis of one of the following medulloblastoma molecular subgroups per Central Review.
* Medulloblastoma SHH-1
* Medulloblastoma SHH-3
* Medulloblastoma SHH-4
* Medulloblastoma SHH-NOS
* Includes medulloblastoma cases that could not be assigned to a molecular subgroup using the DNA methylation classifier, but which are in the SHH group and/or cases defined as SHH by IHC.
* Participant must be \< 36 months of age at time of enrollment
* Note: Patients who are \< 36 months of age, regardless of metastatic status (M0/M+), are eligible for enrollment on stratum S-1.
Inclusion Criteria - Stratum N
* Participant must have confirmed diagnosis of one of the following medulloblastoma molecular subgroups per Central Review.
* Medulloblastoma G3
* Medulloblastoma G4
* Medulloblastoma - Not classified into SHH (i.e., NWNS or indeterminate)
* Includes medulloblastoma cases that could not be assigned to a molecular group using the DNA methylation classifier but which are in the NWNS class and/or defined as NWNS by IHC.
* Participant must be \<36 months of age at time of enrollment
* All NWNS patients (M+ and M0) are eligible for enrollment in stratum N
Exclusion Criteria - All Patients
* CNS embryonal tumor other than medulloblastoma, for example, patients with diagnosis of Atypical Teratoid/Rhabdoid Tumor (ATRT), PNET, Pineoblastoma, Ependymoma, and ETMR are excluded.
* Participant with prior treatment for medulloblastoma, including:
* Radiotherapy
* Chemotherapy
* Cancer directed immunotherapy
* Targeted agents
* NOTE: Corticosteroid therapy is acceptable; prior treatment with chemotherapy, immunotherapy or targeted agents for non-cancer directed indications are acceptable as long as these have been stopped at least 14 days prior to start of therapy or 2 half-lives from last dose. (i.e., methotrexate for juvenile rheumatoid arthritis, JAK inhibitor therapy for eczema, etc.)
* Participant who is actively receiving any other investigational agents.
* Participant with other clinically significant medical disorders (i.e., serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or results.
PROCEDURE: Surgical resection, PROCEDURE: Ommaya/VPS, DRUG: Methotrexate, DRUG: Cisplatin, DRUG: Vincristine, DRUG: Cyclophosphamide, DRUG: Carboplatin, DRUG: Topotecan, DRUG: Etoposide, DRUG: Pegfilgrastim, DRUG: Filgrastim, RADIATION: Irradiation, OTHER: Educational and Media Intervention, OTHER: SOC, Educational and Media Intervention
Medulloblastoma, Brain and Nervous System
SJiMB21, Brain Cancer, Brain Tumors in Children, Medulloblastoma Sonic Hedgehog subgroup 1, Medulloblastoma Sonic Hedgehog subgroup 2, Medulloblastoma Sonic Hedgehog subgroup 3, Medulloblastoma Sonic Hedgehog subgroup 4, Medulloblastoma Sonic Hedgehog-not otherwise specified, Medulloblastoma G3, Medulloblastoma G4, Medulloblastoma indeterminate, MLPNet, Neural Net Classification Pipeline, Non-WNT non-SHH medulloblastoma, Posterior fossa syndrome, St. Jude Brain Tumor Studies, Treatment for Brain Tumors in Infants and Young Children, Untreated Childhood Medulloblastoma
Children’s Health
A Study to Evaluate the Safety and Efficacy of CT1812 in Early Alzheimer's Disease
This is a multicenter randomized, double-blind, placebo-controlled Phase 2 study designed to evaluate the efficacy, safety, and tolerability of two doses of CT1812 compared to placebo in participants diagnosed with early Alzheimer's disease.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Matthew.Jones@UTSouthwestern.edu
Brendan Kelley
ALL
50 Years to 85 Years old
PHASE2
NCT05531656
STU-2024-0467
Inclusion Criteria:
• Ages 50-85 years.
• Diagnosis of either MCI due to AD or mild AD dementia.
• MMSE 20-30 (inclusive).
• Amyloid PET scan of the brain or CSF biomarkers consistent with AD.
• Neuroimaging (MRI) obtained during screening consistent with the clinical diagnosis of Alzheimer's disease, as based on central read.
Exclusion Criteria:
• Screening MRI of the brain indicative of significant abnormality.
• Clinically significant abnormalities in screening laboratory tests.
• Clinical or laboratory findings consistent with:
• Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal dementia, Huntington's disease, Creutzfeldt-Jakob Disease, Down syndrome, etc.).
• Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral sclerosis, etc.).
• Other infectious, metabolic or systemic diseases affecting the central nervous system (syphilis, present hypothyroidism, present vitamin B12, other laboratory values etc.)
• A participant known to be actively infected with hepatitis B or hepatitis C at screening. History of acute/chronic hepatitis B or C and/or carriers of hepatitis B (seropositive for hepatitis B surface antigen \[HbsAg\] or anti-hepatitis C \[HCV\] antibody). Participants who have evidence of resolved hepatitis infection (e.g., HCV RNA negative) may be considered following discussion with the Medical Monitor.
• A current DSM-V diagnosis of active major depression or GDS \> 6, schizophrenia, or bipolar disorder.
DRUG: CT1812, DRUG: Placebo
Early Alzheimer's Disease, Brain and Nervous System
Alzheimer's Disease
UT Southwestern
Pathways Relating Amnestic MCI to a Mild Traumatic Brain Injury History (PATH)
This study will probe if the biological changes in amnestic mild cognitive impairment (aMCI) are related to a history of mild traumatic brain injury (mTBI) using high definition transcranial direct current stimulation (HD-tDCS) and blood-derived biomarker tools. Participants who Do as well as those who Do Not have a history of mTBI will be enrolled in the study.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Hannah.Cabrera@UTSouthwestern.edu
Christian LoBue
ALL
55 Years and over
PHASE2
NCT05446584
STU-2022-0591
Inclusion Criteria:
• Active diagnosis of amnestic mild cognitive impairment
• Presence of an mTBI history for the mTBI+ group; absence of an mTBI history for a control sample
• Female and male subjects
• All races/ethnicities
• Age 55 years and older
• Fluent in English
Exclusion Criteria:
• Mild traumatic brain injury within past year
• Lifetime history of moderate or severe brain injury
• Lifetime major neurologic syndromes (e.g., stroke, epilepsy, brain tumor)
• Lifetime major cardiovascular conditions (e.g., heart attack, heart failure)
• Current substance use disorder
• Current major psychiatric disorders (e.g., major depressive disorder, bipolar disorder)
• Current vision or hearing impairment that interferes with testing
• Any electronic and or metallic implants in the skull or brain
• Current medication use known to alter HD-tDCS reactivity
DEVICE: High Definition Transcranial Direct Current Stimulation
Mild Cognitive Impairment, Amnestic Mild Cognitive Disorder, Amnestic Mild Cognitive Impairment, Mild Traumatic Brain Injury, Concussion, Brain, Brain and Nervous System
MCI, TBI, memory, biomarker, Alzheimer
UT Southwestern; Parkland Health & Hospital System
Blood-Brain Barrier Disruption (BBBD) for Liquid Biopsy in Subjects With GlioBlastoma Brain Tumors
The purpose of this study is to evaluate the safety and efficacy of targeted blood brain barrier disruption with Exablate Model 4000 Type 2.0/2.1 for liquid biopsy in subjects with suspected Glioblastoma brain tumors
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Bhavya Shah
All
18 Years to 80 Years old
N/A
NCT05383872
STU-2022-0890
Inclusion Criteria:
• Male or Female between >18-80 years of age who are able and willing to give informed consent
• Subjects with stereotactically-targetable suspected glioblastoma tumor on pre-operative brain imaging scans
• Subjects that are scheduled, or will be scheduled within 4 weeks, for surgical resection or biopsy per standard clinical tumor care
• Karnofsky Performance Score >70
• Able to communicate sensations during the Exablate BBBD procedure
Exclusion Criteria:
• Tumor originating from the deep midline, thalamus, midbrain, cerebellum or brainstem.
• Multifocal tumors
• Tumor morphology or other imaging findings that precludes the ability to sonicate the planned tumor volume (including significant tumor volume outside the treatment envelope or tumor volume that exceeds the maximum sonication volume allowed, i.e. currently 110 ccs at the treatment volume level). Concern for adequate tumor coverage by sonication based on tumor morphology should be discussed with the Sponsor.
• MRI or clinical findings of:
• Active or chronic infection(s) or inflammatory processes
• Acute or chronic hemorrhages, specifically any lobar microbleeds, and no siderosis, amyloid angiopathy, or macro-hemorrhages
• Intracranial thrombosis, vascular malformation, cerebral aneurysm or vasculitis
• MR non-compatible metallic implants in the skull or the brain or the presence of unknown MR unsafe devices
• Significant cardiac disease or unstable hemodynamic status
• Documented myocardial infarction within six months of enrollment
• Unstable angina on medication
• Unstable or worsening congestive heart failure
• Left ventricular ejection fraction below the lower limit of normal
• History of a hemodynamically unstable cardiac arrhythmia
• Cardiac pacemaker
• History of hypersensitivity to Perflutren lipid microsphere or its components, e.g., polyethylene glycol
• Uncontrolled hypertension (systolic > 180 and diastolic BP > 120 on medication)
• Unable to discontinue use of anti-coagulant/antiplatelet therapy as per local standard.
• History of a liver disease, bleeding disorder, coagulopathy or a history of spontaneous hemorrhage or evidence of increased risk of bleeding
• Abnormal coagulation profile (Platelets < 80,000), PT (>14) or PTT (>36), and INR >
• 3
• Known cerebral or systemic vasculopathy
• Significant depression and at potential risk of suicide
• Known sensitivity/allergy to gadolinium or DEFINITY,
• Active seizures despite medication treatment (defined as >1 seizure per week) which could be worsened by disruption of the blood brain barrier
• Active drug or alcohol disorder which have a higher risk for seizures, infection and/or poor executive functioning
• Positive HIV status, which can lead to increased entry of HIV into the brain parenchyma leading to HIV encephalitis
• Potential blood-borne infections which can lead to increased entry to brain parenchyma leading to meningitis or brain abscess
• Any contraindications to MRI scanning, including:
• Large subjects not fitting comfortably into the scanner
• Difficulty lying supine and still for up to 3 hours in the MRI unit or claustrophobia
• Impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2
• Severe Respiratory Illness: chronic pulmonary disorders e.g. severe emphysema, pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area, subjects with a history of severe drug allergies, asthma or hay fever, and multiple allergies where the benefit/risk of administering Definity® is considered unfavorable by the study physicians in relation to the product labeling for Definity
• Currently in a clinical trial involving an investigational product or non-approved use of a drug or device
• Pregnancy or Lactation
Device: Focused Ultrasound (Exablate Model 4000)
Glioblastoma, Glioma, Liquid Biopsy, Brain and Nervous System
UT Southwestern
Pediatric Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (P-ICECAP) (ICECAP)
This is a multicenter trial to establish the efficacy of cooling and the optimal duration of induced hypothermia for neuroprotection in pediatric comatose survivors of cardiac arrest. The study team hypothesizes that longer durations of cooling may improve either the proportion of children that attain a good neurobehavioral recovery or may result in better recovery among the proportion already categorized as having a good outcome.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Kirstie.LeDoux@UTSouthwestern.edu
Joshua Wolovits
All
2 Days to 17 Years old
N/A
NCT05376267
STU-2022-0800
Inclusion criteria:
• Age 2 days to < 18 years with corrected gestational age of at least 38 weeks
• Chest compressions for at least 2 minutes
• Coma or encephalopathy after resuscitation from Out-of-Hospital Cardiac Arrest (OHCA)
• Requires continuous mechanical ventilation through endotracheal tube or tracheostomy
• Definitive temperature control device initiated
• Randomization within 6 hours of Return of Spontaneous Circulation (ROSC)
• Informed consent from Legally Authorized Representative (LAR) including intent to maintain life support for 120 hours Exclusion criteria:
• Glasgow Coma Motor Score (GCMS) = 6
• LAR does not speak English or Spanish
• Duration of Cardiopulmonary Resuscitation (CPR) > 60 minutes
• Severe hemodynamic instability with continuous infusion of epinephrine or norepinephrine of 2 micrograms per kilogram per minute (μg/kg/minute) or initiation of Extracorporeal membrane oxygenation (ECMO)
• Pre-existing severe neurodevelopmental deficits with Pediatric Cerebral Performance Category (PCPC) =5 or progressive degenerative encephalopathy
• Pre-existing terminal illness, unlikely to survive to one year
• Cardiac arrest associated with brain, thoracic, or abdominal trauma
• Active and refractory severe bleeding prior to randomization
• Extensive burns or skin lesions incompatible with surface cooling
• Planned early withdrawal of life support before 120 hours
• Sickle cell anemia
• Pre-existing cryoglobulinemia
• Non-fatal drowning in ice covered water
• Central nervous system tumor with ongoing chemotherapy
• Previous enrollment in P-ICECAP trial
• Prisoner
• Chronic hypothermia
• New post-cardiac arrest diabetes insipidus
• Pregnancy
• Age 2 days to < 18 years with corrected gestational age of at least 38 weeks
• Chest compressions for at least 2 minutes
• Coma or encephalopathy after resuscitation from Out-of-Hospital Cardiac Arrest (OHCA)
• Requires continuous mechanical ventilation through endotracheal tube or tracheostomy
• Definitive temperature control device initiated
• Randomization within 6 hours of Return of Spontaneous Circulation (ROSC)
• Informed consent from Legally Authorized Representative (LAR) including intent to maintain life support for 120 hours Exclusion criteria:
• Glasgow Coma Motor Score (GCMS) = 6
• LAR does not speak English or Spanish
• Duration of Cardiopulmonary Resuscitation (CPR) > 60 minutes
• Severe hemodynamic instability with continuous infusion of epinephrine or norepinephrine of 2 micrograms per kilogram per minute (μg/kg/minute) or initiation of Extracorporeal membrane oxygenation (ECMO)
• Pre-existing severe neurodevelopmental deficits with Pediatric Cerebral Performance Category (PCPC) =5 or progressive degenerative encephalopathy
• Pre-existing terminal illness, unlikely to survive to one year
• Cardiac arrest associated with brain, thoracic, or abdominal trauma
• Active and refractory severe bleeding prior to randomization
• Extensive burns or skin lesions incompatible with surface cooling
• Planned early withdrawal of life support before 120 hours
• Sickle cell anemia
• Pre-existing cryoglobulinemia
• Non-fatal drowning in ice covered water
• Central nervous system tumor with ongoing chemotherapy
• Previous enrollment in P-ICECAP trial
• Prisoner
• Chronic hypothermia
• New post-cardiac arrest diabetes insipidus
• Pregnancy
Device: Therapeutic Hypothermia
Cardiac Arrest, Out-Of-Hospital, Hypothermia, Induced, Hypoxia-Ischemia, Brain
Bayesian Adaptive Clinical Trial, Hypothermia, therapeutic, Coma, Pediatric
Children’s Health
Validation of Early Prognostic Data for Recovery Outcome After Stroke for Future, Higher Yield Trials (VERIFY)
VERIFY will validate biomarkers of upper extremity (UE) motor outcome in the acute ischemic stroke window for immediate use in clinical trials, and explore these biomarkers in acute intracerebral hemorrhage. VERIFY will create the first multicenter, large-scale, prospective dataset of clinical, transmagnetic stimulation (TMS), and MRI measures in the acute stroke time window.
Call 214-648-5005
studyfinder@utsouthwestern.edu, HEATHER.PAUP@UTSOUTHWESTERN.EDU
Benjamin Nguyen
All
18 Years and over
NCT05338697
STU-2021-1134
Inclusion Criteria:
• Age 18 years or older
• Unilateral stroke due to ischemia or intracerebral hemorrhage
• Motor deficits in the acutely affected UE, defined as a Shoulder Abduction and Finger Extension (SAFE) score ≤ 8 out of 10 points (i.e., excluding full or nearly full motor strength in both shoulder abduction and finger extension) within 48 to 96 hours of stroke onset (or time last known well).
• Provision of signed and dated informed consent form within 48 to 96 hours of stroke onset (or time last known well).
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Fluent in English or Spanish
Exclusion Criteria:
• UE injury or conditions on paretic side that limited use prior to the stroke.
• Legally blind.
• Dense sensory loss indicated by a score of 2 on NIHSS sensory item
• Unable to abduct the shoulder or extend the fingers of the non-paretic arm/hand/wrist on verbal command
• Isolated cerebellar stroke
• Bilateral hemisphere acute strokes
• Co-enrollment in a trial of an intervention targeting the incident stroke (acute treatment or rehabilitation/recovery intervention) after baseline assessments for VERIFY are initiated
• Known or expected inability to maintain follow-up with study procedures through 90 days
• Cognitive or communication impairment precluding informed consent by the participant.
• Major medical, neurological, or psychiatric condition that would substantially affect functional status
• Non-cerebrovascular diagnosis associated with unlikely survival at 90 days
• Pregnancy
• Contraindication to noncontrast MRI (i.e., certain metallic implants, metallic foreign bodies or severe claustrophobia)
• Contraindication to TMS (i.e., cardiac pacemaker or other electronic devices in the body at or above the level of the seventh cervical vertebra, such as cochlear implant, cortical stimulator, deep brain stimulator, vagus nerve stimulator, cervical spine epidural stimulator, or ventriculoperitoneal shunt; Skull defect related to current stroke; Seizure after onset of current stroke; Seizure within the last 12 months while taking anti-epileptic medications; Previous serious adverse reaction to TMS)
• Unable to perform behavioral assessments within 48-120 hours of symptom onset
• Unable to receive TMS or get MRI within 72-168 hours of symptom onset
• Anticipated inability to perform study procedures within 168 hours of symptom onset.
Diagnostic Test: Transcranial Magnetic Stimulation (TMS)
Stroke, Stroke, Acute, Stroke, Ischemic, Stroke Hemorrhagic, Brain and Nervous System, Other
UT Southwestern
A Study of Treatment for Medulloblastoma Using Sodium Thiosulfate to Reduce Hearing Loss
This phase III trial tests two hypotheses in patients with low-risk and average-risk medulloblastoma. Medulloblastoma is a type of cancer that occurs in the back of the brain. The term, risk, refers to the chance of the cancer coming back after treatment. Subjects with low-risk medulloblastoma typically have a lower chance of the cancer coming back than subjects with average-risk medulloblastoma. Although treatment for newly diagnosed average-risk and low-risk medulloblastoma is generally effective at treating the cancer, there are still concerns about the side effects of such treatment. Side effects or unintended health conditions that arise due to treatment include learning difficulties, hearing loss or other issues in performing daily activities. Standard therapy for newly diagnosed average-risk or low-risk medulloblastoma includes surgery, radiation therapy, and chemotherapy (including cisplatin). Cisplatin may cause hearing loss as a side effect. In the average-risk medulloblastoma patients, this trial tests whether the addition of sodium thiosulfate (STS) to standard of care chemotherapy and radiation therapy reduces hearing loss. Previous studies with STS have shown that it may help reduce or prevent hearing loss caused by cisplatin. In the low-risk medulloblastoma patients, the study tests whether a less intense therapy (reduced radiation) can provide the same benefits as the more intense therapy. The less intense therapy may cause fewer side effects. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. The overall goals of this study are to see if giving STS along with standard treatment (radiation therapy and chemotherapy) will reduce hearing loss in medulloblastoma patients and to compare the overall outcome of patients with medulloblastoma treated with STS to patients treated without STS on a previous study in order to make sure that survival and recurrence of tumor is not worsened.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
ALL
4 Years to 21 Years old
PHASE3
NCT05382338
STU-2023-0231
Inclusion Criteria:
* PRE-ENROLLMENT: Patients must be ≥ 4 years and ≤ 21 years of age at the time of enrollment
* PRE-ENROLLMENT: Patient is suspected to have newly-diagnosed medulloblastoma by institutional diagnosis
* Please note: Patients with a pending result of CSF cytology tests are eligible for NCI-2014-02057 (APEC14B1-Central Nervous System \[CNS\]) and CNS/Medulloblastoma Pre Enrollment Eligibility Screening
* PRE-ENROLLMENT: The patient and/or their parents or legal guardians must have signed informed consent for APEC14B1 Part A - Eligibility Screening and consent for the Molecular Characterization Initiative (MCI)
* PRE-ENROLLMENT: The required specimens are projected to be submitted under APEC14B1-CNS as soon as possible, preferably within 5 days of definitive surgery
* PRE-ENROLLMENT: All patients must have rapid central pathology review under APEC14B1-CNS prior to study enrollment on ACNS2031 step 1 in order to avoid discordant diagnoses and to verify diagnosis criterion for treatment on ACNS2031.
* Note: Patients with a pending result of CSF cytology tests are eligible for the rapid central pathology screening review. Confirmation of CSF negativity is needed for enrollment on the ACNS2031 protocol
* PRE-ENROLLMENT: All patients must have rapid central molecular screening review under APEC14B1-CNS prior to study enrollment on ACNS2031 step 1, in order to avoid discordant diagnoses and to verify diagnosis criterion for treatment on ACNS2031
* PRE-ENROLLMENT: All patients who have histopathology confirmed must have rapid central imaging screening review under APEC14B1 prior to study enrollment on ACNS2031 step 1
* Note: Patients must not have metastatic disease on cranial or spinal MRI. Patients with \> 1.5 cm\^2 residual tumor after initial surgical resection may undergo a second surgical resection prior to subsequent therapy to render them eligible for this study. The day of the second resection to remove residual tumor will be regarded as the day of definitive surgery (Day 0) and must be within a month (31 days) of the initial resection
* PRE-ENROLLMENT: All patients who have histopathology confirmed must have rapid central audiology review under APEC14B1-CNS prior to study enrollment on ACNS2031 step 1
* Patients must be \>= 4 years and =\< 21 years of age at the time of enrollment
* Patients must be newly diagnosed and have eligibility confirmed by rapid central pathology and molecular screening reviews performed on APEC14B1 and via the Molecular Characterization Initiative
* Average-risk cohort
* Clinico-pathologic criteria:
* M0 disease
* No diffuse anaplastic histology AND
* Molecular criteria:
* SHH, p53wt, GLI2 normal, MYCN normal, no chromosome 14q loss
* Group 3, MYC normal, no isochromosome 17q
* Group 4, no chromosome 11 loss
* Low-risk features cohort
* Clinico-pathologic criteria:
* M0 disease
* No diffuse anaplastic histology AND
* Molecular criteria:
* Group 4, chromosome 11 loss
* Patients must have negative lumbar CSF cytology
* Note: CSF cytology for staging should be performed no sooner than 14 days post operatively to avoid false positive CSF. Ideally, CSF should be obtained between day 14 and day 21 to allow for final staging status before enrollment onto the study. Patients with positive CSF cytology obtained 0 to 14 days after surgery should have cytology repeated to determine eligibility and final CSF status. Patients with negative CSF cytology from lumbar puncture obtained 0 to 14 days after surgery do not need cytology repeated. Patients with negative CSF cytology from lumbar puncture obtained prior to surgery do not need cytology repeated post-operatively
* Patients must have eligibility confirmed by Rapid Central Imaging Review performed on APEC14B1. Patients must have =\< 1.5 cm\^2 cross-sectional area of residual tumor. Whole brain MRI with and without gadolinium and spine MRI with gadolinium must be performed
* Patients must weigh \> 10 kg
* Patients must be enrolled, and protocol therapy must be projected to begin, no later than 31 days after definitive diagnostic surgery (day 0)
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL (within 7 days prior to enrollment)
* Platelet count \>= 100,000/uL (transfusion independent) (within 7 days prior to enrollment)
* Hemoglobin \>= 8.0 g/dL (may receive red blood cell count \[RBC\] transfusions) (within 7 days prior to enrollment)
* A serum creatinine (within 7 days prior to enrollment) based on age/sex as follows:
* 4 to \< 6 years (age); 0.8 mg/dL (male) 0.8 mg/dL (female)
* 6 to \< 10 years (age); 1 mg/dL (male) 1 mg/dL (female)
* 10 to \< 13 years (age); 1.2 mg/dL (male) 1.2 mg/dL (female)
* 13 to \< 16 years (age); 1.5 mg/dL (male) 1.4 mg/dL (female)
* \>= 16 years (age); 1.7 mg/dL (male) 1.4 mg/dL (female) OR a 24 hour urine Creatinine clearance \>= 70 mL/min/1.73 m\^2 (within 7 days prior to enrollment) OR a glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 (within 7 days prior to enrollment). GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
* Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
* Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (within 7 days prior to enrollment)
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* Central nervous system function defined as:
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
* Patients must not be in status epilepticus, a coma or assisted ventilation at the time of study enrollment
* Auditory function defined as:
* Patients must have normal hearing (defined as International Society of Pediatric Oncology \[SIOP\] grade 0) in at least one ear confirmed by rapid central audiology review performed on APEC14B1 prior to enrollment
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
* Patients with metastatic disease by either MRI evaluation or lumbar CSF cytology are not eligible. Patients who are unable to undergo a lumbar puncture for assessment of CSF cytology are ineligible
* Patients must not have received any prior radiation therapy or chemotherapy (tumor-directed therapy) other than surgical intervention and/or corticosteroids
* Patients must not have any known hypersensitivity to STS, sulfates/sulfites, or other thiol agents (e.g., amifostine, n-acetylcysteine, MESNA, and captopril)
* Pregnancy and Breastfeeding:
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation PROCEDURE: Audiometric Test, PROCEDURE: Auditory Brainstem Response, PROCEDURE: Biospecimen Collection, DRUG: Cisplatin, DRUG: Cyclophosphamide, DRUG: Lomustine, PROCEDURE: Magnetic Resonance Imaging, OTHER: Quality-of-Life Assessment, RADIATION: Radiation Therapy, DRUG: Sodium Thiosulfate, OTHER: Survey Administration, DRUG: Vincristine
Childhood Medulloblastoma, Brain and Nervous System
Children’s Health
Impact of Intensive Treatment of SBP on Brain Perfusion, Amyloid, and Tau (IPAT Study) (IPAT)
The purpose of this study is to determine if intensive lowering of systolic blood pressure (SBP), using FDA approved medications (antihypertensive), reduces Alzheimer's Disease pathology (i.e., excessive brain amyloid and tau protein deposition) in older adults at high risk for memory decline or dementia.
Call 214-648-5005
studyfinder@utsouthwestern.edu, TristynHall@texashealth.org
Rong Zhang
ALL
60 Years to 85 Years old
PHASE2
NCT05331144
STU-2021-1210
Inclusion Criteria:
* Age 60-85, all races/ethnicities, and both sexes are eligible;
* Mini-Mental State Exam (MMSE) ≥ 26 to exclude gross dementia; based on clinical judgment, may be rescreened in ≥ 7 days;
* Individuals with SBP ≥ 130 and SBP ≤ 180 if on 0 or 1 antihypertensive medications; ≥130 and ≤170 on up to 2 medications; ≥130 and ≤160 on up to 3 medications; ≥130 and ≤150 on up to 4 medications. Those on antihypertensives are eligible. If an individual, not treated for hypertension (HTN), has a SBP ≥ 125 mmHg, consider rescreening after 24 hours;
* Willingness to be randomized into the treatment groups and ability to return to clinic for follow-up visits over 24 months;
* Fluency in English or Spanish or both, adequate visual and auditory acuity to allow neuropsychological testing;
* Participants must have a regular healthcare provider.
Exclusion Criteria:
* Clinically documented history of stroke, focal neurological signs or other major cerebrovascular diseases based on clinical judgment or MRI/CT scans such as evidence of infection, infarction, or other brain lesions;
* Diagnosis of AD or other type of dementia, or significant neurologic diseases such as Parkinson's disease, seizure disorder, multiple sclerosis, history of severe head trauma or normal pressure hydrocephalus;
* Evidence of severe major depression (GDS ≥ 12, may be rescreened after 12 weeks or longer if evidence of reactive depression or temporary mood disturbances) or clinically significant psychopathology, (e.g., psychosis and schizophrenia); if hospitalized in past year, can be rescreened in 6 months; or presence of a major psychiatric disorder that in the investigator's opinion, could interfere with adherence to research assessments or procedures.
* Unstable heart disease based on clinical judgment (e.g., heart attack/cardiac arrest, cardiac bypass procedures within previous 6 months and congestive heart failure), or other severe medical conditions;
* History of atrial fibrillation and evidence on ECG with any of the following: active symptoms of persistent palpitation, dizziness, history of syncope, chest pain, dyspnea, orthopnea, shortness of breath at rest, or paroxysmal nocturnal dyspnea within the past 6 months; resting heart rate of \< 30 or \> 110 bpm; taking class I or III antiarrhythmic drugs including flecainide, propafenone, dronedarone, sotalol, dofetilide, and amiodarone; or clinical concerns for safely participating in lowering blood pressure.
* Systolic BP equal or greater than 180 mmHg and/or diastolic BP equal or greater than 110 mmHg, may be rescreened in 1 week.
* Orthostatic hypotension, defined as the third standing SBP \< 100mmHg, may be rescreened after 2 weeks;
* History of significant autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis or polymyalgia rheumatica;
* Significant history of alcoholism or drug abuse within the last five years;
* Uncontrolled diabetes mellitus, defined as hemoglobin A1C \> 7.5%, or requiring insulin treatment;
* Regularly smoking cigarettes within the past year;
* Pacemaker or other medical device of metal that precludes performing MRI;
* Women with a potential for pregnancy, lactation/childbearing (2 year post-menopausal or surgically sterile to be considered not childbearing potential);
* Participant enrolled in another investigational drug or device study, either currently or within the past 2 months;
* Severe obesity with BMI \> 40 ; clinical judgment should be applied in all cases to assess patient safety and anticipated compliance;
* Allergy to angiotensin receptor blockers (ARBs), i.e., drugs that have a suffix "-sartan"; allergy to amlodipine;
* Abnormal screening laboratory tests (e.g., liver ALT and AST \> 3 x ULN, GFR \< 30 or Hct \< 28%); may be rescreened after 2 weeks or longer;
* A medical condition likely to limit survival to less than 3 years;
* Participant has any condition(s) judged by the study investigator to be medically inappropriate, risky or likely to cause poor study compliance. For example:
• Plans to move outside the clinic catchment area in the next 2 years;
• Significant concerns about participation in the study from spouse, significant other, or family members;
• Lack of support from primary health care provider;
• Residence too far from the study clinic site such that transportation is a barrier including persons who require transportation assistance provided by the study clinic funds for screening or randomization visits;
• Residence in a nursing home; persons residing in an assisted living or retirement community are eligible if they meet the other criteria;
• Other medical, psychiatric, or behavioral factors that, in the judgment of the site PI or clinician, may interfere with study participation or the ability to follow the study Protocol.
• Couples or significant partners who live together cannot be enrolled or participate simultaneously in the study.
DRUG: Angiotensin II Receptor Blockers (ARBs, losartan) and Calcium Channel Blockers (CCB, amlodipine), OTHER: PCP
Cognitively Normal Older Adults, Hypertension, Subjective Cognitive Decline, Family History of Dementia, Brain and Nervous System
Dementia, Alzheimer's Disease, Cognitive Function, Blood Pressure, Amyloid, Tau
UT Southwestern
Tofacitinib in Recurrent GBM Patients
The purpose of this study is to examine the effects of Tofacitinib in patients with recurrent Glioblastoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Michael Youssef
ALL
18 Years and over
PHASE3
NCT05326464
STU-2021-1029
Inclusion Criteria:
• Histologically confirmed GBM (MGMT unmethylated, IDH wild type) at first, second, third, or fourth recurrence after concurrent chemoradiotherapy. Patients with an initial diagnosis of a lower-grade glioma are eligible if a subsequent biopsy determined the progressive tumor to be GBM.
• Imaging confirmation of first tumor progression or regrowth as defined by the Response Assessment in Neuro-Oncology (RANO) criteria. A minimum of 12 weeks must have elapsed from the completion of radiotherapy to study entry to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, unless there is a new lesion outside the radiation field or unequivocal evidence of viable tumor on histopathological sampling.
• Karnofsky Performance Status (KPS) ≥ 60%.
• Patients must be willing and able to provide written informed consent and to comply with the study protocol as judged by the investigator.
• Age ≥ 18 years.
• Patients must be able to swallow oral medications.
• For women who are of child-bearing potential and who are sexually active and who are not surgically sterile (absence of ovaries and/or uterus): to use an adequate method of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly) during the treatment period and for at least 6 months after last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. For male patients who are partners of premenopausal women: agreement to use a barrier method of contraception during the treatment period and for at least 6 months after the last dose of study drug.
• 1 A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Patients who have undergone recent surgery for recurrent or progressive tumor are eligible provided that:
• 1 Surgery must have confirmed the recurrence.
• 2 A minimum of 28 days must have elapsed from the day of surgery to study entry. For core or needle biopsy, a minimum of 7 days must have elapsed prior to study entry.
• 3 Craniotomy or intracranial biopsy site must be adequately healed and free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of randomization.
• Patients must have recovered (Common Terminology Criteria for Adverse Events CTCAE version 6\] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to randomization. Minimum times from prior therapies include:
• 1 Greater than or equal to 28 days elapsed from the administration of any investigational agent.
• 2 Greater than or equal to 28 days elapsed from the administration of any prior cytotoxic agents, except ≥ 42 days from nitrosoureas. NOTE: Prior treatment with Novo-TTF therapy is allowed at initial diagnosis but must be discontinued prior to study entry.
• GBMs of the study patients must have EGFR gene amplification, which will be detected by next generation sequencing of tumor tissue from resected sample.
• Prior use of bevacizumab is allowed, however patient must be off of this medication for 180 days.
• Patients must have adequate organ and marrow function as defined by the following criteria: * ANC ≥1.5 × 10(9)/L * Platelets ≥100 × 10(9)/L * Hemoglobin ≥8 g/dL * Total bilirubin ≤1.5 × ULN Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted. ALT and AST ≤3 × ULN
Exclusion Criteria:
• Prior treatment with an EGFR or JAK inhibitor.
• Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
• Patients unable to undergo brain MRI scans with IV gadolinium contrast.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Tofacitinib
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Prior history of hypertensive crisis, hypertensive encephalopathy, or inadequately controlled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg while on antihypertensive medication).
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant gastrointestinal resection that would preclude adequate absorption of the trial medications.
• History of another malignancy in the previous 3 years, with a disease-free interval of \< 3 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.
• Concurrent use of Bevacizumab.
DRUG: Tofacitinib 10mg
Glioblastoma, Brain and Nervous System
UT Southwestern
Efficacy and Safety of REC-2282 in Patients With Progressive Neurofibromatosis Type 2 (NF2) Mutated Meningiomas (POPLAR-NF2)
This is a two-staged, Phase 2/3, randomized, multi-center study to investigate the efficacy and safety of REC-2282 in patients with progressive NF2 mutated meningiomas.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
All
12 Years and over
Phase 2/Phase 3
NCT05130866
STU-2021-1151
Inclusion Criteria:
• ≥12 years of age and weighing at least 40 kg
• Progressive meningioma that is amenable to volumetric analysis
• Has either 1) sporadic meningioma with confirmed NF2 mutation; or, 2) confirmed diagnosis of NF2 disease (revised Manchester criteria); or, 3) at least one NF2-related tumor (with pathogenic germline or proven mosaic NF2 variant)
• Adequate bone marrow function
• Has provided written informed consent/assent to participate in the study
Exclusion Criteria:
• Progressive disease associated with significant or disabling clinical symptoms likely to require surgery or radiation therapy within the next 3 months.
• Received prior surgery, radiosurgery, or laser interstitial thermal therapy in the target tumor, or immediately adjacent to the target tumor within 6 months prior to screening.
• Received an anti- tumor agent for meningioma within 3 months, or 5 half-lives (whichever is longer), prior to screening.
• History of an active malignancy within the previous 3 years except for localized cancers that are considered cured, and, in the opinion of the investigator, present a low risk of recurrence.
• Received another investigational drug within 30 days prior to screening
• Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during this study or within 90 days after the last dose of IMP.
Drug: REC-2282, Drug: Placebo
Neurofibromatosis Type 2, Brain and Nervous System
Neurofibromatosis Type 2, Neurofibromatosis Type II
UT Southwestern; Children’s Health
Testing the Addition of the Chemotherapy Drug Lomustine (Gleostine) to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed MGMT Methylated Glioblastoma
This phase III trial compares the effect of adding lomustine to standard chemotherapy with temozolomide and radiation therapy versus temozolomide and radiation therapy alone in shrinking or stabilizing newly diagnosed MGMT methylated glioblastoma. MGMT methylated tumors are more likely to respond to temozolomide chemotherapy. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill tumor cells and slow down or stop tumor growth. Lomustine is a chemotherapy drug and in a class of medications called alkylating agents. It damages the cell's DNA and may kill tumor cells. Radiation therapy uses high energy x-ray photons to kill tumor cells and shrink tumors. Adding lomustine to standard chemotherapy with temozolomide and radiation therapy may shrink or stabilize glioblastoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nawal Shaikh
ALL
18 Years to 70 Years old
PHASE3
NCT05095376
STU-2022-0465
Inclusion Criteria:
* STEP 1 REGISTRATION: No known IDH mutation. (If tested before step 1 registration, patients known to have IDH mutation in the tumor on local or other testing are ineligible and should not be registered)
* STEP 1 REGISTRATION: Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block and hematoxylin and eosin (H\&E) stained slide to be sent for central pathology review for confirmation of histology and MGMT promoter methylation status. Note that tissue for central pathology review and central MGMT assessment must be received by the New York University (NYU) Center for Biospecimen Research and Development (CBRD) on or before postoperative calendar day 30. If tissue cannot be received by postoperative calendar day 30, then patients may NOT enroll on this trial as central pathology review will not be complete in time for the patient to start treatment no later than 8 weeks following surgery. Results of central pathology review and central MGMT analysis will generally be completed within 10 business days of receipt of tissue. Results will be entered by the central lab directly into Rave. Note: In the event of an additional tumor resection(s), tissue must be received within 30 days of the most recent resection and the latest resection must have been performed within 30 days after the initial resection. Surgical resection is required; stereotactic biopsy alone is not allowed because it will not provide sufficient tissue for MGMT analysis
* STEP 1 REGISTRATION: Willing to use highly effective method of contraception for participants of childbearing potential (participants who may become pregnant or who may impregnate a partner) during therapy and for 6 months after completing treatment; this inclusion is necessary because the treatment in this study may be significantly teratogenic
* STEP 1 REGISTRATION: The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
* STEP 2 REGISTRATION: Histopathologically proven diagnosis of glioblastoma (or gliosarcoma as a subtype of glioblastoma) confirmed by central pathology review
* STEP 2 REGISTRATION: MGMT promoter with methylation confirmed by central pathology review. Note: Patients with tissue that is insufficient or inadequate for analysis, fails MGMT testing, or has indeterminate or unmethylated MGMT promoter are excluded
* Note: Any MGMT result other than methylated would require step 2 registration to be reported as a "central review failure"
* STEP 2 REGISTRATION: Contrast-enhanced brain MRI performed either after surgery or prior to step 2 registration
* STEP 2 REGISTRATION: IDH mutation testing by at least one method (such as immunohistochemistry for IDH1 R132H) must be performed as part of standard of care and no mutation must be found (i.e IDH wildtype). (If a mutation is identified then the patient will be ineligible and must be registered as ineligible at step 2.)
* STEP 2 REGISTRATION: History/physical examination within 28 days prior to step 2 registration
* STEP 2 REGISTRATION: Karnofsky performance status (KPS) \>= 70 within 28 days prior to step 2 registration
* STEP 2 REGISTRATION: Neurologic function assessment within 28 days prior to step 2 registration
* STEP 2 REGISTRATION: Age 18-70 years
* STEP 2 REGISTRATION: Hemoglobin \>= 10 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 10.0 g/dl is acceptable) (Within 14 days prior to step 2 registration)
* STEP 2 REGISTRATION: Leukocytes \>= 2,000/mm\^3 (Within 14 days prior to step 2 registration)
* STEP 2 REGISTRATION: Absolute neutrophil count \>= 1,500/mm\^3 (Within 14 days prior to step 2 registration)
* STEP 2 REGISTRATION: Platelets \>= 100,000/mm\^3 (Within 14 days prior to step 2 registration)
* STEP 2 REGISTRATION: Total bilirubin =\< 1.5 x institutional/lab upper limit of normal (ULN) (Within 14 days prior to step 2 registration)
* STEP 2 REGISTRATION: Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) =\< 2.5 x ULN (Within 14 days prior to step 2 registration)
* STEP 2 REGISTRATION: Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN (Within 14 days prior to step 2 registration)
* STEP 2 REGISTRATION: Serum creatinine =\< 1.5 x ULN OR creatinine clearance (CrCl) \>= 50 mL/min (if using the Cockcroft-Gault formula) (Within 14 days prior to step 2 registration)
* STEP 2 REGISTRATION: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B)
* STEP 2 REGISTRATION: For patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Note: Known positive test for hepatitis C virus ribonucleic acid (HCV ribonucleic acid \[RNA\]) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy
* STEP 2 REGISTRATION: Known human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to step 2 registration are eligible for this trial. Testing is not required for entry into protocol
* STEP 2 REGISTRATION: Negative serum or urine pregnancy test (in persons of childbearing potential) within 14 days prior to step 2 registration
* Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
Exclusion Criteria:
* STEP 2 REGISTRATION: Prior therapy for tumor except for resection or prior laser interstitial thermal therapy (LITT). For example, prior chemotherapy, immunotherapy, or targeted therapy for GBM or lower grade glioma is disallowed (including but not limited to temozolomide, lomustine, bevacizumab, any viral therapy, ipilimumab or other CTLA-4 antibody, PD-1 antibody, CD-137 agonist, CD40 antibody, PDL-1 or 2 antibody, vaccine therapy, polio or similar viral injection as treatment for the tumor, and/or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) as is Gliadel wafer, radiotherapy, radiosurgery, vaccine or other immunotherapy, brachytherapy, or convection enhanced delivery
* Note: 5-aminolevulinic acid (ALA)-mediated fluorescent guided resection (FGR) photodynamic therapy (PDT) or fluorescein administered prior to/during surgery to aid resection is not exclusionary and is not considered a chemotherapy or intracerebral agent. Prior laser interstitial thermal therapy (LITT) is allowed
* STEP 2 REGISTRATION: Current or planned treatment with any other investigational agents for the study cancer
* STEP 2 REGISTRATION: Definitive clinical or radiologic evidence of metastatic disease outside the brain
* STEP 2 REGISTRATION: Prior invasive malignancy (except non-melanomatous skin cancer, cervical cancer in situ and melanoma in situ) unless disease free for a minimum of 2 years
* STEP 2 REGISTRATION: Prior radiotherapy to the head or neck that would result in overlap of radiation therapy fields
* STEP 2 REGISTRATION: Pregnancy and individuals unwilling to discontinue nursing due to the potential teratogenic effects and potential risk for adverse events in nursing infants
* STEP 2 REGISTRATION: History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or lomustine
* STEP 2 REGISTRATION: History of pulmonary fibrosis
* STEP 2 REGISTRATION: Uncontrolled intercurrent illness including, but not limited to:
* Ongoing or active infection requiring intravenous (IV) antibiotics, IV antiviral, or IV antifungal treatment
* Symptomatic congestive heart failure, defined as New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)
* Unstable angina pectoris within 6 months prior to Step 2 registration
* Uncontrolled cardiac arrhythmia
* Psychiatric illness/social situations that would limit compliance with study requirements
* STEP 2 REGISTRATION: No evidence of diffuse leptomeningeal disease that requires whole brain irradiation DRUG: Lomustine, PROCEDURE: Magnetic Resonance Imaging, RADIATION: Photon Beam Radiation Therapy, OTHER: Questionnaire Administration, DRUG: Temozolomide
Glioblastoma, Gliosarcoma, Brain and Nervous System
UT Southwestern; Parkland Health & Hospital System
Evaluating the Addition of the Immunotherapy Drug Atezolizumab to Standard Chemotherapy Treatment for Advanced or Metastatic Neuroendocrine Carcinomas That Originate Outside the Lung
This phase II/III trial compares the effect of immunotherapy with atezolizumab in combination with standard chemotherapy with a platinum drug (cisplatin or carboplatin) and etoposide versus standard therapy alone for the treatment of poorly differentiated extrapulmonary (originated outside the lung) neuroendocrine cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). The other aim of this trial is to compare using atezolizumab just at the beginning of treatment versus continuing it beyond the initial treatment. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cisplatin and carboplatin are in a class of medications known as platinum-containing compounds that work by killing, stopping or slowing the growth of cancer cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair, and it may kill cancer cells. Giving atezolizumab in combination with a platinum drug (cisplatin or carboplatin) and etoposide may work better in treating patients with poorly differentiated extrapulmonary neuroendocrine cancer compared to standard therapy with a platinum drug (cisplatin or carboplatin) and etoposide alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Namrata Peswani
ALL
18 Years and over
PHASE2
NCT05058651
STU-2023-0750
Inclusion Criteria:
* Participants must have histologically-confirmed (local site pathological confirmation sufficient) extrapulmonary poorly differentiated, neuroendocrine carcinoma (NEC)
* Participants must have disease that is unresectable or metastatic and not eligible for definitive therapy as deemed per the treating investigator
* Participants must have radiologically evaluable disease, measurable or non-measurable, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. All measurable and nonmeasurable lesions must be assessed by CT scan with IV contrast of the chest/abdomen/and pelvis (or CT chest without contrast and MRI abdomen/pelvis with gadolinium contrast, if contraindication to CT iodinated contrast) within 28 days prior to registration. While may be used for routine clinical evaluation, PET scans and bone scans alone are not acceptable for disease assessment while participating in this study. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form
* Participants must have brain MRI (or CT head with contrast if there is contraindication to MRI brain) if clinically indicated within 28 days prior to registration. Note: Brain imaging is not required in participants without known and/or clinical concern for brain metastases. Participants with asymptomatic central nervous system (CNS) metastases are eligible if one or more of the following apply:
* Participants who have received treatment for brain metastases must have:
* No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration
* Discontinued all corticosteroids at least 14 days prior to registration
* Participants with treatment-naive brain lesions must have:
* No lesion measuring \> 2.0 cm in size in any axis
* MRI brain or CT head with contrast (if there is contraindication to MRI brain) demonstrating no evidence for mass effect, edema, or other impending neurological compromise within 28 days prior to registration
* No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration
* No need for \> 2 mg of dexamethasone (or equivalent of \> 10 mg prednisone) per day at time of registration
* Participants must not have symptomatic central nervous system (CNS) metastases
* Participants must not have known or suspected leptomeningeal disease
* Participants with prior history of non-metastatic (localized/locally advanced disease) extrapulmonary poorly differentiated NEC may have had prior platinum-based therapy +/- radiation +/- surgery provided that all therapy was completed \>= 6 months prior to registration
* Participants must discontinue denosumab prior to study registration and plan to replace with a bisphosphonate while on the study
* Participants must not have had prior treatment for advanced or metastatic NEC EXCEPT one cycle of platinum (carboplatin/cisplatin) + etoposide is allowed prior to registration. Other chemotherapy regimens are not allowed. For participants with prostate or urothelial NEC, prior chemotherapy for the non-NEC component (e.g. adenocarcinoma or urothelial) is allowed as long as such therapy was completed \>= 24 weeks prior to registration and participants have recovered from all prior toxicities to =\< grade 1.
* Participants must not have had prior treatment with an anti-PD-1, anti-PD-L1, antiPD-L2, CD137 agonists, anti-CTLA-4 agent, or any other immune checkpoint inhibitors for any neuroendocrine neoplasm. Immune checkpoint inhibitors given for other cancer indications are allowed provided last therapy was given at least 12 months prior to study registration
* Participants must not have received treatment with systemic immunostimulatory agents including, but not limited to, interferon and interleukin2 \[IL-2\] within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to registration
* Participants must not have had history of known severe allergy, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies, including to Chinese hamster ovary cell products or to any component of the atezolizumab formulation, cisplatin, carboplatin, or etoposide
* Participants must not be on active systemic therapy for another cancer with the exception of hormonal therapy including androgen deprivation therapy (e.g., gonadotropin-releasing hormone \[GnRH\] agonists or antagonists), which can be continued while participants are receiving protocol therapy. Use of enzalutamide or apalutamide is permitted after completion of chemotherapy and must be held during chemotherapy for participants receiving prior to enrollment. Use of darolutamide is permitted during chemotherapy. Glucocorticoid-containing regimens, including abiraterone, are not permitted.
* Participants must be \>= 18 years of age
* Participants must have a Zubrod performance status of =\< 2 within 28 days prior to registration
* Participants must have a complete medical history and physical exam within 28 days prior to registration
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9 /L (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Hemoglobin \>= 9.0 g/dl (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Platelet count \>= 100 x 10\^9/L (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x institutional upper limit of normal (ULN) (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Serum total bilirubin =\< 1.5 x ULN (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Adequate renal function as defined by any 1 of the following: 1) Measured creatinine clearance (CL) \> 50 mL/min OR 2) Calculated creatinine CL \> 50 mL/min by the Cockcroft-Gault formula OR by 24-hour urine collection for determination of creatinine clearance (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Participants must not have uncontrolled or symptomatic hypercalcemia (\> 1.5 mmol/L ionized calcium or calcium \> 12 mg/dL or corrected serum calcium \> ULN) within 14 days prior to registration. Participants who have asymptomatic hypercalcemia are eligible provided that medical therapy to treat the hypercalcemia is planned
* Participants must not have a diagnosis of immunodeficiency nor be receiving systemic steroid therapy (equivalent of \> 20 mg of hydrocortisone per day) or any other form of immunosuppressive therapy within 14 days prior to registration
* Participants must not have active or history of autoimmune disease or immune deficiency, including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis with the following exceptions:
* Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study
* Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
* Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
* Rash must cover \< 10% of body surface area
* Disease is well controlled at baseline and requires only low-potency topical corticosteroids
* No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
* Participants must not have history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. NOTE: History of radiation pneumonitis in the radiation field (fibrosis) is permitted
* Participants must not have significant cardiovascular disease, such as New York Heart Association class II or greater cardiac disease, myocardial infarction within 3 months prior to registration, unstable arrythmias, or unstable angina
* Participants must not have had a major surgical procedure other than for diagnosis within 28 days prior to registration. Participant must not plan to receive a major surgical procedure during the course of protocol treatment. NOTE: Patient port placement is not considered a major surgery
* Participants must not have severe infections (i.e., Common Terminology Criteria for Adverse Events \[CTCAE\] grade \>= 2) at time of registration, including but not limited to hospitalization for complications for infection, bacteremia, or severe pneumonia
* Participants must not have known active tuberculosis
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load, with testing performed as clinically indicated
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with active HCV infection who are currently on treatment must have an undetectable HCV viral load, with testing performed as clinically indicated
* Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at time of registration and have undetectable HIV viral load within 6 months of registration
* Participants must not have prior allogeneic bone marrow transplantation or solid organ transplant
* Participants must not have received administration of a live, attenuated vaccine (e.g., FluMist \[registered trademark\]) within 28 days prior to initiation of study treatment, during treatment with atezolizumab, and not plan to receive for 5 months after the last dose of atezolizumab
* Participants must not be pregnant due to the possibility of harm to the fetus. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method (with details provided as a part of the consent process) during the treatment period and for 5 months after the final dose of atezolizumab. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a sideeffect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
* Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines BIOLOGICAL: Atezolizumab, PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Etoposide, PROCEDURE: Magnetic Resonance Imaging, OTHER: Patient Observation
Advanced Extrapulmonary Neuroendocrine Carcinoma, Metastatic Extrapulmonary Neuroendocrine Carcinoma, Recurrent Extrapulmonary Neuroendocrine Carcinoma, Unresectable Extrapulmonary Neuroendocrine Carcinoma, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Urinary Bladder
UT Southwestern; Parkland Health & Hospital System
Intraventricular Administration of Rhenium-186 NanoLiposome for Leptomeningeal Metastases (ReSPECT-LM)
This is an open-label Phase I clinical study that will administer a single dose of 186RNL via intraventricular catheter for treatment of Leptomeningeal Metastases (LM).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Michael Youssef
All
18 Years and over
Phase 1
NCT05034497
STU-2021-0950
Inclusion Criteria:
• At least 18 years of age at time of screening.
• Ability to understand the purposes and risks of the study and has signed a written informed consent document approved by the site-specific IRB.
• Subject has proven and documented LM that meets the requirements for the study: a. Current EANO-ESMO Clinical Practice Guidelines Type 1 and 2 LM of any primary type. 2D is excluded.
• Karnofsky performance status of 60 to 100.
• Acceptable liver function:
• Bilirubin 1.5 times upper limit of normal
• AST (SGOT) and ALT (SGPT) ≤ 3.0 times upper limit of normal for subjects with normal liver
• AST (SGOT) and ALT (SGPT) ≤ 5.0 times upper limit of normal for subjects with liver metastasis
• Acceptable renal function with serum creatinine ≤ 2 times upper limit of normal
• Acceptable hematologic status (without hematologic support):
• ANC ≥ 1000 cells µL
• Platelet count ≥ 75,000/µL
• Hemoglobin ≥ 9.0 g/dL
• All women of childbearing potential must have a negative serum pregnancy test at screening. Male and female subjects must agree to use effective means of contraception (for example, surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose.
• Subjects with a creatinine clearance greater than or equal to 60 mL/min (using the Cockcroft-Gault Equation) for males and females.
Exclusion Criteria:
• The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v5.0) Grade ≤ 1 from AEs due to antineoplastic agents, investigational drugs, or other medications that were administered prior to study. Prior AEs due to alopecia, anemia, and lymphopenia are not required to be recovered to Grade ≤ 1 prior to 186RNL treatment, assuming other inclusion criteria are satisfied.
• Obstructive or symptomatic communicating hydrocephalus.
• Ventriculo-peritoneal or ventriculo-atrial shunts without programable valves or contraindications to placement of Ommaya reservoir.
• Females of childbearing potential who are pregnant, breast feeding, or may possibly be pregnant without a negative serum pregnancy test (see inclusion criteria).
• Serious intercurrent illness, such as progressive systemic (extra leptomeningeal) disease, clinically significant cardiac arrhythmias, uncontrolled systemic infection, symptomatic congestive heart failure or unstable angina pectoris within 3 months prior study drug, myocardial infarction, stroke, transient ischemic attack within 6 months, seizure disorder with any seizure occurring within 14 days prior to consenting or encephalopathy.
• Active severe non hematologic organ toxicity such as renal, cardiac, hepatic, pulmonary, or gastrointestinal systemic toxicity grade 3 or above.
• Significant coagulation abnormalities such as inherited bleeding diathesis or acquired coagulopathy with unacceptable risks of bleeding.
• Patients who had any dose to the spinal cord or whole brain radiation therapy, regardless of when the radiation treatment was delivered. Prior, non-CNS radiation for primary tumor is allowed.
• Systemic chemotherapeutic agents with CNS penetration (such as temozolomide, carmustine, lomustine, capecitabine, carboplatin, vinorelbine, bevacizumab, irinotecan or topotecan) are excluded if given within 14 days or 5 half-lives, whichever is shorter, prior to 186RNL treatment.
• If the washout period is satisfied, the patient may be enrolled, providing all other I/E criteria are satisfied.
• If the patient is undergoing systemic chemotherapy with CNS penetration (such as temozolomide, carmustine, lomustine, capecitabine, carboplatin, vinorelbine, bevacizumab, irinotecan or topotecan) and they develop or have progressive/persistent LM while on the agent, they may be included in the trial at the PI's discretion.
• Systemic therapy (including investigational agents and small-molecule kinase inhibitors) is excluded if given within 14 days or 5 half-lives, whichever is shorter, prior to 186RNL treatment. a. If the washout period is satisfied, the patient may be enrolled, providing all other I/E criteria are satisfied.
• Nitrosoureas or mitomycin C within 42 days, or metronomic/protracted low-dose chemotherapy within 14 days, or other cytotoxic chemotherapy within 28 days, are excluded if given within the above timepoints prior to 186RNL treatment. a. If the washout period is satisfied, the patient may be enrolled, providing all other I/E criteria are satisfied.
• Impaired CSF Flow Study, within 4 +/- 3 days of 186RNL treatment, based on study imaging and as determined by the investigator.
Drug: 186RNL
Leptomeningeal Metastasis, Brain and Nervous System
UT Southwestern
A Randomized, Controlled Trial to Evaluate the Safety and Effectiveness of the Route 92 Medical Reperfusion System (SUMMIT MAX)
The SUMMIT MAX study is a prospective, randomized, controlled, interventional clinical trial to evaluate the safety and effectiveness of the Route 92 Medical MonoPoint® Reperfusion System for aspiration thrombectomy in acute ischemic stroke patients.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Charlton.Starcke@UTSouthwestern.edu
Roberta Novakovic
All
18 Years to 85 Years old
N/A
NCT05018650
STU-2022-0053
Inclusion Criteria:
• The consent process has been completed and documented according to applicable country regulations and as approved by the IRB / Ethics Committee
• Age >=18 years and <= 85
• Patient presenting with clinical signs consistent with an acute ischemic stroke
• Baseline National Institutes of Health Stroke Scale (NIHSS) score >= 6
• Pre-stroke modified Rankin Score (mRS) <= 1
• Baseline ASPECTS >= 6
• Endovascular treatment initiated (defined as time of first angiogram) within 8 hours from time last known well
• If indicated, thrombolytic therapy shall be initiated per clinical guidelines. If eligible for thrombolytic therapy, subjects should be treated as soon as possible and lytic use should not be delayed regardless of potential eligibility for mechanical neurothrombectomy.
• The patient is indicated for aspiration neurothrombectomy with the Route 92 Medical Reperfusion System as determined by the Investigator
• Angiographic confirmation of a large vessel occlusion of the M1 segment of the middle cerebral artery or distal internal carotid artery
Exclusion Criteria:
• Known pregnancy or breast feeding
• In the Investigator's opinion, any known comorbidity (including COVID-19 positivity) that may complicate treatment or prevent improvement or follow-up
• Known serious, advanced, or terminal illness with anticipated life expectancy < 12 months
• Known history of severe allergy to contrast medium
• Known to have suffered a stroke in the past 90 days
• Known connective tissue disorder affecting the arteries (e.g. Marfan syndrome, Ehlers-Danlos syndrome)
• Any known previous cerebral hemorrhagic event
• Any known pre-existing coagulation deficiency
• Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR >3.0
• Known baseline platelet count <50,000/µL
• Known baseline blood glucose of <50 mg/dL or >400 mg/dL
• Known to be participating in another study involving an investigational device or drug
• Clinical symptoms suggestive of bilateral stroke or stroke in multiple territories.
• Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) evidence of recent/ fresh cerebral hemorrhage (the presence of microbleeds is allowed)
• Baseline CT or MRI showing intracranial tumor (except small meningioma <= 2cm) or significant mass effect with midline shift due to the tumor
• Presumed septic thrombus, or suspicion of bacterial endocarditis
• Inability to access the cerebral vasculature in the opinion of the neurointerventional team
• Unlikely to be available for a 90-day follow-up (e.g. no fixed home address)
• Evidence of carotid dissection
• Evidence of cervical carotid artery high-grade stenosis or occlusion (i.e., tandem occlusion)
• Active or recent history of drug abuse (within last 6 months)
• Known history or presence of aneurysm or arteriovenous malformation (AVM) in the territory of the target lesion
• For all patients, severe sustained hypertension with SBP >200 and/or DBP >120; for patients treated with IV tPA, sustained hypertension despite treatment with SBP >185 and/or DBP >110
• Treatment with heparin within 48 hours with a partial thromboplastic time more than two times the laboratory normal
• Renal failure with serum creatinine >3.0 or Glomerular Filtration Rate (GFR) <30
• Ongoing seizure due to stroke
• Evidence of active systemic infection
• Known cancer with metastases
• Cervical carotid stenosis requiring balloon angioplasty or stenting at the time of the procedure
• Angiographic evidence of multiple cerebrovascular occlusions (e.g., bilateral anterior circulation, anterior/posterior circulation)
• Angiographic evidence of known or suspected underlying intracranial vasculopathy or atherosclerotic lesions responsible for the target occlusion
• Angiographic evidence or suspicion of aortic dissection
Device: Route 92 Medical Reperfusion System
Acute Ischemic Stroke, Brain and Nervous System
UT Southwestern
Motor Network Physiology
The brain networks controlling movement are complex, involving multiple areas of the brain. Some neurological disorders, like Parkinson's disease (PD) and essential tremor (ET), cause abnormalities in these brain networks. Deep brain stimulation is a treatment that is used to treat these types of neurological diseases and is thought to help patients by modulating brain networks responsible for movement. Levodopa medication is also used to modulate this brain networks in patients with PD. The overall objective is to develop a unified theory of basal ganglia thalamocortical (BGTC) circuit dynamics that accounts for disease symptomatology, movement, and their inter-relationship. The underlying hypothesis, is that the rigidity and bradykinesia of PD are fundamentally related to excessive functional coupling across nodes in the BGTC motor circuit impeding effective information flow. In this research, the investigator will take advantage of the unique opportunity provided by awake deep brain stimulation surgery to learn more about how the brain functions in a diseased state and how deep brain stimulation changes these networks to make movement more normal. The investigator will simultaneously assess cortical and subcortical electrophysiology in relation to clinical symptoms and behavioral measures and in response to deep brain stimulation, cortical stimulation, and pharmacologic therapy in patients undergoing Deep Brain Stimulation (DBS) implantation surgery.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Sahil.Chilukuri@UTSouthwestern.edu
Nader Pouratian
ALL
18 Years to 89 Years old
NA
NCT04957095
STU-2021-0376
Inclusion Criteria:
* Diagnosis of Parkinson's disease who have been recommended to undergo deep brain stimulation for management of their movement disorder
* Preoperative MRI without evidence of cortical or subdural adhesions or vascular abnormalities
* Willingness and ability to cooperate during conscious operative procedure for up to 40 minutes
Exclusion Criteria:
* Patients with recent use (within one week) of anticoagulant or antiplatelet agents
* Neurocognitive testing indicating amnestic cognitive deficits DRUG: Apomorphine Injectable Solution, OTHER: Subcortical Stimulation
Parkinson Disease, Essential Tremor, Brain and Nervous System
deep brain stimulation, levodopa medication, motor cortex, basal ganglia, thalamus
UT Southwestern
Olanzapine Versus Megestrol Acetate for the Treatment of Loss of Appetite Among Advanced Cancer Patients
This phase III trial compares the effects of olanzapine versus megestrol acetate in treating loss of appetite in patients with cancer that has spread to other places in the body (advanced). Olanzapine may stimulate and increase appetite. This study aims to find out if olanzapine is better than the usual approach (megestrol acetate) for stimulating appetite and preventing weight loss.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Namrata Peswani
ALL
18 Years and over
PHASE3
NCT04939090
STU-2021-1170
Inclusion Criteria:
* Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)
* Diagnosis of advanced cancer
* Patient-reported 2-month weight loss of at least 5 pounds (2.3 kilograms) and/or physician-estimated caloric intake of less than 20 calories/kilogram of body weight per day
* The patient must perceive loss of appetite and/or weight as a problem; and have an appetite score of 4 or worse on the "Please rate your appetite...." question that requires a patient response on a 0-10 numeric rating scale
* Not receiving ongoing tube feedings or parenteral nutrition at the time of registration
* Not currently using systemic adrenal steroids (with the exception of short-term dexamethasone within 3 days of chemotherapy for control of chemotherapy side effects)
* No use of androgens, progesterone analogs, or other appetite stimulants within the past month
* Patient should not have poorly controlled hypertension or congestive heart failure at registration
* Patient should not have an obstruction of the alimentary canal, malabsorption, or intractable vomiting (defined as vomiting more than 3 times per day over the preceding week)
* Not currently using olanzapine for another medical condition or had previously used olanzapine for chronic nausea or for any pre-existing psychotic disorder
* Patient should not have had a previous blood clot at any time in the past
* No history of poorly controlled diabetes
* No symptomatic leptomeningeal disease or known brain metastases as these patients may have difficulty taking oral medications
* No history of hypersensitivity to olanzapine or megestrol acetate
* No COVID-19 infection in the past that, in the opinion of the treating physician, had left patients with compromised taste, which has not resolved at the time of registration
* Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done =\< 14 days prior to registration is required
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
* Estimated life expectancy of 3 months or longer
* Serum creatinine =\< 2.0 mg/dL
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 3 x upper limit of normal (ULN)
* Fasting glucose \< 140 mg/dL
* Granulocytes \> 1000/hpf
* No treatment with another antipsychotic agent, such as risperidone, quetiapine, clozapine, butyrophenone within 30 days of enrollment
* In order to complete the mandatory patient-completed measures, participants must be able to speak and/or read English or Spanish. Sites seeking to enroll Spanish-speaking patients should have access to Spanish speaking staff on site or through the use of a translation service to be able to conduct the informed consent discussion in Spanish, and to conduct the weekly phone calls
Exclusion Criteria:
* Psychiatric illness which would prevent the patient from giving informed consent
* Medical condition such as uncontrolled infection (including human immunodeficiency virus \[HIV\]), uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
* Patients who cannot swallow oral formulations of the agents
* Patients with impaired decision-making capacity (such as with a diagnosis of dementia or memory loss) are not eligible for this study
* No presence of a hormone-sensitive tumor, such as breast, endometrial, or prostate cancer (this exclusion criterion is intended to circumvent any confounding antineoplastic effects of megestrol acetate) DRUG: Olanzapine, DRUG: Megestrol Acetate, OTHER: Questionnaire Administration
Advanced Malignant Solid Neoplasm, Anorexia, Hematopoietic and Lymphoid Cell Neoplasm, Anklylosing Spondylitis, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Carcinoid Tumor, Cardiovascular, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Eye and Orbit, Gall Bladder, Head and Neck, Heart, Hodgkins Lymphoma, Ill - Defined Sites, Kaposis sarcoma, Kidney, Larynx, Leukemia, Not Otherwise Specified, Leukemia, Other, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Lymphoid Leukemia, Lymphoma, Melanoma, skin, Multiple Myeloma, Mycosis Fungoides, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Nose, Other, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Psychiatric Disorders, Rectum, Sarcoma, Small Intestine, Soft Tissue, Stomach, Throat, Thyroid, Unknown Sites, Urinary Bladder, Uterine (Endometrial), Vulva
UT Southwestern
Aging and Disease Course: Contributions to Lifespan Neurobiology of Schizophrenia
The 2020 NIMH Strategic Plan for Research calls for investigations targeting neurobiology of mental illness across the lifespan. Growing evidence suggests that lifespan neurobiology of schizophrenia (SZ) incorporates two distinct dimensions: aging and disease course. However, their clinical correlates, associated biomarker trajectories, and implications for treatment are unknown. This study will investigate differential aspects of SZ neurobiology captured by aging and disease course, in order to develop specific biomarkers which may offer actionable targets for SZ stage-dependent intervention. The study is predicated on a novel mechanistic Model of SZ Trajectories across the Adult Lifespan, positing distinct biological fingerprints within the anterior limbic system for aging and disease course in SZ: (1) alterations in the circuit's function and structure that occur earlier in the lifespan and are larger in magnitude than the alterations expected with normal aging (accelerated aging dimension); and (2) regionally-specific anterior limbic "hyperactivity" in early SZ, with a subsequent transformation into "hypoactivity" in advanced SZ (disease course dimension). In a sample of SZ and matched healthy controls (n=168, 84/group) aged 18-75 years the investigators will ascertain a broad panel of biomarkers \[via multimodal brain imaging: optimized 1H-MRS, high-resolution task-based fMRI, perfusion (Vascular Space Occupancy) and structural MRI\], along with comprehensive cognitive and clinical assessments. All measures will be acquired at baseline and repeated at 2-year longitudinal follow-up. Using cutting-edge computational approaches, the study will examine (i) effects of aging and SZ course on anterior limbic system biomarkers; (ii) lifespan trajectories for different biomarkers; (iii) patterns of limbic system biomarkers in age- and SZ course-based subgroups (e.g., Younger vs. Older, Early-Course vs. Advanced SZ), as well as in data-driven subgroups (e.g., those with vs. without accelerated aging profiles); and (iv) associations between biomarkers and cognitive and clinical outcomes. This research will advance the field by providing novel biomarkers that capture unique neurobiological contributions of aging and disease course in SZ, and will motivate future studies on SZ mechanisms across the lifespan and development of precision treatments.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Monserrat.Feria-Vargas@UTSouthwestern.edu
Elena Ivleva
ALL
18 Years to 75 Years old
NCT04951700
STU-2021-0413
Inclusion Criteria:
* 18-65 years of age (SZ); 18-75 years of age (CON)
* Women and men
* All races and ethnicities
* Psychiatric diagnoses:
Patient participants (SZ): Meet DSM-5 criteria for schizophrenia or schizoaffective disorder Healthy control participants (CON): No personal history of lifetime psychiatric disorders, or a family history of psychotic disorders in 1st-or 2nd- degree relatives
* Able to read, speak, and understand English
* Able and willing to provide written informed consent; and willing to commit to the study protocol, including 2-year longitudinal follow-up
Exclusion Criteria:
• Compromised cognitive function: Both SZ and CON participants: Estimated premorbid intellectual ability \<75 age-corrected score on Wide Range Achievement Test-4/Word Reading Subtest (WRAT-4) CON participants: \<26 score on the Montreal Cognitive Assessment (MoCA)
* Neurological or medical disorder that may affect brain function (history of stroke, head injury with a loss of consciousness \>10 min, seizure disorder, AIDS, poorly controlled hypertension, poorly controlled diabetes, decompensated lung disease, etc.)
* Co-morbid DSM-5 diagnosis of drug/alcohol use disorder in prior 3 months
* Current treatment with benzodiazepine or non-benzodiazepine sedatives/hypnotics, and/or anticonvulsants
* Presence of ferromagnetic objects in body
* Weight or body size exceeding MRI scanner capacity \[\>300 lbs\]
* Claustrophobia in MRI scanner
* Pregnant women
* Breastfeeding women (VASO scan will not be administered. All other imaging modalities are safe to administer.)
* Impaired kidney function: Glomerular Filtration Rate (GFR) \< 30 ml/min/1.73m2 (VASO scan will not be administered due to an association between Gadolinium-based MR contrast use and Nephrogenic Systemic Fibrosis in individuals with severely impaired renal function. All other imaging modalities are safe to administer.)
* History of hypersensitivity to any MRI contrast agent (VASO scan will not be administered. All other imaging modalities are safe to administer.) OTHER: Other
Schizophrenia, Aging, Disease Course, Biomarker, Neuroimaging, Cognitive Dysfunction
UT Southwestern