UTSW - Study Finder

Percutaneous Intervention Versus Observational Trial of Arterial Ductus in Low Weight Infants (PIVOTAL)

Description:

Patent Ductus Arteriosus is a developmental condition commonly observed among preterm infants. It is a condition where the opening between the two major blood vessels leading from the heart fail to close after birth. In the womb, the opening (ductus arteriosus) is the normal part of the circulatory system of the baby, but is expected to close at full term birth. If the opening is tiny, the condition can be self-limiting. If not, medications/surgery are options for treatment. There are two ways to treat patent ductus arteriosus - one is through closure of the opening with an FDA approved device called PICCOLO, the other is through supportive management (medications). No randomized controlled trials have been done previously to see if one of better than the other. Through our PIVOTAL study, the investigators aim to determine is one is indeed better than the other - if it is found that the percutaneous closure with PICCOLO is better, then it would immediately lead to a new standard of care. If not, then the investigators avoid an invasive costly procedure going forward.

Contact(s):

Call 214-648-5005
studyfinder@utsouthwestern.edu, Emilie.Vannguyen@UTSouthwestern.edu

Principal Investigator: Sushmita Yallapragada

Gender: ALL

Age: 7 Days to 32 Days old

Phase: NA

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05547165

IRB Number: STU-2022-1102

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Inclusion Criteria:

• EPIs born between 22-weeks+0 days (220/7 wks) and 27-weeks+6 days (276/7 wks) gestation, inclusive
• Admitted to a study NICU
• Birth weight ≥700-grams
• Mechanically ventilated at time of consent and randomization
• HSPDA ("PDA Score" ≥6) noted on echocardiogram (ECHO)
• Randomization is able to be performed within 5 days of the qualifying ECHO and when infant is 7-32 days postnatal

Exclusion Criteria:

Clinical Exclusion Criteria
• Life-threatening congenital defects (including congenital heart disease such as aortic coarctation or pulmonary artery stenosis). PDA and small atrial/ventricular septal defects are permitted;
• Congenital lung abnormalities, (e.g. restrictive lung disease);
• Pharyngeal or airway anomalies (tracheal stenosis, choanal atresia);
• Treatment for acute abdominal process (e.g., necrotizing enterocolitis);
• Infants with planned surgery;
• Active infection requiring treatment;
• Chromosomal defects (e.g., Trisomy 18);
• Neuromuscular disorders;
• Infants whose parents have chosen to allow natural death (do not resuscitate order) or for whom limitation of intensive care treatment is being considered (e.g. severe intraventricular hemorrhage)
• Physician deems that the infant would not be a Percutaneous PDA Closure candidate due to clinical instability; however, if the infant's clinical status improves before 30-days postnatal and all inclusion criteria are still met, then the infant may be enrolled. ECHO-based Exclusion Criteria
• Pulmonary hypertension (defined by ductal right to left shunting for \>33% of the cardiac cycle) in which early PDA closure may increase right ventricular afterload and compromise pulmonary and systemic blood flow;
• Evidence of cardiac thrombus that might interfere with device placement;
• PDA diameter larger than 4 mm at the narrowest portion (consistent with FDA-approved instructions for Piccolo™ device use).
• PDA length smaller than 3 mm (consistent with FDA-approved instructions for Piccolo™ device use).
• PDA that does not meet inclusion requirements ("PDA Score" \<6).\* \* If a potential participant is found to have a PDA meeting eligibility requirements on a subsequent ECHO during the required period of 7 - 30 postnatal days of age, they may then be declared eligible to participate and enrolled, provided all other inclusion criteria are met and exclusion criteria are not met. Other Exclusion Criteria
• Parents or legal guardian do not speak English or Spanish

Interventions: DEVICE: Percutaneous Patent Ductus Arteriosus Closure (PPC), COMBINATION_PRODUCT: Responsive Management Intervention, DIAGNOSTIC_TEST: Echocardiogram, cardiac

Conditions: Ductus Arteriosus, Patent

Keywords: PDA

Sites: Children’s Health

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Study of JANX007 in Subjects With Metastatic Castration-Resistant Prostate Cancer (ENGAGER-PSMA-01)

Description:

This study is a first-in-human, Phase 1, open-label, multicenter study to assess the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and the preliminary efficacy of JANX007 in adults with metastatic castration-resistant prostate cancer (mCRPC).

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Tian Zhang

Gender: MALE

Age: 18 Years to 100 Years old

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05519449

IRB Number: STU-2024-0923

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Inclusion Criteria:

* Male ≥18 years of age at the time of signing informed consent * Histologically or cytologically confirmed adenocarcinoma of the prostate * For Dose Escalation and Backfill: Having mCRPC that progressed after at least one novel anti-androgen therapy and at least one taxane containing regimen. Participants who have actively refused a taxane containing regimen or are medically unsuitable to receive taxane are eligible * Adequate organ function * For Monotherapy Expansion Part a: Have received ≤ 2 anti-androgen therapies in either the HSPC or CRPC setting and no more than 1 prior taxane regimen in the HSPC or CRPC setting. Participants who have actively refused a taxane regimen or are medically unsuitable to receive taxane are eligible. * For Monotherapy Expansion Part b: Have received ≤ 2 anti-androgen therapies in either the HSPC or CRPC settings * For Monotherapy Expansion Part d: Have received ≤ 1 anti-androgen therapy and a poly(ADP-ribose) polymerase (PARP) inhibitor for mCRPC and have progressed following treatment with the PARP inhibitor * For Combination Expansion: Have received ≤ 1 anti-androgen therapy other than darolutamide in the HSPC setting and ≤ 1 taxane in the mCRPC setting. Participants who have actively refused a taxane regimen or are medically unsuitable to receive taxane are eligible.

Exclusion Criteria:

* Prior solid organ transplant * Prior treatment with PSMA-targeted CAR-T cell therapy or PSMA-CD3, PSMA-CD28 or other CD3 T-cell engaging bispecific antibodies or radioligand therapy * Clinically significant cardiovascular disease * For Monotherapy Expansion Part a: Prior receipt of any treatment other than an ARPI or taxane in the mCRPC setting * For Monotherapy Expansion Part b: Prior receipt of any treatment other than an anti-androgen therapy or prior receipt of a taxane containing regimen or more than 1 prior line of therapy for mCRPC * For Monotherapy Part d: More than 1 prior line of therapy for mCRPC or prior receipt of any treatment other than an anti-androgen therapy and PARP inhibitor for mCRPC or prior receipt of a taxane in the mCRPC setting * For Combination expansion: More than 1 prior line of therapy for mCRPC or prior receipt of any treatment other than a taxane for mCRPC or prior receipt of Darolutamide or prior receipt of a taxane for HSPC * Active clinically significant infection (bacterial, viral, fungal, mycobacteria or other) * Any medical condition or clinical laboratory abnormality likely to interfere with assessment of safety or efficacy of study treatment

Interventions: BIOLOGICAL: JANX007, DRUG: Darolutamide

Conditions: Prostate Cancer, Metastatic Castration-resistant Prostate Cancer, Castration Resistant Prostatic Cancer, Prostate

Keywords: Prostate Cancer, Castration-resistant prostate cancer

Sites: UT Southwestern

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Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)

Description:

MELPIDA is proposed for the treatment of subjects with SPG50 and targets neuronal cells to deliver a fully functional human AP4M1 cDNA copy via intrathecal injection to counter the associated neuronal loss. Outcomes will evaluate the safety and tolerability of a single dose of MELPIDA, which will be measured by the treatment-associated adverse events (AEs) and serious adverse events (SAEs). Secondarily, the trial will explore efficacy in terms of disease burden assessments.

Contact(s):

Call 214-648-5005
studyfinder@utsouthwestern.edu, Sydney.Cooper@UTSouthwestern.edu

Principal Investigator: Susan Iannaccone

Gender: ALL

Age: 4 Months to 10 Years old

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05518188

IRB Number: STU-2022-0886

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Inclusion Criteria:

• Age 4 months-10 years old
• Confirmed diagnosis of SPG50 disease by:
• Genomic DNA mutation analysis demonstrating homozygous or compound heterozygous, confirmed pathogenic variants in the AP4M1 gene
• Clinical history or examination features consistent with SPG50 and that include neurologic dysfunction
• Parent/legal guardian willing to provide written informed consent for their child prior to participation in the study
• Subject able to comply with all protocol requirements and procedures
• Ability to stand for more than 5 seconds OR
• Ability to take 5 steps independently or with a walker OR
• Modified Ashworth Scale score 2 or below (Ankles).

Exclusion Criteria:

• Inability to participate in study procedures (as determined by the site investigator)
• Presence of a concomitant medical condition that precludes lumbar puncture (LP) or use of anesthetics
• History of bleeding disorder or any other medical condition or circumstance in which lumbar puncture is contraindicated according to local institutional policy
• Inability to be safely sedated in the opinion of the clinical anesthesiologist
• Active infection, at the time of dosing, based on clinical observations
• Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer
• Inability of the patient to undergo MRI according to local institutional policy
• Inability of the patient to undergo any other procedure required in this study
• The presence of significant non-SPG50 related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study
• Have received an investigational drug within 30 days prior to screening or plan to receive an investigational drug (other than gene therapy) during the study.
• Enrollment and participation in another interventional clinical trial
• Contraindication to MELPIDA or any of its ingredients
• Contraindication to any of the immune suppression medications used in this study
• Clinically significant abnormal laboratory values (GGT, ALT, and AST, or total bilirubin \> 3 × ULN, creatinine ≥ 1.5 mg/dL, hemoglobin \[Hgb\] \< 6 or \> 20 g/dL; white blood cell \[WBC\] \> 20,000 per cmm) prior to gene replacement therapy.

Interventions: BIOLOGICAL: MELPIDA

Conditions: Spasticity, Muscle, Microcephaly, Intellectual Deficiency, Growth Retardation, SPG50, Spastic Paraplegia

Sites: Children’s Health

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

Description:

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.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Daniel Bowers

Gender: ALL

Age: to 59 Months old

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05535166

IRB Number: STU-2023-0119

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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.

Interventions: 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, DRUG: Methotrexate

Conditions: Medulloblastoma, Brain and Nervous System

Keywords: 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

Sites: Children’s Health

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A 2-Part Study to Learn Whether Litifilimab (BIIB059) Injections Can Improve Symptoms of Adult Participants Who Have Active Cutaneous Lupus Erythematosus (AMETHYST)

Description:

In this study, researchers will learn more about a study drug called litifilimab (BIIB059) in participants with cutaneous lupus erythematosus (CLE). The study will focus on participants who have either active subacute CLE or chronic CLE, or both. They may also have systemic lupus erythematosus (SLE). The participants did not respond to antimalarial therapy or had problems with the treatment that made it hard to continue. The main objective of the study is to learn about the effect litifilimab has on lowering the activity of the skin disease. Researchers will measure symptoms and signs of CLE over time using a variety of scoring tools. These include the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), the Cutaneous Lupus Activity of Investigator's Global Assessment-Revised (CLA-IGA-R), and the SELENA-SLEDAI Flare Index (SFI). The main questions researchers want to answer are: * How many participants have a score of 0 or 1 on the CLA-IGA-R looking at skin redness after treatment? * How many participants have their skin disease activity go down by at least 70% as measured by CLASI? Researchers will also learn more about the safety of litifilimab. They will study how participants' immune systems respond to litifilimab. Additionally, they will measure the effect litifilimab and CLE have on the quality of life of participants using a group of questionnaires. The study will be split into 2 parts - Part A and Part B. Both parts will be done as follows: * After screening, participants will be randomized to receive either litifilimab or placebo for the 1st treatment period. A placebo looks like the study drug but contains no real medicine. * Participants will receive either litifilimab or placebo as injections under the skin once every 4 weeks. * The 1st treatment period will be double blinded which means neither the researchers nor the participants will know if the participants are receiving litifilimab or placebo. * This double blinded treatment period will last 24 weeks, after which the 2nd treatment period will begin. * During the 2nd treatment period, all participants will receive litifilimab for 28 weeks. * After completing treatment in this study, participants that qualify will be given the choice to join the Long-Term Extension study, 230LE305. If they do not, they will move into a follow-up safety period that will last up to 24 weeks. * The total study duration for participants will be up to 80 weeks.

Contact(s):

studyfinder@utsouthwestern.edu

Principal Investigator:

Gender: ALL

Age: 18 Years and over

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05531565

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Interventions: DRUG: Litifilimab, DRUG: Placebo

Conditions: Subacute Cutaneous Lupus Erythematosus, Chronic Cutaneous Lupus Erythematosus

Keywords: Cutaneous Lupus Erythematosus (CLE), Discoid Lupus Erythematosus (DLE), Systemic Lupus Erythematosus (SLE), Lupus, Subacute Cutaneous Lupus Erythematosus (SCLE)

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Treatment of Obstructive Sleep Apnea With Personalized Surgery in Children With Down Syndrome (TOPS-DS) (TOPS-DS)

Description:

The overall objective of this randomized clinical trial is to test the effectiveness of a personalized approach to the surgical treatment of OSA in children with Down syndrome (DS).The estimated prevalence of obstructive sleep apnea (OSA) in children with DS ranges from 45-83%, compared to 1-6% in the general pediatric population. Untreated OSA in children has been associated with daytime sleepiness, cognitive or behavioral problems, and cardiovascular complications, all which are common in children with DS. Adenotonsillectomy (AT) is the first line treatment for OSA in children, however, most large studies of AT outcomes have excluded children with DS. Available evidence demonstrates that AT is far less effective in children with DS than in the general pediatric population, with 48 to 95% of children with DS having persistent OSA after AT. Medical treatments such as positive airway pressure (PAP) therapy are frequently inadequate or poorly tolerated in this population, so many children with DS and OSA remain untreated. Drug-induced sleep endoscopy (DISE) enables direct observation of the sites and patterns of obstruction during sedated sleep using a flexible endoscope passed through the nose into the pharynx. DISE was developed to guide surgical decisions in adult OSA, and in recent years has also been used to design personalized surgical interventions in children. Using this DISE Rating Scale, the investigators have demonstrated that children with DS are more prone to tongue base and supraglottic obstruction than non-DS children, suggesting the need for more personalized surgical treatments that are tailored to the common sources of obstruction in this population. Several small case series demonstrate that DISE-directed surgery can be effective in treating OSA in children with DS. However, because there have been few prospective studies and no randomized trials comparing different treatment options in this population, there remains uncertainty about whether such a personalized approach leads to superior outcomes compared to the first line AT. It is the investigators' hypothesis that personalized DISE-directed surgery that uses existing procedures to address specific fixed and dynamic anatomic features causing obstruction in each child with DS will be superior to the current first line approach of AT. This novel approach may improve OSA outcomes and reduce the burden of unnecessary AT or secondary surgery for persistent OSA after an ineffective AT.

Contact(s):

Call 214-648-5005
studyfinder@utsouthwestern.edu, Francesca.Chambers@UTSouthwestern.edu

Principal Investigator: Ron Mitchell

Gender: ALL

Age: 2 Years to 17 Years old

Phase: NA

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05508971

IRB Number: STU-2022-0838

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Interventions: PROCEDURE: DISE-Directed Surgery, PROCEDURE: Adenotonsillectomy

Conditions: Obstructive Sleep Apnea, Down Syndrome

Sites: Children’s Health

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A Study to Give Treatment Inside the Eye to Treat Retinoblastoma

Description:

This phase II trial tests the safety and side effects of adding melphalan (by injecting it into the eye) to standard chemotherapy in early treatment of patients with retinoblastoma (RB). RB is a type of cancer that forms in the tissues of the retina (the light-sensitive layers of nerve tissue at the back of the eye). It may be hereditary or nonhereditary (sporadic). RB is considered harder to treat (higher risk) when there are vitreous seeds present. Vitreous seeds are RB tumors in the jelly-like fluid of the eye (called the vitreous humor). The term, risk, refers to the chance of the cancer not responding to treatment or coming back after treatment. Melphalan is in a class of medications called alkylating agents. It may kill cancer cells by damaging their deoxyribonucleic acid (DNA) and stopping them from dividing. Other chemotherapy drugs given during this trial include carboplatin, vincristine, and etoposide. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Adding melphalan to standard chemotherapy early in treatment may improve the ability to treat vitreous seeds and may be better than standard chemotherapy alone in treating retinoblastoma.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Daniel Bowers

Gender: ALL

Age: up to 18 Years old

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05504291

IRB Number: STU-2023-0581

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Inclusion Criteria:

* Patient must be \< 18 years of age at enrollment * Patient must have newly diagnosed intraocular (localized) retinoblastoma and meet one of the following criteria: * Unilateral Group D retinoblastoma with vitreous seeding; OR * Bilateral retinoblastoma with worst eye Group D, with vitreous seeding present and the contralateral eye is Group A-C; OR * Bilateral Group D retinoblastoma with at least one eye with vitreous seeding; OR * Bilateral retinoblastoma with one Group D eye with vitreous seeding and one Group E eye where the Group E eye has been enucleated prior to any therapy. Note exclusion for high-risk features * Bilateral retinoblastoma with one Group D eye with vitreous seeding and one Group E eye where the Group E eye has not been enucleated prior to any therapy at the discretion of the treating physician. Note exclusion for patients with evidence of metastatic or extra orbital spread * Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\<16 years of age * Peripheral absolute neutrophil count (ANC) \>= 750/uL (must be performed within 7 days prior to enrollment unless otherwise indicated) * Platelet count \>= 75,000/uL (transfusion independent) (must be performed within 7 days prior to enrollment) * A serum creatinine based on age/sex as follows (must be performed within 7 days prior to enrollment; must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment): * 1 month to \< 6 months = 0.4 (male and female) * 6 months to \< 1 year = 0.5 (male and female) * 1 to \< 2 years = 0.6 (male and female) * 2 to \< 6 years = 0.8 (male and female) * 6 to \< 10 years = 1.0 (male and female) * 10 to \< 13 years = 1.2 (male and female) * 13 to \< 16 years = 1.5 (male) and 1.4 (female) * \>= 16 years = 1.7 (male) and 1.4 (female) 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 serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility * For patients \< 1 month of age, serum creatinine levels must be \< 1.5 x the treating institution's creatinine upper limit of normal (ULN) for patients \< 1 month of age or the creatinine clearance or radioisotope GFR must be \>= 70 mL/min/1.73 m\^2 * The threshold creatinine values were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Center for Disease Control (CDC) * Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment; must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment) * Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (must be performed within 7 days prior to enrollment; must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment) * Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L

Exclusion Criteria:

* Patients with evidence of metastatic or extra-orbital spread * Patients must not have an invasive infection at time of protocol entry * Patients must not have had any prior anti-cancer therapy other than cryotherapy and/or laser therapy (green or infrared) to the study eye(s) and non-study eye, including systemic chemotherapy, intra-arterial chemotherapy, radioactive plaque, brachytherapy, or radiation therapy. * Note: A study eye is defined as being Group D with vitreous seeding. Patients may have had enucleation of one eye as long as the remaining eye is Group D with vitreous seeds * Patients with bilateral disease who undergo enucleation of a Group E eye prior to initiation of therapy and show evidence of high-risk histopathology features in the enucleated eye. High-risk histopathology includes choroid involvement \>= 3 mm, post lamina optic nerve involvement, full thickness scleral invasion or optic nerve invasion to the cut end * 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 * 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

Interventions: PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Etoposide, PROCEDURE: Examination Under Anesthesia, PROCEDURE: Magnetic Resonance Imaging, DRUG: Melphalan, PROCEDURE: Ultrasound Biomicroscopy, DRUG: Vincristine

Conditions: Bilateral Retinoblastoma, Childhood Intraocular Retinoblastoma, Group D Retinoblastoma, Stage I Retinoblastoma, Unilateral Retinoblastoma, Eye and Orbit

Sites: Children’s Health

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The GORE® VIABAHN® FORTEGRA Venous Stent Iliofemoral Study

Description:

This study is a prospective, non-randomized, multicenter, single-arm, clinical study to evaluate the performance, safety and efficacy of the GORE® VIABAHN® FORTEGRA Venous Stent (formerly known as GORE® VIAFORT Vascular Stent) for treatment of symptomatic iliofemoral venous obstruction.

Contact(s):

Call 214-648-5005
studyfinder@utsouthwestern.edu, christian.marsh@UTSouthwestern.edu

Principal Investigator: Michael Siah

Gender: ALL

Age: 18 Years and over

Phase: NA

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05489588

IRB Number: STU-2023-1240

Show full eligibility criteria

Preoperative

Inclusion Criteria:

* Patient is at least 18 years of age. * Patient is willing and able to comply with all follow-up evaluations as well as any required medication or compression regimen. * Patient is able to provide informed consent. * One of the following: Clinical severity class of CEAP 'C' classification ≥3 or rVCSS pain score ≥2. * Intention to treat the target areas with only the GORE® VIAFORT Vascular Stent. * Estimated life expectancy ≥1 year. * Patient is ambulatory (use of assistive walking device such as a cane or walker is acceptable). * Patient has adequate inflow to the target lesion(s), per investigator/sub-investigator discretion, involving at least a patent femoral or deep femoral vein. * Presence of non-malignant symptomatic unilateral iliofemoral venous obstruction. Preoperative

Exclusion Criteria:

* Patient has DVT in the target areas with symptom onset date greater than 14 days but less than or equal to 90 days prior to treatment. * Patient is a pregnant or breastfeeding woman, or a woman planning to become pregnant through the 12-month visit. * Patient has clinically significant (e.g., symptoms of chest pain, hemoptysis, dyspnea, hypoxia, etc.) pulmonary embolism (confirmed via Computed Tomography Angiography) at the time of enrollment. * Patient has a known uncorrectable bleeding diathesis or active coagulopathy meeting the following definitions (all must be tested for):
• uncorrected INR\>2 (not as a result of warfarin or DOAC therapy), OR
• platelet count \<50,000 or \>1,000,000 cells/mm3, OR
• white blood cell count \<3,000 or \>12,500 cells/mm3 * Patient has impaired renal function (eGFR \<30 mL/min/1.73m2) or is currently on dialysis. * Patient has uncorrected hemoglobin of \<9 g/dL. * Patient has known history of antiphospholipid syndrome (APS). * Patient has known homozygous or acquired coagulation defect (e.g., Protein C or Protein S deficiency) that cannot be treated with therapeutic anticoagulation. * Patient has a planned surgical intervention that has the potential to clinically interfere with the endpoints of this treatment (other than pre-stenting procedures such as thrombolysis or thrombectomy) within 30 days prior to or within 30 days after the planned study procedure. Examples include surgical interventions that may impact mobility, and surgical interventions that require cessation of therapeutic antiplatelet or anticoagulation within 30 days following the index procedure. * Patient has had or requires open deep venous surgery in the target limb. * Patient is currently participating in another investigational drug or device study that has not completed the primary endpoint or that clinically interferes with the endpoints of this treatment, in the opinion of the investigator/sub-investigator. Observational studies are permitted. * Patient has had a previous major (i.e., above the ankle) amputation of the target lower limb. * Patient has known sensitivity to device materials. * Patient has had prior stenting or grafts in the target vessels. * Patient has a known or suspected active systemic infection at the time of the index procedure. Patients with a chronic infection (e.g., HIV, hepatitis C) that can be managed, and with an active clinical plan in place may be eligible. * Patient has known history of intravenous drug abuse within one year of treatment. * Patient has significant peripheral arterial disease (chronic Rutherford Type 2 or greater, acute Rutherford Type IIa or greater). * Patient has a BMI \>45. Patients with a BMI of up to 45 may be enrolled provided that diagnostic quality ultrasound of the implant sites can be performed. * Patient is actively undergoing or plans to begin cancer treatment. * Patients with hypercoagulable states that are unwilling to take anticoagulant medications on a long-term basis. * Patient has contraindication to thrombolytics, anticoagulants, or iodinated contrast necessary for the index procedure and long-term medical therapy (contrast pre-medication is acceptable). Intraoperative

Inclusion Criteria:

* Presence of non-malignant unilateral obstruction of the common femoral vein, external iliac vein, and/or common iliac vein defined as occlusion or at least 50% reduction in target vessel lumen as measured by procedural IVUS and venogram. * Patient can accommodate an appropriately sized GORE® VIAFORT Vascular Stent as per reference vessel diameter (see IFU), as determined by intraoperative IVUS post pre-dilation. * Patient must have appropriate access vessels to accommodate the delivery sheath for the selected device size. * Patient has adequate landing zones free from significant disease requiring treatment within the native vessels beyond the proximal and distal margins of the lesion. * Patient has adequate inflow to the target lesion(s), per investigator/sub-investigator discretion, involving at least a patent femoral or deep femoral vein. * Lesion can be traversed with a guidewire. * Disease involves only unilateral iliofemoral venous segments with intent to stent all affected iliofemoral segments. Patients with disease extending into the inferior vena cava or contra-lateral iliofemoral veins who are anticipated to require endovascular or surgical treatment within 12 months after investigational device implant will be excluded. * Patient does not have significant (i.e., \>20% residual thrombosis) acute thrombus within the target stent area at the time of investigational device placement. Patients with acute thrombus within the target stent area must have thrombus successfully treated prior to investigational device placement. Successful thrombus treatment is defined as reestablishment of antegrade flow with ≤20% residual thrombosis as confirmed by IVUS and venogram, AND freedom from bleeding, vascular injury, or hemodynamically significant pulmonary embolism. After successful thrombus treatment, investigational device placement can occur within the same procedure.

Interventions: DEVICE: GORE® VIAFORT Vascular Stent

Conditions: Venous Thromboses, Venous Disease, Venous Leg Ulcer, Venous Stasis, Venous Ulcer, Venous Stenosis, Venous Occlusion, Vein Thrombosis, Vein Occlusion, Vein Disease, Cardiovascular

Keywords: VIAFORT, Vein Stent, Venous Thrombosis, Venous Stenosis, Gore, Venous Occlusion, FORTEGRA, VIABAHN FORTEGRA, Venous Disease, Deep Venous Insufficiency, Venous disease treatment Options, Deep venous, DVT Treatment, Venous Stent, Venous insufficiency treatment options

Sites: UT Southwestern

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Safety, Efficacy, and Pharmacokinetics of Tafamidis in Patients With Transthyretin-mediated Amyloidosis Post Orthotopic Heart Transplantation

Description:

Transthyretin cardiac amyloidosis (ATTR-CA) is a relentlessly progressive disease that can progress to end stage heart failure, at which point recently approved transthyretin production silencing or structure stabilizing therapies provide no clinical benefit. For well-selected individuals, heart transplantation is an excellent therapeutic option to improve survival. Historically, concomitant liver transplantation has been used to halt the progression of non-cardiac transthyretin amyloidosis (ATTR) manifestations, especially for individuals with TTR genotypes associated with significant neuropathy. However, despite this, patients continue to experience progressive non-cardiac manifestations, particularly gastrointestinal and neuropathic, which can have a substantial influence on post-heart transplantation morbidity. Concomitant liver transplantation is also associated with substantial morbidity and its future therapeutic role is questionable with recently established therapies for ATTR. Therefore, there is a clear unmet need to determine the utility and safety of ATTR targeted therapies for patients with recent heart transplantation for end-stage ATTR-CA. The central hypothesis of this proposal is that in patients who have received a heart transplantation for end-stage ATTR-CA, tafamidis therapy will be efficacious and well-tolerated. We aim to determine the safety and efficacy of tafamidis in stable patients who have undergone heart or combined heart/liver transplantation for ATTR (wild-type or variant) cardiac amyloidosis. The proposed study will be a single-arm intervention clinical trial with tafamidis. Because of the efficacy of tafamidis for both variant ATTR-CA and wild-type ATTR-CA, there is no clinical equipoise for an inactive-comparator placebo arm. The primary endpoint of this study will be serial change in plasma transthyretin (TTR) levels from baseline to 12 months at 3-month intervals. The secondary endpoints of this study will include serial changes in neuropathy assessments, modified body mass indices, incident transplant-specific adverse events, and pharmacokinetics of tafamidis. Observations from this study will establish the role of tafamidis use for the management of ATTR in patients after transplantation for end-stage ATTR-CA.

Contact(s):

Call 214-648-5005
studyfinder@utsouthwestern.edu, YAMEI.CHENG@UTSouthwestern.edu

Principal Investigator: Justin Grodin

Gender: ALL

Age: 18 Years to 90 Years old

Phase: PHASE4

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05489523

IRB Number: STU-2022-0583

Show full eligibility criteria

Interventions: DRUG: Tafamidis 61 MG

Conditions: Transthyretin Cardiac Amyloidosis, Heart

Keywords: heart transplantation, transthyretin amyloidosis, ATTR, tafamidis

Sites: UT Southwestern

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Subclinical Transthyretin Cardiac Amyloidosis in V122I TTR Carriers

Description:

Approximately 1.5 million of the 44 million Blacks in the United States are carriers of the valine-to-isoleucine substitution at position 122 (V122I) in the transthyretin (TTR) protein. Virtually exclusive to Blacks, this is the most common cause of hereditary cardiac amyloidosis (hATTR-CA) worldwide. hATTR-CA leads to worsening heart failure (HF) and premature death. Fortunately, new therapies that stabilize TTR improve morbidity and mortality in hATTR-CA, especially when prescribed early in the disease. However, hATTR-CA is often diagnosed at an advanced stage and conventional diagnostic tools lack diagnostic specificity to detect early disease. The overall objectives of this study are to determine the presence of subclinical hATTR-CA and to identify biomarkers that indicate amyloid progression in V122I TTR carriers. The central hypothesis of this proposal is that hATTR-CA has a long latency period that will be detected through subclinical amyloidosis imaging and biomarker phenotyping. The central hypothesis will be tested by pursuing 2 specific aims: Aim 1) determine the association of V122I TTR carrier status with CMRI evidence of amyloid infiltration; Sub-aim 1) determine the association of V122I TTR carrier status with cardiac reserve; Aim 2) determine the association between amyloid-specific biomarkers and V122I TTR carrier status; and Sub-aim 2) determine the association of amyloid-specific biomarkers with imaging-based parameters and evaluate their diagnostic utility for identifying subclinical hATTR-CA. In Aim 1, CMRI will be used to compare metrics associated with cardiac amyloid infiltration between a cohort of V122I TTR carriers without HF formed by cascade genetic testing and age-, sex-, and race-matched non-carrier controls. For Sub-Aim 1, a sub-sample of carriers and non-carrier controls enrolled in Aim 1 will undergo novel exercise CMRI to measure and compare cardiac systolic and diastolic reserve. Aim 2 involves measuring and comparing amyloid-specific biomarkers in V122I TTR carriers without HF with samples matched non-carriers (both from Aim 1) and individuals with symptomatic V122I hATTR-CA from our clinical sites. These biomarkers detect and quantify different processes of TTR amyloidogenesis and include circulating TTR, retinol binding protein 4, TTR kinetic stability, and misfolded TTR oligomers. Sub-aim 2 will establish the role of these biomarkers to detect imaging evidence of subclinical hATTR-CA disease.

Contact(s):

Call 214-648-5005
studyfinder@utsouthwestern.edu, Amy.Browning@UTSouthwestern.edu

Principal Investigator: Justin Grodin

Gender: ALL

Age: 30 Years to 80 Years old

Phase:

Healthy Volunteers:

System ID: NCT05489549

IRB Number: STU-2022-0404

Show full eligibility criteria

(V122I TTR carriers (or matched non-carriers))

Inclusion Criteria:

* Men and women ages 30-80 who are V122I TTR carriers (or matched non-carriers) without history of HF (this will be assessed by study personnel) and defined as: a) No history of hospitalization within the previous 12 months for management of HF; b) Without an elevated B-type natriuretic peptide level ≥100 pg/mL or NT-proBNP ≥360 pg/mL within the previous 12 months; or c) No clinical diagnosis of HF from a treating clinician * Signed informed consent

Exclusion Criteria:

* A self-reported history or clinical history of HF * Other known causes of cardiomyopathy * History of light-chain cardiac amyloidosis * Prior type 1 myocardial infarction (non-ST segment elevation myocardial Infarction {NSTEMI} or ST-elevation myocardial infarction {STEMI}) * Cardiac transplantation * Body weight \>250 lbs * Estimated glomerular filtration rate ≤30 mL/min/1.73 m2 * Inability to safely undergo CMRI (For participants with symptomatic V122I hATTR-CA, we will enroll probands with HF from Aim 1 or patients with suspected symptomatic V122I hATTR-CA from the three study sites.)

Inclusion Criteria:

* Men and women ages 30-80 who have symptomatic V122I hATTR-CA as determined by a history of HF (this will be assessed by study personnel) and defined as: a) History of hospitalization within the previous 12 months for management of HF; b) An elevated B-type natriuretic peptide level ≥100 pg/mL or NT-proBNP ≥360 pg/mL within the previous 12 months; or c) A clinical diagnosis of HF from a treating clinician. * Have an established or suspected diagnosis of hATTR-CA based on either a) Biopsy confirmed by Congo red (or equivalent) staining with tissue typing with immunohistochemistry or mass spectrometric analysis or immunoelectron microscopy, OR b) positive technetium-99m (99mTc)-pyrophosphate or -bisphosphonate scan, combined with accepted laboratory criteria without abnormal M-protein. * TTR gene sequencing that is pending or that is confirming the V122I variant * Signed informed consent

Exclusion Criteria:

* Other known causes of cardiomyopathy * History of light-chain cardiac amyloidosis * Cardiac transplantation * Liver transplantation * Previous treatment with a TTR stabilizer (tafamidis, acoramidis) within the prior 14 days or TTR any silencer (inotersen, patisiran, eplontersen) * Estimated glomerular filtration rate ≤30 mL/min/1.73 m2

Conditions: Amyloidosis, Hereditary, Amyloidosis Cardiac, Amyloidosis, Familial, Transthyretin-Related (ATTR) Familial Amyloid Cardiomyopathy, Transthyretin Gene Mutation, Cardiovascular

Keywords: Amyloidosis, Transthyretin Amyloidosis, V122I TTR, p.Val142Ile TTR, Cardiac magnetic resonance imaging

Sites: UT Southwestern

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Heat Waves and the Elderly - Cooling Modalities

Description:

The purpose of this study is to assess how well cooling modalities work in reducing cardiovascular stress of the elderly to heat wave conditions

Contact(s):

Call 214-648-5005
studyfinder@utsouthwestern.edu, craig.crandall@utsouthwestern.edu

Principal Investigator: Craig Crandall

Gender: ALL

Age: 65 Years and over

Phase: NA

Healthy Volunteers:

This study is also accepting healthy volunteers

System ID: NCT05484739

IRB Number: STU-2022-0625

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Interventions: OTHER: Water Spray, OTHER: Fan, OTHER: Water Spray and Fan, OTHER: Control

Conditions: Aging, Hyperthermia

Keywords: aging, heat wave, cardiovascular, low-energy cooling

Sites: UT Southwestern

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Study of Inebilizumab in Pediatric Subjects With Neuromyelitis Optica Spectrum Disorder

Description:

A Phase 2, open-label, multicenter study to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of inebilizumab in eligible pediatric participants 2 to \< 18 years of age with recently active neuromyelitis optica spectrum disorder (NMOSD) who are seropositive for autoantibodies against aquaporin-4 (AQP4-immunoglobulin \[Ig\]G).

Contact(s):

Call 214-648-5005
studyfinder@utsouthwestern.edu, patricia.plumb@utsouthwestern.edu

Principal Investigator: Cynthia Wang

Gender: ALL

Age: 2 Years to 17 Years old

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05549258

IRB Number: STU-2022-0915

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Inclusion Criteria:

* Male or female participants, minimum body weight of 15 kg, age 2 to \< 18 years at the time of screening. * Positive serum anti-AQP4-IgG result at screening and diagnosed with NMOSD according to the criteria of Wingerchuk et al, 2015. * Documented history of one or more NMOSD acute relapses within the last year, or 2 or more NMOSD acute relapses within 2 years prior to screening.

Exclusion Criteria:

* Any condition that, in the opinion of the Investigator, would interfere with the evaluation or administration of the Investigational Product or interpretation of participant safety or study results. * Concurrent/previous enrollment in another clinical study involving an investigational treatment within 4 weeks or 5 published half-lives of the investigational treatment, whichever is the longer, prior to Day 1. * Evidence of significant hepatic, renal, or metabolic dysfunction or significant hematological abnormality (one repeat test may be conducted to confirm results within the same screening period). * B-cell counts \< one-half of the lower limit of normal (LLN) for age according to the central laboratory. * Receipt of the following at any time prior to Day 1:
• Alemtuzumab
• Total lymphoid irradiation
• Bone marrow transplant
• T-cell vaccination therapy * Receipt of rituximab or any experimental B-cell depleting agent within 6 months prior to screening unless B-cell counts have returned to ≥ one-half the LLN. * Receipt of intravenous immunoglobulin (IVIG) within one month prior to Day 1. * Receipt of any of the following within 2 months prior to Day 1:
• Cyclosporine
• Methotrexate
• Mitoxantrone
• Cyclophosphamide
• Tocilizumab
• Satralizumab
• Eculizumab * Receipt of natalizumab (Tysabri®) within 6 months prior to Day 1. * Severe drug allergic history or anaphylaxis to 2 or more food products or medicine (including known sensitivity to acetaminophen/paracetamol, diphenhydramine or equivalent antihistamine, and methylprednisolone or equivalent glucocorticoid). * Diagnosed with a concurrent autoimmune disease that is uncontrolled (unless approved by the medical monitor). * Recent receipt of live/attenuated vaccine or blood transfusion. Receipt of any of the following:
• Any live or attenuated vaccine within 4 weeks prior to Day 1 (administration of killed vaccines and nucleoside-modified mRNA-based vaccines is acceptable; the Sponsor recommends that Investigators ensure all participants are up to date on required vaccinations prior to study entry).
• Bacillus Calmette Guérin vaccine within one year of screening.
• Blood transfusion within 4 weeks prior to screening or during screening. * Clinically significant serious active or chronic viral, bacterial, or fungal infection that requires treatment with anti-infectives, hospitalization, or, in the Investigator's opinion, represents an additional risk to the participant, within 2 months prior to Day 1. * Known history of congenital or acquired immunodeficiency (e.g., due to human immunodeficiency virus \[HIV\] infection, splenectomy, immunosuppression-related or idiopathic T-cell deficiencies) that predisposes the participant to infection. * Positive test for chronic hepatitis B infection at screening, defined as either: a. Positive hepatitis B surface antigen (HBsAg), or b. Positive hepatitis B core (HBc) antibody (anti-HBc) plus negative hepatitis B surface (HBs) antibody (anti-HBs). * Positive test for hepatitis C virus antibody. * Negative test for varicella zoster virus (VZV)-IgG. * History of cancer, apart from squamous cell or basal cell carcinoma of the skin treated with documented success of curative therapy \> 3 months prior to Day 1. * History of active or latent tuberculosis (TB), or a positive QuantiFERON®-TB Gold test at screening, unless treatment for TB was completed per local guidelines. Participants with latent TB or a positive QuantiFERON®-TB Gold test who are actively on anti-TB treatment can enroll if they have completed at least one month of anti-TB treatment and intend to complete the full course of anti-TB treatment. Participants with an indeterminate QuantiFERON®-TB Gold test result can enroll if a repeat QuantiFERON®-TB Gold test is negative or a tuberculin skin test is negative. * For participants who may undergo MRI scans:
• Unable to undergo an MRI scan (e.g., hypersensitivity to Gd-containing MRI contrast agents, implanted pacemakers, defibrillators, or other metallic objects on or inside the body that limit performing MRI scans), or
• Unable to tolerate or comply with the MRI procedure.

Interventions: DRUG: Inebilizumab

Conditions: Neuromyelitis Optica Spectrum Disorder

Keywords: NMOSD

Sites: Children’s Health

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MASA Valve Early Feasibility Study (MVEFS)

Description:

The MASA Valve Early Feasibility Study (MVEFS) multi-site interventional clinical trial within the United States of America with each center following a common protocol.The objective of the trial is to evaluate the safety and probable benefit of MASA Valve in the indicated subset of patients requiring Right Ventricular Outflow Tract Reconstruction (RVOTR). As an early feasibility study, the purpose is determine the feasibility of success of the device in order to gather early data towards a future pivotal study and/or regulatory clearance submission.

Contact(s):

Call 214-648-5005
studyfinder@utsouthwestern.edu, madison.munson@childrens.com

Principal Investigator: Karl Reyes

Gender: All

Age: 0 Years to 22 Years old

Phase: N/A

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05452720

IRB Number: STU-2023-0657

Show full eligibility criteria

Inclusion Criteria:

• At least one of the following: Right Ventricular to Pulmonary Artery mean gradient > 35mm Hg, moderate or severe Pulmonary regurgitation (≥3+), or clinical indication for replacement of their native or prosthetic pulmonary valve with a prosthesis.
• Age < 22 years
• Patient is geographically stable and willing to return for 1 year follow-up for the trial.
• Patient's legal guardian should be willing to provide informed consent (IC) at the hospital location where they are being enrolled.
• The patient, and the patient's parent / legal representative where appropriate, and the treating physician agree that the subject will return for all required post-procedure follow up visits and the subject will comply with clinical investigation plan required follow-up visits.

Exclusion Criteria:

• Patient is in need of or has presence of a prosthetic heart valve at any other position
• Patient has a need for concomitant surgical procedures (non-cardiac)
• Patients with previously implanted pacemaker (including defibrillators) or mechanical valves
• Patient has an active bacterial or viral infection or requiring current antibiotic therapy (if temporary illness, patient may be a candidate 4 weeks after discontinuation of antibiotics)
• Patient has an active endocarditis
• Leukopenia, according to local laboratory evaluation of white blood cell count
• Acute or chronic anemia, according to local laboratory evaluation of hemoglobin Patients can be transfused to meet eligibility criteria
• Thrombocytopenia, defined as Platelet count < 150,000/mm3 Patients can be transfused to meet eligibility criteria
• Severe chest wall deformity, which would preclude placement of the PV conduit
• Known hypersensitivity to anticoagulants and antiplatelet drugs and to the device materials
• Immunocompromised patient defined as: autoimmune disease, patients receiving immunosuppressant drugs or immune stimulant drugs
• Patient has chronic inflammatory / autoimmune disease
• Need for emergency cardiac or vascular surgery or intervention
• Major or progressive non-cardiac disease (liver failure, renal failure, cancer) that has a life expectancy of less than one year
• Currently participating, or participated within the last 30 days, in an investigational drug or device study
• Alcohol or drug abuse as defined by DSM IV-TR criteria for substance abuse - this includes the illicit use of cannabis within the last 12 months
• Patient has medical, social or psychosocial factors that, in the opinion of the Investigator, could have impact on safety or compliance

Interventions: Device: Surgical Right Ventricular Outflow Tract Reconstruction

Conditions: Tetrology of Fallot, Pulmonary Stenosis, Truncus Arteriosus, Transposition of Great Vessels, Pulmonary Atresia, Ross Procedure

Keywords: Right Ventricular Outflow Tract Reconstruction, Pulmonary Valve, MASA Valve, Pulmonary Valve Replacement

Sites: Children’s Health

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A Study of LP-300 With Carboplatin and Pemetrexed in Never Smokers With Advanced Lung Adenocarcinoma (HARMONIC)

Description:

The goal of this clinical trial is to determine clinical advantages for LP-300 in combination with carboplatin and pemetrexed in the never smoker patient population. The primary objectives of this study are to determine progression-free survival (PFS) and overall survival (OS) in the study-defined patient population when LP-300 is co-administered with the standard of care chemotherapy drugs carboplatin and pemetrexed compared to carboplatin and pemetrexed alone. This has been designed as a multicenter, open label, phase II trial with 90 patients to be enrolled in the United States.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Jonathan Dowell

Gender: ALL

Age: 18 Years and over

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05456256

IRB Number: STU-2023-0857

Show full eligibility criteria

Inclusion Criteria:

• Patients with confirmed histopathological diagnosis of inoperable advanced (Stage III or IV) primary adenocarcinoma (including bronchioalveolar cell carcinoma) of the lung with specific actionable genomic alterations (e.g., mesenchymal epithelial transition (MET) exon14 skipping mutations, anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR), neurotrophic tyrosine receptor kinase (NTRK) fusions, etc.). If pathological or radiological findings are inconclusive for a diagnosis of primary adenocarcinoma of the lung, additional studies must be performed to confirm primary lung versus metastatic adenocarcinoma. Patients with no known actionable genomic alterations are ineligible to enroll in the study.
• Locally advanced inoperable or metastatic lung cancer.
• Patients must be never smokers: a never smoker is an adult who has never smoked, or who has smoked less than 100 cigarettes (or equivalent in other products such as vapes, cigars, pipes, hookahs, and marijuana use) in his or her lifetime. Note: a patient with actionable genomic alteration(s) who is a former smoker may be enrolled if such a patient would ordinarily be treated with pemetrexed and carboplatin combination based on institutional standard clinical practice; consultation with the sponsor's Medical monitor would be required
• Patients who have received systemic treatment with tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer but have experienced disease progression, unacceptable TKI-related toxicities, or are unable to tolerate the further use of TKIs.
• Prior radiation therapy is allowed, provided (1) that at least one area of measurable tumor (by computed tomography (CT) scan with at least one target lesion) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 that has not been subject to prior irradiation, and (2) that any such therapy is completed and any radiation-induced sequelae are recovered at least 21 days before randomization.
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Patients who are at least 18 years of age.
• Patients with documented stable central nervous system (CNS) metastases with no cognitive deficits, or progressive sensory or motor deficits, or seizures during the last 21 days prior to enrollment are eligible. Patients must have discontinued anti-seizure medications and steroids at least 14 days prior to patient enrollment.
• Patients must have fully recovered from any prior major surgical or diagnostic staging procedure (e.g., thoracotomy, mediastinoscopy), and have a post-operative status of at least 30 days before enrollment.
• Patients must have adequate bone marrow, adequate hepatic function, and baseline creatinine levels documented by specific laboratory criteria within 21 days prior to enrollment, including the following: * White blood cell count ≥ 2 x 10\*9/L * Absolute neutrophil count (ANC) ≥ 1.5 x 10\*9/L * Hemoglobin ≥ 10 g/dL * Platelet count ≥ 100 x 10\*9/L * Total bilirubin \< 1.5 x the upper limit of normal (ULN). For patients with Gilbert's syndrome, total bilirubin \< 2.5 x ULN * Aspartate aminotransferase/ serum glutamic oxaloacetic transaminase (AST/SGOT) ≤ 2.5 x ULN * Alanine aminotransferase/ serum glutamic pyruvic transaminase (ALT/SGPT) ≤ 2.5 x ULN * Alkaline phosphatase ≤ 2.5 x ULN * Baseline serum creatinine level no greater than 1.5 mg/dL or 133 μmol/L. * Creatinine clearance ≥ 45 mL/min as calculated using the Cockcroft-Gault methodology (Cockcroft 1976) * Magnesium ≥ 1.7 mg/dL
• Female patients of child-bearing potential must have a negative pregnancy test and must agree to use an acceptable contraceptive method during the study and for 12 weeks after their last dose of study treatment. Male patients with partners of child-bearing potential must also agree to use an adequate method of contraception for the duration of the study and for 12 weeks after their last dose of study treatment. Note: a) A patient is considered of childbearing potential if she is biologically capable of having children and is sexually active. Medically acceptable contraceptives include: (1) surgical sterilization (such as a tubal ligation, hysterectomy, or vasectomy), (2) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (3) barrier methods (such as a condom or diaphragm) used with a spermicide (only if used in combination with another mentioned method), or (4) an intrauterine device (IUD). Contraceptive measures and other medications sold for emergency use after unprotected sex, are not acceptable methods for routine use. If a female patient becomes pregnant, study therapy must be discontinued immediately. Lastly, b) the period for use of contraception after last dose of pemetrexed or carboplatin should be determined by the domestic drug labels and/or institutional standard clinical practice. For S Korea, contraception is to be used for 6 months after the last dose.
• Patients must have been disease-free at least two years for other malignancies, excluding: * Curatively-treated basal cell carcinoma, * Ductal carcinoma in situ (DCIS) of the breast * Non-melanomatous carcinoma of the skin, or * Carcinoma in situ of the cervix.
• Be willing to provide an archival tumor tissue sample, if available. The archival sample must be from a tumor lesion that was not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. The sample must have been obtained less than 36 months prior to consent.
• Provide signed, written, Institutional Review Board (IRB) approved informed consent prior to any screening procedures.

Exclusion Criteria:

• Patients with small cell, squamous cell, large cell, undifferentiated, mesothelioma, or any form of mixed (e.g., small cell and adenocarcinoma or squamous and adenocarcinoma) histopathological diagnosis of primary lung cancer.
• Patients with metastatic adenocarcinoma arising from any primary site other than the lung.
• Patients who have received any prior investigational agents except for investigational TKI drugs. The minimum drug washout period for all TKIs, including approved and investigational, is ≥ 5 half-lives or 2 weeks, whichever is shorter.
• Patients who have received chemotherapy and/or immunotherapy but transitioned to a TKI with no evidence of disease progression will be allowed to enroll. Patients who experienced disease progression while on chemotherapy and/or immunotherapy will be ineligible for the trial.
• Patients taking medications that are sensitive substrates of CYP2C19 or P-gp transporters
• Patients with recent onset (within 6 months of randomization) of congestive heart failure (New York Heart Association Classification Class II or greater), angina pectoris, unstable angina pectoris, serious uncontrolled cardiac arrhythmias, myocardial infarction, stroke, or transient ischemic attacks.
• Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of \> 470 msec. (average of triplicate ECGs) at Screening and/or on C1D1 (pre- dose) except for a documented bundle branch block or unless secondary to pacemaker. In the case of a documented bundle branch block or a pacemaker, discussion with the Medical Monitor is required prior to enrollment.
• Patients with unstable CNS metastases (characterized by progressive sensory/motor impairment, cognitive/speech impairment, or seizure activity) within 21 days before enrollment.
• Patients who do not have at least one (1) measurable disease site that has not been previously irradiated.
• Patients who are known to be positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HbsAg) or hepatitis C virus (HCV).
• Patients with active infections, active interstitial lung disease, uncontrolled high blood pressure, uncontrolled diabetes mellitus, uncontrolled seizures (not due to CNS metastases) within the last 3 months, or other serious underlying medical condition.
• Patients with documented hypersensitivity to any of the study medications (LP-300, pemetrexed, carboplatin and/or excipients) or supportive agents that may be used.
• Patients who are pregnant or are breastfeeding.
• Patients who have undergone blood transfusions within 10 days before randomization.
• Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence to study requirements or confound the interpretation of study results.
• Patients who have a life expectancy of less than 3 months.

Interventions: DRUG: LP-300, DRUG: Pemetrexed, DRUG: Carboplatin

Conditions: Adenocarcinoma of Lung, Carcinoma, Non-Small-Cell Lung, Lung/Thoracic

Keywords: never smoker, non smoker, EGFR, ALK, ROS, MET, tyrosine kinase inhibitor, TKI, pemetrexed, carboplatin, NSCLC, never-smoker, non-smoker, TK inhibitor, lung cancer

Sites: UT Southwestern; Parkland Health & Hospital System

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A Study of TTI-101 as Monotherapy and in Combination in Participants With Locally Advanced or Metastatic, and Unresectable Hepatocellular Carcinoma

Description:

The primary objectives of Cohort A Phase 1b are to evaluate the safety and tolerability of TTI-101 orally administered as a single agent to participants with locally advanced or metastatic, and unresectable Hepatocellular Carcinoma (HCC) and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of TTI-101 as a single agent. The primary objectives of Cohort A Phase 2 are to evaluate the safety and tolerability of TTI-101 orally administered as a single agent at the RP2D to participants with locally advanced or metastatic, and unresectable HCC and to assess the preliminary efficacy of TTI-101 as a single agent in participants with locally advanced or metastatic, and unresectable HCC. The secondary objectives of Cohort A Phase 2 are to assess response, progression, survival, and pharmacokinetics. The primary objectives of Cohorts B and C Phase 1b are to evaluate the safety and tolerability of TTI-101 orally administered in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) to participants with locally advanced or metastatic, or unresectable HCC and to determine the MTD and/or RP2D of TTI-101 when used in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C). The primary objectives of Cohorts B and C Phase 2 are to evaluate the safety and tolerability of TTI-101 orally administered in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) at the RP2D to participants with locally advanced or metastatic, and unresectable HCC and to assess the preliminary efficacy of TTI-101 in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) to participants with locally advanced or metastatic, and unresectable HCC. The secondary objectives of Cohorts B and C Phase 2 are to assess response, progression, survival, and pharmacokinetics.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: David Hsieh

Gender: All

Age: 18 Years and over

Phase: Phase 1/Phase 2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05440708

IRB Number: STU-2022-0622

Show full eligibility criteria

Inclusion Criteria:

• Able to understand and willing to provide informed consent and able to comply with the study procedures and restrictions.
• Age ≥18 years at the time of informed consent.
• Have histologically or radiographically (Liver Imaging Reporting and Data Systems category 5) confirmed diagnosis of locally advanced or metastatic, and unresectable HCC. Participants without cirrhosis require histological confirmation.
• Cohorts A and B only: Willing to provide a representative fresh tumor tissue specimen prior to enrollment. The fresh tumor specimen must be obtained after progression on the prior therapy. No biopsy is required for participants in Cohort C.
• Measurable disease as per RECIST Version 1.1. Participants who received prior local therapy are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST Version 1.1.
• Able to swallow tablets.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has adequate hematologic and organ function as defined by the following local laboratory values at screening:
• Absolute neutrophil count (ANC) ≥1.5 × 10^9/L (1500/μL) without granulocyte colony-stimulating factor support.
• Lymphocyte count ≥0.5 × 10^9/L (500/μL).
• Platelet count ≥75 × 10^9/L (75,000/μL) without transfusion.
• Hemoglobin ≥90 g/L (9 g/dL). Participants may be transfused to meet this criterion.
• Serum albumin ≥28 g/L (2.8 g/dL).
• AST, ALT, and alkaline phosphatase (ALP) ≤5 × upper limit of normal (ULN).
• Serum bilirubin ≤2 mg/dL.
• Adequate renal function defined as either:
• creatinine clearance ≥40 mL/min calculated using the Cockcroft-Gault formula, or
• 24-hour urine collection.
• Prothrombin time/international normalized ratio (PT/INR) and activated partial thromboplastin time (aPTT) ≤2 × ULN, except for participants receiving anticoagulation therapy.
• Child-Pugh class A or B7 within 7 days prior to enrollment.
• Females of childbearing potential (ie, ovulating, premenopausal, and not surgically sterile) must:
• Have a negative serum pregnancy test at screening.
• Not be breastfeeding or lactating.
• Agree to use a highly effective method of birth control for the duration of the study and for at least 30 days after the last dose in the study. Effective forms of birth control include barrier methods used in conjunction with a spermicidal agent (according to standard local practices), nonhormonal intrauterine devices, or permanent sterilization.
• Males must:
• Agree to use a condom for at least 30 days after the last dose in the study even if vasectomized in order to prevent delivery of the drug via seminal fluid.
• Agree to abstain from sperm donation through 30 days after administration of the last dose of the study treatment.
• Unless surgically sterile, males with female partners of childbearing potential must agree to use 2 methods of acceptable birth control for at least 30 days after the last dose in the study. Effective forms of birth control include barrier methods used in conjunction with a spermicidal agent (according to standard local practices), nonhormonal intrauterine devices in female partners, or permanent sterilization. Cohort A:
• In addition to the general inclusion criteria, participants enrolled in Cohort A must have demonstrated objective progression on up to 3 prior lines of systemic antitumor drug therapy. Cohort B:
• In addition to the general inclusion criteria, participants enrolled in Cohort B must have demonstrated objective progression following at least 2 cycles of first-line anti-PD-1 or anti-PD-L1 monotherapy or combination therapy. Participants may have received no more than one line of prior therapy.
• Agree to use contraception as specified in the general inclusion criteria for at least 4 months following the last dose of pembrolizumab in accordance with the approved prescribing information. Cohort C:
• In addition to the general inclusion criteria, participants enrolled in Cohort C must be naïve to systemic treatment for locally advanced or metastatic, and unresectable HCC.
• Must have had an evaluation (gastroduodenoscopy) for the presence of varices within 6 months prior to initiation of bevacizumab therapy.
• Agree to use contraception as specified in the general inclusion criteria for at least 5 months after the last dose of atezolizumab and at least 6 months after the last dose of bevacizumab in accordance with the approved prescribing information.

Exclusion Criteria:

• Pregnant or breastfeeding.
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
• History of leptomeningeal disease.
• Previous treatment of the current malignancy with a signal transducer and activator of transcription (STAT) inhibitor.
• Previous therapy with:
• Standard therapy including chemotherapy, immunotherapy, biologic therapy, or any other anticancer therapy within 28 days (or 5 elimination half-lives for non-cytotoxics, whichever is shorter) of Cycle 1 Day 1 (6 weeks for nitrosoureas or mitomycin).
• Any investigational agent within 28 days (or 5 elimination half-lives for a non-cytotoxic investigational therapy, whichever is shorter) of Cycle 1 Day 1 or 5 half-lives for a small molecule/targeted therapy.
• Extensive prior radiotherapy to more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation within 5 years from enrollment.
• Herbal preparations are not allowed throughout the study. These herbal medications include but are not limited to St. John's wort, kava, ephedra (mahung), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Participants should stop using herbal medications 7 days prior to the first dose of study treatment.
• Is not fully recovered from all coronavirus disease 2019 (COVID-19)-related symptoms for 2 weeks prior to Cycle 1 Day 1, if previously tested positive for COVID-19.
• Ongoing toxicity (except alopecia) due to a prior therapy, unless returned to baseline or Grade 1 or less.
• Has had major surgery within 3 weeks prior to starting investigational product (IP) or has not recovered from major side effects due to surgery.
• Significantly impaired cardiac function such as unstable angina pectoris, congestive heart failure with New York Heart Association Class III or IV, myocardial infarction within the last 12 months prior to study entry; serious arrhythmia (including QTc prolongation of >470 ms and/or pacemaker) or prior diagnosis of congenital long QT syndrome or left ventricular ejection fraction <50% on screening echocardiogram.
• Pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Participants with indwelling catheters for control of effusions or ascites are allowed.
• History of cerebrovascular accident or stroke within the previous 2 years.
• History of hepatic encephalopathy.
• Uncontrolled or symptomatic hypercalcemia (ionized calcium >1.5 mmol/L, calcium >12 mg/dL, or corrected serum calcium >ULN).
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
• History of Grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition as TTI-101 (hydroxyl-naphthalene sulfonamides).
• Known active metastases in the central nervous system (unless stable by brain imaging studies for at least 1 month without evidence of cerebral edema and no requirements for corticosteroids or anticonvulsants).
• History of difficulty swallowing oral medications, malabsorption, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the IP.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Participants with chronic hepatitis B virus (HBV) infection, unless screening viral load <500 IU/mL on stable doses of antiviral therapy. Note: Participants with chronic hepatitis C virus (HCV) infection are allowed to enroll into the study but do not have a defined maximum viral load requirement for study entry. Participants with both HBV and HCV infection are excluded unless they have negative HCV ribonucleic acid (RNA).
• History of malignancy other than HCC within 3 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (eg, 5-year overall survival [OS] rate >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
• Has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate participation in the clinical study, or compromise compliance with the protocol such as:
• Chronic pancreatitis.
• Active untreated or uncontrolled fungal, bacterial, or viral infections (including COVID-19), sepsis, etc.
• Acute and chronic, active infectious disorders including viral and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy.
• Is unable to understand and to comply with study instructions and requirements. Cohort B: In addition to the general exclusion criteria, participants enrolled in Cohort B must fulfill the following additional exclusion criteria:
• Discontinued prior treatment with anti-PD-1 or anti-PD-L1 for any reason other than disease progression. Cohort C: In addition to the general exclusion criteria and Cohort B criteria, participants enrolled in Cohort C must fulfill the following additional exclusion criteria:
• Inadequately controlled arterial hypertension (defined as systolic blood pressure [BP] ≥150 mmHg and/or diastolic BP ≥100 mmHg), based on an average of ≥3 BP readings on ≥2 sessions.
• Participant has received prior systemic chemotherapy for locally advanced or metastatic and/or unresectable HCC. However, participant may have received either neo-adjuvant or adjuvant chemotherapy as long as it was completed at least 6 months prior to the first dose of study treatment.
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding and a prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment.
• Urine dipstick for proteinuria ≥2+ at screening. If a 24-hour urine collection shows <1 g of protein in 24 hours, the participant is eligible.
• Current or recent (within 10 days of first dose of study treatment) use of aspirin (>325 mg/day) or treatment with dipyridamole, ticlopidine, clopidogrel, and cilostazol.
• Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants. Prophylactic anticoagulants (eg, low-dose warfarin with target INR <1.5 × ULN or low-dose low molecular weight heparin) are allowed.
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 3 days prior to the first dose of bevacizumab.
• History of gastrointestinal perforation or evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
• Metastatic disease that involves major airways or blood vessels. Participants with portal or hepatic vein involvement are not excluded.
• Participant has experienced any of the following within 6 months prior to enrollment: arterial thromboembolic event (including myocardial infarction, coronary arterial disease, transient ischemic attack, stroke, etc), congestive heart failure, hemoptysis, or pulmonary embolism.
• Participant has experienced a fistula. Cohorts B and C: In addition to the general exclusion criteria and the cohort-specific criteria listed above, participants enrolled in Cohorts B and C must fulfill the following additional exclusion criteria:
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during pembrolizumab treatment or within 5 months after the last dose of pembrolizumab treatment.
• Active or history of immune-mediated 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, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
• Participants with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
• Participants with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (eg, participants with psoriatic arthritis are excluded) are eligible for the study provided all of the 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.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor α [TNF-α] agents) within 2 weeks prior to initiation of study treatment. Participants receiving low-dose corticosteroids (equivalent of prednisone 10 mg/day or lower) or who receive pulse corticosteroids due to intravenous (IV) contrast allergy are not excluded.
• Active tuberculosis.
• Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Participants receiving prophylactic antibiotics (eg, to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• Prior allogeneic stem cell or solid organ transplantation.
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.

Interventions: Drug: TTI-101, Drug: Pembrolizumab, Drug: Atezolizumab, Drug: Bevacizumab

Conditions: Hepatocellular Carcinoma, Liver

Keywords: Hepatocellular carcinoma, TTI-101, Pembrolizumab, Atezolizumab, Bevacizumab, revert

Sites: UT Southwestern; Parkland Health & Hospital System

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Pathways Relating Amnestic MCI to a Mild Traumatic Brain Injury History (PATH)

Description:

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.

Contact(s):

Call 214-648-5005
studyfinder@utsouthwestern.edu, Hannah.Cabrera@UTSouthwestern.edu

Principal Investigator: Christian LoBue

Gender: ALL

Age: 55 Years and over

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05446584

IRB Number: STU-2022-0591

Show full eligibility criteria

Interventions: DEVICE: High Definition Transcranial Direct Current Stimulation

Conditions: Mild Cognitive Impairment, Amnestic Mild Cognitive Disorder, Amnestic Mild Cognitive Impairment, Mild Traumatic Brain Injury, Concussion, Brain, Brain and Nervous System

Keywords: MCI, TBI, memory, biomarker, Alzheimer

Sites: UT Southwestern; Parkland Health & Hospital System

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Pediatric Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (P-ICECAP) (ICECAP)

Description:

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.

Contact(s):

Call 214-648-5005
studyfinder@utsouthwestern.edu, Kirstie.LeDoux@UTSouthwestern.edu

Principal Investigator: Joshua Wolovits

Gender: All

Age: 2 Days to 17 Years old

Phase: N/A

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05376267

IRB Number: STU-2022-0800

Show full eligibility criteria

Interventions: Device: Therapeutic Hypothermia

Conditions: Cardiac Arrest, Out-Of-Hospital, Hypothermia, Induced, Hypoxia-Ischemia, Brain

Keywords: Bayesian Adaptive Clinical Trial, Hypothermia, therapeutic, Coma, Pediatric

Sites: Children’s Health

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A Study of ASP2138 Given by Itself or Given With Other Cancer Treatments in Adults With Stomach Cancer, Gastroesophageal Junction Cancer, or Pancreatic Cancer

Description:

Claudin 18.2 protein, or CLDN18.2 is a protein found on cells in the digestive system. It is also found on some tumors. Researchers are looking at ways to attack CLDN18.2 to help control tumors. ASP2138 is thought to bind to CLDN18.2 and a protein on a type of immune cell called a T-cell. This "tells" the immune system to attack the tumor. ASP2138 is a potential treatment for people with stomach cancer, gastroesophageal junction cancer (GEJ cancer) or pancreatic cancer. GEJ is where the tube that carries food (esophagus) joins the stomach. Before ASP2138 is available as a treatment, the researchers need to understand how it is processed by and acts upon the body. In this study, ASP2138 will either be given by itself, or given together with standard treatments for gastric, GEJ and pancreatic cancer. Pembrolizumab and mFOLFOX6, and ramucirumab and paclitaxel are standard treatments for gastric and GEJ cancer. mFOLFIRINOX is a standard treatment for pancreatic cancer. This information will help find a suitable dose of ASP2138 given by itself and together with the standard cancer treatments and to check for potential medical problems from the treatments. The main aims of the study are: * To check the safety of ASP2138 and how well people can tolerate medical problems during the study. * To find a suitable dose of ASP2138 to be used later in the study. * These are done for ASP2138 given by itself and when given together with the standard cancer treatments. Adults 18 years or older with stomach cancer, GEJ cancer, or pancreatic cancer can take part. Their cancer is locally advanced unresectable or metastatic. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body. There should also be the CLDN18.2 marker in a tumor sample. People cannot take part if they need to take medicines to suppress their immune system, have blockages or bleeding in their gut, have specific uncontrollable cancers, have specific infections, have a condition such as hemophagocytic lymphohistiocytosis (HLH) which is when the body over-reacts to a "trigger" such as infection, or have a specific heart condition ("New York Heart Association Class III or IV"). Phase 1: Lower to higher doses of ASP2138 * ASP2138 is either given through a vein (intravenous infusion) or just under the skin (subcutaneous injection). * Different small groups are given lower to higher doses of ASAP2138. * ASP2138 is either given by itself, or given with 1 of 3 standard treatments: * Pembrolizumab and mFOLFOX6 (first treatment for gastric GEJ cancer) * Ramacirumab and paclitaxel (Second treatment for gastric or GEJ cancer) * ASP2138 with mFOLFIRINOX (first treatment for pancreatic cancer) Phase 1b: doses of ASP2138 worked out from Phase 1 * ASP2138 is either given through a vein or just under the skin. This depends on the findings from Phase 1. * People with gastric cancer, GEJ cancer or pancreatic cancer are given doses of ASP2138, worked out from Phase 1. * This includes doses of ASP2138 given by itself and ASP2138 given with the standard cancer treatments. * The standard cancer treatments given depends on the type of cancer they have. End of treatment visit: This is 7 days after final dose of study treatment or if the study doctor decides to stop the person's treatment. People who have locally advanced unresectable pancreatic cancer will not receive ASP2138 by itself.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Syed Kazmi

Gender: ALL

Age: 18 Years and over

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05365581

IRB Number: STU-2022-0586

Show full eligibility criteria

Inclusion Criteria:

* Participant is considered an adult according to local regulation at the time of signing the informed consent form (ICF). * Female participant is not pregnant, confirmed by serum pregnancy test \&vmedical evaluation by interview \& at least 1 of the following conditions apply: * Not a woman of childbearing potential (WOCBP) * WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 6 months after final study intervention administration. * Female participant must agree not to breastfeed starting at screening \& throughout the study period \& for 6 months after the final study intervention administration. * Female participant must not donate ova starting at screening \& throughout the study period \& for 6 months after the final study intervention administration. * Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period \& for 6 months after the final study intervention administration. * Male participant must not donate sperm during the treatment period \& for 6 months after the final study intervention administration. * Male participant with pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period \& for 6 months after the final study intervention administration. * Participant's tumor sample is positive for claudin (CLDN)18.2 expression by central immunohistochemistry (IHC) testing. * Participant has radiographically-confirmed, locally advanced, unresectable or metastatic disease within 28 days prior to the first dose of study intervention. * Participant has at least 1 measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 within 28 days prior to the first dose of study intervention. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. * Participant has QT interval by Fredericia (QTcF) =\< 470 msec. * Participant agrees not to participate in another interventional study while receiving study Intervention in the present study. * Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Participant has predicted life expectancy \>= 12 weeks. * Participant must meet all of criteria based on laboratory tests within 7 days prior to the first dose of study Intervention. In case of multiple laboratory data within this period, the most recent data should be used. If a participant has received a recent blood transfusion, the laboratory tests must be obtained \>= 1 week after any blood transfusion. Monotherapy Disease specific Criteria: Gastric/GEJ Cancer * Participant has histologically confirmed metastatic, locally advanced unresectable gastric/gastroesophageal junction (GEJ) adenocarcinoma. * Escalation: Participant with gastric/GEJ adenocarcinoma who has progressed, is intolerant, has refused, or for whom there is no standard approved therapies that impart significant clinical benefit (no limit to the number of prior treatment regimens). * Unique to South Korea: Participant with gastric/GEJ adenocarcinoma who has refused standard approved therapies is not allowed. * Expansion: Participant with gastric/GEJ adenocarcinoma must have received no more than 3 prior lines of systemic chemotherapy treatment. * Unique to EU: Expansion: Participant with gastric/GEJ adenocarcinoma must have received at least first-line standard therapies in the metastatic setting, must have received ramucirumab treatment if eligible \& where ramucirumab is available, \& no more than 3 prior lines of systemic chemotherapy treatment. Monotherapy Disease specific Criteria: Pancreatic Cancer * Participant has histologically or cytologically confirmed metastatic pancreatic adenocarcinoma. * Escalation: Participant with pancreatic adenocarcinoma who has progressed, is intolerant, has refused, or for whom there is no standard approved therapies that impart significant clinical benefit (no limit to the number of prior treatment regimens). * Unique to South Korea: Participant with pancreatic adenocarcinoma who has refused standard approved therapies is not allowed. * Expansion: Participants with pancreatic adenocarcinoma must have received no more than 2 prior lines of systemic chemotherapy treatment. Note: Participants with locally advanced unresectable pancreatic adenocarcinoma will not be admitted in monotherapy arms. * Unique to EU: Participant with pancreatic adenocarcinoma must have received at least first-line standard therapies in the metastatic setting \& no more than 2 prior lines of systemic chemotherapy treatment. For all participants in combination therapy (CT) administration: * If a participant has received a recent blood transfusion, the laboratory tests must be obtained ≥ 1 week after any blood transfusion. Combination Therapy Disease-specific (CTDS)

Inclusion Criteria:

ASP2138 in Combination with Pembrolizumab \& mFOLFOX6 as First-line Therapy in Gastric/GEJ Cancer * Participant has histologically confirmed diagnosis of gastric/GEJ adenocarcinoma. * Participant has metastatic or locally advanced unresectable gastric/GEJ adenocarcinoma. * Participant with gastric/GEJ adenocarcinoma has progressed \& must not have been previously treated for metastatic disease with either chemotherapy or prior checkpoint inhibitor therapy. * Participant has a human epidermal growth factor receptor 2 (HER2)-negative tumor per local testing. * For CT with oxaliplatin, follow contraception guidelines from time of informed consent through at least 9 months after final study intervention. (Unique to South Korea: For CT with oxaliplatin, follow contraception guidelines from time of informed consent through at least 15 months after final study intervention for women \& 12 months after final study intervention for men). Unique to EU: * Participant must have a PD-L1 CPS ≥ 1. CTDS

Inclusion Criteria:

ASP2138 in Combination with Ramucirumab \& Paclitaxel as Second-line Therapy in Gastric/GEJ Cancer * Participant has histologically confirmed diagnosis of gastric/GEJ adenocarcinoma. * Participant has metastatic or locally advanced unresectable gastric/GEJ adenocarcinoma. * Participant with gastric/GEJ adenocarcinoma must have previously received 1 line of systemic chemotherapy treatment (i.e., documented objective radiological or clinical disease progression after first line platinum \& fluoropyrimidine treatment in the metastatic setting or disease progression during or within 4 months of the last dose of perioperative treatment. CTDS

Inclusion Criteria:

ASP2138 in Combination with mFOLFIRINOX as First-line Therapy in Pancreatic Cancer * Participant has histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma. * Participant has confirmed metastatic or locally advanced unresectable pancreatic adenocarcinoma. * Participant has pancreatic adenocarcinoma, has progressed \& must not have received prior systemic anticancer therapy for their advanced disease. * For CT with oxaliplatin, follow contraception guidelines from time of informed consent through at least 9 months after final study intervention. (Unique to South Korea: For CT with oxaliplatin, follow contraception guidelines from time of informed consent through at least 15 months after final study intervention for women \& 12 months after final study intervention for men). Japan \& Korea Specific: For All Participants in ASP2138 in Combination with Pembrolizumab \& CAPOX: \- If a participant has received a recent blood transfusion, the laboratory tests must be obtained ≥ 1 week after any blood transfusion. CTDS

Inclusion Criteria:

ASP2138 in Combination with Pembrolizumab \& CAPOX as First-line Therapy in Gastric/GEJ Cancer * Participant has histologically confirmed diagnosis of gastric/GEJ adenocarcinoma. * Participant has metastatic or locally advanced unresectable gastric/GEJ adenocarcinoma. * Participant with gastric/GEJ adenocarcinoma must not have been previously treated for metastatic disease with either chemotherapy or prior checkpoint inhibitor therapy. * Participants have a HER2-negative tumor per local testing. * For CT with oxaliplatin, follow contraception guidelines from time of informed consent through at least 9 months after final study intervention.

Exclusion Criteria:

* Participant has received other investigational agents, or antineoplastic therapy including other immunotherapy or devices concurrently or within 21 days or 5 times the half-life, whichever is shorter, prior to first dose of study intervention administration. * Participant has any condition which makes the participant unsuitable for study participation. * Participant has known immediate or delayed hypersensitivity or contraindication to any component of study intervention. * Participant has had prior severe allergic reaction or intolerance to known ingredients of ASP2138 or other antibodies, including humanized or chimeric antibodies. * Participant weighs \< 40 kg. * Participant has received systemic immunosuppressive therapy, including systemic corticosteroids 14 days prior to first dose of study intervention. Participant using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 10 mg per day of prednisone or equivalent), receiving a single daily dose of systemic corticosteroids or receiving systemic corticosteroids as pre-medication for radiologic imaging contrast use are allowed. * Participant has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting. * Participant has significant gastric bleeding \&/or untreated gastric ulcers that exclude the participant from participation. * Participant has symptomatic CNS metastases or participant has evidence of unstable CNS metastases even if asymptomatic (e.g., progression on scans). Participants with previously treated CNS metastases are eligible, if they are clinically stable \& have no evidence of CNS progression by imaging for at least 4 weeks prior to start of study intervention \& are not requiring immunosuppressive doses of systemic steroids (\> 10 mg per day of prednisone or equivalent) for longer than 2 weeks. * Participant is known to have HIV infection. However, participants with cluster of differentiation (CD4) + T cell counts \>= 350 cells/µL \& no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within the past 6 months are eligible. NOTE: Screening for human immunodeficiency virus (HIV) infection should be conducted per local requirements. * Participant is known to have active hepatitis B (positive hepatitis B surface antigen \[HBsAg\]) or hepatitis C infection. Testing is required for known history of these infections or as mandated by local requirements. NOTE: Screening for these infections should be conducted per local requirements. * For participant who is negative for HBsAg, but hepatitis B core antibody (HBc Ab) positive, a hepatitis B virus (HBV) deoxyribonucleic acid (DNA) test will be performed \& if positive the participant will be excluded. * Participant with positive hepatitis C virus (HCV) serology, but negative HCV ribonucleic acid (RNA) test results are eligible. * Participant treated for HCV with undetectable viral load results are eligible * Participant has had within 6 months prior to first dose of study intervention any of the following: unstable angina, myocardial infarction, ventricular arrhythmia requiring intervention or hospitalization for heart failure. * Participant has active infection requiring systemic therapy that has not completely resolved within 7 days prior to the start of study intervention. * Participant has active autoimmune disease that has required systemic immunosuppressive treatment within the past 1 month prior to the start of study intervention. * Participant has a clinically significant disease or co-morbidity that may adversely affect the safe delivery of treatment within this study or make the participant unsuitable for study participation. * Participant has psychiatric illness or social situations that would preclude study compliance. * Participant has had a major surgical procedure 28 days before start of study intervention \& has not fully recovered. * Participant has received radiotherapy metastatic or for locally advanced unresectable gastric/GEJ or metastatic pancreatic adenocarcinoma 14 days prior to start of study intervention \& has NOT recovered from any related toxicity. * Participant has another malignancy for which treatment is required. * Participant who has received CLDN18.2-targeted therapy (e.g., zolbetuximab or chimeric antigen receptor CLDN18.2-specific T cells) prior to first dose of study intervention administration is not eligible for dose escalation cohorts. However, a participant who has received CLDN18.2-targeted therapy greater than 28 days or 5 half-lives (whichever is longer) prior to first dose study intervention administration is eligible for dose expansion cohorts only, with the exception of participants who have experienced Grade \>= 3 gastrointestinal toxicity after receiving an CLDN18.2-targeted therapy. * Participant has a history or complication of interstitial lung disease. China Specific: Participant who has received treatment with herbal medications that have known antitumor activity within 28 days prior to first dose of study treatment. For all participants in CT administration: * Participant has prior severe allergic reaction; suspected, known immediate or delayed hypersensitivity; or intolerance or contraindication to any study intervention (i.e., pembrolizumab \& mFOLFOX6 \[all components\], ramucirumab \& paclitaxel or mFOLFIRINOX \[all components\]). * For 5 FU (fluorouracil): Participant has known dihydropyrimidine dehydrogenase (DPD) deficiency. (NOTE: Screening for DPD deficiency should be conducted per local requirements). * Participants who have received systemic immunosuppressive therapy, including systemic corticosteroids 14 days prior to the first dose of study intervention are generally excluded; however, participants using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 10 mg per day of prednisone or equivalent), receiving a single daily dose of systemic corticosteroids or receiving systemic corticosteroids as pre-medication for radiologic imaging contrast or for chemotherapy (as part of CT administration) are allowed. * Participant is known to have HIV infection. * NOTE: Differing from monotherapy administration, participants with CD4+ T cell counts ≥ 350 cells/µL \& no history of AIDS-defining opportunistic infections within the past 6 months remain ineligible. * NOTE: Screening for HIV infection should be conducted per local requirements. * Participant has had uncontrolled high blood pressure within 6 months prior to the first dose of study intervention (Unique to EU: high blood pressure Stage 2 is defined as ≥ 140/90 mmHg). * Participant has a history of ascites requiring drainage more than twice in the past 7 days. CTDS

Exclusion Criteria:

ASP2138 in Combination with Pembrolizumab \& mFOLFOX6 as First-line Therapy in Gastric/GEJ Cancer: * Participant has history of (non-infectious) pneumonitis that required steroids, current pneumonitis, or has a history of interstitial lung disease. * Participant received live-virus vaccination within 30 days prior to the first dose of study intervention. * Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention or has been diagnosed with an autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Patients that require replacement therapy (e.g., thyroxine \[T4\], insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) may be enrolled. CTDS

Exclusion Criteria:

ASP2138 in Combination with Ramucirumab \& Paclitaxel as Second-line Therapy in Gastric/GEJ Cancer: * History of cerebrovascular accident or transient ischemic attack within 6 months prior to study intervention. * Participant has significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to study intervention. * Participant has evidence of a bleeding diathesis or significant coagulopathy. * Participant has initiated new treatment with medications that affect the coagulation cascade with an INR ≥ 2 such as vitamin K antagonists, heparins \& direct thrombin inhibitors or the use of factor Xa inhibitors within 28 days prior to the start of study intervention. Note: If the participant started receiving such medications more than 28 days prior to the start of study intervention \& needs to continue, this is allowed. However, new anticoagulation medications may not be initiated within 28 days prior to the start of study intervention. Japan \& Korea Specific: For All Participants in ASP2138 in Combination with Pembrolizumab \& CAPOX: * Participant has prior severe allergic reaction; suspected, known immediate or delayed hypersensitivity; or intolerance or contraindication to any study intervention (i.e., pembrolizumab \& CAPOX \[all components\]). * Participants who have received systemic immunosuppressive therapy, including systemic corticosteroids 14 days prior to the first dose of study intervention are generally excluded, however, participants using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 10 mg per day of prednisone or equivalent), receiving a single dose of systemic corticosteroids or receiving systemic corticosteroids as pre-medication for radiologic imaging contrast or for chemotherapy (as part of CT administration) are allowed. * Participant is known to have HIV infection. * NOTE: Differing from monotherapy administration, participants with CD4+ T cell counts ≥ 350 cells/μL \& no history of AIDS-defining opportunistic infections within the past 6 months remain ineligible. * NOTE: Screening for HIV infection should be conducted per local requirements. * Participant has had uncontrolled high blood pressure within 6 months prior to the first dose of study intervention. * Participant has a history of ascites requiring drainage more than twice in the past 7 days. * Participant has known DPD deficiency. (NOTE: Screening for DPD deficiency should be conducted per local requirements). CTDS

Exclusion Criteria:

ASP2138 in Combination with Pembrolizumab \& CAPOX as First-line Therapy in Gastric/GEJ Cancer: * Participant has history of (noninfectious) pneumonitis that required steroids, current pneumonitis, or has a history of interstitial lung disease. * Participant received live-virus vaccination within 30 days prior to the first dose of study intervention. * Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention or has been diagnosed with an autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Participants who require replacement therapy (e.g., thyroxine \[T4\], insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) may be enrolled.

Interventions: DRUG: ASP2138, DRUG: Pembrolizumab, DRUG: Oxaliplatin, DRUG: Leucovorin, DRUG: Fluorouracil, DRUG: Ramucirumab, DRUG: Paclitaxel, DRUG: Irinotecan, DRUG: Capecitabine

Conditions: Gastric Adenocarcinoma, Gastroesophageal Junction (GEJ) Adenocarcinoma, Pancreatic Adenocarcinoma, Other Digestive Organ, Pancreas, Small Intestine, Stomach

Keywords: Claudin (CLDN) 18.2, ASP2138, Pharmacokinetics, Safety, Tolerability

Sites: UT Southwestern

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Genetic Testing to Select Therapy for the Treatment of Advanced or Metastatic Kidney Cancer, OPTIC RCC Study

Description:

This phase II trial tests whether using genetic testing of tumor tissue to select the optimal treatment regimen works in treating patients with clear cell renal cell (kidney) cancer that has spread to other places in the body (advanced or metastatic). The current Food and Drug Administration (FDA)-approved regimens for advanced kidney cancer fall into two categories. One treatment combination includes two immunotherapy drugs (nivolumab plus ipilimumab), which are delivered by separate intravenous infusions into a vein. The other combination is one immunotherapy drug (nivolumab infusion) plus an oral pill taken by mouth (cabozantinib). Nivolumab and ipilimumab are "immunotherapies" which release the brakes of the immune system, thus allowing the patient's own immune system to better kill cancer cells. Cabozantinib is a "targeted therapy" specifically designed to block certain biological mechanisms needed for growth of cancer cells. In kidney cancer, cabozantinib blocks a tumor's blood supply. The genetic (DNA) makeup of the tumor may affect how well it responds to therapy. Testing the makeup (genes) of the tumor, may help match a treatment (from one of the above two treatment options) to the specific cancer and increase the chance that the disease will respond to treatment. The purpose of this study is to learn if genetic testing of tumor tissue may help doctors select the optimal treatment regimen to which advanced kidney cancer is more likely to respond.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Tian Zhang

Gender: ALL

Age: 18 Years and over

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05361720

IRB Number: STU-2023-0365

Show full eligibility criteria

Inclusion Criteria:

* Histological confirmation of RCC with a clear cell component * Advanced (not amenable to curative surgery or radiation therapy) or metastatic (American Joint Committee on Cancer \[AJCC\] stage IV) RCC * Patient can comprehend and sign the study informed consent form * Male or female \>= 18 years of age at the time of informed consent * Karnofsky performance status (KPS) of \>= 70% * No prior systemic therapy for RCC in the neoadjuvant, adjuvant or metastatic setting * At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 * Tumor tissue for ribonucleic acid (RNA)-sequencing (tumor tissue from bony metastasis is not suitable but a soft tissue component around bone is acceptable) * Screening tissue consent- Patient must be assigned to either Cluster 1/2 or 4/5. Patients assigned to cluster 3/6/7 will not be eligible for the treatment study * Adequate renal function defined as calculated creatinine clearance \>= 30 mL/min per the Cockcroft and Gault formula * Adequate liver function defined by: * Total bilirubin =\< 1.5 times the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert's syndrome * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN * Women of childbearing potential (WOCBP) must have a negative serum pregnancy test during screening and prior to receiving first dose of protocol-indicated treatment * Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal * Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 years of age in the absence of other biological or physiological causes

Exclusion Criteria:

* =\< 14 days before first dose of protocol-indicated treatment: * Major surgery requiring general anesthesia * Inadequately controlled hypertension (systolic blood pressure \[SBP\] \> 160/90 mmHg) * Anti-hypertensive medications are permitted. * Active infection requiring infusional treatment * Has preexisting gastrointestinal or non-gastrointestinal fistula * Proteinuria \> 2 g/ 24 hours (hrs) * If patient has 1+ protein on urine dipstick then a 24 hr urine collection is required * Non-healing wounds on any part of the body (for patients assigned to Cabo/Nivo only) * Known clinically significant active bleeding including hemoptysis * Inability to swallow oral medication; or the presence of a poorly controlled gastrointestinal disorder that could significantly affect the absorption of oral study drug (for patients assigned to Cabo/Nivo only) - e.g., Crohn's disease, ulcerative colitis, chronic diarrhea (defined as \> 4 loose stools per day), malabsorption, or bowel obstruction * Significant cardiovascular disease or condition including: * Class III or IV cardiovascular disease according to the New York Heart Association (NYHA) functional criteria * Unstable angina pectoris (i.e., last episode =\< 3 months prior to first dose of protocol-indicated treatment) * Myocardial infarction within 3 months prior to starting treatment * Subjects with central nervous system (CNS) metastases are eligible after they have completed local therapy (e.g., whole brain radiation therapy \[WBRT\], surgery or radiosurgery) * Any condition requiring systemic treatment with either systemic corticosteroids (\> 10 mg/day prednisone or equivalent daily) or other immunosuppressive medications within 14 days prior to initiating protocol-indicated treatment * In the absence of active autoimmune disease: Subjects are permitted the use of corticosteroids with minimal systemic absorption (e.g., topical, ocular, intra-articular, intranasal, and inhalational), =\< 10 mg/day prednisone or equivalent daily; and physiologic replacement doses of systemic corticosteroids =\< 10 mg/day prednisone or equivalent daily (e.g., hormone replacement therapy needed in patients with hypophysitis)

Interventions: DRUG: Cabozantinib, BIOLOGICAL: Ipilimumab, BIOLOGICAL: Nivolumab

Conditions: Advanced Clear Cell Renal Cell Carcinoma, Metastatic Clear Cell Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Kidney

Sites: UT Southwestern

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Testing of Tazemetostat in Combination With Topotecan and Pembrolizumab in Patients With Recurrent Small Cell Lung Cancer

Description:

This phase I trial tests the safety, side effects, and best dose of tazemetostat in combination with topotecan and pembrolizumab in treating patients with small cell lung cancer that has come back after a period of improvement (recurrent). Tazemetostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving tazemetostat in combination with topotecan and pembrolizumab may shrink or stabilize recurrent small cell lung cancer.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Jonathan Dowell

Gender: ALL

Age: 18 Years and over

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05353439

IRB Number: STU-2023-0503

Show full eligibility criteria

Inclusion Criteria:

* Patients enrolled to the primary cohort must have limited- or extensive-disease SCLC at diagnosis, with relapse at study entry with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, and with prior therapy with platinum doublet. Patients with extensive stage disease should have received chemo-immunotherapy. Both platinum-sensitive and platinum-resistant patients will be included * Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of pembrolizumab in combination with tazemetostat and topotecan in patients \< 18 years of age, children are excluded from this study * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 70%) * Leukocytes \>= 3000/mcL * Absolute neutrophil count \>= 1,500/mcL * Platelets \>= 100,000/mcL * Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L * Total bilirubin =\< 1.5 institutional upper limit of normal (ULN) OR direct bilirubin =\< ULN for patients with total bilirubin levels \> 1.5 × ULN * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN * Creatinine =\< 1.5 institutional ULN OR glomerular filtration rate (GFR) \>= 60 mL/min/1.73 m\^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m\^2 * Note: Creatinine clearance (CrCl) should be calculated per institutional standard. Glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl * International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants * Activated (a)PTT =\< 1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load (CD4 count of greater than 250 cells/mcL) within 6 months are eligible for this trial. They must not be receiving prophylactic therapy for an opportunistic infection * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * 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 * Patients with treated brain metastases are eligible if they are symptomatically stable while off steroid therapy for a minimum of 7 days * Patients should be class 2B or better on the New York Heart Association Functional Classification * Ability to understand and the willingness to sign a written informed consent document * The effects of pembrolizumab and tazemetostat on the developing human fetus are unknown. For this reason and because monoclonal antibodies, EZH2 inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study treatment and for 6 months after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of study treatment administration

Exclusion Criteria:

* Patients who have had chemotherapy, immune checkpoint inhibitors, or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. * Note: Patients who have had palliative radiotherapy may be included as long as they have recovered from any radiotherapy related adverse events (allow at least 3 days between radiotherapy completion and study treatment) * Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1). * Note: Patients with =\< grade 2 neuropathy or =\< grade 2 alopecia are an exception to this criterion and may qualify for the study * Note: If patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy * Untreated immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the study principal investigator (PI) * Patients who are receiving any other investigational agents * Patients with symptomatic brain metastasis are not eligible due to their extremely poor prognosis and since it is unclear whether the investigational agent penetrates the blood-brain barrier. However, subjects who have had treatment for their brain metastasis and are symptomatically stable while off steroid therapy for a minimum of 7 days may be enrolled. The use of physiologic doses of corticosteroids may be approved after consultation with the study PI * History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab and tazemetostat or other agents used in study * Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment * Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis * Patients with uncontrolled intercurrent illness but not limited to, ongoing or active infection, interstitial lung disease or active, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Patients with psychiatric illness/social situations that would limit compliance with study requirements * Pregnant women are excluded from this study because pembrolizumab as a monoclonal antibody, and tazemetostat as a EZH2 inhibitor may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pembrolizumab or tazemetostat, breastfeeding should be discontinued if the mother is treated with these agents and for 1 week after the last dose of tazemetostat. These potential risks may also apply to other agents used in this study * Has known active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C * Has received a live vaccine within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted * Has thrombocytopenia, neutropenia, or anemia of grade \>= 3 (per Common Terminology Criteria for Adverse Events \[CTCAE\] 5.0 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS) * Has abnormalities known to be associated with MDS (e.g. del 5q, chromosome \[chr\] 7 abnormality \[abn\]) and myeloproliferative neoplasm (MPN) (e.g. JAK2 V617F) observed in cytogenetic testing and DNA sequencing * Has a prior history of T-cell lymphoblastic lymphoma (T-LBL), T-cell acute leukemia (T-ALL) or B-cell acute lymphoblastic leukemia (B-ALL)

Interventions: PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, BIOLOGICAL: Pembrolizumab, DRUG: Tazemetostat Hydrobromide, DRUG: Topotecan Hydrochloride

Conditions: Extensive Stage Lung Small Cell Carcinoma, Limited Stage Lung Small Cell Carcinoma, Platinum-Resistant Lung Small Cell Carcinoma, Platinum-Sensitive Lung Small Cell Carcinoma, Recurrent Extensive Stage Lung Small Cell Carcinoma, Recurrent Lung Small Cell Carcinoma, Lung/Thoracic

Sites: UT Southwestern

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Clinical Trial to Evaluate the Safety and Efficacy of DWN12088 in Patients With IPF

Description:

This is a randomized, double-blinded, placebo-controlled multicenter study to evaluate the safety and efficacy of DWN12088 in patients with Idiopathic Pulmonary Fibrosis.

Contact(s):

Call 214-648-5005
studyfinder@utsouthwestern.edu, YU.WANG@UTSouthwestern.edu

Principal Investigator: John Fitzgerald

Gender: ALL

Age: 40 Years and over

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05389215

IRB Number: STU-2023-0864

Show full eligibility criteria

Interventions: DRUG: DWN12088, DRUG: Placebo

Conditions: Idiopathic Pulmonary Fibrosis, Lung/Thoracic

Sites: UT Southwestern

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A Study of Treatment for Medulloblastoma Using Sodium Thiosulfate to Reduce Hearing Loss

Description:

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.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Daniel Bowers

Gender: ALL

Age: 4 Years to 21 Years old

Phase: PHASE3

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05382338

IRB Number: STU-2023-0231

Show full eligibility criteria

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

Interventions: 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

Conditions: Childhood Medulloblastoma, Brain and Nervous System

Sites: Children’s Health

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Validation of Early Prognostic Data for Recovery Outcome After Stroke for Future, Higher Yield Trials (VERIFY)

Description:

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.

Contact(s):

Call 214-648-5005
studyfinder@utsouthwestern.edu, HEATHER.PAUP@UTSOUTHWESTERN.EDU

Principal Investigator: Benjamin Nguyen

Gender: ALL

Age: 18 Years and over

Phase:

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05338697

IRB Number: STU-2021-1134

Show full eligibility criteria

Inclusion Criteria:

• Age 18 years or older
• Unilateral symptomatic stroke due to ischemia. (Note: Bilateral acute stroke is permitted if the stroke that is contralateral to the index stroke is asymptomatic).
• Motor deficits in the acutely affected UE, defined as a Shoulder Abduction and Finger Extension (SAFE) score ≤ 8 out of 10 points20,61 (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). a. Please note that, if significant imbalance is observed in SAFE score or MEP+ rates, the enrollment threshold for SAFE score may be updated with a formal study memo.
• Provision of signed and dated informed consent form within 24 to 96 hours of stroke onset, (or time last known well). Note: Participant is considered "enrolled" upon starting TMS (at least one stimulation is delivered) or starting study-specific MRI pulse sequence (at least one MRI beep occurs)
• Stated willingness to comply with all study procedures and availability for the duration of the study, including Day 90 visit which must occur in-person.
• Fluent in study approved languages (i.e., English or Spanish)

Exclusion Criteria:

• UE injury or conditions on paretic side that limited use prior to the stroke
• Legally blind
• Dense sensory loss on paretic side indicated by a score of 2 on NIHSS sensory item
• Unable to abduct the shoulder or extend the fingers of the non-paretic UE on verbal command
• Isolated cerebellar stroke
• Symptomatic stroke in any location within 30 days prior to index stroke.
• 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 (certain metallic implants, metallic foreign bodies or severe claustrophobia)
• Contraindication to TMS
• Implanted electronic cardiac devices (e.g., Automatic Implantable Cardioverter-Defibrillator \[AICD\] or pacemaker)
• Any 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)
• Ferromagnetic intracranial metallic implant
• 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
• Anticipated inability to perform study procedures within 168 hours of symptom onset
• Unable to perform behavioral assessments within 48-120 hours of symptom onset (or time last known well).
• Unable to receive TMS within 72-168 hours or get MRI within 48-168 hours of symptom onset (or time last known well).

Interventions: DIAGNOSTIC_TEST: Transcranial Magnetic Stimulation (TMS)

Conditions: Stroke, Stroke, Acute, Stroke, Ischemic, Brain and Nervous System, Other

Keywords: VERIFY

Sites: UT Southwestern

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Impact of Intensive Treatment of SBP on Brain Perfusion, Amyloid, and Tau (IPAT Study) (IPAT)

Description:

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.

Contact(s):

Call 214-648-5005
studyfinder@utsouthwestern.edu, Margaret.Mcgregor@UTSouthwestern.edu

Principal Investigator: Rong Zhang

Gender: ALL

Age: 60 Years to 85 Years old

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05331144

IRB Number: STU-2021-1210

Show full eligibility criteria

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.

Interventions: DRUG: Angiotensin II Receptor Blockers (ARBs, losartan) and Calcium Channel Blockers (CCB, amlodipine), OTHER: PCP

Conditions: Cognitively Normal Older Adults, Hypertension, Subjective Cognitive Decline, Family History of Dementia, Brain and Nervous System

Keywords: Dementia, Alzheimer's Disease, Cognitive Function, Blood Pressure, Amyloid, Tau

Sites: UT Southwestern

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Testing the Addition of Stereotactic Radiation Therapy With Immune Therapy for the Treatment of Patients With Unresectable or Metastatic Renal Cell Cancer, SAMURAI Trial (SAMURAI)

Description:

This phase II trial tests whether the addition of radiation to the primary tumor, typically given with stereotactic ablative radiation therapy (SABR), in combination with standard of care immunotherapy improves outcomes in patients with renal cell cancer that is not recommended for surgery and has spread from where it first started (primary site) to other places in the body (metastatic). Radiation therapy uses high energy photons to kill tumor cells and shrink tumors. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses of radiation over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, avelumab, and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib, cabozantinib, and lenvatinib are in a class of medications called antiangiogenic agents. They work by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving SABR in combination with standard of care immunotherapy may help shrink or stabilize the cancer in patients with renal cell cancer.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Raquibul Hannan

Gender: ALL

Age: 18 Years and over

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05327686

IRB Number: STU-2023-0448

Show full eligibility criteria

Inclusion Criteria:

* Pathologically (histologically or cytologically) proven diagnosis of renal cell carcinoma prior to registration * Node-positive unresectable (TxN1Mx) or metastatic (TxNxM1) based on the following diagnostic workup: * History/physical examination within 45 days prior to registration * CT/magnetic resonance imaging (MRI) of the chest/abdomen/pelvis within 45 days prior to registration * Patients must have IMDC intermediate (1-2 factors) or poor risk disease (\>= 3 factors) * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial * Patients with measurable disease (node positive or metastatic) as defined by RECIST version 1.1 excluding the primary renal tumor * Patient not recommended for or refused immediate cytoreductive nephrectomy * Candidate for standard of care therapy with either immuno-oncology (IO)-IO or IO-VEGF combination regimen * Primary renal tumor measuring 20 cm or less in anterior to posterior dimension only on axial imaging * Age \>= 18 * Karnofsky performance status \>= 60 within 45 days prior to registration * Hemoglobin \>= 8 g/dL (transfusions are allowed) (within 45 days prior to registration) * Platelet count \>= 50,000/mm\^3 (within 45 days prior to registration) * Absolute neutrophil count (ANC) \>= 1500/mm\^3 (within 45 days prior to registration) * Calculated (Calc.) creatinine clearance \>= 30 mL/min (within 45 days prior to registration) * Creatinine clearance (CrCl) \>= 30 mL/min estimated by Cockcroft-Gault Equation * For African American patients specifically whose renal function is not considered adequate by the formula above, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) should be used for calculating the related estimated glomerular filtration rate (GFR) with a correction factor for African American race creatinine clearance for trial eligibility, where GFR \>= 30 mL/min/1.73m\^2 will be considered adequate * Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL) (within 45 days prior to registration) * Aspartate aminotransferase and alanine aminotransferase (AST and ALT) =\< 3 x upper limit of normal (ULN) or \< 5 x ULN if hepatic metastases present (within 45 days prior to registration) * Patients with known human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Testing is not required for entry into protocol * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load * The patient must agree to use a highly effective contraception, including men with vasectomies if they are having sex with a woman of childbearing potential or with a woman who is pregnant, while on study drug and for 6 months following the last dose of study drug. 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 * 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

Exclusion Criteria:

* Patients with planned treatment of all metastatic disease with definitive therapy including either surgery, ablative (non-palliative) doses of radiation, or intervention of some type (definitive interventional radiology techniques) to ALL metastatic sites rendering the patient without extra-renal measurable disease. Patients NOT planned for definitive treatment of all metastatic sites are eligible. Lesions radiated palliatively are not eligible for response assessment * Patients with untreated or unstable brain metastases or cranial epidural disease * Note: Patients who have been adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator are eligible. Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator * Prior radiotherapy to the kidney that would result in overlap of radiation therapy fields treatment of the primary tumor * Any systemic therapy for metastatic renal cell carcinoma (RCC) that was initiated \> 90 days before registration, note that prior chemotherapy for a different cancer is allowed (completed \> 3 years prior to registration) * Severe, active comorbidity defined as follows: * Active autoimmune disease requiring ongoing therapy including systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications daily. Inhaled steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease * History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies * Active tuberculosis (purified protein derivative \[PPD\] response without active tuberculosis \[TB\] is allowed) * Uncontrolled hypertension (systolic blood pressure \[BP\] \>= 190 mmHg or diastolic BP \> 110 mmHg) * Major surgery requiring hospital admission =\< 28 days prior to registration * Any serious (requiring hospital stay or long term rehab) non-healing wound, ulcer, or bone fracture within 45 days prior to registration * Any arterial thrombotic (ST elevation myocardial infarction \[STEMI\], non-ST elevation myocardial infarction \[NSTEMI\], cerebrovascular accident \[CVA\], etc) events within 180 days prior to registration * Active New York (NY) Heart Association class 3-4 heart failure symptoms * Moderate or severe hepatic impairment (Child-Pugh B or C) * Any history of untreated pulmonary embolism or deep venous thrombosis (DVT) within 180 days prior to registration. (Any asymptomatic or treated pulmonary embolism or asymptomatic treated deep venous thrombosis \> 30 days prior to registration is allowed) * Unstable cardiac arrhythmia within 180 days prior to registration * History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to registration * History of or active inflammatory bowel disease * Malabsorption syndrome within 45 days prior to registration * Pregnancy and individuals unwilling to discontinue nursing. For women of child bearing potential must have a negative pregnancy test =\< 45 days prior to registration

Interventions: BIOLOGICAL: Avelumab, DRUG: Axitinib, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, DRUG: Cabozantinib, PROCEDURE: Computed Tomography, BIOLOGICAL: Ipilimumab, DRUG: Lenvatinib, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Nivolumab, BIOLOGICAL: Pembrolizumab, RADIATION: Stereotactic Ablative Radiotherapy

Conditions: Metastatic Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Unresectable Renal Cell Carcinoma, Kidney

Sites: UT Southwestern; Parkland Health & Hospital System

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Phase 2/3 Adaptive Study of VX-147 in Adult and Pediatric Participants With APOL1- Mediated Proteinuric Kidney Disease (AMPLITUDE)

Description:

The purpose of this study is to evaluate the efficacy, safety, tolerability, and pharmacokinetics (PK) of VX-147 in adult and pediatric participants with apolipoprotein L1 (APOL1)-mediated proteinuric kidney disease.

Contact(s):

Call 214-648-5005
studyfinder@utsouthwestern.edu, ZHENGNAN.WANG@UTSouthwestern.edu

Principal Investigator: Robert Toto

Gender: ALL

Age: 10 Years to 65 Years old

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05312879

IRB Number: STU-2023-1084

Show full eligibility criteria

Interventions: DRUG: VX-147, DRUG: Placebo

Conditions: Proteinuric Kidney Disease

Keywords: APOL1-mediated kidney disease (AMKD)

Sites: UT Southwestern; Parkland Health & Hospital System

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Neoadjuvant Lenvatinib and Pembrolizumab for IVC Tumor Thrombus

Description:

This study will be evaluating safety and efficacy of the combination of lenvatinib and pembolizumab neoaadjuvant therapy prior to surgical resection of locally advanced renal cell carcinoma with IVC tumor thrombus.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Vitaly Margulis

Gender: ALL

Age: 18 Years and over

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05319015

IRB Number: STU-2021-1240

Show full eligibility criteria

Inclusion Criteria:

• Male/female participants who are at least 18 years of age on the day of signing informed consent
• Have histologically confirmed cT3-4,N0-1,M0-1 (clinical stage III-IV) diagnosis of renal cell carcinoma (any subtype) with level II-IV inferior vena cava tumor thrombus as per the Mayo classification of macroscopic venous invasion in renal cell carcinoma:
• Level 1 tumor thrombus is either at the entry of renal vein or within the IVC \< 2 cm from the confluence of renal vein and IVC
• Level II tumor thrombus extends within the IVC \> 2 cm above the confluence of renal vein and IVC, but still remains below the hepatic veins.
• Level III tumor Thrombus involves the intrahepatic IVC.
• Level IV tumor thrombus extends above diaphragm or into the right atrium.
• The primary tumor and thrombus may be assessed to be resectable or unresectable at the time of enrollment.
• Male participants: A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the 120 day neoadjuvant treatment period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period. Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 30 days after the last dose of study treatment.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 14 days prior to the first dose of study intervention.
• Criteria for known Hepatitis B and C positive subjects Hepatitis B and C screening tests are not required unless: * Known history of HBV or HCV infection * As mandated by local health authority Hepatitis B positive subjects: Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization. Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. Hepatitis C positive subjects: Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening.
• Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization
• HIV-positive participants may be enrolled.
• HIV-infected participants must have well-controlled HIV on ART, defined as: 1\. Participants on ART must have a CD4+ T-cell count ≥350 cells/mm3 at the time of screening 2. Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening 3. It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months. 4\. Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (Day 1) and agree to continue ART throughout the study 5. The combination ART regimen must not contain any antiretroviral medications that interact with CYP3A4 inhibitors/inducers/substrates (https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers) 12\. Have adequate organ function as defined in the following table (Table 4). Specimens must be collected within 14 days prior to the start of study intervention.

Exclusion Criteria:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents prior to allocation.
• Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. COVID-19 vaccines are permitted provided they are not live attenuated vaccines.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention with the exception of participating in the exploratory imaging trial utilizing 89Zr-DFO-Atezolizumab ImmunoPET/CT (STU-2019-0714).
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past year. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical cancer, bladder in situ) that have undergone potentially curative therapy are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
• Has more than three different sites of metastatic renal cell carcinoma.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and lenvatinib and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
• Has had an allogenic tissue/solid organ transplant.
• Has prolongation of QTcF interval to \>480 ms.
• Has a left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO).
• Patients with an ejection fraction (LVEF) of 50 or greater are eligible to enroll on the study
• Patients with an ejection fraction (LVEF) of 40 to 49 are eligible to enroll on the study if they they DO NOT have signs of New York Heart Association Class III or IV congestive heart failure: i. NYHA Class III signs of congestive heart failure include marked limitation of physical activity - ordinary activity or movements cause significant fatigue, heart palpitations, or shortness of breath ii. NYHA Class IV signs of congestive heart failure include being unable to carry out physical activity without discomfort, having symptoms of heart failure at rest, if physical activity or movement is undertaken, discomfort increase c. Patients with an ejection fraction (LVEF) of 39 or less are not eligible to enroll on the study.
• Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted.
• If urinalysis reveals proteinuria of 2+ or 500mg/dL greater based on the scale below, the patient will need to undergo a 24 hour urine collection, if the patient has 2000mg/24 hour or great of protein in the 24 hour the urine collection they are NOT ELIGIBLE for the study. If urinalysis protein is negative, trace, 1+, or urinalysis protein is reported in the range 0-499mg/dL protein, the patient IS ELIGIBLE to enroll on the study and does not need to complete a 24 hour urine collection:
• 1+ = 200 - 500 mg/24 hours
• 2+ = 500 - 1500 mg/24 hours
• 3+ = over 2500 mg/24 hours
• 4+ = over 3000 mg/24 hours.
• Uncontrolled blood pressure defined as consistently elevated blood pressure with a Systolic BP\>140 mmHg or diastolic BP \>90 mmHg in spite of an optimized regimen of antihypertensive medication are not able to enroll on the study. However, patients with borderline, isolated, or occasional elevation of blood pressure readings are eligible to enroll on the trial. If the treating physician believes the blood pressure elevation is transient the patient may enroll and blood pressure will be monitored during the study. Patients with persistent hypertension may be initiated on antihypertensive medication by the treating physician if deemed necessary and may enroll on the study. The treating physician may also adjust antihypertensive medication in the attempt to achieve a normal blood pressure while the patient is in screening and on study. It is at the discretion of the enrolling physician to continue adjusting the hypertension medication while the patient is enrolled and treated on the study to maintain adequate blood pressure readings.
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
• Patients with active Hepatitis B infection (defined as HBsAg positive and/or detectable HBV DNA).
• Patients with active Hepatitis C infection (defined as anti-HCV Ab positive and detectable HCV RNA).
• Hepatitis B and C screening tests are not required unless there is a known history of HBV and HCV infection or as mandated by local health authority.

Interventions: DRUG: Neoadjuvant Lenvatinib, DRUG: Neoadjuvant Pembrolizumab, PROCEDURE: Radical nephrectomy, IVC thrombectomy, retroperitoneal lymph node dissection, DRUG: Adjuvant Pembrolizumab

Conditions: Renal Cell Carcinoma, Kidney, Cardiovascular

Keywords: Renal Cell Carcinoma, IVC tumor thrombus, Neoadjuvant therapy, Immunotherapy, Nephrectomy

Sites: UT Southwestern

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SIGMA (Safusidenib in IDH1 Mutant Glioma Maintenance) (SIGMA)

Description:

This is a 3-part study. The purpose of Part 1 of the study is to evaluate the efficacy, safety, and pharmacokinetic (PK) characteristics of safusidenib in participants with recurrent/progressive IDH1-mutant World Health Organization (WHO) Grade 2 or Grade 3 glioma. The purpose of Part 2 will be to evaluate the efficacy of maintenance safusidenib treatment versus placebo in IDH1-mutant Grade 2 or Grade 3 astrocytoma with high-risk features or IDH1-mutant Grade 4 astrocytoma, following standard-of-care radiation or chemoradiation and adjuvant temozolomide. Part 2 will be randomized, double-blind, and placebo-controlled. The purpose of Part 3 will be to evaluate the efficacy of safusidenib in participants with residual or recurrent IDH1-mutant Grade 3 oligodendroglioma who have received surgery as their only treatment. Part 3 will be an open-label single-arm cohort and will enroll participants concurrently with Part 2.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Michael Youssef

Gender: ALL

Age: 18 Years to old

Phase: PHASE3

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05303519

IRB Number: STU20251570

Show full eligibility criteria

Key Inclusion Criteria for Part 1:
• Patient must be ≥ 18 years of age at the time of signing the informed consent form (ICF).
• Patient must have histologically confirmed recurrent or progressive WHO Grade 2 glioma or Grade 3 glioma with IDH1 R132H or R132C mutation confirmed by immunohistochemistry or molecular genetic testing.
• The IDH mutation, and other applicable gene/molecular alterations (see Table 10-2) are determined by a validated assay as performed in Clinical Laboratory Improvement Amendments (CLIA)-certified/College of American Pathologists (CAP)-accredited or locally equivalent clinical laboratories. Prior clinical pathology report fulfilling the diagnosis criteria prior to screening with tumor samples collected is acceptable for patient enrollment in both Part 1 and Part 2.
• Patient has received no more than 2 prior therapies for disease recurrence/progression.
• Patient has disease recurrence or progression or cannot tolerate the most recent therapy.
• Patient must have a measurable lesion(s) as per the RANO-HGG criteria for primarily enhancing lesions or RANO-LGG criteria for primarily non-enhancing lesions. The lesion (s) must be visible on 2 or more axial slices and have perpendicular diameters of at least 10 × 10 mm. The definition of primarily enhancing lesions or primarily non-enhancing lesions is referred to Section 8.3.1. Key Inclusion Criteria for Part 2 and 3:
• Must be ≥18 years old at the time of signing the ICF.
• Must agree to submit sufficient tumor tissue for retrospective biomarker and histological analyses. This requirement may be waived in rare circumstances with approval by the Sponsor.
• Has adequate hematologic and organ function Key Inclusion Criteria for Part 2:
• Diagnosis of histologically confirmed IDH1-mutant Grade 2, Grade 3 with high risk features or Grade 4 astrocytoma, per WHO 2021 classification and Investigator Assessment.
• Have an IDH1 mutation (R132H/C/G/S/L) based on IHC (R132H only), polymerase chain reaction (PCR), or next-generation sequencing (NGS). CDKN2A/B status and at least 1 of the following must be confirmed: absence of 1p19q co-deletion by fluorescence in situ hybridization, array comparative genomic hybridization, or NGS; presence of an ATRX loss of function mutation by NGS; or loss of normal ATRX expression by IHC. A validated assay performed in a CLIA-certified/CAP-accredited (or local equivalent) clinical laboratory must be used for all of the aforementioned results. Documentation of biomarker status, including redacted molecular pathology and NGS reports, must be provided during Screening.
• Must not have experienced tumor recurrence or progression between first day of radiotherapy and randomization by local assessment per RANO 2.0.
• Participants must have completed radiation therapy with a minimum of 80% of planned treatment completed (with or without concurrent temozolomide) and between 6 and 12 cycles of adjuvant . Randomization must occur at least 28 days and not more than 75 days after the final dose of temozolomide. Key Inclusion Criteria for Part 3:
• Have had at least 1 prior surgery for glioma (biopsy, sub-total resection, or gross total resection), with the most recent surgery having occurred at least 90 days and no longer than 5 years before the date of enrollment, have not had any other prior anticancer therapy, including chemotherapy and radiotherapy, and are not in need of immediate chemotherapy or radiotherapy in the opinion of the Investigator.
• Have histologically confirmed Grade 3 IDH-mutant oligodendroglioma according to WHO 2021 criteria per local assessment.
• Have residual or recurrent measurable disease per RANO 2.0 and confirmed by BICR, at the time of enrollment.
• Have an IDH1 mutation (R132H/C/G/S/L). The presence of 1p19q co-deletion must also be confirmed. All results must be generated using a validated assay performed in a CLIA-certified/CAP-accredited (or local equivalent) clinical laboratory. Key Exclusion Criteria for Part 1:
• Prior anti-cancer therapy, within the applicable periods shown below, before the start of the protocol treatment:
• Systemic drug therapies: within 3 weeks (lomustine within 6 weeks)
• Surgery: within 3 weeks
• Radiation therapy: within 12 weeks
• Investigational agents: within 5 half-lives for other investigational agents
• Patient did receive the prior therapy targeted to IDH1 mutation..
• Known hypersensitivity to safusidenib or to any drug with similar chemical structure or to any other excipient present in the pharmaceutical form of safusidenib. Key Exclusion Criteria for Part 2 and 3:
• Participants with prior or anticipated treatment with anti-angiogenic agents such as Avastin (bevacizumab), agents known to target IDH1 or IDH2, or investigational agents for glioma are excluded.
• Have brainstem or spinal cord involvement either as primary location, site of multifocal involvement, or by significant tumor extension.
• Significant functional or neurocognitive deficits, including uncontrolled seizures, that would preclude participation in protocol-defined study activities, as assessed by Investigator.
• Evidence of diffuse leptomeningeal disease.
• History of significant cardiac disease within 12 months prior to randomization (if applicable) or first dose of study drug (if randomization does not apply).
• If taking corticosteroids, must be on a stable or decreasing dose for the 14 days prior to randomization (if applicable) or first dose of study drug (if randomization does not apply).
• Participants with other malignancies must have received curative treatment and been disease-free for at least 3 years. Curatively resected skin cancer or curatively treated carcinoma in situ is allowed.
• Have a condition that would interfere with, or increase the risk of, study participation. Key Exclusion Criteria for Part 2 1. Participants may not have received any anticancer treatments other than surgery, radiation, concurrent/adjuvant temozolomide, and tumor-treating fields. Tumor-treating fields must be discontinued prior to randomization. Key Exclusion Criteria for Part 3: 1\. Participants may not have received any prior anticancer therapy other than surgery (biopsy, sub-total, or gross total resection) for treatment of glioma, including radiotherapy.

Interventions: DRUG: safusidenib, DRUG: Placebo

Conditions: Glioma, Astrocytoma, Grade IV, IDH1-mutant Glioma, Astrocytoma, IDH-Mutant, Grade 3, Astrocytoma, IDH-Mutant, Grade 4, Astrocytoma, IDH-Mutant, Grade 2, Oligodendroglioma, Oligodendroglioma, IDH-Mutant and 1p/19q-Codeleted, Brain and Nervous System

Keywords: safusidenib, IDH1-mutant glioma, astrocytoma

Sites: UT Southwestern

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Ocrelizumab Discontinuation in Relapsing Multiple Sclerosis (AMS05)

Description:

This study is a prospective, multi-center, randomized, double blinded, placebo-controlled study of OCR treatment-discontinuation in patients with early RMS. All eligible participants will be initiated on OCR using the standard approved administration schedule of two 300 mg infusions separated by 14 days (i.e., Days 0 and 14) for a total of 600 mg, followed by 600 mg infusions at Month 6,12, 18, and 24. At Month 24, participants will be randomized (2:1) to one of two Arms with randomized treatment beginning at Month 30: Arm 1: placebo infusions every 6 months; or Arm 2: OCR infusions every 6 months. The treatment period will be for a total of 48 months.

Contact(s):

Call 214-648-5005
studyfinder@utsouthwestern.edu, Manuel.Huichapa@UTSouthwestern.edu

Principal Investigator: Benjamin Greenberg

Gender: ALL

Age: 18 Years to 55 Years old

Phase: PHASE4

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05285891

IRB Number: STU-2022-1218

Show full eligibility criteria

Inclusion Criteria:

• Have at least one clinical episode that satisfies McDonald 2017 criteria for early Multiple sclerosis (MS) with a dissemination in time that can be met clinically, by Magnetic Resonance Imaging (MRI), or based on oligoclonal band (OCB) positivity
• Have a length of disease duration, from first symptom, of ≤ 3 years at time of informed consent
• For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use effective methods of contraception during the treatment period and for at least 6 months after the last dose of study drug:
• A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus)
• Examples of contraceptive methods include bilateral tubal ligation, male sterilization, established hormonal contraceptives that inhibit ovulation, hormone- releasing intrauterine devices, and copper intrauterine devices
• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception
• Barrier methods must always be supplemented with the use of a spermicide

Exclusion Criteria:

• Inability or unwillingness of a participant to give written informed consent or comply with study protocol
• History of primary progressive multiple sclerosis (PPMS), progressive relapsing multiple sclerosis (PRMS), or secondary progressive multiple sclerosis (SPMS)
• Any metallic material or electronic device in the body, or condition that precludes the participant from undergoing MRI
• Known presence or history of other neurological disorders, including but not limited to the following: * Ischemic cerebrovascular disorders, including but not limited to transient ischemic attack, subarachnoid hemorrhage, cerebral thrombosis, cerebral embolism, or cerebral hemorrhage * CNS or spinal cord tumor, metabolic or infectious cause of myelopathy, genetically inherited progressive CNS disorder, CNS sarcoidosis, or systemic autoimmune disorders potentially causing progressive neurologic disease or affecting ability to perform the study assessments
• Pregnancy or lactation • Female participants of childbearing potential must have a negative urine pregnancy test at screening
• Any concomitant disease that may require chronic systemic treatment with corticosteroids or immunosuppressants during the course of the study
• Lack of peripheral venous access
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• Significant, inadequately controlled (e.g., diagnostic evaluations indicated or change in medications warranted) disease, such as cardiovascular (including cardiac arrhythmia), pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine, and gastrointestinal or any other significant disease that in the opinion of the investigator may preclude participant from participating in the study
• Functional status of New York Heart Association (NYHA) Class III or higher for heart failure at the screening visit
• Known active bacterial, viral, fungal, mycobacterial infection or other infection (including tuberculosis (TB) or atypical mycobacterial disease but excluding limited superficial fungal or viral infections of the skin or nails) or any severe episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to Mo 0/Day 0 infusion or oral antibiotics within 2 weeks prior to Mo 0/Day 0 infusion
• Active or chronic infection with human immunodeficiency virus (HIV), syphilis or TB (see laboratory tests below)
• Evidence of past hepatitis B (including treated hepatitis B) or untreated hepatitis C infection (treated hepatitis C is not considered exclusionary). Hepatitis B surface antibody following hepatitis B immunization is not considered to be evidence of past infection (see laboratory tests below).
• Known active malignancy or active monitoring for recurrence of malignancy, including solid tumors and hematological malignancies, except basal cell, in situ squamous cell carcinoma of the skin, and in situ carcinoma of the cervix or the uterus that have been excised with clear margins
• Substance use disorder, including the recurrent use of alcohol and/or drugs within the past year associated with clinically significant impairment associated with failure to meet major responsibilities at work, school, or home
• Receipt of live or live-attenuated vaccines within 4 weeks prior to Mo 0/Day 0 infusion
• Contraindications to or severe intolerance of oral or IV corticosteroids, including IV methylprednisolone administered according to the country label, including: * Psychosis not controlled by a treatment * Hypersensitivity to any of the constituents or excipients of the preceding steroids
• Current or prior treatment with the following MS DMTs: fingolimod and other S1P receptor modulators, cladribine, natalizumab, anti-CD20 molecules, alemtuzumab, and chemotherapeutic agents
• Treatment with fumarates within 30 days prior to collection of Mo 0/Day 0 mechanistic samples, Mo 0/Day 0 MRI, and Mo 0/Day 0 infusion
• (a) Current or prior treatment with any approved or experimental immunomodulatory therapies, unless reviewed and approved by the SAC (Section 3.6), or (b) Treatment with any experimental procedure for MS (e.g., treatment for chronic cerebrospinal venous insufficiency)
• Systemic corticosteroid therapy within 4 weeks prior to the collection of screening mechanistic samples and the screening MRI
• Systemic corticosteroid therapy within 4 weeks prior to the Mo 0/Day 0 infusion
• Screening laboratory test results as follows: * Positive infection screening tests for: i. Hepatitis B surface antigen (HbsAg) or hepatitis B core antibody (HbcAb) ii. Hepatitis C (HCV) antibody if positive screen for HCV RNA Polymerase Chain Reaction (PCR) iii. Rapid plasma reagin (RPR) * A reactive RPR test unless followed by a subsequent negative RPR OR * A reactive RPR test unless successful completion of treatment has been documented as well as a consultation with and clearance by infectious disease department iv. HIV v. At or within twelve months of screening: * Positive QuantiFERON®-TB Gold test or positive purified protein derivative tuberculin skin test (PPD) (\>5mm induration, regardless of Bacille Calmette-Guerin (BCG) vaccine administration) unless completion of treatment has been documented for active TB OR * An indeterminate QuantiFERON®-TB Gold test unless followed by a subsequent negative PPD or negative QuantiFERON®-TB Gold test as well as a consultation with and clearance by infectious disease department * Levels of serum immunoglobulin G (IgG) \< 3.3g/L * Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m2 using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 2.0 x the upper limit of normal (ULN) * Platelet count \< 100,000 plt/µL (\<100 x 10⁹/L) * Hemoglobin \< 10 g/dL * Absolute neutrophil count \< 1.5 x 10⁹/L * Absolute lymphocyte count \< 1.2 x 10⁹/L
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study.

Interventions: DRUG: Ocrelizumab, DRUG: Placebo for Ocrelizumab

Conditions: Multiple Sclerosis

Keywords: Ocrelizumab, Multiple sclerosis, Relapse

Sites: UT Southwestern

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Chemotherapy for the Treatment of Patients With Newly Diagnosed Very Low-Risk and Low Risk Fusion Negative Rhabdomyosarcoma

Description:

Rhabdomyosarcoma is a type of cancer that occurs in the soft tissues in the body. This phase III trial aims to maintain excellent outcomes in patients with very low risk rhabdomyosarcoma (VLR-RMS) while decreasing the burden of therapy using treatment with 24 weeks of vincristine and dactinomycin (VA) and examines the use of centralized molecular risk stratification in the treatment of rhabdomyosarcoma. Another aim of the study it to find out how well patients with low risk rhabdomyosarcoma (LR-RMS) respond to standard chemotherapy when patients with VLR-RMS and patients who have rhabdomyosarcoma with DNA mutations get separate treatment. Finally, this study examines the effect of therapy intensification in patients who have RMS cancer with DNA mutations to see if their outcomes can be improved.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Matthew Campbell

Gender: ALL

Age: up to 21 Years old

Phase: PHASE3

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05304585

IRB Number: STU-2022-0692

Show full eligibility criteria

Inclusion Criteria:

* All patients must be enrolled on APEC14B1 (NCT02402244) and consented to the Molecular Characterization Initiative (Part A) prior to enrollment and treatment on ARST2032 (this trial). * Patients must be =\< 21 years at the time of enrollment. * Patients must have newly diagnosed embryonal rhabdomyosarcoma (ERMS), spindle cell/sclerosing RMS, or FOXO1 fusion negative alveolar rhabdomyosarcoma (ARMS) (institutional FOXO1 fusion results are acceptable). RMS types included under ERMS include those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the 2020 World Health Organization (WHO) classification as ERMS (classic, dense and botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical spindle cell ERMS variant and the newly recognized sclerosing RMS variant). Enrollment in APEC14B1 is required for all patients. * All patients will be evaluated for stage and clinical group. Note that clinical group designation assigned at the time of enrollment on study remains unchanged regardless of any second-look operation that may be performed. * Patients will be eligible for the very low-risk stratum (Regimen VA) if they have Stage 1, CG I disease. * Patients will be eligible for the low-risk stratum (Regimen VAC/VA) if they have Stage 1, CG II disease, Stage 2, CG I or II disease, or Stage 1, CG III (orbit only) disease. * Paratesticular Tumors: Staging ipsilateral retroperitoneal lymph node sampling (SIRLNS) is required for all patients \>= 10 years of age with paratesticular tumors who do not have gross nodal involvement on imaging. * Extremity Tumors: Regional lymph node sampling is required for histologic evaluation in patients with extremity tumors. * Clinically or radiographically enlarged nodes must be sampled for histologic evaluation. * Patients must have a Lansky (for patients =\< 16 years of age) or Karnofsky (for patients \> 16 years of age) performance status score of \>= 50. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing performance score. * Peripheral absolute neutrophil count (ANC) \>= 750/uL (within 7 days prior to enrollment). * Platelet count \>= 75,000/uL (transfusion independent) (within 7 days prior to enrollment). * Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine (within 7 days prior to enrollment) based on age/gender as follows: * Age: 1 month to \< 6 months; Maximum serum creatinine (mg/dL): 0.4 (male) : 0.4 (female) * Age: 6 months to \< 1 year; Maximum serum creatinine (mg/dL): 0.5 (male) : 0.5 (female) * Age: 1 to \< 2 years; Maximum serum creatinine (mg/dL): 0.6 (male) : 0.6 (female) * Age: 2 to \< 6 years; Maximum serum creatinine (mg/dL): 0.8 (male) : 0.8 (female) * Age: 6 to \< 10 years; Maximum serum creatinine (mg/dL): 1 (male) : 1 (female) * Age: 10 to \< 13 years; Maximum serum creatinine (mg/dL): 1.2 (male) : 1.2 (female) * Age: 13 to \< 16 years; Maximum serum creatinine (mg/dL): 1.5 (male) : 1.4 (female) * Age \>= 16 years; Maximum serum creatinine (mg/dL): 1.7 (male) : 1.4 (female) * Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment), and * If there is evidence of biliary obstruction by the tumor, then the total bilirubin must be \< 3 x ULN for age. * Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L. * Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L * If there is evidence of biliary obstruction by the tumor, then the total bilirubin must be \< 3 x ULN for age * Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L * 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 who have received prior chemotherapy and/or radiation therapy for cancer prior to enrollment. Surgical resection alone of previous cancer(s) is permitted. * Patients who have received chemotherapy or radiation for non-malignant conditions (e.g., autoimmune diseases) are eligible. Patients must discontinue chemotherapy for non-malignant conditions prior to starting protocol therapy. * Vincristine is sensitive substrate of the CYP450 3A4 isozyme. Patients must not have received drugs that are moderate to strong CYP3A4 inhibitors and inducers within 7 days prior to study enrollment. * Patients unable to undergo radiation therapy, if necessary, as specified in the protocol. * Evidence of uncontrolled infection. * 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.

Interventions: PROCEDURE: Biopsy Procedure, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, BIOLOGICAL: Dactinomycin, PROCEDURE: Magnetic Resonance Elastography, PROCEDURE: Positron Emission Tomography, RADIATION: Radiation Therapy, DRUG: Vincristine

Conditions: Embryonal Rhabdomyosarcoma, Fusion-Negative Alveolar Rhabdomyosarcoma, Spindle Cell/Sclerosing Rhabdomyosarcoma, Sarcoma

Sites: Children’s Health

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