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407 Study Matches
A Study of Gilteritinib in Adults With Advanced ALK-positive Non-small Cell Lung Cancer (NSCLC)
Genes give your body instructions on how to make proteins. Proteins are needed to keep the body working properly. Many types of cancer are caused by changes in certain genes, making them faulty. Some people with non small cell lung cancer (NSCLC) have a faulty ALK gene. ALK stands for anaplastic lymphoma kinase. People with NSCLC who have the faulty ALK gene are called ALK-positive. ALK inhibitors are an approved treatment for people with ALK positive NSCLC. Some people stop responding to treatment with ALK inhibitors over time due to more changes happening in their faulty ALK gene, so there is an unmet medical need. Gilteritinib is an approved treatment for people with acute myeloid leukemia (AML) with the faulty FLT3 gene who haven't responded to previous treatment, or their cancer came back after previous treatment. Gilteritinib also blocks changes in the ALK gene which could help people with ALK-positive NSCLC. A study needs to be done with gilteritinib in people with ALK-positive NSCLC.
The main aim of the study is to check the safety of gilteritinib in people with ALK-positive NSCLC and if they tolerate gilteritinib.
People in this study will be adults with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC). Locally advanced means the cancer has spread to nearby tissue. Metastatic means the cancer has spread to other parts of the body. They have stopped responding to treatment with ALK inhibitors, including alectinib or lorlatinib, over time. The key reasons people cannot take part are if they have symptomatic cancers in the brain or nervous system, their cancer has spread to the thin tissue that covers the brain and spinal cord (leptomengingeal metastasis), have recently had or planning to have major surgery, have certain heart conditions, or have recently had an infection, a stroke or mini-stroke.
People in the study will take tablets of gilteritinib once a day in a 28-day cycle. They may be given up to 2 different doses of gilteritinib. People in the study will start on the lower dose but can eventually switch to the higher dose if they tolerate the lower dose and meet the safety checks.
Whilst taking gilteritinib, people will have regular scans of their tumors. People will continue taking gilteritinib until their cancer gets worse, they have medical problems from gilteritinib that they can't tolerate, they ask to stop taking gilteritinib, they start other cancer treatment or, sadly pass away. People will visit the clinic about 7 days and then 30 days after they stop taking gilteritinib. They will be asked about any medical problems and will have a safety check. After this, people who stopped taking gilteritinib, but their cancer hadn't become worse, will continue to have regular scans of their tumors. If their cancer does get worse, they will no longer have scans of their tumors. After finishing gilteritinib, people will be phoned every 12 weeks to check on their health. People will be in the study for up to 4 years, depending on how they respond to gilteritinib.
* Participant has histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) with a documented anaplastic lymphoma kinase (ALK) rearrangement and is not amenable to curative intent treatment.
* Participant is willing to submit, prior to enrollment, a fresh tumor tissue sample that was collected after completion of the most recent anti-cancer treatment and before the first dose of study intervention. If it is not medically feasible for a participant to provide a fresh tumor tissue sample, enrollment into the study should be confirmed with the Astellas medical monitor. In this case, an archival tumor tissue sample must be provided.
* Participant must have at least one prior line of ALK inhibitor-based therapy and meet one of the following criteria:
* Participant received alectinib as the only prior ALK inhibitor regimen. Participant is ineligible or unable to tolerate approved and available second-line therapy or is determined to potentially benefit from gilteritinib in this setting. Participant is eligible if chemotherapy was received in the neoadjuvant or adjuvant setting, and relapse or disease progressed after 12 months from completion of the treatment.
* Participant received lorlatinib as one of the prior ALK inhibitor regimens.
* Participant has measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
* Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
* Participant must have had progression or recurrence of NSCLC during or following receipt of the most recent therapy.
* Female participant is not pregnant and at least 1 of the following conditions apply:
* Not a woman of childbearing potential (WOCBP).
* WOCBP who has a negative urine or serum pregnancy test within 7 days prior to the first dose of study intervention and agrees to follow the contraceptive guidance from the time of informed consent through at least 180 days after final study intervention administration.
* Female participant must not be breastfeeding or lactating starting at screening and throughout the investigational period and for 60 days after final study intervention administration.
* Female participant must not donate ova starting at the first administration of study intervention and throughout the investigational period and for 180 days after final study intervention administration.
* Male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period and for 120 days after final study intervention administration.
* Male participant must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 120 days after final study intervention administration.
* Male participant must not donate sperm during the treatment period and for 120 days after final study intervention administration.
* Participant must meet the criteria as indicated on the clinical laboratory tests.
* Participant agrees not to participate in another interventional study while receiving study intervention in the present study/participating in the present study.
Exclusion Criteria:
* Participant has known oncogenic driver alterations other than ALK rearrangement.
* Participant has symptomatic central nervous system (CNS) metastases or leptomeningeal metastasis.
* Participant has a history of malignancy other than NSCLC within 2 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix or malignancy considered cured with minimal risk of recurrence).
* Participant had major surgery (e.g., requiring general anesthesia) within 4 weeks prior to first dose of study intervention, or will not have fully recovered from surgery, or has surgery planned during the study treatment.
* Participant has ongoing clinically significant toxicity (Grade 2 or higher with the exception of alopecia) associated with prior anti-cancer treatment.
* Participant has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 28 days prior to first dose of study intervention.
* Participant has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease or a family history of long QT syndrome.
* Participant has a history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction or cardiac symptoms (including congestive heart failure) consistent with New York Heart Association Class III-IV within 6 months prior to the first dose of study intervention.
* Participant has a history of interstitial pneumonia.
* Participant had completed target therapy, radiotherapy, chemotherapy, biologics and/or immunotherapy within 14 days prior to first dose of study intervention.
* Participant requires treatment with strong inducers of cytochrome P450 (CYP) 3A.
* Participant requires treatment with concomitant drugs that target serotonin 5HT1 or 5HT2B receptors or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the participant.
* Participant has received any investigational therapy within 14 days or 5 half-lives, whichever is longer, prior to screening.
* Participant has a mean Fridericia-corrected QT interval (QTcF) of \> 450 msec at screening.
* Participant has known active hepatitis B virus (HBV) infection (defined as hepatitis B surface antigen (HBsAg)-positive and/or anti-HBV core antibody-positive) or known active hepatitis C virus (HCV) infection (defined as HCV RNA \[qualitative\] detected).
* Participant with HBsAg-positivity and/or anti-HBV core antibody-positivity but with a negative HBV DNA PCR assay is permitted with appropriate antiviral prophylaxis or routine monitoring according to local practice.
* Participant who has been curatively treated for HCV infection is permitted if he/she has documented sustained virologic response of 12 weeks.
* Participant has a known history of human immunodeficiency virus (HIV) infection with acquired immunodeficiency syndrome (AIDS)-related complications.
* Participant has echocardiogram (ECHO) or multigated acquisition scan (MUGA) at screening revealing left ventricular ejection fraction \< 45%.
* Participant has any condition that makes the participant unsuitable for study participation.
* Participant has a known or suspected hypersensitivity to gilteritinib or any components of the formulation used.
Key Inclusion Criteria
* 12 to 75 years of age, inclusive
* No clinically significant laboratory, ECG, or vital signs results
* Documented diagnosis consistent with VWD of any type
* Historical annualized bleeding rate (ABR; excluding menstrual bleeds and bleeds under the skin) of both untreated and treated bleeds ≥12 per year
* Patients with VWD who are judged by the investigator to be suitable candidates for routine prophylaxis to reduce the frequency of bleeding episodes
* Hemoglobin level ≥ 8 g/dL and platelet count ≥ 100 x 109/L at Screening
Key Exclusion Criteria
* Use of routine prophylaxis of VWF-containing concentrates defined as at least 1 VWF-containing concentrate infusion to prevent or reduce bleeding per week during the previous 6 months prior to screening
* Planning to initiate routine prophylaxis with VWF-containing concentrates or any other hemostatic treatment during the study
* Patients with pro-thrombotic disorders or abnormal findings on laboratory thrombophilia evaluation performed at screening or previously documented
* History of arterial or venous thrombosis, including superficial thrombophlebitis, or embolism
* Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular disease, cerebrovascular disease, peripheral vascular disease, or metabolic dysfunction
* Baseline FVIII activity \> lower limit of normal (LLN)
DRUG: VGA039
Von Willebrand Disease (VWD)
VWD, von Willebrand Disease, VIVID-6, Vega Therapeutics, Star Therapeutics, VGA039
Long-Term Safety Study of Deucravacitinib Versus Ustekinumab in Participants With Psoriasis (PRAGMATYK)
A study to evaluate the long-term safety of Deucravacitinib versus Ustekinumab in participants with psoriasis
studyfinder@utsouthwestern.edu
ALL
40 Years to old
PHASE3
This study is NOT accepting healthy volunteers
NCT07116967
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Inclusion Criteria:
* Participants with moderate-to-severe plaque psoriasis:
• Deemed by the Investigator to be a candidate for phototherapy or systemic treatment for psoriasis, including ustekinumab;
• Have at least 1 of the following cardiovascular risk factors:
* Current cigarette smoker
* Diagnosis of hypertension
* Diagnosis of hyperlipidemia
* Diabetes mellitus type 1 or 2
* History of one or more of the following cardiovascular events: Coronary intervention (PCI) or coronary artery bypass grafting (CABG), myocardial infarction (heart attack), cardiac arrest, hospitalization for unstable angina, acute coronary syndrome, stroke, or transient ischemic attack
* Obesity
* Family history of premature coronary heart disease or sudden death in a first-degree male relative younger than 55 years of age or in a first-degree female relative younger than 65 years of age.
Exclusion Criteria:
* Participants must not have recent history of 1 of the following cardiovascular events: MI, stroke, or coronary revascularization, or VTE within 90 days prior to Day 1.
* Participants must not have unstable CVD, defined as a recent clinical cardiovascular event (eg, unstable angina, rapid atrial fibrillation), or a cardiac hospitalization (eg, pacemaker implantation, HF) within 90 days prior to Day 1.
* Participants must not have evidence of active cancer or history of cancer (solid organ or hematologic malignancy including myelodysplastic syndrome) or lymphoproliferative disease within the previous 5 years (other than resected cutaneous basal cell or squamous cell carcinoma, or carcinoma of cervix in situ that has been treated with no evidence of recurrence).
* Other protocol define inclusion/exclusion criteria apply.
Measuring the pressure inside the skull, which is called intracranial pressure, is important to treat severe neurological illness. Currently, measuring intracranial pressure requires doctors to place an invasive pressure monitor. Recently, a non-invasive intracranial pressure monitor has been developed. This monitor has a tiny pin that is placed on the head which measures the tiny movements of the skull every time the heart beats. This produces a waveform that looks very similar to an invasive intracranial pressure waveform. However, we don't know enough about how the non-invasive device to make it clinically useful yet.
* Adult patients (age \>18) undergoing craniotomy for any indication requiring hyperosmolar agents as a part of their surgery
* Adult patients (age \>18) in the neuro-oncology or neurosurgery clinic who are receiving diagnostic/therapeutic lumbar puncture as a part of their ordinary care
* Adult patients (age \>18) in the neurosurgery clinic with ventriculo-peritoneal shunts who require adjustments to increase or decrease drainage of cerebrospinal fluid.
Exclusion Criteria:
* Age \<18
* Lacking capacity to provide informed consent on their own behalf
Treatment of Inflammatory Myelitis and Optic Neuritis With Early vs Rescue Plasma Exchange (TIMELY-PLEX) (TIMELY-PLEX)
The purpose of this research is to evaluate if early vs rescue Therapeutic Plasma Exchange (PLEX) treatment algorithm leads to better visual outcomes in severe Optic Neuritis and leads to better neurological disability outcomes in severe Transverse Myelitis.
Study Population and Setting
The proposal will recruit participants presenting to participating sites with severe ON or severe TM to two separate sub-trials. The detailed inclusion and exclusion criteria for each sub-trial are listed below:
Optic Neuritis Sub-Trial:
Inclusion criteria:
* ≥18 years of age
* MRI orbits demonstrating evidence of new T2 hyperintensity and/or post-gadolinium contrast enhancement of the optic nerve(s) and meeting the clinical criteria for Optic Neuritis
* Visual acuity 20/200 or worse
* Within 8 days of onset of visual symptoms
* Able to initiate PLEX within 72h of the first dose of HDCS (if randomized to the "Early PLEX" treatment arm)
* Able to sign and date informed consent form
* Willingness to comply with all study procedures and availability for the duration of the study
Exclusion criteria:
* Evidence of prior episode of optic neuritis in the affected eye (by history or ophthalmological evaluation)
* Ophthalmological comorbidity that would significantly affect best corrected visual acuity or visual fields
* Pregnancy
* Presence of any contraindication to receiving HDCS or PLEX, including, but not limited to, hemodynamic instability, significant bleeding/coagulopathy, or sepsis.
* Any medical condition that, in the opinion of the investigator, may interfere with the patient's participation in the trial, pose any added risk for the patient, or confound the assessment of the patient (including but not limited to concurrent neurological disease and/or medical comorbidity)
* Treatment with any investigational agent within 6 months of baseline or five half-lives of the investigational agent (whichever is longer)
* Ongoing/prior treatment with immune-modulating/immunosuppressive therapy including:
* Mycophenolate mofetil, azathioprine, methotrexate, fingolimod, siponimod, ponesimod, ozanimod, tocilizumab, satralizumab, eculizumab or ravulizumab within 3 months of randomization
* Anti-CD20 (rituximab, ocrelizumab, ofatumumab, ublituximab) or anti-CD19 (inebilizumab) therapy within 6 months of randomization
* Intravenous or subcutaneous immune globulin within 3 months of randomization
* Plasma exchange within 3 months of randomization
* Interferon-beta, glatiramer acetate, fumarates (dimethyl fumarate, monomethyl fumarate, diroximel fumarate) within 1 month of randomization
* Teriflunomide use within prior 24 months
* Systemic corticosteroid therapy (intravenous or oral; excluding inhaled or topical corticosteroids) within 1 month of randomization
* Any previous treatment with alemtuzumab, cladribine, mitoxantrone or cyclophosphamide
* Previous treatment with any immune-modulating or immunosuppressive therapy not mentioned above within 6 months of randomization or five-half-lives (whichever is longer)
Transverse Myelitis Sub-Trial:
Inclusion criteria:
* ≥18 years of age
* Diagnosis of Transverse Myelitis (defined based on modified criteria adapted from the 2002 Transverse Myelitis Consortium Working Group; ALL are required)
* Development of sensory, motor and/or autonomic symptomatology attributable to spinal cord dysfunction
* Onset of symptoms to nadir \>12 hours
* Exclusion of extra-axial compressive etiology by neuroimaging
* Demonstration of inflammation within the spinal cord by presence of intramedullary T2 lesion (post-gadolinium enhancing OR non-enhancing) on MRI
* Expanded Disability Status Scale \[EDSS\] ≥3.0 (excluding visual and cerebral functional systems)
* EDSS Pyramidal Functional System Score ≥ 2
* Within 8 days of onset of motor symptoms
* Able to initiate PLEX within 48h of the first dose of HDCS (if randomized to the "Early PLEX" treatment arm)
* Able to sign and date informed consent form
* Willingness to comply with all study procedures and availability for the duration of the study
Exclusion criteria:
* Pre-existing ambulatory, motor, sensory, or bowel/bladder disability of any cause that could confound trial assessments
* Fulfillment of possible, probable or definite spinal cord infarction diagnosis per proposed diagnostic criteria (Zalewski et al. JAMA Neurology 2018)
* History of radiation to the spine
* Pregnancy
* High clinical suspicion for infectious etiology of myelitis (e.g., fever, rash or other findings)
* Presence of any contraindication to receiving HDCS or PLEX, including, but not limited to, hemodynamic instability, significant bleeding/coagulopathy, or sepsis.
* Any medical condition that, in the opinion of the investigator, may interfere with the patient's participation in the trial, pose any added risk for the patient, or confound the assessment of the patient (including but not limited to concurrent neurological disease and/or medical comorbidity)
* Treatment with any investigational agent within 24 weeks of baseline or five half-lives of the investigational agent (whichever is longer)
* Ongoing/prior treatment with immune-modulating/immunosuppressive therapy including: Mycophenolate mofetil, azathioprine, methotrexate, fingolimod, siponimod, ponesimod, ozanimod, tocilizumab, satralizumab, eculizumab or ravulizumab within 3 months of randomization
* Anti-CD20 (rituximab, ocrelizumab, ofatumumab, ublituximab) or anti-CD19 (inebilizumab) therapy within 6 months of randomization
* Intravenous or subcutaneous immune globulin within 3 months of randomization
* Plasma exchange within 3 months of randomization
* Interferon-beta, glatiramer acetate, fumarates (dimethyl fumarate, monomethyl fumarate, diroximel fumarate) within 1 month of randomization
* Teriflunomide use within prior 24 months
* Systemic corticosteroid therapy (intravenous or oral; excluding inhaled or topical corticosteroids) within 1 month of randomization
* Any previous treatment with alemtuzumab, cladribine, mitoxantrone or cyclophosphamide
* Previous treatment with any immune-modulating or immunosuppressive therapy not mentioned above within 6 months of randomization or five-half-lives (whichever is longer)
DRUG: High-dose corticosteroids (HDCS), DRUG: High-dose corticosteroids (HDCS) and PLEX
A Phase 2 Neoadjuvant Study of Zanidatamab in Combination With Chemotherapy in Participants With HER2-positive Breast Cancer (EmpowHER 208)
The purpose of this study is to see if zanidatamab is safe and effective, when combined with chemotherapy, in treating people who has Human Epidermal Growth Factor Receptor 2 (HER2)-positive, early-stage breast cancer
• Has Stage II or III histologically confirmed invasive breast carcinoma.
• Has histologically confirmed HER2-positive breast cancer
• Has a known hormone receptor (HR) status of the primary tumor
• Participants with multifocal or multicentric disease are eligible if the largest tumor (which must be larger than or equal to 2 cm in diameter) is HER2-positive, and the treating physician has determined the participant should be treated as HER2-positive.
• Agrees to undergo a mastectomy or breast conserving surgery (BCS) after neoadjuvant therapy.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function
• Has an LVEF ≥ 50% as determined by either ECHO or MUGA obtained within 4 weeks prior to first dose of study intervention.
• Adequate contraceptive precautions
Exclusion Criteria:
• Has Stage IV (metastatic) breast cancer.
• Has bilateral breast cancer.
• Has a history of any severe and/or uncontrolled medical conditions or other conditions that, in the opinion of the investigator, could affect the participant's involvement in the study.
• Has uncontrolled hypertension
• Has significant symptoms from peripheral neuropathy
• Has an active uncontrolled infection
• Has a history of life-threatening hypersensitivity to monoclonal antibodies or to recombinant proteins or excipients in the drug formulation of zanidatamab or other study interventions.
• Known active hepatitis B or C infection.
• Has another malignancy diagnosed within the last 5 years. Exceptions include previously treated non melanomatous skin cancers, carcinoma in-situ, and melanoma in-situ.
• Was treated with chemotherapy, anti-HER2 therapy, radiation therapy, endocrine therapy, or experimental therapy for invasive breast cancer
• Is planning to receive concurrent therapy with any other investigational agent or anti-cancer therapy not specified in the protocol
• Receipt of a live vaccine within 4 weeks prior to enrollment
• Has a known hypersensitivity to any components of the study interventions, including chemotherapy
The purpose of this research study is to assess whether inhibiting nerve activity to the prostate delays progression of disease in men with high-risk clinical features for prostate cancer. Prostate cancer has been shown to invade nerves, a mechanism that is thought to be involved in prostate cancer spread in men with high-risk cancer. When nerve activity to the prostate is blocked in mice with prostate cancer, prostate cancer growth and spread are inhibited. In a previous study we showed that doing so in humans was safe and may have anticancer therapeutic effect. In this study we will test whether one versus two injections of nerve blocking agent is more effective at reducing nerves in the prostate and whether it will slow/stop spread of prostate cancer after treatment.
Inclusion criteria:
High risk prostate cancer as defined by NCCN criteria Desires surgical disease treatment (radical prostatectomy) Surgical candidate (for radical prostatectomy)
≤cT3a on MRI No seminal vesicle, lymph node, or metastatic disease on PSMA PET No prior prostate cancer treatment (including androgen deprivation therapy, radiation therapy, focal therapy, cryo therapy)
PROCEDURE: Periprostatic neurolysis with dehydrated alcohol (ethanol)
Prostate Cancer, NERVES, NEUROBIOLOGY OF CANCER, NEUROLYSIS, Prostate
EASi-PROTKT™ - A Study to Test Vicadrostat (BI 690517) Taken Together With Empagliflozin in People With Type 2 Diabetes, High Blood Pressure, and Cardiovascular Disease
This study is open to adults with type 2 diabetes, high blood pressure, and cardiovascular disease. People can join the study if they have these conditions and do not have a history of heart failure. The purpose of this study is to find out if a medicine called vicadrostat, when taken with empagliflozin, helps reduce cardiovascular risk in people with these conditions. The study will compare this combination to a placebo version of vicadrostat with empagliflozin.
Participants are put into 2 groups randomly, which means by chance. One group takes vicadrostat and empagliflozin tablets, and the other group takes placebo tablets with empagliflozin. Placebo tablets look like vicadrostat tablets but do not contain any medicine.
Participants take a tablet once per day for 2 and a half years and up to 4 years and 3 months. All participants also continue their medication for type 2 diabetes, high blood pressure, and cardiovascular disease. Participants have an equal chance of receiving the study medicine or placebo.
Participants are in the study for up to 4 years and 3 months. During this time, they visit the study site regularly. During these visits, doctors collect information about participants' health and take blood samples. The doctors document when participants experience cardiovascular events. The doctors also regularly check participants' health and take note of any unwanted effects.
Inclusion Criteria :
* At least 18 years old at time of consent
* Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
* Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per ICH M3 (R2).
* Participants with medical history of hypertension and on active pharmacological treatment
* Participants with medical history of type 2 diabetes mellitus (T2DM) and on active pharmacological treatment
* Established cardiovascular (CV) disease and on active pharmacological treatment
* At least one additional risk factor for developing heart failure (HF)
Exclusion Criteria:
* History of HF or hospitalization for HF or treatment of HF
* Atrial fibrillation or Atrial flutter with a resting heart rate \>110 beats per minute (bpm) documented by echocardiogram (ECG) at Visit 1 (screening)
* Advanced untreated conduction disease or untreated clinically relevant ventricular arrhythmia at Visit 1 (screening)
* Treatment with an Mineralocorticoid receptor antagonist (MRA)
* Treatment with amiloride or other potassium-sparing diuretic
* Receiving the following treatments at Visit 1 (screening) or requiring such treatment before Visit 2 (randomisation), or planned during the trial:
* A direct renin inhibitor (e.g. aliskiren)
* More than one Angiotensin-converting enzyme inhibitor (ACEi) and/or Angiotensin receptor blocker (ARB) (including Angiotensin receptor-neprilysin inhibitor (ARNi)) used simultaneously
* Other aldosterone synthase inhibitors (e.g. baxdrostat)
* Systemic mineralocorticoid replacement therapy (e.g. fludrocortisone) Further exclusion criteria apply.
Combining Immunotherapy and Radiation Therapy to Help Patients Avoid Bladder Removal After Treatment Shrinks Muscle Invasive Bladder Cancer, BRIGHT Trial
This phase II trial tests the effect of giving pembrolizumab in combination with radiation therapy after chemotherapy in preventing surgery to remove the bladder in patients with muscle invasive bladder cancer. Standard of care therapy includes chemotherapy before surgery (neoadjuvant) to shrink or get rid of the tumor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Photon beam radiation therapy is a type of radiation therapy that uses x-rays or gamma rays that come from a special machine called a linear accelerator. The radiation dose is delivered at the surface of the body and goes into the tumor and through the body. Giving pembrolizumab in combination with radiation therapy after neoadjuvant chemotherapy may help prevent surgical removal of the bladder in patients with muscle invasive bladder cancer.
* Participants must have histologic evidence of cT2-T4aN0M0 muscle invasive urothelial carcinoma of the bladder within 180 days prior to starting neoadjuvant therapy (NAT)
* Participants must have had CT chest/abdomen/pelvis (C/A/P), MRI C/A/P or PET within 60 days prior to starting NAT to determine cT2-T4aN0M0
* Participants must have undergone TURBT with biopsy of areas of prior disease and systematic biopsies (left and right lateral, dome, posterior wall and trigone) and radiologic staging showing clinically T0-T1 disease within 60 days after the last dose of NAT. At least 4 out of 5 systematic biopsies must be performed
* NOTE: This TURBT must be within 90 days prior to registration. Registration must be within 90 days after the last dose of NAT
* Participants must have imaging of the chest, abdomen, and pelvis performed using CT or MRI preferably with contrast. Fludeoxyglucose F-18 (FDG) PET-CT can also be used for staging. If FDG PET-CT is used, then it is at the discretion of the investigator if they want to additionally obtain diagnostic CT or MRI with contrast within 60 days after the last dose of NAT
* Participants with lymph nodes ≥ 1.0 cm in the shortest cross-sectional diameter on imaging (CT or MRI of abdomen and pelvis) after completion of NAT must have a PET-CT within 70 days prior to registration. A biopsy in the setting of negative PET-CT is not required unless there is strong clinical suspicion for nodal involvement with tumor. Participants with a positive PET are deemed ineligible unless a biopsy is performed and shows no evidence of tumor involvement
* NOTE: For questions regarding the above eligibility criteria, please contact the study chairs in addition to the Southwest Oncology Group (SWOG) Statistics and Data Management Center (SDMC)
* Participants must not have evidence of ≥ T2, or N1-3, or M1 disease after NAT
* Participants must not have the presence of small cell, neuroendocrine carcinoma, plasmacytoid variants on any pathology
* Participants must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder within 24 months prior to registration except Ta/T1/carcinoma in situ (CIS) of the upper urinary tract, including renal pelvis or ureter if the participant underwent complete nephroureterectomy
* NOTE: Participants with mixed variant histology will be eligible for the trial if the majority (\> 50%) of the tumor is urothelial cell carcinoma
* Participants will be allowed to continue PD-1/L-1 inhibitor therapy received as part of standard of care neoadjuvant therapy while they undergo pre-registration assessments (TURBT and imaging)
* Participants must have received at least 3 and no more than 6 cycles of Food and Drug Administration (FDA) approved NAT for MIBC. These include cisplatin-based combination chemotherapy (e.g. cisplatin and gemcitabine \[GC\] with or without PD-1/L1 inhibitors) dose dense or accelerated methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) or enfortumab vedotin with PD-1/L1 inhibitor
* Participants must not have had anti-PD-1, anti PD-L1, anti PD-L2 or anti-CTLA4 antibody, any other antibody or drug targeting T-cell co-stimulation, enfortumab vedotin, or any other drug targeting nectin-4 other than for neoadjuvant treatment for MIBC
* NOTE: Prior intravesical immunotherapy or chemotherapy for non-muscle invasive disease is allowed
* Participants must not have had prior pelvic radiotherapy
* Participants must not have received a live attenuated vaccination within 28 days prior to registration
* Participants with conditions requiring immunosuppressive doses of steroids (\> 10 mg/day of prednisone or equivalent) or other immunosuppressive medications must not be taking steroids at time of trial registration
* Participants must be ≥ 18 years old at the time of registration
* Participants must have Zubrod performance status of 0-2
* Participants must have a complete medical history and physical exam within 28 days prior to registration
* Leukocytes ≥ 3 x 10\^3/uL (within 28 days prior to registration)
* Absolute neutrophil count ≥ 1.5 x 10\^3/uL (within 28 days prior to registration)
* Platelets ≥ 100 x 10\^3/uL (within 28 days prior to registration)
* Total bilirubin ≤ institutional upper limit of normal (ULN) unless history of Gilbert's disease (within 28 days prior to registration)
* Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x institutional ULN (within 28 days prior to registration)
* Participants must have a creatinine ≤ the institutional (I)ULN OR measured OR calculated creatinine clearance ≥ 40 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration
* Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
* Participants with a history of human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration
* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured (defined as undetectable HCV viral load)
* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
* Participants must be offered the opportunity to participate in specimen banking
* Participants who can complete the PRO-CTCAE questionnaire in English or Spanish will be offered the opportunity to participate in the optional patient-reported outcome study
* NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
* For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and central institutional review board (CIRB) regulations
Induction Pembrolizumab and Chemotherapy Followed by Pembrolizumab Before Chemoradiation and Pembrolizumab Maintenance Compared to Standard Chemoradiation With Pembrolizumab Followed by Pembrolizumab Maintenance in High-Risk Cervical Cancer
This phase III trial compares the addition of induction chemotherapy, with carboplatin, paclitaxel and pembrolizumab, to chemotherapy and radiation, with cisplatin and pembrolizumab followed by pembrolizumab maintenance for the treatment of patients with cervical cancer that has spread to nearby tissue or lymph nodes (locally advanced). 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. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. 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. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer 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. Adding induction chemotherapy to the usual treatment of chemotherapy and radiation followed by maintenance may be more effective in treating patients with high risk, locally advanced cervical cancer.
* Patients must have pathologically confirmed newly diagnosed cervical cancer. Eligible pathologic types: squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma
* Patients must have locally advanced cervical cancer (LACC) with T3 or T4 disease with or without lymph node involvement:
* IIIA (T3aN0M0)
* IIIB (T3bN0M0)
* IIIC1(T3aN1M0, T3bN1M0)
* IIIC2 (T3aN2M0, T3bN2M0)
* IVA (T4aN0M0, T4aN1M0, T4aN2M0) No prior hysterectomy defined as removal of the entire uterus.
* NOTE: prior partial/subtotal hysterectomy for reasons other than cervical cancer are eligible to participate in the study. No plan to perform a hysterectomy as part of initial cervical cancer therapy.
No paraaortic lymph node (PALN) metastases above the T12/L1 interspace.
* Note: Nodal status can be confirmed by imaging (CT, MRI, or PET/CT), fine needle aspirate/core biopsy, extra peritoneal biopsy, laparoscopic biopsy, or lymphadenectomy.
Radiologic definition of lymph node staging:
* N1:
* One or more pelvic lymph nodes with short axis diameter of ≥ 15 mm (axial plane) by CT or MRI, and/or
* One or more pelvic lymph nodes with short axis diameter of ≥ 10 mm and standardized uptake value maximum (SUVmax) ≥ 2.5 by fludeoxyglucose (FDG)-PET
* N2:
* One or more para-aortic lymph node with short axis diameter of ≥ 15 mm (axial plane) by CT or MRI, and/or
* One or more para-aortic lymph node with short axis diameter of ≥ 10 mm and SUVmax ≥ 2.5 by FDG-PET
* No prior definitive surgical, radiation, or systemic therapy for cervical cancer
* No prior immunotherapy
* No prior pelvic radiation therapy for any disease
* Age ≥ 18
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
* Not pregnant and not nursing
* Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3
* Platelets ≥ 100,000 cells/mm\^3
* Hemoglobin ≥ 8 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobulin \[Hgb\] ≥ 8 g/dl is acceptable)
* Creatinine clearance (CrCL) of ≥ 50 mL/min by the Cockcroft-Gault formula
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x institutional ULN may be enrolled)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional ULN
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* No active infection requiring parenteral antibiotics
* No live vaccine within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacille Calmette Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed
* No 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 registration
* No active autoimmune disease that has required systemic treatment in 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) is not considered a form of systemic treatment and is allowed
* No history of (non-infectious) pneumonitis that required steroids, or current pneumonitis
* No history of allergic reaction to the study agent(s) or compounds of similar chemical or biologic composition to the study agent(s) (or any of its excipients)
A Study to Evaluate the Safety and Efficacy of Oral Nizubaglustat (AZ-3102) in Late-infantile and Juvenile Forms of GM1 Gangliosidosis or GM2 Gangliosidosis
An 18-month double-blind, randomized, placebo-controlled, multicenter, Phase 3 study to evaluate the safety and efficacy of oral nizubaglustat (AZ-3102) in late-infantile and juvenile forms of GM1 gangliosidosis or GM2 gangliosidosis
studyfinder@utsouthwestern.edu
ALL
4 Years to old
PHASE3
This study is NOT accepting healthy volunteers
NCT07082543
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Inclusion Criteria:
* Confirmed GM1 gangliosidosis or Tay-Sachs, Sandhoff, or GM2AB variant
* Male and female participants aged 4 years and older at the time of informed consent
* Onset of neurological symptoms from 1 to 10 years
* Disability level at Baseline: Ataxic disturbances with a total SARA score of ≥3 and ≤30 at Baseline
* Females of childbearing potential who are sexually active willing to follow the contraceptive guidance
* Male participants with a female partner of childbearing potential willing to follow the contraceptive guidance
Exclusion Criteria:
* A history of medical conditions other than GM1 or GM2 gangliosidosis that, in the opinion of the Principal Investigator, would confound scientific rigor or the interpretation of results
* Body weight of \<10 kg
* The presence of another neurologic disease
* The presence of moderate or severe hepatic impairment
* The presence of moderate or severe renal impairment
* Platelet count of \<100x10\^9/L
* The dose of any anti-epileptic treatment(s) was not stable (required a change in dose within the previous 3 months) and/or a new anti-epileptic treatment (drug or procedure) was prescribed in the month before Baseline
* Prior use of an investigational drug within the 3 months before Screening; or prior participation in a clinical study involving gene therapy or stem cell transplantation within 2 years prior to Screening
* A positive serum pregnancy test (for women of childbearing potential)
A Study to Evaluate the Safety and Efficacy of Oral Nizubaglustat (AZ-3102) in Late-infantile and Juvenile Forms of Niemann-Pick Type C Disease, GM1 Gangliosidosis or GM2 Gangliosidosis
An 18-month double-blind, randomized, placebo-controlled, multicenter, Phase 3 study to evaluate the safety and efficacy of oral nizubaglustat (AZ-3102) in late-infantile and juvenile forms of Niemann-Pick type C disease and in late-infantile and juvenile-onset forms of GM1 gangliosidosis or GM2 gangliosidosis
studyfinder@utsouthwestern.edu
ALL
4 Years to old
PHASE3
This study is NOT accepting healthy volunteers
NCT07054515
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Inclusion Criteria:
* Male and female participants, aged 4 years and older with a diagnosis of the late-infantile or juvenile form of NPC disease. Detailed inclusion criteria are presented in the NPC disease-specific subprotocol AZA-001-301-NPC (NCT07082725).
* Male and female participants, aged 4 years and older with a diagnosis of GM1 or GM2 (Tay-Sachs, Sandhoff, or GM2AB variant disease) gangliosidosis of late-infantile/ juvenile onset. Detailed inclusion criteria are presented in the GM1/GM2 gangliosidosis-specific subprotocol AZA-001-301-GMx (NCT07082543).
Exclusion Criteria:
* Detailed exclusion criteria are presented in the NPC disease-specific subprotocol AZA-001-301-NPC
* Detailed exclusion criteria are presented in the GM1/GM2 gangliosidosis-specific subprotocol AZA-001-301-GMx
DRUG: AZ-3102, DRUG: Placebo
Niemann-Pick Type C Disease, GM1 Gangliosidosis, GM2 Gangliosidosis
A Study to Evaluate the Safety and Efficacy of Oral Nizubaglustat (AZ-3102) in Late-infantile and Juvenile Forms of Niemann-Pick Type C Disease (NPC)
An 18-month double-blind, randomized, placebo-controlled, multicenter, Phase 3 study to evaluate the safety and efficacy of oral nizubaglustat (AZ-3102) in late-infantile and juvenile forms of Niemann-Pick type C disease
studyfinder@utsouthwestern.edu
ALL
4 Years to old
PHASE3
This study is NOT accepting healthy volunteers
NCT07082725
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Inclusion Criteria:
* Signed informed consent
* Confirmed diagnosis of NPC disease
* Patient is unable or unwilling to take miglustat, or is, in the opinion of the investigator, unsatisfactorily treated with miglustat
* Male and female participants aged 4 years and older at the time of informed consent
* Onset of neurological symptoms from 2 to 15 years
* Disability level at Baseline: Ataxic disturbances with a total SARA score of ≥3 and ≤30 at Baseline
* Female of childbearing potential who are sexually active willing to follow the contraceptive guidance
* Male participants with a female partner of childbearing potential willing to follow the contraceptive guidance
Exclusion Criteria:
* A history of medical conditions other than NPC disease that, in the opinion of the Principal Investigator, would confound scientific rigor or the interpretation of results
* Body weight of \<10 kg
* The presence of another neurologic disease
* The presence of moderate or severe hepatic impairment
* The presence of moderate or severe renal impairment
* Platelet count of \<100x10\^9/L
* The dose of any anti-epileptic treatment(s) was not stable (required a change in dose within the previous 3 months) and/or a new anti-epileptic treatment (drug or procedure) was prescribed in the month before Baseline
* Prior use of an investigational drug within the 3 months before Screening; or prior participation in a clinical study involving gene therapy or stem cell transplantation within 2 years prior to Screening
* A positive serum pregnancy test (for women of childbearing potential)
* Current treatment with miglustat, provided the patient has been using the recommended dose for most of the past 12 months AND is, in the opinion of the investigator, satisfactorily treated with miglustat. Any participants receiving miglustat are required to undergo a 1-month washout period before starting study medication
The current study aims to investigate whether combining the standard medications prescribed after acute coronary syndrome (ACS)-aspirin, P2Y12 inhibitors, and statins-into a single polypill can improve outcomes following an ACS event. Although these therapies are effective, gaps in adherence and uptake significantly contribute to risk or adverse events in the post-ACS period. This study is designed as a pragmatic, multi-center, randomized trial to assess the feasibility and effectiveness of a polypill-based strategy for treatment of ACS.
* Age ≥ 18
* Hospitalization for acute coronary syndrome with percutaneous coronary intervention
* Discharged on aspirin, prasugrel or clopidogrel, and a high-intensity statin
Exclusion Criteria:
* Current need for systemic anticoagulation
* Contraindication to receive any components of the polypill
* History of allergic reaction or intolerance to aspirin, prasugrel or clopidogrel, or rosuvastatin
* Comorbidities that might be expected to limit lifespan within the 12-month study period
* Increased risk of bleeding or planned urgent surgery that would necessitate use of DAPT for \< 12 months
* Inability to provide written informed consent
* Pregnancy
COMBINATION_PRODUCT: Polypill
Acute Coronary Syndrome, Cardiovascular
Acute Coronary Syndrome, Polypill, Adherence
UT Southwestern; Parkland Health & Hospital System
Evaluating the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerotic Cardiovascular Disease and Overweight or Obesity (MARITIME-CV)
The primary objective of this trial is to demonstrate that maridebart cafraglutide is superior to placebo when given as an adjunct to standard of care with respect to reducing cardiovascular (CV) morbidity and mortality.
Inclusion Criteria
* Age ≥ 45 years at screening.
* BMI of ≥ 27.0 kg/m\^2 at screening.
* History of Atherosclerotic Cardiovascular Disease (ASCVD) with a documented history of at least one of the following:
* Prior MI (presumed atherothrombotic event due to plaque rupture/erosion).
* Prior ischemic stroke (presumed due to atherosclerosis; may include ischemic stroke with hemorrhagic transformation).
* Symptomatic peripheral arterial disease (PAD), as evidenced by intermittent claudication with ankle-brachial index (ABI) \< 0.9 (at rest), or peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease.
Exclusion Criteria
* History of any of the following within 60 days before screening or between screening and randomization: MI, hospitalization for unstable angina, arterial revascularization (eg, coronary, cerebrovascular or peripheral) major cardiovascular surgery, stroke, or transient ischemic attack (TIA).
* New York Heart Association (NYHA) class IV HF during screening or hospitalization for HF within 60 days before screening or between screening and randomization.
* Type 1 DM, or any other type of diabetes with the exception of T2DM or prior gestational diabetes. Participants with a history of gestational diabetes should be stratified according to their current diabetes classification.
* For participants with T2DM (including those without a prior history of T2DM but with a HbA1c ≥ 6.5% during screening):
* HbA1c \> 10.0% (86 mmol/mol) at screening.
* History of diabetic ketoacidosis or hyperosmolar state/coma within 12 months before randomization.
* One or more episodes of severe hypoglycemia within 6 months before randomization and/or history of hypoglycemia unawareness.
* History of proliferative diabetic retinopathy, diabetic maculopathy, severe non-proliferative diabetic retinopathy, or currently receiving or planning to receive treatment for diabetic retinopathy and/or diabetic macular edema.
* Use of any glucagon-like peptide-1 receptor agonist (GLP-1 RA), glucose-dependent insulinotropic polypeptide (GIP) agonists or antagonists, or amylin analogs within 90 days before randomization or planned use during the conduct of the trial.
* History of chronic pancreatitis or history of acute pancreatitis in the 180 days before screening or between screening and randomization.
* Family (first-degree relative\[s\]), or personal history of medullary thyroid carcinoma (MTC), or multiple endocrine neoplasia syndrome type 2 (MEN-2).
* Calcitonin ≥ 50 ng/L (pg/mL) at screening.
* Acute or chronic hepatitis; signs and symptoms of any liver disease other than metabolic dysfunction-associated steatotic liver disease, or alanine aminotransferase (ALT) \> 3.0 x the upper limit of normal (ULN) during screening, or total bilirubin (TBL) \> 1.8 x ULN during screening (for participants with a known diagnosis of Gilbert syndrome, direct bilirubin should be used instead of TBL).
* History of malignancy within the last 5 years before screening or between screening and randomization (except for the following treated with curative intent: non-melanoma skin cancer, breast ductal carcinoma in situ, cervical carcinoma in situ, or prostate cancer in situ).
* Participants of childbearing potential planning to become pregnant while on study or unwilling to use protocol-specified methods of contraception during treatment.
REGN7508 Versus Apixaban and Enoxaparin for Thromboprophylaxis After Total Knee Arthroplasty in Adults (ROXI-APEX)
This study is researching an experimental drug called REGN7508 (called "study drug"). The study is focused on adults undergoing elective, unilateral (one side) total knee replacement surgery.
The aim of the study is to see how effective the study drug is at preventing Venous Thromboembolism (VTE) and other related diseases after total knee replacement surgery.
The study is looking at several other research questions, including:
* What side effects may happen from taking the study drug
* How much study drug is in the blood at different times
* Whether the body makes antibodies against the study drug (which could make the study drug less effective or could lead to side effects)
studyfinder@utsouthwestern.edu
ALL
18 Years to old
PHASE3
This study is NOT accepting healthy volunteers
NCT07015905
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Key
Inclusion Criteria:
• Is undergoing a primary elective unilateral TKA
• Is in good health based on laboratory safety testing as described in the protocol
• Body weight ≤130 kg at screening visit as described in the protocol
Key
Exclusion Criteria:
• Any condition that, as assessed by the investigator, may confound the results of the study or pose an additional risk to the participant by study participation
• History of bleeding in the 6 months prior to randomization requiring hospitalization or transfusion as described in the protocol
• History of thromboembolic disease or thrombophilia
• History of major surgery, including brain, spinal, or ocular, or major trauma within approximately the past 6 months prior to randomization
• Has an estimated Glomerular Filtration Rate (GFR) of \<30 mL/min/1.73 m2 at the screening visit as described in the protocol
Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
This study will test the ability of myoelectric interface for neurorehabilitation (MINT) training to improve walking function.
Yasin Dhaher, PhD yasin.dhaher@utsouthwestern.edu
ALL
18 Years to 85 Years old
NA
This study is NOT accepting healthy volunteers
NCT07041775
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Inclusion Criteria:
* Age at enrollment is 18 to 85
* Leg impairment from unilateral stroke at least 6 months prior to screening
* Severe to moderate gait impairment (ambulatory with a maximum walking speed of 0.8 m/s, i.e., half of normal speed)
* Able to stand without assistance
* Clinically observable gait asymmetry
* Abnormal co-activation between adductor magnus and rectus femoris (R greater than or equal to 0.5)
Exclusion Criteria:
* Cognitive impairment with at least moderately impaired attention on digit-span test, or unable to follow instructions of the MINT task
* Visual impairment (such as hemianopia) preventing sufficient perception of the screen to play the games
* Anesthesia or severe neglect in the affected leg, or visual hemineglect (score of 2 on the NIH Stroke Scale Extinction and Inattention subtest) that impairs ability to play the games
* Participation in another study on the affected leg, or any pharmacological study, within 6 weeks of enrollment
* Inability to understand or follow commands in English due to aphasia or other reason that makes it impossible to perform the training
* Diffuse or multifocal infarcts
* Substantial leg or other pain preventing participation for 60 minutes a day
* Spasticity treatment (pharmacological or Botox) on the affected leg within past 3 months
* Severe osteoporosis causing hip or other fractures
* History of multiple falls within the last year, use of walker for balance, or falling during stance while in the lab in the first session.
* Contracture limiting the range of motion of the leg
* Current pregnancy
* From the TMS portion of the study only: History of epilepsy in adulthood requiring antiseizure medications; recent/current alcoholism or benzodiazepine/barbiturate abuse or recent history of alcohol/benzodiazepine/barbiturate withdrawal, recent history of cocaine or amphetamine use, skull fractures or skull deficits, concussion within the last 6 months, unexplained recurring headaches, vagus nerve stimulator, cochlear implant, deep brain stimulator, intracranial/carotid stents, cardiac pacemaker/AICD.
OTHER: myoelectric interface for neurorehabilitation (MINT) conditioning, OTHER: One muscle myoelectric feedback
A Study With NKT5097 for Adults With Advanced/Metastatic Solid Tumors
The goal of this open-label dose escalation and expansion study is to evaluate the safety and tolerability of NKT5097 in adults with advanced/metastatic tumors (emphasis on breast cancer and solid tumors with CCNE1 amplification). Main questions to answer include:
* What is the recommended dose for expansion and/or Phase 2, for both monotherapy and in combination with ET
* What medical issues/symptoms do participants experience when taking NKT5097 as monotherapy as well as in combination with ET
* Able to provide written informed consent
* Advanced unresectable or metastatic solid tumor (Part 1, 2 \& 3 only)
* Advanced unresectable or metastatic HR+/HER2- breast cancer (Part 4 \& 5 only)
* Refractory to or unable to tolerate existing therapies (Part 1, 2 \& 4 only)
* Measurable or evaluable disease (Part 1, 2, \& 4 only).
* Measurable disease (Part 3 \& 5 only)
* Eighteen years of age or older
* ECOG status of 0 or 1
* Adequate organ function
* Patients with female reproductive organs must be surgically sterile, post- menopausal or willing to use effective contraception per protocol
* Patients who are capable of insemination must be willing to use highly effective contraception and to refrain from sperm donation during treatment and for 28 days after the last dose
* Able to swallow oral meds
* Willing to provide tumor tissue
Exclusion Criteria:
* Advanced solid tumor that is a candidate for curative treatment
* History of another malignancy except for the following: adequately treated local basal cell or squamous carcinoma of the skin, in situ cervical cancer, adequately treated papillary noninvasive bladder cancer, other adequately treated Stage I or Stage II cancers currently in complete remission
* Not recovered from the effects of prior anticancer therapy
* Clinically significant cardiovascular event, including myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism, within 6 months
* Known active CNS metastases and/or carcinomatous meningitis
* Active interstitial lung disease requiring treatment
* History of uveitis, retinopathy, or other clinically significant retinal disease
* Major surgery within 30 days of administration of first dose
* Active uncontrolled infectious disease
* Significant liver disease (Child Pugh class B or C)
* Should not have received any prior selective investigational inhibitors or degraders (Part 5 only)
HR+ Breast Cancer, Triple Negative Breast Cancer (TNBC), CCNE1 Amplified Advanced Solid Tumors, HR+ HER2- Breast Cancer, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Liver, Lung/Thoracic, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Urinary, Ovary, Pancreas, Prostate, Small Intestine, Stomach, Urinary Bladder, Uterine (Endometrial)
CCNE1, cyclin E1, triple negative breast cancer, TNBC, estrogen receptor positive, HER2-, breast cancer, post CDK4/6i, HER2 expression, Fulvestrant, Letrozole, endocrine therapy, refractory, endocrine resistant, endocrine sensitivity, metastatic
ASPEN-09-03: A Study of Evorpacept in Combination With Trastuzumab and Chemotherapy in Metastatic HER2-Positive Breast Cancer (ASPEN-09-03)
The Substudy Protocol ASPEN-09-03 is a Phase 2, single-arm, multicenter study evaluating the efficacy, safety, and tolerability of evorpacept in combination with trastuzumab and chemotherapy in participants with HER2-positive metastatic breast cancer who have previously received trastuzumab-deruxtecan. This substudy is actively recruiting.
ASPEN-09-03 is a substudy under Master Protocol ASPEN-09, and additional substudies are as follows:
* Metastatic colorectal cancer (CRC) - dose escalation phase to evaluate evorpacept in combination with other drugs. This substudy is not open.
* Recurrent/metastatic head and neck cancer (HNSCC) - dose escalation phase to evaluate evorpacept in combination with other drugs. This substudy is not open.
* Histologically confirmed invasive HER2+ breast cancer.
* Received at least one prior line of therapy including T-DXd (ENHERTU) for locally advanced/metastatic HER2+ breast cancer. Prior neoadjuvant therapy which resulted in relapse within 6 months of completion of T-DXd will be considered a line of treatment for metastatic disease. Participants who discontinue T-DXd due to intolerance are considered eligible.
* Progressed on or following the most recent line of therapy.
* Eligible to receive one of the following chemotherapy options (capecitabine, eribulin, gemcitabine, paclitaxel or vinorelbine).
* Measurable disease as defined by RECIST v1.1.
* LVEF ≥50%.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0 to 1.
* Life expectancy of at least 3 months.
* Adequate renal function (estimated creatinine clearance ≥30 mL/min as calculated using the Cockcroft-Gault equation or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
* Adequate liver function:
* Total bilirubin ≤1.5 x upper limit of normal (ULN) (≤3.0 x ULN if the participant has documented Gilbert syndrome);
* Aspartate and alanine transaminase (AST and ALT) ≤3 x ULN (≤5.0 x ULN if liver involved by metastatic disease).
* Participants must have recovered from all AEs due to previous therapies, procedures, and surgeries to baseline severity or ≤Grade 1 per NCI CTCAE v5.0 except for AEs not deemed reversible and which do not constitute a safety risk by Investigator judgment.
Exclusion Criteria:
* Participants with known CNS metastases unless treated and stable prior to enrollment.
* Prior exposure to any anti-CD47 or anti-SIRPα agent.
* Any condition that would be contraindicated to receiving trastuzumab
* Has a diagnosis of complete dihydropyrimidine dehydrogenase (DPD) deficiency or significant toxicity with prior flurouracil (5FU) based regimen
* Following anti-cancer therapy with insufficient washout before start of treatment:
• chemotherapy, hormonal therapy, radiation therapy or small molecule anti-cancer therapy within 14 days or 5 half-lives (whichever is shorter) of start of treatment.
• Immune therapy or other biologic therapy (e.g., monoclonal antibodies, antibody-drug conjugates) for the treatment of cancer for: 28 days or 5 half-lives (whichever is shorter) of start of treatment).
* History of autoimmune hemolytic anemia, autoimmune thrombocytopenia, or hemolytic transfusion reaction.
* Had an allogeneic tissue/solid organ transplant.
* Any active, unstable cardiovascular disease.
* Intolerance to or who have had a severe allergic or anaphylactic reaction to antibodies or infused therapeutic proteins or participants who have had a severe allergic or anaphylactic reaction to any of the substances included in the study drug (including excipients).
* Has an active autoimmune disease that has required systemic treatment in past 2 years.
* Other primary malignancy within 2 years.
A Clinical Study of Calderasib (MK-1084) With Targeted Therapy and Chemotherapy in People With Colorectal Cancer (MK-1084-012/KANDLELIT-012)
Researchers are looking for other ways to treat locally advanced or metastatic colorectal cancer (mCRC) that is unresectable and has a gene mutation called KRAS G12C.
Standard (or usual) treatments for this type of colorectal cancer may include mFOLFOX6 with or without bevacizumab. Researchers want to learn if adding calderasib (the study medicine) and cetuximab to mFOLFOX6 can treat locally advanced or mCRC with the KRAS G12C mutation. Calderasib and cetuximab are targeted therapies.
The goals of this study are to learn:
* About the safety of calderasib with cetuximab and mFOLFOX6 and if people tolerate the treatments
* If people who receive calderasib with cetuximab and mFOLFOX6 live longer without mCRC growing or spreading compared to people who receive mFOLFOX6 with or without bevacizumab.
The main inclusion criteria include but are not limited to the following:
* Has a histologically confirmed diagnosis of locally advanced unresectable or metastatic (unresectable Stage III or Stage IV as defined by American Joint Committee on Cancer \[AJCC\] eighth edition) colorectal adenocarcinoma
* Part 2 only: Has not received systemic anticancer therapy for locally advanced unresectable or metastatic colorectal cancer; an exception is permitted for 1-2 cycles of FOLFOX or 1 cycle of CAPOX as optional chemotherapy before or during the screening period
* Demonstrates presence of a Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
* Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral load
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, chronic diarrhea)
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
* Has known partial or complete dihydropyrimidine dehydrogenase (DPD) deficiency
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization, with the exception of the optional chemotherapy
* Has 1 or more conditions that, in the opinion of the investigator, make the participant ineligible for treatment with bevacizumab
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease
* Has active infection requiring systemic therapy
* Has not adequately recovered from major surgery or have ongoing surgical complications
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
An International Observational Study of Adults With Acute Infection
Prospective, longitudinal studies of people with acute infections are essential to understand risk factors, clinical manifestations, pathobiology, and management strategies. Observational studies can provide data necessary to select interventions and strategies for testing in clinical trials and to develop key design features of trials. Observational studies can be particularly important for establishing an early knowledge base after emergence of a new pathogen, as illustrated by the recent emergence of influenza A (H1N1), SARS-CoV-2, and Mpox. This observational study protocol describes collection of data and biospecimens from sites across the world for characterizing acute infections in hospitalized patients. The protocol is designed to study respiratory infections, infections outside the respiratory tract, established infectious diseases, and emerging infectious diseases. Data generated in this study will be used to efficiently characterize acute infectious diseases and plan future clinical trials.
studyfinder@utsouthwestern.edu
ALL
18 Years to old
This study is NOT accepting healthy volunteers
NCT07069400
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Inclusion Criteria:
* Age ≥18 years old
* Admitted to hospital (or in an emergency department with anticipated hospital admission) for the management of a suspected or confirmed acute infectious disease.
* Onset of symptoms of an infectious disease within the past 30 days.
* Informed consent for study participation by the participant or a surrogate decision maker if the participant lacks capacity for consent.
Exclusion Criteria:
* Current imprisonment (this does not include quarantine for an infectious disease).
* Patient undergoing comfort care measures only such that treatment focuses on end- of-life symptom management over prolongation of life.
* Expected inability or unwillingness to participate in study procedures.
* In the opinion of the investigator, participation in the study is not in the best interest of the patient.
Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer (ReDiscover-2)
This is a global, multicenter, open-label, randomized Phase 3 study comparing the efficacy and safety of RLY-2608 + fulvestrant to capivasertib + fulvestrant for the treatment of patients with HR+/HER2- ABC with PIK3CA mutation following recurrence or progression on or after treatment with a CDK4/6 inhibitor.
* Patient has ECOG performance status of 0-1
* One or more known primary oncogenic PIK3CA mutation(s)
* Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with a gonadotropin-releasing hormone (GnRH) agonist. Patients are to have commenced treatment with a GnRH agonist at least 4 weeks prior to randomization and must be willing to continue on it for the duration of the study.
* Histologically or cytologically confirmed diagnosis of HR+/HER2- locally advanced or metastatic breast cancer (ABC) with radiological or objective evidence of recurrence or progression; locally advanced disease must not be amenable to resection with curative intent
* Measurable disease per RECIST v1.1 or evaluable bone-only disease.
* Must have radiological evidence of progression on or after previous treatment for HR+/HER2- ABC with:
• At least 1 and no more than 2 lines of endocrine therapy (ET) in the (neo)adjuvant setting with recurrence on or within 12 months of completion or in the ABC setting
• 1 prior line of CDK4/6 inhibitor therapy in one of the following settings:
• CDK4/6 inhibitor + ET in the ABC setting
• CDK4/6 inhibitor therapy in the adjuvant setting if progression occurred during or within 12 months of completion of adjuvant CDK4/6 inhibitor with ET
• Patients who progressed during or within 12 months of completion of adjuvant CDK4/6 inhibitor and after receiving CDK4/6 inhibitor therapy in the advanced setting are considered to have had \>1 prior line of CDK4/6 inhibitor and are not eligible
Exclusion Criteria:
* Prior treatment with any of the following:
• CDK2 or selective CDK4 inhibitors or any investigational therapies targeting cyclin dependent kinases
• PIK3, AKT, or mTOR inhibitors or any agent whose mechanism of action is the inhibit the PIK3/AKT/mTOR pathway
• Immunotherapy
• Antibody drug conjugates
* Type 1 diabetes, or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥ 140 mg/dL, or glycosylated hemoglobin (HbA1c) ≥7.0% (≥ 53 mmol/mol).
* Clinically significant, uncontrolled cardiovascular disease
* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
* Known active uncontrolled or symptomatic CNS metastases associated with progressive neurological symptoms or requiring ongoing corticosteroids or anticonvulsants for symptomatic control
* Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
* History of hypersensitivity to fulvestrant or drugs in a similar class as fulvestrant, RLY-2608, or capivasertib, including their excipients
* Known activating AKT mutations, loss-of-function PTEN mutations, or loss of PTEN expression resulting in oncogenic pathway activation downstream of PI3K
PIK3CA Mutation, HER2- Negative Breast Cancer, Hormone Receptor Positive Tumor, Breast Cancer, Metastatic Breast Cancer, Advanced Breast Cancer, Breast - Female, Breast - Male
Recovery Through Inspiration, Support, and Empowerment (RISE)
The goal of this pilot study is to test the effectiveness of a novel intervention for young adults (ages 18-27) with mental health conditions who have been released from an acute care psychiatric facility. The intervention aims to reduce suicidality, depression, anxiety, re-hospitalization, and improve mental health recovery by using outpatient services.
The current standard of care (SOC) for these patients at discharge includes a discharge plan with a list of their medications, anticipated outpatient appointments, and information on when and where to find community resources.
The intervention being tested involves the implementation of a mental health recovery education and support program, involving one-on-one and small group meetings led by Peer Support Specialists (PSS) and Recovery Community Organizations (RCO).
Participants will be assigned to either Cohort A or B for 8 weeks.
Cohort A will be the intervention group with PSS and RCOs.
* Weeks 1-4: One-on-one meetings with PSS for education and support. Assessments will be completed at weeks 2 and 4.
* Weeks 5 and 7: One-on-one meetings with PSS for education and support.
* Week 6 and 8: Group meetings with PSS and other participants from RCOs. Assessments will be completed during these weeks.
Cohort B will be the SOC group with no PSS or RCOs.
* Weeks 1-4: Weekly check in phone calls with a member of the research team. Assessments will be completed at weeks 2 and 4.
* Weeks 5-8: Check in phone calls with a member of the research team every other week. Assessments will be completed at weeks 6 and 8.
Data collected from participant assessments, adherence to medication, and re-admittance to a psychiatric facility will be used to compare the intervention to the SOC.
* Chief complaint of suicidal ideation, suicide attempt, depression, and/or anxiety
* discharged from inpatient care or from emergency department
* men and women ages 18-27
Exclusion Criteria:
* primary diagnosis of: substance use disorder, schizophrenia spectrum, intellectual development disorder, autism spectrum disorder (level II or III)
Peer Support Specialist (PSS), Recovery Community Organization (RCO), Mental Health Recovery, Transitional Age Youth (TAY), UT Southwestern Medical Center, Young Adult
A Study to Assess Adverse Events and Change in Disease Activity of Oral Surzetoclax Alone or in Combination With Subcutaneous and/or Oral Antimyeloma Agents in Adult Participants With Multiple Myeloma (MM)
Multiple myeloma (MM) is a plasma cell disease characterized by the growth of clonal plasma cells in the bone marrow. The purpose of this study is to assess the safety and change in disease activity of surzetoclax in adult participants with relapsed/refractory (R/R) MM. Adverse events and change in disease activity will be assessed.
Surzetoclax is an investigational drug being developed for the treatment of R/R MM. In Substudy 1 there will be a dose escalation phase where participants will receive various doses of surzetoclax in combination with daratumumab + dexamethasone, to determine the best dose of surzetoclax. This will be followed by a dose expansion and selection phase where participants will receive 1 of 2 doses of surzetoclax in combination with daratumumab + dexamethasone, or daratumumab + dexamethasone + pomalidomide (only during the expansion phase). In Substudy 2, there will be a dose escalation phase where participants will receive various doses of surzetoclax alone. Approximately 130 adult participants with R/R MM will be enrolled in the study in approximately 40 sites worldwide.
In Substudy 1 escalation phase, participants will receive oral surzetoclax tablets in combination with subcutaneous (SC) daratumumab injections + oral dexamethasone tablets and in the expansion phase, will receive oral surzetoclax tablets in combination with SC daratumumab injections + oral dexamethasone tablets or daratumumab injections + oral pomalidomide + oral dexamethasone tablets. In Substudy 2, Japanese participants will receive oral surzetoclax tablets. The total study duration is approximately 4.5 years.
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 an approved institution. The effect of the treatment will be frequently checked by medical assessments, blood tests, and side effects.
* Documented diagnosis of multiple myeloma (MM) based on standard international myeloma working group (IMWG) diagnostic criteria.
* All participants must have measurable disease per central laboratory with at least 1 of the following assessed within 28 days prior to enrollment:
* Serum M-protein \>= 0.5 g/dL (\>= 5g/L); OR
* Urine M-protein \>= 200 mg/24 hours; OR
* For participants without measurable serum and urine M-protein: Serum free light chain (sFLC) ≥ 10 mg/dL (100 mg/L), provided sFLC ratio is abnormal.
* B-cell lymphoma (BCL)-2 inhibitor treatment naïve.
* t(11;14) positive status and/or BCL2 high status.
* Substudy 1 Dose Escalation Cohorts and Substudy 2:
\-- Must be triple class exposed (PI, IMiD and anti-CD38) and have received 3 to 5 lines of prior antimyeloma therapy, and who have no other appropriate treatment options as deemed by the investigator.
* Substudy 1 Dose Expansion Cohorts:
* Must be double class exposed (PI, IMiD) and have received 1 to 3 lines of prior antimyeloma therapy.
Exclusion Criteria:
* Major surgery within 4 weeks of study treatment or planned during study participation.
* Active infections: no recent infection requiring systemic treatment that was completed \<= 7 days before first dose of study treatment and/or uncontrolled systemic infection.
* Recent infection requiring systemic treatment that was completed \<= 7 days before first dose of study treatment and/or uncontrolled active systemic infection.
This Study Will Explore Whether a Combination of the Investigational Drug Mevrometostat (PF-06821497) and Enzalutamide Will Work Better Than Taking Enzalutamide Alone in Participants With mCSPC Who Are ARPI naïve.
This study will explore whether a combination of the investigational drug mevrometostat (PF-06821497) and enzalutamide will work better than taking enzalutamide alone in participants with mCSPC who are ARPI naïve and have not yet received chemotherapy in the mCSPC setting.
Inclusion Criteria
* Male participants aged ≥18 years (or the minimum age of consent in accordance with local regulations) at screening.
* Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features.
* Metastatic prostate cancer documented by positive bone scan (for bone disease) or metastatic lesion(s) on CT or MRI (for soft tissue/visceral disease).
* Resolution of acute effects of any prior therapy to either baseline severity or CTCAE Grade ≤1 (except for AEs which do not constitute a safety risk in the investigator's judgement).
* Participants must have ECOG PS 0 or 1.
Exclusion Criteria
* Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
* Clinically significant cardiovascular disease.
* Known or suspected brain metastasis or active leptomeningeal disease.
* Participants must be treatment naïve at the mCSPC stage, eg, participants cannot have received any cytotoxic chemotherapy with the following exceptions: Treatment with first-generation antiandrogen (ADT) agents is allowed for mCSPC.
* Previous administration with an investigational product (drug or vaccine) within 30 days.
* Use of 5-alpha reductase inhibitors is prohibited within 28 days of randomization.
* Prior surgery from which the participant has not fully recovered at least 28 days prior to randomization
* Current use or anticipated need for drugs that are known strong CYP3A4/5 inhibitors and inducers (with exception of enzalutamide as part of this study).
* Inadequate organ function.
A Trial of D-mannose for the Prophylaxis of Recurrent Urinary Tract Infections (DmannoseRCT)
A randomized, double-blind, placebo-controlled, 12-month study to determine the effectiveness of D-mannose (2g daily) supplementation in rUTI (recurrent urinary tract infection) prevention in post-menopausal women.
* Female, post-menopausal, age ≥ 55 years old
* Diagnosis of recurrent UTI, defined as ≥ 3 symptomatic culture-proven UTI episodes in 12 months or ≥ 2 in 6 months.
* Currently free from a UTI determined based on absence of symptoms as determined by the UTI symptom assessment questionnaire79 and negative urine culture (\<103 colony forming units per ml of urine).
* Able to attend all follow-up appointments for the study.
* A negative upper and lower urinary tract evaluation, including pelvic examination for pelvic organ prolapse (less than stage 2), measurement of post-void residual (less than 50 ml), and imaging (renal ultrasound and standing voiding cystourethrogram) to exclude kidney stone, hydronephrosis, reflux, or urethral diverticulum.
Exclusion Criteria:
* Current use of D-mannose. Patients willing to stop taking D-mannose will be offered to join the trial after a 4-week wash-out period.
* Complicated UTIs, including need for catheter drainage or intermittent catheterization, neurogenic bladder, bladder augmentation, or urinary diversion.
* Ongoing supplement use (Box 1). Patients willing to stop taking the listed supplements will be offered to join the trial after a 4-week wash-out period.
* Evidence of upper tract infection (pyelonephritis), including temperature higher than 38°C, flank/lumbar pain or tenderness
* Diagnosis of interstitial cystitis or overactive bladder syndrome
* Prophylactic antibiotics started in the last 3 months and unwilling to discontinue, or intention to start in the next 12 months
* Use of Uromune or other vaccine approaches to reduce rUTI
* Participation in a research study involving an investigational product in the past 12 weeks
* Receipt of phage treatment
* History of chronic diarrhea requiring regular therapy
* Inability to swallow or known history of gastrointestinal malabsorption
* History of recurrent vaginal yeast infections
* Systemic disease precluding enrollment in this study (uncontrolled diabetes with HgA1C above 7, ongoing chemotherapy or immunotherapy, renal insufficiency \[creatinine \> 1.5 g/dl\]), mental or cognitive impairment, weight loss diet requiring excessively large amounts of fluid intake, or other health-related specific diet).
* Nursing home resident
* BMI \>40
Box 1 Supplements to avoid
* Multi-Vitamins and Multi-Mineral capsules
* Specific Vitamins or Minerals (e.g., Calcium, Citrical, Calcium Gummies, Vitamin A, D, Niacin, Pyridoxine, Selenium, Vitamin E, B6, Iron, Omega 3, D3, Magnesium, B-Complex, Women's Ultra MultiVitamin, GNC B-Complex, B-12, PreserVision Areds2, Vitamins D, B Pollen)
* Probiotics
* Cranberry Mannose or Cranberry Extract Weight loss products to avoid
* Medifast
* Vitafusion
* OptiVin Products
* Appetite Suppressants
* Keto-Fuel
Testing the Addition of Docetaxel (Chemotherapy) to the Usual Treatment (Hormonal Therapy and Apalutamide) for Metastatic Prostate Cancer, ASPIRE Trial
This phase III trial compares the effect of adding docetaxel to hormonal therapy and apalutamide versus hormonal therapy and apalutamide alone in treating patients with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Hormone therapy for prostate cancer, also called androgen deprivation therapy (ADT), uses surgery or drugs to lower the levels of male sex hormones in a man's body. This helps slow the growth of prostate cancer. Apalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of tumor cells. Giving docetaxel in addition to the usual treatment of hormonal therapy and apalutamide may work better in treating patients with metastatic prostate cancer than the usual treatment alone.
* Documentation of disease:
\* Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology
* Must have had evidence of metastatic disease (American Joint Committee on Cancer \[AJCC\] metastasis \[M\]1 disease) based on conventional CT/MRI and/or bone scan. This will be defined as:
* Bone metastases detected by CT, radionuclide technetium-99 (99Tc)- methylene bisphosphonate bone scan, or MRI as defined by PCWG3 criteria; OR
* Non-pelvic lymph node metastases (measurable lymph nodes above the aortic bifurcation; lymph nodes are measurable if the short axis diameter is ≥ 15 mm) detected on CT or MRI as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Subjects with regional lymph node metastases only (nodes \[N\]1, below the aortic bifurcation) will not be eligible for the study; OR
* Visceral or soft tissue metastases detected on CT or MRI as defined by RECIST version 1.1. Soft tissue/visceral lesions are measurable if the long axis diameter is ≥ 10 mm
* Evidence of metastatic disease by PSMA-PET only and not visible by CT, radionuclide bone scan, or MRI will not satisfy eligibility criteria
* No metachronous low-volume disease (defined as recurrent metastatic disease after definitive treatment of prostate primary) and with ≤ 4 bone metastasis and no visceral metastasis on conventional imaging by CT, radionuclide 99Tc-biphosphonate bone scan, or MRI)
* Next generation sequencing (NGS) results from any tissue based Clinical Laboratory Improvement Act (CLIA) test must be available at the time of registration. NGS from soft tissue or visceral lesion if available is preferred. NGS from bone or primary prostate will be accepted. Patients with failed NGS testing are not eligible
* Prior treatment
* ADT (luteinizing hormone-releasing hormone \[LHRH\] agonist/antagonist or orchiectomy) with or without first generation anti-androgen, or second-generation androgen receptor signaling inhibitor (ARSI) within 120 days of registration is permitted. No washout period will be needed for the first generation- androgen or ARSI prior to registration. Anti-androgen treatment is only permitted if used within 120 days of registration
* No prior chemotherapy for prostate cancer
* Age ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Absolute neutrophil count (ANC) ≥ 1,500/mm\^3
* Hemoglobin ≥ 9.0 g/dL
* Platelet count ≥ 100,000/mm\^3
* Total bilirubin ≤ 1 x upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is \> 1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1 × ULN, subject may be eligible)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate transaminase \[SGT\]) ≤ 1.5 x upper limit of normal (ULN)
* Calculated (Calc.) creatinine clearance \> 30 mL/min
* Serum potassium ≥ 3.5 mmol/L
* Comorbid conditions
* 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
* Leptomeningeal metastases: Patients with treated leptomeningeal metastases are eligible if follow-up brain imaging 30 days after central nervous system (CNS)-directed therapy shows no evidence of progression
* HIV: Patients with known HIV infection on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial
* Hepatitis B: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Hepatitis C: 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
* No seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year to randomization, brain arteriovenous malformation or condition requiring CNS surgery or radiation therapy)
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this trial, patients should be class II or better. Any condition that in the opinion of the investigator, would preclude participation in this study. Patients with stable asymptomatic deep venous thromboembolism on stable anti-coagulation will be eligible
* Hypertension: Subjects with uncontrolled hypertension as indicated by a resting systolic blood pressure (BP) \>= 160 mmHg or diastolic BP \>= 100 mmHg despite medical management are not permitted to register
* Allergies: Subjects with known hypersensitivity to any of the study drugs, or excipients in the formulation of the study drugs are not permitted to register
* Concomitant medications
* Chronic concomitant treatment with strong inhibitors of cytochrome P450 3A4 (CYP3A4) is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug prior to registration on the study. See Section 8.1.9 for more information
* Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment
* Medications known to lower the seizure threshold must be discontinued or substituted prior to study entry. See Section 8.1.9 for more information
* Patient agrees to use a condom (even men with vasectomies) and another effective method of birth control if having sex with a woman of childbearing potential or agrees to use a condom if having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug
DRUG: Androgen Therapy, DRUG: Apalutamide, DRUG: Docetaxel, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Bone Scan, PROCEDURE: PSMA PET Scan, PROCEDURE: Biospecimen Collection, OTHER: Questionnaire Administration
A Clinical Study of Ifinatamab Deruxtecan (I-DXd) in People With Metastatic Prostate Cancer (MK-2400-001)
Researchers are looking for new ways to treat metastatic castration-resistant prostate cancer (mCRPC). Researchers have designed a study medicine called ifinatamab deruxtecan (also called I-DXd or MK-2400) to treat mCRPC. The goal of this study is to learn if people who receive I-DXd live longer overall and live longer without the cancer growing or spreading than people who receive chemotherapy.
The main inclusion criteria include but are not limited to the following:
* Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
* Has prostate cancer progression while on androgen deprivation therapy (ADT) (or post bilateral orchiectomy) within 6 months prior to Screening
* Has current evidence of distant metastatic disease (M1 disease) documented by either bone lesions on bone scan and/or soft tissue disease by computed tomography (CT)/magnetic resonance imaging (MRI)
* Has received prior treatment with 1 or 2 androgen receptor pathway inhibitors (ARPIs) and progressed during or after at least 8 weeks of treatment
* Has provided tumor tissue from a core or excisional biopsy from soft tissue not previously irradiated and obtained after disease progression on the most recent prior therapy
* Has recovered from adverse events (AEs) due to previous anticancer therapies
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Is unable to swallow tablets/capsules
* Has any of the following indicators of interstitial lung disease (ILD)/pneumonitis:
• Has any history of ILD/pneumonitis that required steroid use, except for a history of radiation pneumonitis that did not require steroids
• Has current ILD/pneumonitis
• Has a clinical or radiographic suspicion of ILD for which the diagnosis of ILD cannot be ruled out
* Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
* Has uncontrolled or significant cardiovascular disease
* Has received prior treatment with a taxane-based chemotherapy agent for metastatic castration-resistant prostate cancer (mCRPC)
* Has had prior discontinuation of an antibody drug conjugate (ADC) that consists of an exatecan derivative (eg, trastuzumab deruxtecan) due to treatment-related toxicities
* Has a "superscan" bone scan
UTSW NORC Pilot Spinal Cord Injury Dietary Program
The goal of this observational study is to learn about the effects of a 9-week dietician-guided program modified from the National Diabetic Prevention Program (modified DPP-diet) in people with spinal cord injury on body composition and insulin sensitivity.
The main question it aims to answer is:
Does 9 week modified DPP-diet reduce body fat percentage and insulin resistance?
Participants will:
Have 9 weeks of Telehealth visit with dietician certified in providing DPP. Visit the laboratory before, immediately and 9 weeks after completion of the modified DPP-diet.
Share with the researcher on the perceived benefit and obstacles in implementing the modified DPP-diet as part of their daily activities.
* age 18-65 years old
* have had SCI for more than one year
* not independently ambulatory
* primarily uses a wheelchair for mobility
* community-dwelling
* without comorbidities listed in the exclusion criteria
Exclusion Criteria:
* uncontrolled type 2 diabetes mellitus
* pregnancy
* active systemic disease, e.g., heart disease, real failure/insufficiency, multiple myeloma, lupus with nephropathy, sickle cell disease, symptomatic myasthenia gravis, poorly controlled hypo- or hyperthyroidism.
OTHER: Telehealth with dietician
Obesity and Obesity-related Medical Conditions, Spinal Cord Injury, Chronic
Daily Nitrofurantoin Versus Bladder Fulguration Plus Daily Nitrofurantoin for Women With Recurrent Urinary Tract Infections
The goal of this clinical trial is to learn if the drug Nitrofurantoin (NF) taken as a daily antibiotic, works to treat cystitis compared to electrofulguration (EF) and Nitrofurantoin (NF) daily antibiotic.
* Females 18 to 85 years old with at least a 1-year history of culture documented uncomplicated rUTI.
* Diagnosis of rUTI, defined as ≥ 3 symptomatic UTIs in 12 months or ≥ 2 in 6 months.
* Currently free from a UTI determined based on absence of symptoms as determined by the UTI symptom assessment questionnaire and negative urine culture (\<10\^3 colony forming units per ml of urine).
* A negative upper and lower urinary tract evaluation, including pelvic examination for pelvic organ prolapse (less than or equal to stage 2), measurement of post-void residual (less than 50 ml), and imaging (which may include renal ultrasound and standing voiding cystourethrogram) to exclude kidney stone, hydronephrosis, reflux, or urethral diverticulum.
* Office cystoscopy documenting stages 1 or 2 of chronic cystitis.
* Likely to stay in the geographic region for the duration of the study.
* ASA class II or less.
Exclusion Criteria:
* Patients on antibiotics at baseline (i.e., suppressive therapy or antibiotic therapy for non-urinary infections).
* Patients on self-start therapy (i.e., taking antibiotics upon start of urinary symptoms concerning for UTI).
* Patients on prophylactic antibiotics started in the last 3 months and unwilling to discontinue, or intention to start in the next 12 months.
* Complicated UTIs, including neurogenic bladder condition (i.e., multiple sclerosis, Parkinson's disease, spinal cord injury), bladder augmentation, or urinary diversion.
* Patients with urinary catheters (including indwelling Foley, intermittent catheterization, and suprapubic catheters).
* Uncontrolled diabetes (HbA1c \>9).
* Pregnancy
* Allergy or resistance to Nitrofurantoin.
* Chronic lung or liver condition precluding the use of Nitrofurantoin, including abnormal chest X ray or elevated liver function tests.
* Chronic renal insufficiency (creatinine over 1.5 g/dl or GFR less than 40) precluding the use of Nitrofurantoin.
* History of chronic diarrhea requiring regular therapy.
* Patients with psychosis, dementia, swallowing disorders, or any other ability to take Nitrofurantoin reliably at home.
* BMI over 40.
* Use of Uromune or other vaccine approaches to reduce rUTI episodes
* Participation in a research study involving an investigational product in the past 12 weeks.
* Patients receiving phage therapy.
* Current diagnosis of interstitial cystitis.
* Patients with medical conditions requiring excessively large amounts of fluid intake.