The study participant has been diagnosed with non-rhabdomyosarcoma (NRSTS). Primary Objectives Intermediate-Risk - To estimate the 3-year event-free survival for intermediate-risk patients treated with ifosfamide, doxorubicin, pazopanib, surgery, and maintenance pazopanib, with or without RT. - To characterize the pharmacokinetics of pazopanib and doxorubicin in combination with ifosfamide in intermediate-risk participants, to assess potential covariates to explain the inter- and intra-individual pharmacokinetic variability, and to explore associations between clinical effects and pazopanib and doxorubicin pharmacokinetics. High-Risk - To estimate the maximum tolerated dose (MTD) and/or the recommended phase 2 dosage (RP2D) of selinexor in combination with ifosfamide, doxorubicin, pazopanib, and maintenance pazopanib in high-risk participants. - To characterize the pharmacokinetics of selinexor, pazopanib and doxorubicin in combination with ifosfamide in high-risk participants, to assess potential covariates to explain the inter- and intra-individual pharmacokinetic variability, and to explore associations between clinical effects and selinexor, pazopanib and doxorubicin pharmacokinetics. Secondary Objectives - To estimate the cumulative incidence of primary site local failure and distant metastasis-free, disease-free, event-free, and overall survival in participants treated on the risk-based treatment strategy defined in this protocol. - To define and describe the CTCAE Grade 3 or higher toxicities, and specific grade 1-2 toxicities, in low- and intermediate-risk participants. - To study the association between radiation dosimetry in participants receiving radiation therapy and the incidence and type of dosimetric local failure, normal adjacent tissue exposure, and musculoskeletal toxicity. - To evaluate the objective response rate (complete and partial response) after 3 cycles for high-risk patients receiving the combination of selinexor with ifosfamide, doxorubicin, pazopanib, and maintenance pazopanib. - To assess the relationship between the pharmacogenetic variation in drug-metabolizing enzymes or drug transporters and the pharmacokinetics of selinexor, pazopanib, and doxorubicin in intermediate- or high-risk patients. Exploratory Objectives - To explore the correlation between radiographic response, pathologic response, survival, and toxicity, and tumor molecular characteristics, as assessed through next-generation sequencing (NGS), including whole genome sequencing (WGS), whole exome sequencing (WES), and RNA sequencing (RNAseq). - To explore the feasibility of determining DNA mutational signatures and homologous repair deficiency status in primary tumor samples and to explore the correlation between these molecular findings and the radiographic response, survival, and toxicity of patients treated on this protocol. - To explore the feasibility of obtaining DNA methylation profiling on pretreatment, post-induction chemotherapy, and recurrent (if possible) tumor material, and to assess the correlation with this and pathologic diagnosis, tumor control, and survival outcomes where feasible. - To explore the feasibility of obtaining high resolution single-cell RNA sequencing of pretreatment, post-induction chemotherapy, and recurrent (if possible) tumor material, and to characterize the longitudinal changes in tumor heterogeneity and tumor microenvironment. - To explore the feasibility of identifying characteristic alterations in non-rhabdomyosarcoma soft tissue sarcoma in cell-free DNA (cfDNA) in blood as a non-invasive method of detecting and tracking changes during therapy, and to assess the correlation of cfDNA and mutations in tumor samples. - To describe cardiovascular and musculoskeletal health, cardiopulmonary fitness among children and young adults with NRSTS treated on this protocol. - To investigate the potential prognostic value of serum cardiac biomarkers (high-sensitivity cardiac troponin I (hs-cTnI), N-terminal pro B-type natriuretic peptide (NT-Pro-BNP), serial electrocardiograms (EKGs), and serial echocardiograms in patients receiving ifosfamide, doxorubicin, and pazopanib, with or without selinexor. - To define the rates of near-complete pathologic response (>90% necrosis) and change in FDG PET maximum standard uptake value (SUVmax) from baseline to week 13 in intermediate risk patients with initially unresectable tumors treated with induction pazopanib, ifosfamide, and doxorubicin, and to correlate this change with tumor control and survival outcomes. - To determine the number of high-risk patients initially judged unresectable at diagnosis that are able to undergo primary tumor resection after treatment with ifosfamide, doxorubicin, selinexor, and pazopanib. - To identify the frequency with which assessment of volumes of interest (VOIs) of target lesions would alter RECIST response assessment compared with standard linear measurements.

Type: Interventional

Start Date: Mar 2024

open study

The goal of this project is to conduct a clinical trial in 60 participants ranging from age 65-95 who are at risk for age-related macular degeneration (AMD). The study will evaluate the effects of 14g of goji berry intake or an equivalent amount and type of fiber, five days a week for six months, on visual health, gut microbiome profiles, skin carotenoid measures, and lipoprotein profiles.

Type: Interventional

Start Date: Apr 2024

open study

This is a multicenter, global, 26-week, open-label study to assess the safety and tolerability of lumateperone in pediatric patients with schizophrenia, bipolar disorder or autism spectrum disorder.

Type: Interventional

Start Date: Jan 2024

open study

Researchers are looking for a better way to treat participants who have metastatic castration-resistant prostate cancer (mCRPC). mCRPC is a cancer of the prostate (male reproductive gland found below the bladder) that has spread to other parts of the body. This type of prostate cancer does not respond to hormone treatment used to lower the level of testosterone, a male sex hormone, to prevent cancer from growing. The study treatment 225Ac-PSMA-Trillium, also called BAY3563254, is under development to treat advanced metastatic castration-resistant prostate cancer. It works by binding to PSMA and giving off radiation that can damage cancer cells and stop them from growing. The main purpose of this first-in-human study is to learn: - How safe is BAY3563254 in participants. - What is the recommended dose of BAY3563254 that is safe and works well that will be further tested in Part 2 of the study. - How well does BAY3563254 work in participants. To answer this, the researchers will look at: - The number and severity of medical problems including serious medical problems that participants experience after taking BAY3563254 - The number of dose-limiting toxicities (DLT) at each dose level. A DLT is a medical problem caused by a drug that is too severe to continue the use of that specific dose. - The number of participants whose cancer completely disappears (complete response) or reduces by at least 30% (partial response) after taking the treatment (also known as objective response rate (ORR)) - The number of participants who have a decrease in the levels of PSA* by at least 50% in their blood (also known as PSA50). PSA is a protein made by the prostate gland. High levels of PSA may indicate the presence of prostate cancer. - Participants' best response to treatment based on their PSA levels (also known as the best overall PSA response). The study will have two parts. The first part, called dose escalation, is done to find the most appropriate dose of BAY3563254 for use in the second part of the study. For this, each participant will receive one of different increasing amounts of BAY3563254. They will take BAY3563254 as an injection into a vein. All participants in the second part of the study, called dose expansion, will receive the most appropriate dose of BAY3563254 that was identified from the first part of the study. Participants in this study will take the study treatment once every 6 or 8 weeks, which is known as a treatment cycle. Each participant will have up to 4 of these treatment cycles, if the participant benefits from the treatment. Each participant will be in the study for approximately 6 years, including a screening phase of up to 30 days, 6 months of treatment depending on the participant's benefit, and a follow up phase of 60 months after the end of treatment. In addition, substudies performed during both dose escalation and dose expansion parts of the study will evaluate: - the clearance of radioactivity from the body over time - the doses of radiation that are delivered to normal organs and tumors During the study, the doctors and their study team will: - take blood and urine samples - check vital signs such as blood pressure, heart rate, and body temperature - examine heart health using electrocardiogram (ECG) - take tumor samples if required - check if the participants' cancer has grown and/or spread using CT (computed tomography) or MRI (magnetic resonance imaging) and bone scan - check the tumor status using PET (positron emission tomography) - check the amount of radiation absorbed by tumors and normal organs using SPECT/CT (single-photon emission tomography and computed tomography scan) - ask the participants questions about how they are feeling and what adverse events they are having. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatments. In addition, the participants will be asked to complete a questionnaire on quality of life at certain time points during the study. The treatment period ends with a visit in 6-12 weeks after the last BAY3563254 dose. About 6-12 weeks after the last dose and every 6 weeks thereafter, the study doctors and their team will check the participants' health and any changes in their cancer. This active follow-up period ends after 18 months. The long-term follow-up period will start after the end of the active follow-up visit and will continue for up to 60 months after the the last BAY3563254 dose. Participants will be contacted, typically by phone call or clinic visit, approximately every 12 weeks after the end of active follow-up.

Type: Interventional

Start Date: Mar 2024

open study

This phase III trial tests the side effects of stereotactic body radiation therapy (SBRT) compared to hypofractionated radiotherapy for treating patients with prostate adenocarcinoma that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to a limited number of sites (oligometastatic). SBRT is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumors cells and have fewer side effects. SBRT may work just as well as hypofractionated radiation therapy at treating patients with biochemically recurrent or oligometastatic prostate cancer, but with a shorter treatment time and possibly fewer side effects.

Type: Interventional

Start Date: Jan 2024

open study

This study measures the utility of a novel artificial intelligence (AI) algorithm for performing auto-segmentation of computed tomography (CT) scans for radiation therapy planning.

Type: Observational

Start Date: Dec 2024

open study

The purpose of this study is to evaluate if a specific type of additional walking therapy, called body weight supported treadmill training (BWSTT) affects walking ability following a traumatic spinal cord injury. Specifically, the study will look at whether starting BWSTT, which uses a body harness to support body weight while walking on a treadmill at different times within the first 6 months after the injury, makes a difference in how effective this therapy may be, While we know that the brain re-learns patterns following an injury, there has not been a lot of prior research evaluating how starting this type of walking therapy at specific times within the first 6 months after injury may impact any effectiveness of the additional therapy. The study will randomize participants into four groups: those who start this therapy within 60 days, within 3 months, within 6 months or who do not receive this additional research therapy. Randomization means that which group you will be in as part of this study is determined by chance, like the flip of a coin. The additional walking therapy for this research study, if you are randomized for one of the three groups who receives the additional therapy, will be given on top of (meaning in addition to) any standard of care therapies that you may be receiving at that time point after your injury.

Type: Interventional

Start Date: Mar 2024

open study

This is a post-marketing single arm, phase IV trial in which patients with high-risk early-stage HR+HER2- breast cancer will receive adjuvant abemaciclib in combination with endocrine therapy (ET) After study intervention, participants will remain on combination abemaciclib + ET at the discretion of their treating providers

Type: Interventional

Start Date: Dec 2023

open study

This study will evaluate the safety and efficacy of R-DXd therapy in participants with ovarian, peritoneal, or fallopian tube cancer.

Type: Interventional

Start Date: Feb 2024

open study

Multiple myeloma (MM) is a cancer of the blood's plasma cells. The cancer is typically found in the bones and bone marrow (the spongy tissue inside of the bones) and can cause bone pain, fractures, infections, weaker bones, and kidney failure. Treatments are available, but MM can come back (relapsed) or may not get better (refractory) with treatment. This is a study to determine change in disease symptoms of etentamig compared to standard available therapies in adult participants with relapsed/refractory (R/R) MM. Etentamig is an investigational drug being developed for the treatment of R/R MM. This study is broken into 2 Arms; Arm A and Arm B. In Arm A, participants will receive etentamig as a monotherapy. In Arm B, participants will receive the standard available therapy (SAT) identified by the Investigator during screening, in accordance with the local (or applicable) approved label, package insert, summary of product characteristics, and/or the institutional guidelines, as applicable. Around 380 adult participants with relapsed/refractory multiple myeloma will be enrolled at approximately 140 sites across the world. In Arm A participants will receive etentamig as an infusion into the vein in 28 day cycles, during the 3.5 year study duration. In Arm B, participants will receive the SAT identified by the Investigator during screening, in accordance with the local (or applicable) approved label, package insert, summary of product characteristics, and/or the institutional guidelines, as applicable, during the 3.5 year study duration. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and questionnaires.

Type: Interventional

Start Date: May 2024

open study

The purpose of this study is to find out if giving radiation therapy (RT) to areas of metastatic prostate cancer at the time a participant is diagnosed will help control disease better than the usual treatment. This treatment is called metastasis-directed radiotherapy (MDRT). The usual treatment for prostate cancer that has spread to other parts of the body is to give lifelong treatment with hormone therapy (also known as androgen deprivation therapy or ADT). Participants may also be given prostate RT even if the disease is metastatic. Participants will receive hormone therapy (the standard treatment for prostate cancer) for 12 months. The hormone therapy agents may be taken by mouth or given as an injection. Participants will also have prostate RT. Up to 50 participants will have surgery to remove the prostate instead of having prostate RT. A portion of the participants will be randomized to receive MDRT to areas where the cancer has spread. For participants who have surgery to remove their prostate, they will be asked to allow tissue samples collected during the surgery to be sent to an outside lab for research tests and extra blood samples drawn for research tests before starting the study, and at the time the cancer becomes worse if applicable. Participation in the study will last approximately 12 months, and will be followed by their doctor for up to five years per standard of care. The main goal is to compare the efficacy of the standard of care (standard systemic therapy + definitive prostate-directed local therapy) versus the standard of care with metastasis-directed radiotherapy (MDRT) for consolidation of metastatic disease.

Type: Interventional

Start Date: Jul 2024

open study

This is a multicenter, open-label, non-randomized study to investigate the safety, tolerability, and efficacy of a single intravenous (IV) infusion of SGT-003 in participants with Duchenne muscular dystrophy. There will be 5 cohorts in this study. Cohort 1 will include participants 4 to < 7 years of age. Cohort 2 will include participants 7 to < 12 years of age. Cohort 3 will include participants 0 to < 4 years of age. Cohort 4 will include participants 12 to < 18 years of age. Cohort 5 will include participants 10 to < 18 years of age. Initiation of participant enrollment in Cohorts 4 and 5 will be subject to the accrual of safety and efficacy data from Cohorts 1-3. All participants will receive SGT-003 and will be enrolled in the study for 5 total years for long-term follow up.

Type: Interventional

Start Date: May 2024

open study

This clinical trial is studying advanced solid tumors. Solid tumors are cancers that start in a part of your body like your lungs or liver instead of your blood. Once tumors have grown bigger in one place but haven't spread, they're called locally advanced. If your cancer has spread to other parts of your body, it's called metastatic. When a cancer has gotten so big it can't easily be removed or has spread to other parts of the body, it is called unresectable. These types of cancer are harder to treat. Participants in this study must have cancer that has come back or did not get better with treatment. Participants must have a solid tumor cancer that can't be treated with standard of care drugs. This clinical trial uses an experimental drug called PF-08046050. PF-08046050 is a type of antibody-drug conjugate or ADC. ADCs are designed to stick to cancer cells and kill them. They may also stick to some normal cells. This study will test the safety of PF-08046050 in participants with solid tumors that are hard to treat or have spread throughout the body. This study has 5 different study parts. Part A and Part B of the study will find out how much PF-08046050 should be given to participants. Part C will use the information from Parts A and B to see if PF-08046050 is safe and if it works to treat certain solid tumor cancers. Part D and E of the study, together with information from Parts A and B, will find out how much PF-08046050 should be given in combination with other anti-cancer agents. Part E will use the information from Parts A, B, and D to see if PF-08046050 is safe in combination with other anti-cancer agents and if it works to treat a certain solid tumor.

Type: Interventional

Start Date: Nov 2023

open study

This phase II trial tests how well giving durvalumab with standard chemotherapy, gemcitabine and cisplatin, before surgery works in treating patients with high risk liver cancer (cholangiocarcinoma) that can be removed by surgery (resectable). Durvalumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving durvalumab with gemcitabine and cisplatin before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed in patients with high risk resectable cholangiocarcinoma.

Type: Interventional

Start Date: Jul 2024

open study

The mental health of adolescents in the United States has seen a steep decline, roughly coinciding with the increasing popularity of social media and smartphones. But does social media have a causal impact on the mental health of adolescents or are concerns about the effect of social media on kids a form of public hysteria? In this study, the investigators will conduct the first field experiment in 10-14-year-olds to examine whether, how, and for whom social media harms mental health.

Type: Interventional

Start Date: Sep 2024

open study

This is an exploratory natural history protocol that will enroll patients with known genetic diseases, such as VEXAS syndrome, or as yet undiagnosed disorders of inflammation with the goal of improving our understanding of disease processes. Blood, saliva, hair, nail, or buccal samples may be collected for genetic analysis, blood samples will be obtained for immunologic and other functional studies, and a small number of subjects may undergo skin biopsy.

Type: Observational

Start Date: Apr 2022

open study

The purpose of this study is to evaluate the clinical and endoscopic efficacy of guselkumab in pediatric participants with Crohn's Disease (CD) at the end of maintenance therapy (Week 52) among participants who were in clinical response to guselkumab at Week 12.

Type: Interventional

Start Date: Mar 2024

open study

The purpose of this study is to assess the long-term safety and to explore the efficacy of astegolimab in participants with chronic obstructive pulmonary disease (COPD) who have completed the 52-week placebo-controlled treatment period in parent studies GB43311 or GB44332.

Type: Interventional

Start Date: Jun 2023

open study

The COPE-AKI study is a randomized, pragmatic, parallel-arm trial comparing a multimodal intervention to usual care on hospital-free days through 90 days of study follow up. The primary study hypothesis is that patients randomized to the intervention will have increased odds of more hospital-free days through 90 days (primary clinical) compared to those randomized to usual care. Key secondary hypotheses will investigate the impact of the intervention on rates of major adverse kidney events, rates of recurrent AKI, and changes in patient-reported outcomes. Participants (N=2145) will be allocated 1:1 to the intervention or usual care using a web-based system to maintain allocation concealment using stratified randomization with randomly permuted blocks. Randomization will be stratified by clinical site.

Type: Interventional

Start Date: Sep 2023

open study

The researchers will conduct 'Taxi ROADmAP (Realizing Optimization Around Diet And Physical activity)', which also utilizes MOST, and the same 4 obesity intervention components as in SANOS, but targets the overweight/obesity crisis in another at-risk, low socioeconomic status (SES) population, taxi and for-hire vehicle (FHV) drivers (Lyft, Uber, etc.). ROADMAP also utilizes an effectiveness- implementation hybrid type 1 design. Hybrid trials, which blend effectiveness and implementation studies, can lead to more rapid translational uptake and more effective implementation. Taxi and FHV drivers are a growing, multilingual, hard-to-reach, predominantly immigrant and minority essential worker population. There are over 750,000 licensed taxi and FHV drivers in in the U.S. and over 185,000 in New York City (NYC). They have higher rates of overweight/obese range body mass index (BMI) than New Yorkers in general (77% vs 56%) and have high rates of elevated waist circumference, sedentary behavior, poor diets, and health care services underutilization. ROADmAP will test 4 evidence- and theory-based (Social Cognitive Theory [SCT]) behavior change intervention components. We will use MOST to identify which of the 4 components contribute most significantly and cost-effectively to weight loss among NYC drivers recruited at workplace health fairs (HFs) and virtually. Objectives are to apply MOST to design an optimized version of a scalable, lifestyle intervention for taxi/FHV drivers, and then to conduct a mixed methods multistakeholder process evaluation to facilitate widespread intervention implementation.

Type: Interventional

Start Date: Dec 2022

open study

This is a 1:1 randomized, open label, multi-center phase I/II trial to evaluate the safety, dosing, efficacy, and biological activity of adding IMNN-001 to chemotherapy + BEV compared to chemotherapy + BEV alone.

Type: Interventional

Start Date: Feb 2023

open study

The goal of this clinical trial is to test the effectiveness of the study drug, ORC-13361, in preventing hearing loss in patients with NTM infection who are undergoing treatment with IV amikacin therapy. The main question this study aims to answer is: - Is ORC-13661 effective for preventing or lessening hearing loss induced by amikacin treatment? - Is ORC-13661 effective for preventing or lessening other measures of hearing impairment? Participants will be asked to take a study drug while they are being treated with IV amikacin. Participants will take study drug for 90 days or until the end of their amikacin treatment, whichever comes first. During this time, researchers will gather clinical data on the participants' health. Researchers will compare three groups - two groups taking different doses of the study drug and one group taking a placebo drug - to see if dose of drug has any effect on preventing hearing loss. A placebo is a look-alike substance that contains no active drug.

Type: Interventional

Start Date: Jun 2025

open study

This phase I trial tests the safety, side effects, and best dose of combination therapy with liposomal doxorubicin and peposertib in treating patients with sarcoma that has spread from where it first started, to other places in the body (metastatic), or cannot be removed by surgery (unresectable) and for which no known cure is available (advanced). Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. It also blocks a certain enzyme needed for cell division and DNA repair. Liposomal doxorubicin is a form of the anticancer drug doxorubicin that is contained inside very tiny, fat-like particles. Liposomal doxorubicin may have fewer side effects and work better than other forms of the drug. Peposertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It may also enhance the activity of chemo- and radiotherapy. There is some pre-clinical evidence in animal models that combining peposertib with liposomal doxorubicin can shrink or stabilize certain types of cancer for longer than either drug alone, but it is not known if this will happen in people. Combination therapy with liposomal doxorubicin and peposertib may be effective in treating patients with advanced sarcoma.

Type: Interventional

Start Date: Feb 2024

open study

This phase II trial studies how well lutetium Lu 177 dotatate works in treating patients with prostate cancer with neuroendocrine differentiation that has spread to other places in the body (metastatic). Neuroendocrine differentiation refers to cells that have traits of both hormone-producing endocrine cells and nerve cells. These cells release hormones into the blood in response to a signal from the nervous system. Hormones are biological substances that circulate through the bloodstream to control the activity of other organs or cells in the body. Lutetium Lu 177-dotatate is a radioactive drug. It binds to a protein called somatostatin receptor, which is found on some neuroendocrine tumor cells. Lutetium Lu 177-dotatate builds up in these cells and gives off radiation that may kill them. It is a type of radioconjugate and a type of somatostatin analog. Treatment with Lutetium Lu 177 dotatate may shrink the tumor in a way that can be measured in patients with metastatic prostate cancer with neuroendocrine differentiation.

Type: Interventional

Start Date: Dec 2023

open study

This phase III trial compares total ablative therapy and usual systemic therapy to usual systemic therapy alone in treating patients with colorectal cancer that has spread to up to 4 body sites (limited metastatic). The usual approach for patients who are not participating in a study is treatment with intravenous (IV) (through a vein) and/or oral medications (systemic therapy) to help stop the cancer sites from getting larger and the spread of the cancer to additional body sites. Ablative means that the intention of the local treatment is to eliminate the cancer at that metastatic site. The ablative local therapy will consist of very focused, intensive radiotherapy called stereotactic ablative radiotherapy (SABR) with or without surgical resection and/or microwave ablation, which is a procedure where a needle is temporarily inserted in the tumor and heat is used to destroy the cancer cells. SABR, surgical resection, and microwave ablation have been tested for safety, but it is not scientifically proven that the addition of these treatments are beneficial for your stage of cancer. The addition of ablative local therapy to all known metastatic sites to the usual approach of systemic therapy could shrink or remove the tumor(s) or prevent the tumor(s) from returning.

Type: Interventional

Start Date: Oct 2023

open study