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391 Study Matches
Precision Medicine in Action: Phase II Trial of Response Adaptive Ablative Pre-operative SPBI (RAPS) and Non-operative Sentinel Lymph Node Biopsy in Patients With Early-stage ER+ Breast Cancer: RAPS Trial
1\. Efficacy of PULSAR preoperative radiation 2. Evaluate potential of microbubble CEUS as an alternative to operative SLNBx 3. Evaluate potential of OA to evaluate treatment response of pre-operative radiation on the tumor
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Asal Rahimi
FEMALE
18 Years and over
PHASE2
NCT06444269
STU-2024-0561
Inclusion Criteria:
* 1\. Invasive epithelial (ductal, medullary, lobular, papillary, mucinous (colloid), or tubular) histologies of the breast 3 cm or less(T1-T2cN0) in women who have not undergone surgery or neoadjuvant endocrine or chemotherapy for current breast cancer diagnosis. For cohort 1, it is highly recommended those tumors are at least 1 cm.
2\. Tumor must not involve the overlying skin based on imaging evaluation and/or clinical exam 3. Age \>/= 18 years old and female 4. Greatest Tumor dimension is 3cm or less based on US. MRI measurements can be included only if performed BEFORE the biopsy 5. Tumor must be unifocal 6. The tumor must be visible on CT scan and/or preferably marked with clip(s) in tumor if not visible. At least one clip should be placed in or around tumor prior to enrollment 7. Patients must undergo an MRI for work up to aid in tumor delineation and to rule out additional foci of disease. If additional foci of disease are present, they need to have a negative biopsy to proceed with treatment.
8\. Clinically and radiographically node negative on ultrasound of the axilla or MRI on on initial workup prior to microbubble contrast assessment 9. Estrogen receptor positive or Progesterone receptor positive and Her2neu negative 10. Ability to understand and the willingness to sign a written informed consent.
11\. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) prior to the start of study and for the duration of radiation therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months
12\. If patient has had a prior biopsy clip placed in the lymph node deemed the sentinel lymph node at time of microbubble CEUS, it is up to investigator if additional biopsy and clip placement will be obtained.
Exclusion Criteria:
\- 1. Multi-centric disease 2. Prior Radiation to the involved breast 3. Tumor Size \>3cm 4. Patients who are pregnant or lactating due to the potential exposure to the fetus to radiation therapy and unknown effects of radiation therapy to lactating females 5. Prior ipsilateral breast cancer 6. Patients with active lupus or scleroderma 7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Gadolinium or other agents used in study.
8\. If patient has a positive lymph node at time of microbubble contrast enhanced ultrasound, they will be removed from the study. Only N0 patients to be treated on this study. RADIATION: Radiomics on MRI, DRUG: microbubble CEUS Contrast Enhanced Ultrasound (CEUS)
Breast Cancer, Breast - Female
UT Southwestern; Parkland Health & Hospital System
Transcutaneous Auricular Neurostimulation for ICU Patients With Traumatic Brain Injury (tAN-TBI)
The overarching goal of this pilot study is to assess the feasibility and safety of transcutaneous auricular neurostimulation (tan) in ICU patients with TBi and to determine the effect of tan on serum markers of inflammation. exploratory analyses will examine effects on such physiological parameters as blood pressure, heart rate, and intracranial pressure (iCP), as well as measures of neurological function.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Bolutyfe.Oderinde@UTSouthwestern.edu
Alex Valadka
ALL
18 Years and over
NA
NCT06467708
STU-2024-0360
Inclusion Criteria:
• Post-resuscitation GCS score 12 or below and acute trauma-related intradural blood on head CT scan after TB
• Age 18 years or older (pediatric trauma patients are not routinely transported to Parkland)
• Consent from legally authorized representative
Exclusion Criteria:
• Hemodynamic instability
• Expected imminent mortality because of overwhelming neurological and/or systemic injury
• Unclear neurological status because of paralytic medications or intoxication with ethanol or other drugs
• Presence of other electrical stimulation devices (pacemaker, cochlear prosthesis, neurostimulator, etc.)
• Abnormal ear anatomy or ear infection
• Participant is pregnant or lactating
• Any other significant medical or psychosocial problems that, in the opinion of the investigator, would potentially cause harm to the participant, impact their ability to participate, or influence the results of the trial
DEVICE: Sparrow Ascent Transcutaneous Auricular Neurostimulation (tAN)
TBI (Traumatic Brain Injury)
Transcutaneous auricular neurostimulation (tAN)
UT Southwestern; Parkland Health & Hospital System
A Study to Evaluate the Risk of Tumor Lysis Syndrome (TLS) in Adult Participants Receiving Oral Venetoclax in Combination With Intravenously Infused Obinutuzumab or Oral Acalabrutinib for Previously Untreated Chronic Lymphocytic Leukemia (CLL)
Chronic lymphocytic leukemia (CLL) is the most common leukemia (cancer of blood cells). The purpose of this study is to assess the safety of venetoclax in combination with obinutuzumab or acalabrutinib in the treatment of CLL. Adverse events and change in disease activity will be assessed. Venetoclax in combination with obinutuzumab or acalabrutinib is being investigated in the treatment of CLL. Study doctors put the participants in 1 of 4 groups, called treatment arms. Participants will receive oral venetoclax in combination with intravenously (IV) infused obinutuzumab or oral acalabrutinib at in different dosing schemes as part of treatment. Approximately 170 adult participants with CLL who are being treated with venetoclax will be enrolled in the study in approximately 80 sites worldwide. Participants in Arm A will receive oral venetoclax in combination with IV infused obinutuzumab, with a 5 week venetoclax ramp up. Participants in Arm B will receive oral venetoclax in combination with oral acalabrutinib, with a 5 week venetoclax ramp up. Participants in Arm C and Arm D will receive oral venetoclax in combination with oral acalabrutinib, with differing venetoclax ramp up periods. The total study duration is approximately 28 months. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Farrukh Awan
ALL
18 Years to old
PHASE3
NCT06428019
STU-2024-0660
Inclusion Criteria:
* Diagnosis of documented, previously untreated, chronic lymphocytic leukemia (CLL) requiring treatment according to the 2018 international workshop on chronic lymphocytic leukemia (iwCLL) criteria and have a life expectancy of \> 6 months.
* Previously untreated small lymphocytic lymphoma (SLL) meeting the 2018 iwCLL criteria for treatment will also be equally considered as CLL for eligibility, screening, treatment and evaluation.
* Eastern Cooperative Oncology Group (ECOG) performance status \<= 2.
* Adequate marrow function independent of growth factor or transfusion support within 2 weeks of screening, unless cytopenia is due to marrow involvement of CLL as listed in the protocol.
* Creatinine clearance (CrCl) \>= 30 mL/min using the Cockcroft-Gault formula are eligible for inclusion.
Exclusion Criteria:
\- Active/uncontrolled infection, no Richter's transformation, no active immune thrombocytopenia. DRUG: Venetoclax, DRUG: Acalabrutinib, DRUG: Obinutuzumab
Chronic Lymphocytic Leukemia, Lymphoid Leukemia
Chronic Lymphocytic Leukemia, CLL, Venetoclax, ABT-199, Obinutuzumab, Acalabrutinib
UT Southwestern
Bionic Pancreas in CFRD
This multi-center randomized controlled trial (RCT) will compare efficacy and safety endpoints using the insulin-only configuration of the iLet Bionic Pancreas System (BP) versus a control group using their usual care insulin delivery method and continuous glucose monitoring (CGM) during a 13-week study period in individuals ≥14 years old with cystic fibrosis-related diabetes (CFRD). After 13 weeks, participants will continue in a 13-week Extension Phase in which the BP group will continue to use the BP system and the Usual Care group will initiate use of the BP system.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Lindsay.Allen@UTSouthwestern.edu
Melissa Ham
ALL
14 Years to old
PHASE3
NCT06449677
STU-2024-1261
Inclusion
• Age ≥ 14 years old at time of signing informed consent
• Able to provide informed consent (and assent for participants \<18 years old)
• Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria: * Sweat chloride equal to or greater than 60 mmol/liter by quantitative pilocarpine iontophoresis test (QPIT) (when not taking a cystic fibrosis transmembrane conductance regulator (CFTR) modulator) * Two well-characterized mutations in the CFTR gene
• Clinical diagnosis of CFRD, defined as a person with CF and diabetes mellitus, treated with insulin for ≥3 months prior to screening
• Using the same insulin regimen for ≥1 month prior to screening and collection of baseline CGM data, with no plans to change regimen during the study: either multiple daily injections of insulin (MDI), basal-only without bolus insulin, an insulin pump without automation, or an automated insulin delivery (AID) system other than the BP (which is an exclusion)
• Total daily insulin dose must be ≥0.1 units/kg
• Able to speak and read English sufficient to understand the pump user interface and provide written materials for safe operation of the BP • For pediatric participants, this applies to both the participant and caregiver
• For participants \<18 years old, living with one or more parent/legal guardian knowledgeable about emergency procedures for severe hypoglycemia. A designated care partner must be willing to be linked to the participant's Dexcom Follow application with location sharing on.
• For participants \>18 years old who live alone, participant has a relative or acquaintance who lives within 30 minutes of participant and is willing to be contacted to check on participant if study staff feel that participant may be experiencing a medical emergency and cannot be reached. A designated care partner must be willing to be linked to the participant's Dexcom Follow application with location sharing on.
• No use of a non-insulin glucose-lowering medication, except metformin, that is not approved for use in T1D within 3 months prior to signing informed consent and willing to not use any such medications during the course of the trial. Note: such drugs cannot be used even if prescribed for weight loss rather than glucose-lowering.
• If not currently using a rapid-acting insulin that is approved for use in the iLet pump, willing and able to switch to an approved insulin when using the BP.
• Participant has commercial glucagon available for treatment of severe hypoglycemia or will obtain it prior to randomization
• Willing to authorize the study team to contact the participant's primary physician to inform them about their participation in this study.
• Enrolled in the Cystic Fibrosis Foundation Patient Registry (participants may enroll in the Registry at the time of enrollment if not already enrolled).
• No plans for trips of more than 14 consecutive days outside the United States during the period of study participation
• Investigator believes that the participant can safely use the iLet and will follow the protocol • The investigator will take into account the participant's HbA1c level (there is no upper limit for eligibility), compliance with current diabetes management, prior acute diabetic complications, cognitive ability, and general medical condition. For this reason, there is no upper limit on HbA1c specified for eligibility. Exclusion
• Current use of the BP or an AID system not FDA approved for T1D
• Known hemoglobinopathy (sickle cell trait is not an exclusion)
• Current participation in another diabetes-related interventional trial
• Established history of allergy or severe reaction to adhesive or tape that must be used in the study
• Pregnant (positive urine hCG), breast feeding, plan to become pregnant in the next 7 months, or sexually active and can become pregnant but not using contraception
• Current use of hydroxyurea or unable to avoid hydroxyurea use during the study (interferes with accuracy of Dexcom sensor)
• Have started or stopped a CFTR modulator in the 4 weeks prior to screening. • Modifications of the dosing of a CFTR modulator is acceptable
• Anticipated lung or liver transplant (on transplant list)
• Lung or liver transplant within one year prior to screening. If they have had a transplant more than a year ago, but they: * Have had a rejection episode occur in prior 8 weeks, individual is excluded. * Their doses of corticosteroids and/or calcineurin inhibitors have not been stable for one month prior to enrollment and/or is expected to change significantly over the course of the study, individual is excluded.
• Acute pulmonary exacerbation or hospitalization within the 4 weeks prior to screening or treatment with IV antibiotics in the 4 weeks prior to screening
• History of a complete pancreatectomy
• Currently using enteral tube feedings for nutritional support
• Presence of a medical condition or use of a medication that, in the judgment of the investigator, clinical protocol chair, or medical monitor, could compromise the results of the study or the safety of the participant. Conditions to be considered by the investigator may include the following: * Alcohol or drug abuse * Use of prescription drugs that may dull the sensorium, or hinder decision-making during the period of participation in the study such has opioids or short-acting benzodiazepines * Coronary artery disease that is not stable with medical management, including unstable angina, angina that prevents moderate exercise (e.g., climbing a flight of stairs) despite medical management; or within the last 12 months before screening: a history of myocardial infarction, percutaneous coronary intervention, enzymatic lysis of a presumed coronary occlusion, or coronary artery bypass grafting * Congestive heart failure with New York Heart Association (NYHA) Functional Classification III or IV * History of TIA or stroke in the last 12 months * Severe liver disease such as end-stage cirrhosis * Renal failure requiring dialysis or known eGFR \<30 * Untreated or inadequately treated mental illness * History of untreated or inadequately treated eating disorder within the last 2 years, such as anorexia, bulimia, or diabulimia or omission of insulin to manipulate weight * History of intentional, inappropriate administration of insulin leading to severe hypoglycemia requiring treatment
• Employed by, or having immediate family members employed by Beta Bionics, or being directly involved in conducting the clinical trial, or having a direct supervisor at place of employment who is also directly involved in conducting the clinical trial (as a study investigator, coordinator, etc.); or having a first-degree relative who is directly involved in conducting the clinical trial.
• Age ≥ 14 years old at time of signing informed consent
• Able to provide informed consent (and assent for participants \<18 years old)
• Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria: * Sweat chloride equal to or greater than 60 mmol/liter by quantitative pilocarpine iontophoresis test (QPIT) (when not taking a cystic fibrosis transmembrane conductance regulator (CFTR) modulator) * Two well-characterized mutations in the CFTR gene
• Clinical diagnosis of CFRD, defined as a person with CF and diabetes mellitus, treated with insulin for ≥3 months prior to screening
• Using the same insulin regimen for ≥1 month prior to screening and collection of baseline CGM data, with no plans to change regimen during the study: either multiple daily injections of insulin (MDI), basal-only without bolus insulin, an insulin pump without automation, or an automated insulin delivery (AID) system other than the BP (which is an exclusion)
• Total daily insulin dose must be ≥0.1 units/kg
• Able to speak and read English sufficient to understand the pump user interface and provide written materials for safe operation of the BP • For pediatric participants, this applies to both the participant and caregiver
• For participants \<18 years old, living with one or more parent/legal guardian knowledgeable about emergency procedures for severe hypoglycemia. A designated care partner must be willing to be linked to the participant's Dexcom Follow application with location sharing on.
• For participants \>18 years old who live alone, participant has a relative or acquaintance who lives within 30 minutes of participant and is willing to be contacted to check on participant if study staff feel that participant may be experiencing a medical emergency and cannot be reached. A designated care partner must be willing to be linked to the participant's Dexcom Follow application with location sharing on.
• No use of a non-insulin glucose-lowering medication, except metformin, that is not approved for use in T1D within 3 months prior to signing informed consent and willing to not use any such medications during the course of the trial. Note: such drugs cannot be used even if prescribed for weight loss rather than glucose-lowering.
• If not currently using a rapid-acting insulin that is approved for use in the iLet pump, willing and able to switch to an approved insulin when using the BP.
• Participant has commercial glucagon available for treatment of severe hypoglycemia or will obtain it prior to randomization
• Willing to authorize the study team to contact the participant's primary physician to inform them about their participation in this study.
• Enrolled in the Cystic Fibrosis Foundation Patient Registry (participants may enroll in the Registry at the time of enrollment if not already enrolled).
• No plans for trips of more than 14 consecutive days outside the United States during the period of study participation
• Investigator believes that the participant can safely use the iLet and will follow the protocol • The investigator will take into account the participant's HbA1c level (there is no upper limit for eligibility), compliance with current diabetes management, prior acute diabetic complications, cognitive ability, and general medical condition. For this reason, there is no upper limit on HbA1c specified for eligibility. Exclusion
• Current use of the BP or an AID system not FDA approved for T1D
• Known hemoglobinopathy (sickle cell trait is not an exclusion)
• Current participation in another diabetes-related interventional trial
• Established history of allergy or severe reaction to adhesive or tape that must be used in the study
• Pregnant (positive urine hCG), breast feeding, plan to become pregnant in the next 7 months, or sexually active and can become pregnant but not using contraception
• Current use of hydroxyurea or unable to avoid hydroxyurea use during the study (interferes with accuracy of Dexcom sensor)
• Have started or stopped a CFTR modulator in the 4 weeks prior to screening. • Modifications of the dosing of a CFTR modulator is acceptable
• Anticipated lung or liver transplant (on transplant list)
• Lung or liver transplant within one year prior to screening. If they have had a transplant more than a year ago, but they: * Have had a rejection episode occur in prior 8 weeks, individual is excluded. * Their doses of corticosteroids and/or calcineurin inhibitors have not been stable for one month prior to enrollment and/or is expected to change significantly over the course of the study, individual is excluded.
• Acute pulmonary exacerbation or hospitalization within the 4 weeks prior to screening or treatment with IV antibiotics in the 4 weeks prior to screening
• History of a complete pancreatectomy
• Currently using enteral tube feedings for nutritional support
• Presence of a medical condition or use of a medication that, in the judgment of the investigator, clinical protocol chair, or medical monitor, could compromise the results of the study or the safety of the participant. Conditions to be considered by the investigator may include the following: * Alcohol or drug abuse * Use of prescription drugs that may dull the sensorium, or hinder decision-making during the period of participation in the study such has opioids or short-acting benzodiazepines * Coronary artery disease that is not stable with medical management, including unstable angina, angina that prevents moderate exercise (e.g., climbing a flight of stairs) despite medical management; or within the last 12 months before screening: a history of myocardial infarction, percutaneous coronary intervention, enzymatic lysis of a presumed coronary occlusion, or coronary artery bypass grafting * Congestive heart failure with New York Heart Association (NYHA) Functional Classification III or IV * History of TIA or stroke in the last 12 months * Severe liver disease such as end-stage cirrhosis * Renal failure requiring dialysis or known eGFR \<30 * Untreated or inadequately treated mental illness * History of untreated or inadequately treated eating disorder within the last 2 years, such as anorexia, bulimia, or diabulimia or omission of insulin to manipulate weight * History of intentional, inappropriate administration of insulin leading to severe hypoglycemia requiring treatment
• Employed by, or having immediate family members employed by Beta Bionics, or being directly involved in conducting the clinical trial, or having a direct supervisor at place of employment who is also directly involved in conducting the clinical trial (as a study investigator, coordinator, etc.); or having a first-degree relative who is directly involved in conducting the clinical trial.
DEVICE: iLet Bionic Pancreas System (BP), DEVICE: Usual Care (UC)
Cystic Fibrosis-related Diabetes
Cystic fibrosis-related diabetes (CFRD), iLet bionic pancreas, Automated insulin delivery, Continuous glucose monitoring
UT Southwestern; Children’s Health
Treatment ResistAnt Depression Subcallosal CingulatE Network DBS (TRANSCEND) (TRANSCEND)
The goal of this clinical trial is to evaluate the effectiveness and safety of bilateral stimulation of the subcallosal cingulate white matter (SCCwm) using Deep Brain Stimulation (DBS) as an adjunctive treatment of non-psychotic unipolar Major Depressive Disorder (MDD) in adults.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Hila.AbushSegev@UTSouthwestern.edu
Kala Bailey
ALL
22 Years to 70 Years old
NA
NCT06423430
STU-2024-0461
Inclusion Criteria:
• The patient must be diagnosed with non-psychotic unipolar Major Depressive Disorder.
• The patient must be in a major depressive episode for ≥12 months or have had at least 3 lifetime depressive episodes.
• The patient has tried and failed a minimum of four different types of antidepressant treatments as measured by a tool designed for this purpose.
• Depression medication and treatment regimen must be stable for a minimum of 4 weeks before the first baseline visit
Exclusion Criteria:
• Pregnant or those who plan to become pregnant during study
• Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that could limit participation in the study or interfere with adherence to the study protocol.
• Current or lifetime history of psychotic features in any Major Depressive Episode.
• Has an intracranial Central Nervous System disease that impairs motor, sensory or cognitive function or that requires intermittent or chronic medication.
• Significant acute suicide risk.
• Diagnosis of Substance Use Disorder or Alcohol Use Disorder without sustained remission (12 months or longer).
• Current and ongoing use of neurostimulation treatment that may interfere with DBS therapy/system.
• Treatment with another investigational device or investigational drugs.
DEVICE: Sham-stimulation, DEVICE: Active-stimulation
Treatment Resistant Depression, Psychiatric Disorders
DBS, Major Depressive Disorder, Bilateral Stimulation, Antidepressant Treatment, neurostimulation, ABT-CIP-10494
UT Southwestern
A Study to Evaluate the Effect of Aficamten in Pediatric Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy (oHCM). (CEDAR-HCM)
The purpose of this study is to evaluate the efficacy, safety and PK of aficamten in a pediatric population with symptomatic obstructive hypertrophic cardiomyopathy (oHCM).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Kirstie.LeDoux@UTSouthwestern.edu
Nathanya Baez Hernandez
ALL
12 Years to 17 Years old
PHASE2
NCT06412666
STU-2024-0814
Inclusion Criteria:
* Period 1: Treatment Period
* Males and females between 12 and \< 18 years of age at screening and at Day 1.
* Body weight ≥ 45 kg for the initial cohort and then body weight ≥ 35 kg after at least 10 participants in the initial cohort have undergone dose titration up to Week 4 without observed events of LVEF \< 50% at the starting dose of 5 mg qd.
* Core laboratory confirmation of the following oHCM echocardiographic criteria at screening:
* Left ventricular (LV) hypertrophy with nondilated LV chamber in the absence of other cardiac disease.
* LV end-diastolic wall thickness that meets a threshold of:
* Z-score \> 2.5 in the absence of family history OR
* Z-score \> 2 in the presence of positive family history or positive genetic test.
* LVEF ≥ 60% AND Valsalva LVOT-G ≥ 50 mmHg.
* oHCM of sarcomeric origin confirmed by genetic testing or, if unable to confirm by genetic testing, oHCM of sarcomeric origin may be presumed in the absence of history of metabolic disorders, mitochondrial cardiomyopathies, neuromuscular disease, malformation syndromes, infiltrative diseases/inflammation, and endocrine disorders (such as Fabry's disease, Noonan syndrome with left ventricular hypertrophy, and amyloid-cardiomyopathy).
* New York Heart Association (NYHA) Class ≥ II at screening.
* Adequate acoustic windows for echocardiography.
* Participants on beta blockers, verapamil, diltiazem, or disopyramide should have been on stable doses for more than 4 weeks prior to randomization.
* Period 2: Open-Label Extension
* Completed Period 1. If unable to complete Period 1 due to circumstances not related to compliance or safety, the Medical Monitor may review and determine eligibility.
* LVEF ≥ 55% after washout.
* Period 3: Long-term Extension • Completed Period 2.
Exclusion Criteria:
* Period 1: Treatment Period
Any of the following criteria will exclude potential participants from the trial:
* Significant valvular heart disease.
* Moderate or severe valvular aortic stenosis or fixed subaortic obstruction.
* Mitral regurgitation that is greater than mild in severity and not due to systolic anterior motion of the mitral valve (per judgment of Principal Investigator or designee).
* Evidence of fixed left-sided obstruction (eg, subaortic membrane, aortic valve stenosis, or coarctation of the aorta).
* History of LV systolic dysfunction (LVEF \< 45%) or stress cardiomyopathy at any time during their clinical course.
* History of congenital heart disease other than oHCM (may be enrolled if not hemodynamically significant in the judgement of the Principal Investigator and study Medical Monitor).
* Has been treated with SRT (surgical myectomy or percutaneous alcohol septal ablation) within the preceding 6 months or has plans for either treatment during the trial period.
* History of paroxysmal or persistent atrial fibrillation or atrial flutter.
* History of syncope, symptomatic ventricular arrhythmia, or sustained ventricular tachyarrhythmia within 3 months prior to screening.
* History or evidence of any other clinically significant disorder, malignancy, active infection, other condition, or disease that, in the opinion of the Principal Investigator (or designee) or the Medical Monitor, would pose a risk to participant safety or interfere with the trial evaluation, procedures, or completion.
* Current or previous use of drugs known to cause cardiomyopathy (eg, anthracyclines, monoclonal antibodies \[trastuzumab\], alkylating agents \[cyclophosphamide\], and tyrosine kinase inhibitors \[sunitinib and imatinib\]).
* Currently participating in another investigational device or drug trial or received an investigational device or drug \< 1 month (or 5 half-lives for drugs, whichever is longer) prior to screening.
* Implantable cardioverter defibrillator (ICD) implantation within 6 weeks of screening or planned ICD implantation during the trial period.
* Has received prior treatment with aficamten or mavacamten.
* Currently listed for heart transplantation or anticipated to be listed for heart transplantation in the next 12 months. DRUG: Aficamten, DRUG: Placebo
Pediatric, Symptomatic Obstructive Hypertrophic Cardiomyopathy
CK-3773274, CK-274, Aficamten, Symptomatic Obstructive Hypertrophic Cardiomyopathy, oHCM, CEDAR, CEDAR-HCM, CY 6023
Children’s Health
Training for Urinary Leakage Improvement After Pregnancy (TULIP)
This is a multi-center, randomized single-blind nonsurgical trial conducted in approximately 216 primiparous postpartum women at high risk for prolonged/sustained pelvic floor disorders with symptomatic, bothersome urinary incontinence (UI) amenable to nonsurgical treatment. TULIP is a 3-Arm trial with two active interventions (Arms 1 and 2) and a Patient Education control arm (Arm 3). Arm 1 consists of pelvic floor muscle training (PFMT). Arm 2 uses a home biofeedback device (leva®). The primary outcome will be assessed at 6 months postpartum by blinded outcomes assessors, and follow-up will continue until 12 months postpartum.
Call 214-648-5005
studyfinder@utsouthwestern.edu, AGNES.BURRIS@UTSouthwestern.edu
David Rahn
FEMALE
18 Years and over
NA
NCT06411158
STU-2024-0318
Inclusion Criteria:
• ≥18yo primiparous patient s/p singleton vaginal delivery (\>32 weeks), approximately 6wk postpartum
• At increased risk of sustained pelvic floor disorders, as defined by
• neonate ≥3.5kg, and/or
• operative delivery (i.e., forceps or vacuum-assisted vaginal delivery), and/or
• ≥2nd-degree perineal laceration
• Symptomatic, bothersome UI as defined by a score of ≥6 on the ICIQ-SF.
Exclusion Criteria:
• Inability to complete study assessments or procedures, per clinician judgment, or not available for 6mo postpartum follow-up
• Stillbirth or significant maternal or neonatal illness
• Non-English or non-Spanish speaking
• Perineal wound breakdown or cloaca observed on exam
• Severe pain with assessments of PFM integrity and/or strength/function
• Already engaged (since delivery) in in-person physical therapy for strengthening of the pelvic floor
• Unwilling or unable to upload and use external smartphone app(s)
OTHER: Interventionist-guided training, DEVICE: Home pelvic floor exercises guided by the leva® device, OTHER: Education
Urinary Incontinence, Delivery Complication
Urinary Incontinence, Pelvic Floor Disorders, Physical Therapy, Biofeedback, Anal Incontinence
UT Southwestern; Parkland Health & Hospital System
A Study Using Risk Factors to Determine Treatment for Children With Favorable Histology Wilms Tumors (FHWT)
This phase III trial studies using risk factors in determining treatment for children with favorable tissue (histology) Wilms tumors (FHWT). Wilms Tumor is the most common type of kidney cancer in children, and FHWT is the most common subtype. Previous large clinical trials have established treatment plans that are likely to cure most children with FHWT, however some children still have their cancer come back (called relapse) and not all survive. Previous research has identified features of FHWT that are associated with higher or lower risks of relapse. The term "risk" refers to the chance of the cancer coming back after treatment. Using results of tumor histology tests, biology tests, and response to therapy may be able to improve treatment for children with FHWT.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Arhanti Sadanand
ALL
to 30 Years old
PHASE3
NCT06401330
STU20250865
Inclusion Criteria:
* Patients must be enrolled on APEC14B1 and consent to Part A - Eligibility Screening prior to enrollment on AREN2231.
* Patients must be \< 30 years old at enrollment.
* Patients with newly diagnosed Stage I-IV Favorable Histology Wilms Tumor confirmed by central review and with a qualifying Initial Stratum Assignment on APEC14B1.
* Patients must receive a qualifying Initial Stratum Assignment on APEC14B1-REN by Day 14 post-diagnostic procedure (nephrectomy or biopsy), where that procedure is Day 0.
* Patients must enroll on AREN2231 by Day 14.
* Exceptions: If patient reaches Day 14 (post initial diagnostic nephrectomy or biopsy) without receiving an Initial Stratum Assignment on APEC14B1-REN, patient will not be eligible for enrollment on AREN2231 unless all required materials (reports and Case Report Forms and specimens) for an Initial Stratum Assignment arrived by Day 7, but an Initial Stratum Assignment was not completed by Day 14. In these circumstances, after obtaining appropriate protocol consent, the patient may proceed with treatment according to local institutional staging and enroll within 5 calendar days of notification of the central Initial Stratum Assignment being issued, only if the AREN2231 Initial Stratum Assignment is in agreement with any treatment already initiated. If the Initial Stratum Assignment is not in agreement with the local institution's assessment then the patient will be ineligible for AREN2231.
* All sites must have sent or plan to send diagnostic tumor sample for molecular testing through a Clinical Laboratory Improvement Act (CLIA)-certified (or equivalent if outside of the United States \[US\]) laboratory that can detect Loss of Heterozygosity (LOH) of chromosome 1p AND 16q, and gain of chromosome 1q. Patients potentially eligible for mVLR must also have LOH of chromosome 11p15 included.
* Note: Patients are eligible for enrollment prior to obtaining these molecular testing results, and it is strongly recommended that patients are enrolled before these results are available. However, molecular results must be returned and uploaded to APEC14B1-REN for integration into risk stratification by the required timepoints (specific timelines vary by treatment arm). Patients who do not have molecular results available by the arm-specific timepoints may be taken off protocol therapy.
* Patients who have an upfront nephrectomy must have at least one lymph node sampled and confirmed as a lymph node by central pathology review to be eligible.
* Note: Lymph node sampling will also be required at delayed nephrectomy. Patients who do not have a lymph node sampled and confirmed as a lymph node by central pathology review at delayed nephrectomy will be taken off protocol therapy.
* Karnofsky performance status must be ≥ 50 for patients \> 16 years of age and the Lansky performance status must be ≥ 50 for patients ≤ 16 years of age.
* ONLY TO PATIENTS WHO WILL RECEIVE CHEMOTHERAPY: Serum total bilirubin ≤ 1.5 X upper limit of normal (ULN) OR direct bilirubin ≤ 3X ULN for subjects with total bilirubin levels \> 1.5 ULN (within 7 days prior to enrollment).
* ONLY TO PATIENTS WHO WILL RECEIVE CHEMOTHERAPY: Aspartate aminotransferase (AST/serum glutamate oxaloacetic transaminase \[SGOT\]) OR alanine transaminase (ALT/serum glutamic pyruvate transaminase \[SGPT\]) ≤ 3X ULN OR ≤ 5 X ULN for patients with liver metastases (within 7 days prior to enrollment).
* ONLY TO PATIENTS WHO WILL RECEIVE CHEMOTHERAPY: Shortening fraction of ≥ 27% by echocardiogram, or ejection fraction of ≥ 50% (within 7 days prior to enrollment)
* Note: This criteria only applies to patients centrally classified as Stage IV. Stage II and III patients subsequently assigned to a doxorubicin arm will be off protocol therapy if they do not meet this criteria at time of cardiac function assessment.
* Known HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* All patients and/or their parents or legal guardians must sign a written informed consent.
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
Exclusion Criteria:
* Patient with a diagnosis of Stage V Bilateral Wilms Tumor.
* Patients who in the opinion of the investigator are not able to comply with the study procedures are not eligible.
* Patients with any uncontrolled, intercurrent illness including but not limited to symptomatic congestive heart failure.
* Patients with Stage I FHWT with a known or suspected Wilms Tumor predisposition syndrome or condition (contralateral nephrogenic rests and/or unilateral multicentric tumors) are excluded from treatment on the mVLR (Nephrectomy Only) arm.
* Notes:
* In the context of the renal tumor protocols, multicentric tumors and multifocal tumors are equivalent terms, and refer to the occurrence of two or more tumors arising within one kidney.
* Exclusion from the Nephrectomy Only arm applies to two groups of patients:
* Patients \< 4 years with Stage I FHWT other than epithelial subtype AND
* Stage I patients of any age with Epithelial WT
* For the purpose of exclusion from the Nephrectomy Only Arm, known or suspected WT predisposition syndromes or conditions are defined as follows:
* WT Predisposition Syndromes: Beckwith Wiedemann Spectrum, Denys Drash, Trisomy 18, Idiopathic Hemihypertrophy/Isolated Lateralized Overgrowth, WAGR, Simpson-Golabi-Behmel, Bohring-Opitz, or other conditions considered by treating physician to predispose to WT.
* WT Predisposing Conditions:
* A unilateral WT and (radiologic or pathologic) determination of contralateral nephrogenic rest(s) AND/OR
* Unilateral multicentric WT
* Patients treated with partial nephrectomy at initial diagnosis are excluded from mVLR (Nephrectomy Only) arm.
* Patients with lung metastases as the only metastatic site who already had complete resection of all radiologically evident lung nodules, and have at least one nodule confirmed pathologically as tumor.
* Please note: Those with lung metastases as the only metastatic site who have complete resection of all radiologically evident lung nodules after enrollment but prior to the lung imaging following Cycle 2 of DD-4A will be inevaluable for lung assessment and subsequent stratum assignment and will, therefore, come off protocol therapy.
* Patients with known Charcot-Marie-Tooth syndrome.
* Patients who have had prior tumor-directed chemotherapy or radiotherapy for the current diagnosis except for therapy delivered for an emergent issue, as medically indicated.
* Patients who will potentially require doxorubicin on this study and have previously received doxorubicin for another diagnosis.
* Patients receiving concurrent chemotherapy for a different diagnosis.
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
* Lactating females who plan to breastfeed their infants.
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation. PROCEDURE: Bone Scan, DRUG: Carboplatin, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, BIOLOGICAL: Dactinomycin, DRUG: Doxorubicin, DRUG: Etoposide, DRUG: Irinotecan, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Nephrectomy, OTHER: Patient Observation, PROCEDURE: Positron Emission Tomography, PROCEDURE: Ultrasound Imaging, DRUG: Vincristine, PROCEDURE: X-Ray Imaging
Stage I Mixed Cell Type Kidney Wilms Tumor, Stage II Mixed Cell Type Kidney Wilms Tumor, Stage III Mixed Cell Type Kidney Wilms Tumor, Stage IV Mixed Cell Type Kidney Wilms Tumor, Kidney
Children’s Health
Enfortumab Vedotin and Stereotactic Radiation for Localized, Cisplatin Ineligible Muscle Invasive Bladder Cancer (STAR-EV)
STAR-EV will evaluate the combination of enfortumab vedotin plus radiotherapy (RT) as neoadjuvant treatment for muscle invasive bladder cancer prior to radical cystectomy surgery. The study will use "dose escalation" to evaluate the safety and efficacy of study treatment at three dose regimens: Level 0: EV treatment followed by RT to the bladder Level 1: EV treatment with RT starting on Cycle 2, Day 15 Level 2: EV treatment with RT starting on Cycle 1, Day 15 Following completion of EV+RT neoadjuvant therapy, all subjects will undergo surgery as part of routine care.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years to old
PHASE1
NCT06394570
STU-2024-0374
Inclusion Criteria:
• Urothelial carcinoma of the urinary bladder stage cT2-4a (AJCC 8th edition) N0M0 planned for radical cystectomy. Mixed cell types with variant histologies (including squamous, plasmacytoid, adenocarcinoma, sarcomatoid, micropapillary, nested, and lipid cell variants) are allowed as long as any urothelial histology is present (i.e. -not 100% variant histology). Small cell/neuroendocrine component is excluded.
• Ineligibility for cisplatin-based chemotherapy based on treating physician assessment and any of the following "Galsky criteria": renal insufficiency (Creatinine Clearance \<60ml/min by standard institutional calculation method), \>=grade 2 peripheral neuropathy, \>=grade 2 hearing loss, New York Heart Association (NYHA) class III heart failure; a combination of these; or patient refusal.
• Age \>=18.
• Performance status Eastern Cooperative Oncology Group (ECOG) 0-1
• Adequate organ and marrow function as defined below: •Hematologic: -Absolute neutrophil count (ANC) \>=1500/mm3 * Platelet count \>=100x109/L * Hemoglobin ≥ 9 g/dL •Hepatic: * Serum bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects with Gilbert's disease * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN •Renal: * No end stage renal disease requiring dialysis allowed
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 3 months following completion of study neoadjuvant therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. 6a. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
• No prior systemic therapy (except prior therapy for non-muscle invasive bladder cancer \>12 prior to registration) for bladder cancer or prior pelvic radiotherapy. Prior intra-vesical therapies are allowed, including Bacillus Calmette-Guerin (BCG) for non-muscle invasive bladder cancer. Prior chemotherapy for other cancers is allowed if given \>=1 year prior to study registration.
• Baseline \>= Grade 2 sensory or motor neuropathy
• Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to enfortumab vedotin or other agents used in study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
DRUG: Enfortumab vedotin
Bladder Cancer, Urinary Bladder
UT Southwestern
Sacituzumab Tirumotecan (MK-2870) Plus Pembrolizumab Versus TPC in TNBC Who Did Not Achieve pCR (MK-2870-012)
This is a randomized, open-label study comparing the efficacy and safety of adjuvant sacituzumab tirumotecan (MK-2870) in combination with pembrolizumab compared to treatment of physician's choice (TPC) in participants with triple-negative breast cancer (TNBC) who received neoadjuvant therapy and did not achieve a pathological complete response (pCR) at surgery. The primary objective is to compare sacituzumab tirumotecan plus pembrolizumab to TPC (pembrolizumab or pembrolizumab plus capecitabine) with respect to invasive disease-free survival (iDFS) per investigator assessment. It is hypothesized that sacituzumab tirumotecan plus pembrolizumab is superior to TPC with respect to iDFS per investigator assessment.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Heather McArthur
ALL
18 Years to old
PHASE3
NCT06393374
STU-2024-0480
Inclusion Criteria:
* Has centrally confirmed TNBC, as defined by the most recent American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines
* Has no evidence of locoregional or distant relapse, as assessed by the treating physician
* Had neoadjuvant treatment based on the KEYNOTE-522 regimen (pembrolizumab with carboplatin/taxanes and pembrolizumab with anthracycline-based chemotherapy) followed by surgery according to National Comprehensive Cancer Network (NCCN) treatment guidelines for TNBC
* Had adequate excision and surgical removal of all clinically evident disease in the breast and/or lymph nodes and have adequately recovered from surgery
* Has non-pathologic complete response at surgery
* Is able to continue on adjuvant pembrolizumab
* Randomization must be conducted within 16 weeks from surgical resection
* Completed adjuvant radiation therapy (if indicated) and recovered before randomization
* Has provided tissue from the surgical resection for central laboratory determination of trophoblast cell surface antigen 2 (TROP2) status
* If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention (120 days for sacituzumab tirumotecan and 95 days for capecitabine \[no restriction for pembrolizumab\]): agrees to refrain from donating sperm AND is either abstinent and agrees to remain abstinent or uses highly effective contraception
* For females (assigned at birth), is not pregnant or breastfeeding and ≥1 of the following applies: is not a participant of childbearing potential (POCBP) OR is a POCBP and uses highly effective contraception after the last dose of study intervention (210 days for sacituzumab tirumotecan, 120 days for pembrolizumab, and 185 days for capecitabine). Abstains from breastfeeding during the study intervention period and for at least 120 days after study intervention
* Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline (except alopecia)
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
* An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before first dose of study treatment
* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B birus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization
Exclusion Criteria:
* Has a known germline breast cancer gene (BRCA) mutation (deleterious or suspected deleterious) and is eligible for adjuvant therapy with olaparib where olaparib is approved and available
* Has Grade \>2 peripheral neuropathy
* History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to \>480 ms, and/or other serious cardiovascular and cerebrovascular diseases within 6 months prior to study intervention
* Received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)-directed antibody drug conjugate (ADC) or a topoisomerase I inhibitor-containing ADC
* Received anticancer therapy in the adjuvant phase including but not limited to chemotherapy, small molecule anticancer drugs, poly (adenosine diphosphate ribose) polymerase (PARP) inhibitors, ADCs, and/or immunotherapy, with the exception of adjuvant radiation therapy
* Is currently receiving a strong inducer/inhibitor of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of the study. The required washout period before starting sacituzumab tirumotecan is 2 weeks
* Except for pembrolizumab as neoadjuvant therapy for early-stage TNBC: received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein-4 \[CTLA-4\], OX-40 \[cluster of differentiation (CD) 134\], or CD137)
* Except for chemotherapy as neoadjuvant therapy for early-stage TNBC: Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization
* Received prior radiotherapy within 3 weeks of start of study intervention or required corticosteroids for radiation related toxicities that cannot be discontinued before the first dose of study intervention
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed
* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
* Has known additional malignancy that is progressing or has required active treatment within the past 5 years
* Has 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 the first dose of study medication
* Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed
* Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has active infection requiring systemic therapy
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has concurrent active hepatitis B and hepatitis C virus infection
* Has history of allogeneic tissue/solid organ transplant BIOLOGICAL: Pembrolizumab, BIOLOGICAL: Sacituzumab tirumotecan, DRUG: Capecitabine
Triple-Negative Breast Cancer, Breast - Female
UT Southwestern; Parkland Health & Hospital System
A Phase 2 Study of Vosoritide in Children With Idiopathic Short Stature
The purpose of this study is to evaluate i) the effect of multiple doses of vosoritide and ii) the effect of the therapeutic dose of vosoritide compared to human growth hormone (hGH)(hGH; only in the United States), in children with idiopathic short stature (ISS).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Daniel.Peter@UTSouthwestern.edu
Nadia Merchant
ALL
3 Years to 11 Years old
PHASE2
NCT06382155
STU-2024-0776
Key
• Height assessment corresponding to a height Z-score of ≤ -2.25 SDs in reference to the general population of the same age and sex, as calculated using the Centers for Disease Control and Prevention (CDC) growth charts
• Tanner Stage 1, at time of signing the ICF (unless too young to stage). Key Exclusions:
• Known chromosomal imbalance or genetic variant causing short stature syndrome, including but not limited to Laron syndrome, Prader-Willi syndrome, Russell-Silver Syndrome, Turner syndrome, disproportionate skeletal dysplasias, abnormal SHOX gene analysis, or Rasopathy (including Noonan syndrome)
• Previous treatment with a growth promoting agent
Inclusion Criteria:
• Height assessment corresponding to a height Z-score of ≤ -2.25 SDs in reference to the general population of the same age and sex, as calculated using the Centers for Disease Control and Prevention (CDC) growth charts
• Tanner Stage 1, at time of signing the ICF (unless too young to stage). Key Exclusions:
• Known chromosomal imbalance or genetic variant causing short stature syndrome, including but not limited to Laron syndrome, Prader-Willi syndrome, Russell-Silver Syndrome, Turner syndrome, disproportionate skeletal dysplasias, abnormal SHOX gene analysis, or Rasopathy (including Noonan syndrome)
• Previous treatment with a growth promoting agent
DRUG: Vosoritide Injection, DRUG: Human Growth Hormone, DRUG: Placebo
Idiopathic Short Stature
Children’s Health
Optimizing the Diagnostic Approach to Cephalosporin Allergy Testing (DACAT)
Cephalosporin antibiotics are commonly used but can result in allergic reactions and anaphylaxis. There is no clear diagnostic approach for cephalosporin-allergic patients, and guidance for the use of other antibiotics in allergic patients is based on side chain chemical similarity and limited skin testing evidence. This project includes a clinical trial and mechanistic studies to optimize the approach to cephalosporin allergy and advance future diagnostics.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Sophia.Lopez@UTSouthwestern.edu
David Khan
ALL
18 Years to 70 Years old
PHASE2
NCT06406114
STU-2024-1178
Inclusion Criteria:
• Age 18-70 years old.
• Reaction history consistent with a potential immediate hypersensitivity reaction (pruritus, urticaria, erythema, angioedema, bronchospasm, wheezing, shortness of breath, anaphylaxis, or hypotension) to cefazolin, ceftazidime, ceftriaxone, cefepime, cephalexin, cefaclor, cefadroxil, cefuroxime, cefpodoxime, cefdinir, or cefixime.
• English speaking or non-English speaking with translation services available.
Exclusion Criteria:
• Severe concomitant medical condition (e.g., unstable coronary artery disease, congestive heart failure, severe chronic obstructive pulmonary disease, poorly controlled asthma, chronic renal failure, cirrhosis, or end-stage liver disease.)
• History of Clostridioides difficile infection
• Chronic spontaneous urticaria or systemic mastocytosis
• Incident reaction required cardiopulmonary resuscitation
• Reaction to 2 or more cephalosporin antibiotics
• Active infection or antibiotic treatment within 7 days
• Treatment with systemic antihistamines or corticosteroids within 7 days
• Treatment with omalizumab or dupilumab within 60 days
• Significant immunosuppression
• Treatment with a beta-blocker or ACE inhibitor within 7 days
• Use of investigational drugs within 60 days of participation
• Anaphylaxis in the last 30 days
• Penicillin anaphylaxis within the past year confirmed with positive penicillin skin tests
• Prison or jail inmates, pregnant women, severe cognitive impairment
• Current, diagnosed, mental illness or current, diagnosed, or self-reported drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
• Inability or unwillingness of a participant to give written informed consent or comply with study protocol
DRUG: Beta-lactam antibiotic (cefazolin, cefuroxime, cefotaxime, ceftazidime, ceftriaxone, cefepime, pre-pen, penicillin G, ampicillin, and histamine) double-blind skin testing, DRUG: Culprit cephalosporin (cefazolin, ceftazidime, ceftriaxone, cefepime, cephalexin, cefaclor, cefadroxil, cefuroxime, cefpodoxime, cefdinir, or cefixime) double-blind placebo-controlled drug challenge, DRUG: Similar cephalosporin (cefepime, ceftriaxone, cefaclor, cephalexin, cefixime, or cefdinir) antibiotic double-blind placebo-controlled drug challenge, DRUG: Dissimilar cephalosporin (ceftriaxone or cefazolin) antibiotic double-blind placebo-controlled drug challenge, DRUG: Amoxicillin double-blind placebo-controlled drug challenge
Drug Allergy, Cephalosporin Allergy, Drug Hypersensitivity, Antibiotic Allergy, Beta Lactam Adverse Reaction, Drug-Induced Anaphylaxis, Cephalosporin Reaction
Allergy, Antibiotic, Cephalosporin, Penicillin, Beta-lactam, Drug challenge, Skin testing, Adverse reaction, Anaphylaxis, Perioperative anaphylaxis
UT Southwestern
Study of the Clinical and Radiological Impact of Ravulizumab in People With Neuromyelitis Optica Spectrum Disorder (AMAZE)
This is an observational study to: * evaluate the on-treatment clinical performance of ravulizumab in relation to the pre-treatment time period (time period prior to exposure), * enhance knowledge regarding conventional MRI outcomes in people with NMOSD treated with ravulizumab, * identify factors suggestive of subclinical disease progression through conventional MRI sequences, * determine if treatment with ravulizumab, impacts longitudinal 3D conformational MRI measures at the dorsal medulla and other regions of the CNS, and * identify biomarkers (e.g., serum neurofilament light chain (sNfL), conventional and novel MRI markers, etc.) related to disease activity.
Call 214-648-5005
studyfinder@utsouthwestern.edu, JOSE.SANTOYO@UTSouthwestern.edu
Darin Okuda
ALL
18 Years to old
NCT06398158
STU-2023-0744
Inclusion Criteria:
• Signed informed consent available prior to conduct of any study associated activities
• Men and women \> 18 years of age
• Aquaporin-4 IgG positive people with neuromyelitis optica spectrum disorder treated with commercially available ravulizumab in a manner consistent with the approved indication
• Expanded Disability Status Scale score of \<7.0
Exclusion Criteria:
• Individuals who are intolerant to MRI
• Individuals previously exposed to eculizumab with treatment discontinuation due to lack of effective disease control (i.e., clinical relapse or demonstration of MRI advancement after 12 weeks of sustained treatment exposure)
• Unresolved meningococcal disease
• History of an active infection
• Existing participation in neuromyelitis optical spectrum disorder interventional clinical studies
• Pregnant or lactating women
DRUG: Ravulizumab
Neuromyelitis Optica, Brain and Nervous System
UT Southwestern
A Study of Ocular Toxicity Evaluation and Mitigation During Treatment With Mirvetuximab Soravtansine in Participants With Recurrent Ovarian Cancer With High Folate Receptor-Alpha Expression
The purpose of this study is to evaluate the incidence rate and severity of prespecified mirvetuximab soravtansine (MIRV)-related ocular treatment-emergent adverse events (TEAEs) and assess prophylaxis strategies in all participants (symptomatic and asymptomatic) undergoing prospective ophthalmic evaluation with recurrent ovarian cancer (participants with either platinum-sensitive ovarian cancer \[PSOC\] or platinum-resistant ovarian cancer \[PROC\]) with high folate receptor alpha (FRα) expression.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Jayanthi Lea
FEMALE
18 Years and over
PHASE2
NCT06365853
STU-2024-0478
Inclusion Criteria:
* Participants must have a confirmed diagnosis of epithelial ovarian, fallopian tube, and primary peritoneal cancer (EOC) with high FRα expression.
* Participant's tumor must be FRα positive (FRα high) as defined by either the VENTANA FOLR1 (FOLR-2.1) IUO Assay, or the VENTANA FOLR1 ( FOLR1-2.1) RxDx Assay (hereafter collectively termed VENTANA FOLR1 Assay) (≥ 75% cells exhibit ≥ 2+ membrane staining intensity).
* Participants with known breast cancer susceptibility gene (BRCA) mutations (tumor or germline) must have received poly (ADP-ribose) polymerase inhibitors (PARPi).
* Participants must have completed prior therapy within the specified times below:
• Systemic antineoplastic therapy ≥ 5 half-lives or 4 weeks (whichever is shorter) before first dose of MIRV;
• Focal radiation completed ≥ 2 weeks before the first dose of MIRV. * Participants must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia). * Women of childbearing potential (WOCBP) must agree to use highly effective contraceptive method(s) while on MIRV and for ≥ 7 months after the last dose; and must have a negative pregnancy test ≤ 4 days before the first dose of MIRV.
Exclusion Criteria:
* Participants with borderline ovarian tumor or non-epithelial histology or mixed histology including borderline or non-epithelial histology will be excluded.
* PROC participants with primary platinum-refractory disease, defined as disease that did not respond to (complete response \[CR\] or partial response \[PR\]) or progressed within ≤ 3 months of the last dose of first line platinum-containing chemotherapy.
* Participants with \> Grade 1 peripheral neuropathy per National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0).
* Participants with significant active or chronic corneal disorders (for example, corneal dystrophies, degenerations, limbal stem cell deficiency), history of corneal transplantation, significant ocular inflammatory conditions (for example, active or recurrent uveitis), or other active ocular conditions requiring ongoing treatment/monitoring, such as uncontrolled glaucoma, active diabetic retinopathy with macular edema, macular degeneration requiring treatment ≤ 90 days before first dose, presence of papilledema, best corrected visual acuity (BCVA) worse than 20/70 in either eye, or monocular vision.
* Participants receiving corticosteroid or vasoconstricting eyedrops at baseline or within 5 weeks of Cycle 1 Day 1.
* Participants who received prior treatment with MIRV or other FRα-targeting agents. Note: Other protocol-defined inclusion and exclusion criteria may apply. DRUG: Mirvetuximab Soravtansine, DRUG: Lubricating Eye Drops, DRUG: Prednisolone acetate ophthalmic suspension 1% eye drops, DRUG: Brimonidine tartrate ophthalmic solution eye drops
Recurrent Ovarian Cancer, Folate Receptor-Alpha Positive, Ovary
UT Southwestern
A Study of Lower Radiotherapy Dose to Treat Children With CNS Germinoma
This phase II trial studies how well lower dose radiotherapy after chemotherapy (Carboplatin \& Etoposide) works in treating children with central nervous system (CNS) germinomas. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. 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 tumor cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Researchers want to see if lowering the dose of standard radiotherapy (RT) after chemotherapy can help get rid of CNS germinomas with fewer long-term side effects.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Matthew Campbell
ALL
3 Years to 29 Years old
PHASE2
NCT06368817
STU-2024-1003
Inclusion Criteria:
* Patients must be ≥ 3 years and \< 30 years at the time of study enrollment
* Patients must be newly-diagnosed primary localized germinoma of the suprasellar and/or pineal region by pathology and/or serum and/or CSF hCGbeta 5-50 mIU/mL AND institutional normal AFP (or ≤ 10 ng/mL if no institutional normal exists), including tumors with contiguous ventricular or unifocal parenchymal extension. No histologic confirmation required
* Patients with EITHER (A) bifocal (pineal + suprasellar) involvement OR (B) pineal lesion with diabetes insipidus (DI) AND hCGbeta ≤ 100 mIU/mL in serum and/or CSF AND institutional normal AFP (or ≤ 10 ng/mL if no institutional normal exists) in both serum and CSF. No histologic confirmation required
* Patients with hCGbeta 51-100 mIU/mL in serum and/or CSF and institutional normal AFP (or ≤ 10 ng/mL if no institutional normal exists) in both serum and CSF. Histologic confirmation of germinoma IS required
* Patients with germinoma of the basal ganglia and or/thalamic primary sites are eligible
* Patients with metastatic germinoma including non-contiguous disease or distant disease in the brain, ventricles, or spine are eligible
* Patients with germinoma admixed with mature teratoma are eligible
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age
* Patients must have eligibility confirmed by Rapid Central Imaging Review performed on APEC14B1-CNS
* Imaging studies must be obtained within 31 days prior to study enrollment and start of protocol therapy. (Note: for patients that have had surgery and post-operative imaging performed, it is the post-operative MRI that must be obtained within 31 days prior to enrollment.)
* Patients must have a cranial magnetic resonance imaging (MRI) with and without gadolinium at diagnosis/prior to enrollment. If surgical resection is performed, patients must have pre-operative and post-operative brain MRI with and without gadolinium. The post-operative brain MRI should be obtained within 72 hours of surgery. If patient has a biopsy only, post-operative brain MRI is recommended but not required
* Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to enrollment
* Patients must be enrolled, and protocol therapy must begin, no later than 31 days after definitive surgery or clinical diagnosis, whichever is later
* Patients must have eligibility confirmed by Rapid Central Tumor Marker Review performed on APEC14B1-CNS
* Lumbar CSF must be obtained prior to study enrollment unless medically contraindicated. If a patient undergoes surgery and lumbar CSF cytology cannot be obtained at the time of surgery, then it should be performed at least 10 days following surgery and prior to study enrollment. False positive cytology can occur within 10 days of surgery. Of note, lumbar CSF should not be performed prior to obtaining spine MRI, as this can make interpretation of the spine MRI less clear
* Patients must have CSF tumor markers obtained prior to study enrollment unless medically contraindicated. Ventricular CSF obtained at the time of CSF diversion procedure (if performed) is acceptable for tumor markers but lumbar CSF is preferred. In case CSF diversion and biopsy/surgery are combined, CSF tumor markers should be collected first. Ideally serum and CSF tumor markers should be collected at the same time and processed without delay
* For patients with solid tumors: Peripheral absolute neutrophil count (ANC) \>= 1000/uL (Must be performed within 7 days prior to enrollment unless otherwise indicated)
* For patients with solid tumors: Platelet count \>= 100,000/uL (transfusion independent) (Must be performed within 7 days prior to enrollment unless otherwise indicated)
* For patients with solid tumors: Hemoglobin \>= 8.0 g/dL (may receive red blood cell \[RBC\] transfusions) (Must be performed within 7 days prior to enrollment unless otherwise indicated)
* For pediatric patients (age 3-17 years): A serum creatinine based on age/sex as follows (Must be performed within 7 days prior to enrollment unless otherwise indicated):
* Age: 3 to \< 6 years; maximum serum creatinine (mg/dL): 0.8 (male); 0.8 (female)
* Age: 6 to \< 10 years; maximum serum creatinine (mg/dL): 1 (male); 1 (female)
* Age: 10 to \< 13 years; maximum serum creatinine (mg/dL): 1.2 (male); 1.2 (female)
* Age: 13 to \< 16 years; maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (female)
* Age: ≥ 17 years; maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female) OR a 24-hour urine creatinine clearance ≥ 70 mL/min/1.73 m\^2 OR a glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard).
* Note: Estimated GFR (eGFR) from serum or plasma creatinine, cystatin C or other estimates are not acceptable for determining eligibility.
* For adult patients (age 18 years or older) (Must be performed within 7 days prior to enrollment unless otherwise indicated):
* Creatinine clearance ≥ 70 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age (Must be performed within 7 days prior to enrollment unless otherwise indicated)
* Serum glutamic-pyruvic transaminase (SGPT) (alanine transaminase \[ALT\]) ≤ 135 U/L (Must be performed within 7 days prior to enrollment unless otherwise indicated)
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \> 94% if there is clinical indication for determination
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
* CNS toxicity =\< grade 2
* Patients must not be in status epilepticus, coma or assisted ventilation prior to study enrollment
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load are eligible for this study
Exclusion Criteria:
* Patients with any of the following malignant pathological elements are not eligible:
* Endodermal sinus (yolk sac)
* Embryonal carcinoma, choriocarcinoma
* Malignant/immature teratoma and mixed germ cell tumor (GCT) (i.e., may include some germinoma)
* Patients with only mature teratoma upon tumor sampling at diagnosis and negative tumor markers are not eligible
* Patients who have received any prior tumor-directed therapy for their diagnosis of germinoma other than surgical intervention and corticosteroids are not eligible
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
* Note: Serum and urine pregnancy tests may be falsely positive due to HCGbeta-secreting germ cell tumors. Ensure the patient is not pregnant by institutional standards
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met RADIATION: 3-Dimensional Conformal Radiation Therapy, PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Etoposide, RADIATION: Intensity-Modulated Radiation Therapy, PROCEDURE: Lumbar Puncture, PROCEDURE: Magnetic Resonance Imaging, OTHER: Questionnaire Administration, PROCEDURE: Surgical Procedure
Basal Ganglia Germinoma, Diabetes Insipidus, Germinoma, Pineal Region Germinoma, Suprasellar Germinoma, Thalamic Germinoma, Brain and Nervous System
Children’s Health
A Study of Lebrikizumab (LY3650150) in Participants With Chronic Rhinosinusitis and Nasal Polyps Treated With Intranasal Corticosteroids (CONTRAST-NP)
The main purpose of this study is to evaluate the efficacy and safety of lebrikizumab in participants with chronic rhinosinusitis and nasal polyps treated with intranasal corticosteroids. The study will last about 18 months.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Bellanira.Winkelman@UTSouthwestern.edu
Sei Chung
ALL
12 Years to old
PHASE3
NCT06338995
STU-2024-0309
Inclusion Criteria:
* Physician-diagnosed chronic rhinosinusitis (CRS) with bilateral nasal polyps (NP).
* Prior treatment with systemic corticosteroids (SCS) within the last 2 years (or a medical contraindication or intolerance to SCS), prior surgery for NP, or both.
* Endoscopic bilateral NPS score of at least 5 out of 8, with a minimum score of 2 in each nasal cavity performed at screening and baseline.
* Ongoing symptoms for at least 8 weeks prior to study entry (screening), including:
• Nasal congestion with moderate or severe symptom severity (score 2 or 3) at screening and a weekly average severity score of at least 1 (range 0 to 3) at randomization, and
• At least one other symptom, such as partial loss of smell (hyposmia), total loss of smell (anosmia), or anterior or posterior rhinorrhea. * Have concomitant asthma must be stable in the 3 months prior to screening using permitted regular asthma treatment. * Adolescent participants ≥12 to \<18 years of age and weighing ≥40 kg at time of Visit 1.
Exclusion Criteria:
* Have received a dose of lebrikizumab.
* Have received treatment with any rescue medication and/or have the need for surgery for NP during screening and/or run-in period.
* Allergen immunotherapy (subcutaneous immunotherapy \[SCIT\]/sublingual immunotherapy \[SLIT\]) initiated within 6 months prior to screening, that is not on a stable dose (3 months prior to screening).
* Has received a biologic treatment approved for use in CRSwNP, asthma, or AD, even if administered to treat a different condition, within 4 months or 5 half-lives, whichever is longer, prior to screening.
* Have received treatment with any biologic or systemic immunosuppressants for inflammatory disease or autoimmune disease prior to the baseline visit:
• B cell-depleting biologics, including rituximab, within 6 months.
• other biologics within 5 half-lives (if known) or 8 weeks, whichever is longer.
• Systemic immunosuppressants within 4 weeks prior to baseline. * Have had any sinus intranasal surgery (including nasal polypectomy) within 6 months prior to screening * Have had prior sino-nasal surgery or sinus surgery changing lateral wall structure of the nose making it difficult to assess endoscopic NPS * Have a presence of any of the following conditions that may impact the assessment of endpoints at screening or baseline:
• Nasal septal deviation occluding at least one nostril.
• Antrochoanal polyps.
• Acute sinusitis, acute nasal infection, or acute upper respiratory infection.
• Ongoing rhinitis medicamentosa.
• Presence of another diagnosis associated with NP (ie, eosinophilic granulomatosis with polyangiitis, granulomatosis with polyangiitis, Young's syndrome, primary ciliary dyskinesia, cystic fibrosis). Note: for adolescents, documentation for ruling out cystic fibrosis and primary ciliary dyskinesia is required.
• A nasal cavity tumor (malignant or benign).
• Evidence of fungal rhinosinusitis. * Have anosmia from COVID or any reason other than CRSwNP. * Participants with forced expiratory volume in 1 second (FEV1) 50% or less (of predicted normal) at screening. * Female participant who is pregnant, breastfeeding, or is planning to become pregnant, or to breastfeed during the study.
DRUG: LY3650150, DRUG: Placebo, DRUG: Standard therapy for INCS
Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)
UT Southwestern
The ROle of Compression StocKings in Heart Failure Patients (ROCK-HF)
Congestive heart failure (CHF) occurs when the heart is weak and not able to effectively pump blood to the body. One of the common manifestations of CHF is fluid overload and swelling of the legs. Diuretics or "water pills" are usually the treatment for fluid overload and leg swelling; however, in some patients' diuretics are no longer effective or the effectiveness is limited due to poor kidney function. The presence of chronic swelling of the legs could potentially damage the veins; additionally, it could lead to chronic skin changes in the legs and in the worst cases to a leg ulcer. Compression stockings are used in patients with venous diseases to reduce the swelling of the legs and improve mobility and quality of life. Although, there is a theoretical risk that compression stockings might push the fluid of the legs back to the heart and lungs worsening the CHF. The purpose of this study is to determine whether the use of knee-high tight socks (tight stockings with strong compression) vs. knee-high soft socks (soft stockings with minimum compression) are effective in preventing swelling and skin changes and safe in patients with CHF. During the first visit (in-person) a routine medical test will be performed including blood tests, review of the medication doses, current weight, an ultrasound images of the veins, (venous reflux ultrasound), questions about health status and a brief physical exam. The participants will be randomly assigned to receive tight compression vs. soft compression socks. Participants will be asked to wear the socks at least 8 hours a day for 5 days a week. There will be a total of 3 virtual visit (by video or telephone); the first one after one week, then after one month and two months. During the virtual visit participants will be asked about symptoms, current medications and doses, and current weight. The participants are expected to return to the clinic after 3 months for a second in-person visit. During this visit the investigators will ask questions about participant's health, they will perform a brief physical exam of their legs, and check participants weight and medicines; also, a venous ultrasound of the legs, questions about health status will be performed. The duration of the study is 3 months.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Gloria.Shibley@UTSouthwestern.edu
Rafael Cires-Drouet
ALL
18 Years to old
NA
NCT06350695
STU-2024-0855
Inclusion Criteria:
* Age 18 years and older
* Diagnosis of Heart failure NYHA II-III Class A, B, or C.
* Pitting edema of the lower extremities
Exclusion Criteria:
* Peripheral arterial disease with ABI of 0.5 or less
* Severe decompensated heart failure NYHA IV
* Unstable acute coronary syndrome
* Severe valvular stenosis or regurgitation
* Hypertrophic obstructive cardiomyopathy
* Unstable arrhythmia without a defibrillator
* On renal replacement therapy, hemodialysis of peritoneal dialysis
* Morbid obesity with a BMI \> 40
* Pregnancy
* Lymphedema or Lipoedema
* Unable to put the compression stockings on by him/ herself or a person to do it for the patient
* Septic phlebitis, acute bacterial, viral or allergic inflammation of the legs
* Expectancy of life less than 6 months
* Unable to read or understand English language DEVICE: low grade compression stockings (10-15 mmHg), DEVICE: high grade compression stockings (20-30 mmHg)
Heart Failure，Congestive, Leg Edema, Venous Insufficiency, Venous Ulcers
compression stockings, congestive heart failure, venous insufficiency, edema of the legs, venous ulcers
Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia
This phase II trial tests the addition of venetoclax and/or blinatumomab to usual chemotherapy for treating infants with newly diagnosed acute lymphoblastic leukemia (ALL) with a KMT2A gene rearrangement (KMT2A-rearranged \[R\]) or without a KMT2A gene rearrangement (KMT2A-germline \[G\]). Venetoclax is in a class of medications called B-cell lymphoma-2 (Bcl-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding venetoclax and/or blinatumomab to standard chemotherapy may be more effective at treating patients with ALL than standard chemotherapy alone, but it may also cause more side effects. This clinical trial evaluates the safety and effectiveness of adding venetoclax and/or blinatumomab to chemotherapy for the treatment of infants with KMT2A-R or KMT2A-G ALL.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Caroline Smith
ALL
to 365 Days old
PHASE2
NCT06317662
STU20251037
Inclusion Criteria:
* All patients must be enrolled on APEC14B1 and consented to eligibility screening (part A) prior to treatment and enrollment on AALL2321
* Infants (aged 365 days or less) on the date of diagnosis are eligible; infants must be \> 36 weeks gestational age at the time of enrollment
* Patients must have newly diagnosed B-acute lymphoblastic leukemia (B-ALL, 2017 World Health Organization \[WHO\] classification), also termed B-precursor ALL, or acute leukemia of ambiguous lineage (ALAL), which includes mixed phenotype acute leukemia. For patients with ALAL, the immunophenotype of the leukemia must comprise at least 50% B lineage
* Diagnostic immunophenotype: Leukemia cells must express CD19
Exclusion Criteria:
* Patients with Down Syndrome
* Patients with secondary B-ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy
* Patients must not have received any cytotoxic chemotherapy for either the current diagnosis of infant ALL or for any cancer diagnosis prior to the initiation of protocol therapy, with the exception of:
* Steroid pretreatment:
* PredniSONE, prednisoLONE, or methylPREDNISolone for ≤ 72 hours (3 days) in the 7 days prior to enrollment. The dose of predniSONE, prednisoLONE or methylPREDNISolone does not affect eligibility
* Inhaled and topical steroids are not considered pretreatment
* Note: Pretreatment with dexamethasone in the 28 days prior to initiation of protocol therapy is not allowed with the exception of a single dose of dexamethasone used during or within 6 hours prior to or after sedation to prevent or treat airway edema. However, prior exposure to ANY steroids that occurred \> 28 days before enrollment does not affect eligibility
* Intrathecal cytarabine or methotrexate:
* An intrathecal dose of cytarabine or methotrexate in the 7 days prior to enrollment does not affect eligibility
* Note: The preference is to defer the diagnostic lumbar puncture with intrathecal chemotherapy to day 1 of induction to allow for cytoreduction of circulating blasts and decrease the potential for central nervous system (CNS) contamination due to a traumatic tap. If done prior to day 1 of induction, these results will be used to determine CNS status
* Hydroxyurea:
* Pretreatment with ≤ 72 hours (3 days) of hydroxyurea in the 7 days prior to enrollment does not affect eligibility
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA) and National Cancer Institute (NCI) requirements for human studies must be met DRUG: Asparaginase Erwinia chrysanthemi, PROCEDURE: Biospecimen Collection, BIOLOGICAL: Blinatumomab, PROCEDURE: Bone Marrow Aspiration, DRUG: Calaspargase Pegol, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, DRUG: Cytarabine, DRUG: Daunorubicin, DRUG: Dexamethasone, DRUG: Doxorubicin, PROCEDURE: Echocardiography Test, PROCEDURE: FDG-Positron Emission Tomography, DRUG: Leucovorin, DRUG: Levoleucovorin, PROCEDURE: Lumbar Puncture, PROCEDURE: Magnetic Resonance Imaging, DRUG: Mercaptopurine, DRUG: Methotrexate, DRUG: Methylprednisolone, PROCEDURE: Multigated Acquisition Scan, DRUG: Prednisolone, DRUG: Prednisone, DRUG: Therapeutic Hydrocortisone, DRUG: Thioguanine, DRUG: Venetoclax, DRUG: Vincristine
Acute Leukemia of Ambiguous Lineage, B Acute Lymphoblastic Leukemia, Lymphoid Leukemia
Children’s Health
A Study of Sacituzumab Tirumotecan (MK-2870) as a Single Agent and in Combination With Pembrolizumab (MK-3475) Versus Treatment of Physician's Choice in Participants With HR+/HER2- Unresectable Locally Advanced or Metastatic Breast Cancer (MK-2870-010)
The purpose of this study is to compare sacituzumab tirumotecan as a single agent, and in combination with pembrolizumab, versus Treatment of Physician's Choice (TPC) in participants with hormone receptor positive/human epidermal growth factor receptor-2 negative (HR+/HER2-) unresectable locally advanced, or metastatic, breast cancer. The primary hypotheses are that sacituzumab tirumotecan as a single agent and sacituzumab tirumotecan plus pembrolizumab are superior to TPC with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR) in all participants.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Heather McArthur
ALL
18 Years to old
PHASE3
NCT06312176
STU-2024-0526
Inclusion Criteria:
* Has unresectable locally advanced or metastatic centrally-confirmed hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer
* Has radiographic disease progression on one or more lines of endocrine therapy for unresectable locally advanced/metastatic HR+/HER2- breast cancer, with one in combination with a CDK4/6 inhibitor
* Is a chemotherapy candidate
* Has an eastern cooperative oncology group (ECOG) performance status of 0 to 1 assessed within 7 days before randomization
* Has adequate organ function
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy
* Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load
* Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
Exclusion Criteria:
* Has breast cancer amenable to treatment with curative intent
* Has experienced an early recurrence (\<6 months after completing adjuvant/neoadjuvant chemotherapy) and therefore is eligible to receive second-line (2L) treatment
* Has symptomatic advanced/metastatic visceral spread at risk of rapidly evolving into life-threatening complications
* Has received prior chemotherapy for unresectable locally advanced or metastatic breast cancer
* Active autoimmune disease that has required systemic treatment in the past 2 years
* History of (noninfectious) pneumonitis/interstitial lung disease that requires steroids, or has current pneumonitis/interstitial lung disease
* Has an active infection requiring systemic therapy DRUG: Sacituzumab tirumotecan, BIOLOGICAL: Pembrolizumab, DRUG: Paclitaxel, DRUG: Nab-paclitaxel, DRUG: Capecitabine, DRUG: Liposomal doxorubicin
Breast Neoplasms, Breast - Female, Breast - Male
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
UT Southwestern; Parkland Health & Hospital System
Investigation of the BrioVAD System for the Treatment of Left Ventricular Heart Failure (INNOVATE)
The goal of this study is to evaluate the safety and efficacy of the BrioVAD System by demonstrating non-inferiority to the HeartMate 3 Left Ventricular Assist System when used for the treatment of advanced, refractory, left ventricular heart failure.
Call 214-648-5005
studyfinder@utsouthwestern.edu, salina.shrestha@utsouthwestern.edu
Matthias Peltz
ALL
18 Years to 100 Years old
NA
NCT06310031
STU20251696
Inclusion Criteria:
• Patient is ≥ 18 years of age.
• Patient has received institutional approval for LVAD implantation.
• Patient has a body surface area (BSA) ≥ 1.2 m2.
• Patient is classified as NYHA Class IV with advanced heart failure refractory to advanced heart failure management or NYHA Class III with dyspnea upon mild physical activity.
• Patient has a left ventricular ejection fraction (LVEF) ≤ 25% or LVEF \< 30% on inotropes or temporary MCS.
• Patient is inotrope dependent, OR has a cardiac index (CI) ≤ 2.2 liters/min/m2, while not on inotropes, and also meets one of the following criteria:
• Is on optimal medical management (OMM), based on current heart failure practice guidelines for at least 45 out of the last 60 days and is failing to respond or is not able to tolerate OMM; or
• Has advanced heart failure for at least 14 days and is dependent on an intra-aortic balloon pump (IABP) or temporary mechanical circulatory support device (MCSD) for at least seven days.
• Patient has provided voluntary and informed consent.
• Females of childbearing age agree to use adequate contraception and have a negative pregnancy test.
Exclusion Criteria:
• Patient's heart failure etiology is related to restrictive or constrictive physiology (e.g., nondilated hypertrophic cardiomyopathy, cardiac amyloidosis/senile or other infiltrative disease), complex congenital heart disease (e.g., transposition of the great vessels), uncorrected thyroid disease, and/or pericardial disease.
• Patient had a myocardial infarction within seven days of study enrollment.
• Patient had cardiothoracic surgery within 30 days of implant with the exception of a procedure to implant temporary MCS: Impella 5.5, Impella CP or TandemHeart.
• Patient has physiological conditions or comorbidities which pose high surgical risk or obstacles as determined by the Investigator.
• Patient has contraindications to warfarin anticoagulation.
• Patient has known hypo- or hypercoagulable state \[e.g., disseminated intravascular coagulation (DIC)\], or has a positive heparin-induced thrombocytopenia (HIT) assay and positive serotonin release assay or requires use of a non-heparin alternative anticoagulation strategy for cardiopulmonary bypass in the judgement of the Investigator.
• Patient is on durable MCS (e.g., LVAD or RVAD).
• Planned need for durable or temporary RVAD support concomitant with LVAD implant.
• Patient is on any form of pre-implant temporary MCS other than isolated LVAD support with an intra-aortic balloon pump, Impella 5.5, Impella CP, or TandemHeart.
• Patient is on any form of pre-implant temporary MCS and has a serum lactate dehydrogenase greater than 2.5 times the upper limits of normal or plasma free hemoglobin \> 40 g/dL.
• Patient has a history of organ transplantation.
• Patient has a mechanical aortic valve that may not be converted to a bioprosthetic valve at the time of VAD implant.
• Patient has a platelet count \< 50 k/μl.
• Patient has a history of confirmed untreated abdominal aortic aneurysm (AAA) \> 5 cm in diameter.
• Patient has moderate or severe aortic insufficiency that will not be corrected during the VAD implant procedure.
• Patient has an uncontrolled systemic infection.
• Patient has a positive COVID 19 test within 21 days of study enrollment and at least one high risk feature including need for supplemental oxygen or ferritin \>1000 ug/L.
• Patient has severe end-organ dysfunction as evidenced by one or more of the following criteria:
• Total bilirubin \> 3.0 mg/dL or cirrhosis confirmed by liver imaging or hemodynamic assessment with or without biopsy confirmation.
• International normalized ratio (INR) ≥ 2.0 or PTT \> 2.5 times control that is not related to anticoagulation therapy.
• Glomerular filtration rate (GFR) \< 30 mL/ min/1.73 m2 or need for renal replacement therapy.
• Severe pulmonary arterial hypertension with a pulmonary vascular resistance (PVR) ≥ 8 Wood units that is not acutely reversible with pharmacologic intervention.
• Severe chronic obstructive pulmonary disease (COPD) or restrictive lung disease requiring home oxygen or an FEV1/FVC \< 0.7 and FEV1 \< 40% predicted.
• Mechanical ventilation for more than three days present at the time of study enrollment.
• Documented history of pulmonary embolism or pulmonary infarct within 60 days of study enrollment.
• History of stroke within 90 days of study enrollment or history of stroke with a mRS ≥ 3 at the time of study enrollment.
• Symptomatic cerebrovascular disease and/or uncorrected carotid stenosis \> 80%.
• Significant peripheral vascular disease (PVD) accompanied by pain at rest or extremity ulceration.
• Pre-albumin \< 15 mg/dL and/or albumin \< 2.5 g/dL.
• Patient has a non-cardiac comorbidity or illness that would limit survival to less than two years.
• Patient has a psychiatric disease or disorder, or irreversible cognitive dysfunction, and/or insufficient social support or a history of non-adherence with medical instructions that is likely to impair study compliance.
• Patient is participating in an interventional clinical trial that may impact or confound the results of the INNOVATE Trial.
DEVICE: BrioVAD System, DEVICE: HeartMate 3
Cardiovascular Diseases, Heart Diseases, Heart Failure
Heart Failure, Left Ventricular Assist Device, Ventricular Dysfunction, Heart Disease, Cardiovascular Disease, Heart-assist Devices, Left Ventricular Assist System, BrioHealth Solutions
UT Southwestern
Study of Arlocabtagene Autoleucel (BMS-986393) a GPRC5D-directed CAR T Cell Therapy in Adult Participants With Relapsed or Refractory Multiple Myeloma (QUINTESSENTIAL)
The purpose of this study is to evaluate the effectiveness and safety of Arlocabtagene Autoleucel (BMS-986393) in participants with relapsed or refractory multiple myeloma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Larry Anderson
ALL
18 Years to old
PHASE2
NCT06297226
STU-2024-0516
Inclusion Criteria
* Documented diagnosis of multiple myeloma (MM) as per International Myeloma Working Group (IMWG) criteria.
* Received at least 4 classes of MM treatment \[including immunomodulatory drug (IMiD), proteasome inhibitor (PI), anti CD38 mAb, anti-BCMA therapy, and at least 3 prior lines of therapy (LOT).
* Documented disease progression during or after their last anti-myeloma regimen as per IMWG 2016 criteria.
* Participants must have measurable disease during screening.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Exclusion Criteria
* Active or history of central nervous system involvement with MM.
* Active systemic fungal, bacterial, viral, or other infection despite appropriate anti-infective treatment at the time of leukapheresis. Participants with severe infection, severe sepsis or bacteremia in the last 28 days prior to leukapheresis are excluded.
* Received any prior therapy directed at G protein-coupled receptor class C, group 5, member D (GPRC5D) or has received other prior treatment for MM without the required washout prior to leukapheresis.
* Other protocol-defined Inclusion/Exclusion criteria apply.
BIOLOGICAL: Arlocabtagene Autoleucel
Multiple Myeloma
Relapsed or Refractory Multiple Myeloma, Multiple Myeloma, BMS-986393, CAR T Cell Therapy, RRMM, Arlocabtagene Autoleucel
UT Southwestern
Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy for Advanced HER2-positive Biliary Tract Cancer
The purpose of this study is to evaluate the efficacy and safety of Zanidatamab plus CisGem (Cisplatin and Gemcitabine) with or without the addition of a programmed death protein 1/ligand-1 (PD-1/L1) inhibitor (physician's choice of either Durvalumab or Pembrolizumab, where approved under local regulations) as first line of treatment for participants with human epidermal growth factor receptor 2 (HER2)-positive biliary tract cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Hsieh
ALL
18 Years to old
PHASE3
NCT06282575
STU-2024-0655
Inclusion Criteria
• Histologically- or cytologically-confirmed Biliary Tract Cancer (BTC), including Gallbladder Cancer (GBC), Intrahepatic Cholangiocarcinoma (ICC), or Extrahepatic Cholangiocarcinoma (ECC).
• Locally advanced unresectable or metastatic BTC and not eligible for curative resection, transplantation, or ablative therapies.
• Received no more than 2 cycles of systemic therapy which is limited to Cisplatin and Gemcitabine (CisGem) with or without a PD-1/L1 inhibitor (physician's choice of durvalumab or pembrolizumab, where approved under local regulations) for advanced unresectable or metastatic disease.
• HER2-positive disease (defined as IHC 3+; or IHC 2+/ ISH+) by IHC and in situ Hybridization (ISH) assay (in participants with IHC 2+ tumors) at a central laboratory on new biopsy tissue or archival tissue from the most recent biopsy.
• Assessable (measurable or non-measurable) disease as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), per investigator assessment.
• Male or female ≥ 18 years or age (or the legal age of adulthood per country-specific regulations).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function
• Females of childbearing potential must have a negative pregnancy test result.
• Females of childbearing potential and males with a partner of childbearing potential must be willing to use 2 methods of birth control. Exclusion Criteria
• Prior treatment with a HER2-targeted agent
• Prior treatment with checkpoint inhibitors, other than durvalumab or pembrolizumab
• The following BTC histologic subtypes are excluded: small cell cancer, neuroendocrine tumors, lymphoma, sarcoma, mixed tumor histology, and mucinous cystic neoplasms detected in the biliary tract region.
• Use of systemic corticosteroids.
• Brain metastases
• Severe chronic or active infections
• History of allogeneic organ transplantation.
• Active or prior autoimmune inflammatory conditions
• History of interstitial lung disease or non-infectious pneumonitis.
• Participation in another clinical trial with an investigational medicinal product within the last 3 months.
• Females who are breastfeeding
• Any other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures.
• Use of phenytoin
• Histologically- or cytologically-confirmed Biliary Tract Cancer (BTC), including Gallbladder Cancer (GBC), Intrahepatic Cholangiocarcinoma (ICC), or Extrahepatic Cholangiocarcinoma (ECC).
• Locally advanced unresectable or metastatic BTC and not eligible for curative resection, transplantation, or ablative therapies.
• Received no more than 2 cycles of systemic therapy which is limited to Cisplatin and Gemcitabine (CisGem) with or without a PD-1/L1 inhibitor (physician's choice of durvalumab or pembrolizumab, where approved under local regulations) for advanced unresectable or metastatic disease.
• HER2-positive disease (defined as IHC 3+; or IHC 2+/ ISH+) by IHC and in situ Hybridization (ISH) assay (in participants with IHC 2+ tumors) at a central laboratory on new biopsy tissue or archival tissue from the most recent biopsy.
• Assessable (measurable or non-measurable) disease as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), per investigator assessment.
• Male or female ≥ 18 years or age (or the legal age of adulthood per country-specific regulations).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function
• Females of childbearing potential must have a negative pregnancy test result.
• Females of childbearing potential and males with a partner of childbearing potential must be willing to use 2 methods of birth control. Exclusion Criteria
• Prior treatment with a HER2-targeted agent
• Prior treatment with checkpoint inhibitors, other than durvalumab or pembrolizumab
• The following BTC histologic subtypes are excluded: small cell cancer, neuroendocrine tumors, lymphoma, sarcoma, mixed tumor histology, and mucinous cystic neoplasms detected in the biliary tract region.
• Use of systemic corticosteroids.
• Brain metastases
• Severe chronic or active infections
• History of allogeneic organ transplantation.
• Active or prior autoimmune inflammatory conditions
• History of interstitial lung disease or non-infectious pneumonitis.
• Participation in another clinical trial with an investigational medicinal product within the last 3 months.
• Females who are breastfeeding
• Any other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures.
• Use of phenytoin
DRUG: Zanidatamab, DRUG: Cisplatin, DRUG: Gemcitabine, DRUG: Pembrolizumab, DRUG: Durvalumab
Biliary Tract Cancer, Other Digestive Organ
JZP598, ZW25, HER-2 positive BIliary Tract cancer, Gallbladder Cancer, Intrahepatic Cholangiocarcinoma (ICC), Extrahepatic Cholangiocarcinoma (ECC), Zanidatamab, HER-2 overexpression, HER-2 amplification
UT Southwestern
Study of Pembrolizumab and Lenvatinib in Metastatic and Recurrent Cervix Cancer (LenPem Cervix)
The main purpose of this study is to gather information about an investigational drug combination, Lenvatinib in combination with pembrolizumab, that may help to treat cervical cancers. In this study, we are looking to see whether the combination of lenvatinib and pembrolizumab has any effect on slowing tumor growth in cervical cancer tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Jayanthi Lea
FEMALE
18 Years and over
PHASE2
NCT06266338
STU-2023-1118
Inclusion Criteria:
Participants are eligible to be included in the study only if all the following criteria apply:
• Female participants who are at least 18 years of age on the day of signing informed consent.
• Histologically confirmed diagnosis of squamous, adenocarcinoma or adenosquamous cervical cancer, that is recurrent or metastatic.
• Prior therapy: May have received up to 2 prior lines of systemic chemotherapy in the setting of advanced, metastatic (Stage IVB) or recurrent cervical cancer. May have received prior checkpoint inhibitor for advanced, metastatic (Stage IVB) or recurrent cervical cancer. May have received prior bevacizumab or antiangiogenic agent for recurrent or metastatic cervical cancer,
• Include whether prior checkpoint inhibitor was used in first line setting or second line setting.
• Prior Radiation therapy will be allowed and not counted as a line of treatment.
• Prior chemotherapy used as radiation sensitizer (e.g. cisplatin) used as treatment during chemoradiation will be allowed and counted as a line of treatment.
• Female participants: * A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: * Not a woman of childbearing potential (WOCBP) OR Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days post pembrolizumab or 30 days post lenvatinib whichever occurs last. The investigator should evaluate the potential for contraceptive method failure (i.e., noncompliance, recently initiated) in relationship to the first dose of study intervention. * A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention. * If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. * The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
• Participants must have a PD-L1 diagnostic test of primary or recurrent archival tumor tissue.
• Participants may have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all the following criteria:
• Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
• Has demonstrated disease progression after anti-PD-1/L1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented disease progression, in the absence of rapid clinical progression.
• Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb. i. Progressive disease is determined according to iRECIST. ii. This determination is made by the investigator. Once disease progression is confirmed, the initial date of disease progression documentation will be considered the date of disease progression.
• Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Archival tumor tissue sample or newly obtained \[core, incisional or excisional\] biopsy of a tumor lesion not previously irradiated has been provided. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
• Have an Eastern Cooperative Oncology Group performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
• Have adequate organ and marrow function as defined in the following table (Table 2). Specimens must be collected within 10 days prior to the start of study intervention.
• Criteria for known Hepatitis B and C positive subjects. Hepatitis B and C screening tests are not required unless: * Known history of HBV or HCV infection * As mandated by local health authority
• Hepatitis B positive subjects * Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization. * Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.
• Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening. \- Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.
• Have adequately controlled BP with or without antihypertensive medications, defined as BP ≤150/90 mmHg with no change in antihypertensive medications within 1 week prior to randomization.
• Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
• A WOCBP who has a positive urine pregnancy test within 72 hours prior to enrollment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
• Has received prior systemic anti-cancer therapy including investigational agents within 2 weeks prior to allocation.
• Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids. Note: 2 weeks or fewer of palliative radiotherapy for non-CNS disease, with a 1-week washout, is permitted.
• Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed. Note: please refer to Section 4.9 for information on COVID-19 vaccines.
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within seven days prior to the first dose of study drug.
• Known additional malignancy that is progressing or has required active treatment within the past five years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid)
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authority.
• Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection. Note: Hepatitis B and C screening tests are not required unless: * Known history of HBV and HCV infection * As mandated by local health authority
• Has had major surgery within three weeks prior to first dose of study interventions. Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
• Has had an allogenic tissue/solid organ transplant.
• Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula.
• Has urine protein ≥1 g/24 hours. Note: Participants with proteinuria ≥2+ (≥100 mg/dL) on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria.
• Has a LVEF below the institutional (or local laboratory) normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO).
• Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation. Note: The degree of proximity to major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy
• Prolongation of QTcF interval to \>480 ms.
• Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted.
• Gastrointestinal malabsorption or any other condition that might affect the absorption of Lenvatinib.
• Active hemoptysis (bright red blood of at least 0.5 teaspoon) within three weeks prior to the first dose of study drug.
DRUG: Pembrolizumab, DRUG: Lenvatinib
Cervix Cancer, Cervical Cancer, Cervix
UT Southwestern; Parkland Health & Hospital System
A Study of KK2269 in Adult Participants With Solid Tumors
This is a first-in-human study of KK2269. Part 1 and Part 2 will be conducted as a multicenter, open-label, non-randomized, dose-escalation study. Participants with advanced or metastatic solid tumors for which no standard therapy is available will be enrolled in Part 1. In Part 1, the primary objective is to assess the safety and tolerability of KK2269. In Part 2, only participants with gastric adenocarcinoma, GEJ adenocarcinoma, esophageal adenocarcinoma, or NSCLC who have experienced at least one systemic therapy will be enrolled. In Part 2, the primary objective is to assess the safety and tolerability of KK2269 in combination with docetaxel and to determine the recommended dose(s) and dose interval(s) of KK2269 in combination with docetaxel for subsequent studies. In both Part 1 and Part 2, participants who refuse to undergo standard therapy are also eligible.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Timothy Brown
ALL
18 Years to old
PHASE1
NCT06266299
STU-2024-1166
* Key Common Inclusion Criteria for Parts 1 and 2:
* Patients who are ≥ 18 years old at the time of informed consent
* Patients who have disease measurable by RECIST v1.1
* Patients with an ECOG PS of 0 or 1
* Patients with a life expectancy of at least 3 months in the judgement of the investigator or subinvestigator
* The specified periods have passed respectively after the completion of previous cancer treatments as of the date of enrollment at the time of the first dose of KK2269
* Patients who agree to use a medically effective method of contraception
* Key Additional Inclusion Criterion for Part 1:
•Patients with histological or cytological evidence of at least one locally advanced or metastatic non-CNS solid tumor
* Key Additional Inclusion Criteria for Part 2:
•Patients with histological or cytological evidence of any of the following disease: Gastric adenocarcinoma, GEJ adenocarcinoma, or esophageal adenocarcinoma, NSCLC (Only patients with NSCLC will be enrolled in the expansion part)
•Patients who are suitable for docetaxel treatment
* Key Common Exclusion Criteria for Parts 1 and 2:
* Patients with an uncontrolled or serious intercurrent illness
* Patients with known active central nervous system metastasis
* Patients with a history of ≥ Grade 3 allergic reaction to any antibody drug
* Patients with a history of autoimmune disease
* Patients with a history of HIV, HBV, or HCV at screening
* Patients who have a history of primary immunodeficiency
* Key Additional Exclusion Criterion For Part 2:
* Patients with a history of treatment with docetaxel
DRUG: KK2269, DRUG: Docetaxel
Advanced Solid Tumor, Metastatic Solid Tumor, Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Esophageal Adenocarcinoma, Non Small Cell Lung Cancer, Esophagus, Lung/Thoracic, Other Digestive Organ
UT Southwestern
A Long Term, Post-marketing Study of Immune Response in Patients Receiving Palynziq Treatment for PKU (PALisade)
This is a 10-year multi-center, prospective, longitudinal, single arm study evaluating immunologic, inflammatory and laboratory parameters associated with long-term Palynziq treatment in subjects with phenylketonuria (PKU) in the United States (US). Subjects in the US for whom a clinical decision has been made that they will receive pegvaliase to treat their PKU within 30 days following the date of enrollment in Study 165-501 (incident-users) or who have previously started treatment with pegvaliase at the date of enrollment in Study 165-501 (prevalent-users) are eligible for participation in Study 165-503.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Juana.Luevano@UTSouthwestern.edu
Markey McNutt
ALL
NCT06305234
STU-2023-0625
Inclusion Criteria:
* Subjects enrolled at US sites participating in the 165-501 study.
Exclusion Criteria:
* Legal incapacity or limited legal capacity without legal guardian representation.
* Subject is unable or unwilling to provide informed consent for the additional interventional burden of the study (blood sampling). DRUG: Pegvaliase
Phenylketonuria (PKU)
PKU, Phenylketonuria, Palynziq, pegvaliase, observational, safety study, immunogenicity assessment, inflammatory assessment
UT Southwestern
VO and Nivolumab vs Physician's Choice in Advanced Melanoma That Progressed on Anti-PD-1 & Anti-CTLA-4 Drugs [IGNYTE-3]
This is a randomized, controlled, multicenter, open-label Phase 3 clinical study comparing VO in combination with nivolumab versus Physician's Choice treatment for patients with unresectable Stage IIIb-IV cutaneous melanoma whose disease progressed on an anti PD-1 and an anti-CTLA-4 containing regimen (administered either as a combination regimen or in sequence) or who are not candidates for treatment with an anti-CTLA-4 therapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Wang
ALL
12 Years to old
PHASE3
NCT06264180
STU-2024-0547
Key
• Treatment with prior anti-PD-1 therapy must have continued for a minimum of 8 weeks (note: treatment with prior pembrolizumab therapy when administered every 6 weeks must have continued for a minimum of 12 weeks \[ie, 2 treatment cycles\]). Any number of doses of prior anti-CTLA-4 therapy may have been administered in combination with an anti-PD-1. The anti-PD-1-containing therapy must be the immediate prior line of treatment before randomization (for patients with BRAF mutation, see I 4).
• Patients who in the physician's judgement are not candidates for treatment with an anti-CTLA-4 antibody (eg, due to documented clinically significant comorbidities or history of immune-related adverse events) are eligible for the study if they have confirmed PD on an anti-PD-1 antibody (including unresectable disease relapse during adjuvant therapy or \< 6 months from completion of adjuvant therapy).
• Disease progression must have been confirmed and documented using clinical or radiological assessment by 2 assessments at least 4 weeks apart while being treated with an anti-PD-1 antibody and an anti-CTLA-4 antibody. Radiological confirmation of PD can occur during the Screening period for this study. Treatment with prior anti-PD-1 therapy must have continued from the time of initial tumor progression until confirmation of PD (ie, such that no doses of anti-PD-1 therapy were missed). Note: If radiographic progression at the initial scan where PD was documented is accompanied by clear clinical progression, defined as a decline in performance status directly attributed to disease or increased disease-related symptoms, anti-PD-1 therapy does not need to continue. For patients with documented PD while on adjuvant therapy with an anti-PD-1 therapy, a confirmatory biopsy can be used in place of a confirmatory scan. I 4. Has documented BRAF V600 mutation status or must consent to BRAF V600 mutation testing per local institutional standards during the Screening period. Patients with BRAF mutation should have received prior BRAF-directed therapy (with or without a MEK inhibitor) prior to randomization, unless deemed not clinically indicated at Investigator's discretion due to concurrent medical condition or prior toxicity. Note: Prior exposure to BRAF-directed therapy (with or without a MEK inhibitor) includes treatment in the adjuvant setting. One line of BRAF-directed therapy (with or without a MEK inhibitor) can be the most recent systemic treatment administered before randomization. I 5. Has least 1 measurable tumor of ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes) and injectable lesion(s) of at least 1 cm in longest diameter. I 6. Has adequate hematologic function, including:
• White blood cell (WBC) count ≥ 2.0 × 109/L
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
• Platelet count ≥ 75 × 109/L
• Hemoglobin ≥ 8 g/dL (without packed red blood cell \[RBC\] transfusion within 2 weeks of dosing) I 7. Has adequate hepatic function, including:
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN; \< 2.0 × ULN for patients with known Gilbert syndrome or liver metastases)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × ULN (or ≤ 5.0 × ULN, if liver metastases are present)
• Alkaline phosphatase (ALP) ≤ 2.5 × ULN (or ≤ 5.0 × ULN, if liver or bone metastases are present) I 8. Has adequate renal function, defined as serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 3 0 mL/minute/1.73 m2 (measured using Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula). I 9. Prothrombin time (PT) ≤ 1.5 × ULN (or international normalization ratio \[INR\] ≤ 1.3) and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. Note: Patients who are on chronic anticoagulant therapy may be randomized if the target INR is ≤ 2.5. For patients requiring deep injection of VO, the INR must be \<1.5 at the time of injection. I 10. ECOG performance status (PS) 0 to 1 for patients 18 and older or a Lansky PS ≥ 80 for patients 12 to 17 years of age. I 11. Life expectancy of at least 3 months. I 12. Female and male patients of reproductive potential must agree to avoid becoming pregnant or impregnating a partner and adhere to highly effective contraception requirements during the treatment period and for at least 6 months after the last dose of any study treatment. I 13. Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) test with a minimum sensitivity of 25 IU/L or equivalent units or β hCG within 7 days before the first dose of study treatment. I 14. Capable of giving signed informed consent which includes willingness to comply with the requirements and restrictions listed in the informed consent form (ICF) Key
Inclusion Criteria:
I 1. Male or female who is 12 years of age or older at the time of signed informed consent.
I 2. Patients with histologically or cytologically confirmed unresectable or metastatic Stage IIIb through IV/M1a through M1d cutaneous melanoma, as per AJCC staging system, 8th edition).
I 3. Confirmed disease progression (PD) on an anti-PD-1 antibody treatment and an anti-CTLA-4 antibody treatment, administered as either a combination regimen (eg, nivolumab + ipilimumab) or in sequence.
• Treatment with prior anti-PD-1 therapy must have continued for a minimum of 8 weeks (note: treatment with prior pembrolizumab therapy when administered every 6 weeks must have continued for a minimum of 12 weeks \[ie, 2 treatment cycles\]). Any number of doses of prior anti-CTLA-4 therapy may have been administered in combination with an anti-PD-1. The anti-PD-1-containing therapy must be the immediate prior line of treatment before randomization (for patients with BRAF mutation, see I 4).
• Patients who in the physician's judgement are not candidates for treatment with an anti-CTLA-4 antibody (eg, due to documented clinically significant comorbidities or history of immune-related adverse events) are eligible for the study if they have confirmed PD on an anti-PD-1 antibody (including unresectable disease relapse during adjuvant therapy or \< 6 months from completion of adjuvant therapy).
• Disease progression must have been confirmed and documented using clinical or radiological assessment by 2 assessments at least 4 weeks apart while being treated with an anti-PD-1 antibody and an anti-CTLA-4 antibody. Radiological confirmation of PD can occur during the Screening period for this study. Treatment with prior anti-PD-1 therapy must have continued from the time of initial tumor progression until confirmation of PD (ie, such that no doses of anti-PD-1 therapy were missed). Note: If radiographic progression at the initial scan where PD was documented is accompanied by clear clinical progression, defined as a decline in performance status directly attributed to disease or increased disease-related symptoms, anti-PD-1 therapy does not need to continue. For patients with documented PD while on adjuvant therapy with an anti-PD-1 therapy, a confirmatory biopsy can be used in place of a confirmatory scan. I 4. Has documented BRAF V600 mutation status or must consent to BRAF V600 mutation testing per local institutional standards during the Screening period. Patients with BRAF mutation should have received prior BRAF-directed therapy (with or without a MEK inhibitor) prior to randomization, unless deemed not clinically indicated at Investigator's discretion due to concurrent medical condition or prior toxicity. Note: Prior exposure to BRAF-directed therapy (with or without a MEK inhibitor) includes treatment in the adjuvant setting. One line of BRAF-directed therapy (with or without a MEK inhibitor) can be the most recent systemic treatment administered before randomization. I 5. Has least 1 measurable tumor of ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes) and injectable lesion(s) of at least 1 cm in longest diameter. I 6. Has adequate hematologic function, including:
• White blood cell (WBC) count ≥ 2.0 × 109/L
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
• Platelet count ≥ 75 × 109/L
• Hemoglobin ≥ 8 g/dL (without packed red blood cell \[RBC\] transfusion within 2 weeks of dosing) I 7. Has adequate hepatic function, including:
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN; \< 2.0 × ULN for patients with known Gilbert syndrome or liver metastases)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × ULN (or ≤ 5.0 × ULN, if liver metastases are present)
• Alkaline phosphatase (ALP) ≤ 2.5 × ULN (or ≤ 5.0 × ULN, if liver or bone metastases are present) I 8. Has adequate renal function, defined as serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 3 0 mL/minute/1.73 m2 (measured using Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula). I 9. Prothrombin time (PT) ≤ 1.5 × ULN (or international normalization ratio \[INR\] ≤ 1.3) and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. Note: Patients who are on chronic anticoagulant therapy may be randomized if the target INR is ≤ 2.5. For patients requiring deep injection of VO, the INR must be \<1.5 at the time of injection. I 10. ECOG performance status (PS) 0 to 1 for patients 18 and older or a Lansky PS ≥ 80 for patients 12 to 17 years of age. I 11. Life expectancy of at least 3 months. I 12. Female and male patients of reproductive potential must agree to avoid becoming pregnant or impregnating a partner and adhere to highly effective contraception requirements during the treatment period and for at least 6 months after the last dose of any study treatment. I 13. Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) test with a minimum sensitivity of 25 IU/L or equivalent units or β hCG within 7 days before the first dose of study treatment. I 14. Capable of giving signed informed consent which includes willingness to comply with the requirements and restrictions listed in the informed consent form (ICF) Key
Exclusion Criteria:
E 1. Primary mucosal or uveal melanoma. E 2. More than 2 lines of systemic therapy for advanced melanoma. Note: One additional line of anti-PD-1 therapy in the adjuvant or neoadjuvant setting is allowed if the patient was free of treatment and of PD for at least 6 months and subsequently had confirmed PD on an anti-PD-1 and an anti-CTLA-4 antibody therapy administered in the advanced setting.
E 3. Known acute or chronic hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known acute or chronic hepatitis C virus (defined as HCV RNA \[qualitative\] is detected).
Note: Patients who have been effectively treated are eligible for randomization. Patients must be negative for HBsAg and HCV RNA.
E 4. Known human immunodeficiency virus (HIV) infection. Note: Testing for HIV is not required unless mandated by local health authority or clinically indicated.
E 5. Active significant herpetic infections or prior complications of HSV-1 infection (eg, herpetic keratitis or encephalitis) or requires intermittent or chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir).
Note: Patients with sporadic cold sores may be randomized if no active cold sores are present at the time of first dose of study treatment.
E 6. Had systemic infection requiring IV antibiotics or other serious active infection requiring antimicrobial, antiviral, or antifungal treatment within 14 days prior to the first dose.
E 7. Evidence of spinal cord compression or at high risk of spinal cord compression.
E 8. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis at time of screening. Patients with known central nervous system metastases are eligible if they have received standard-of-care therapy for central nervous system disease (such as stereotactic radiosurgery or radical surgical resection followed by radiotherapy) and have evidence of disease stability on 2 subsequent scans performed at least at a 4-week interval.
E 9. Serum lactate dehydrogenase (LDH) \> 2 × ULN. E 10. Major surgery ≤ 2 weeks prior to starting study treatment. Note: Patients must have recovered adequately from all acute complications of all previous procedures prior to randomization.
E 11. Prior malignancy active within the previous 3 years, except for locally curable cancers that have apparently been cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ (without invasive component) of the prostate, cervix, or breast.
E 12. History of significant cardiac disease including myocarditis or congestive heart failure (defined as New York Heart Association Functional Classification III or IV), or unstable angina, serious uncontrolled cardiac arrhythmia, cerebral vascular accident, or myocardial infarction within 6 months from first dose of VO.
E 13. History of life-threatening toxicity related to prior immune therapy except those that are unlikely to recur with standard countermeasures (eg, hormone replacement after adrenal crisis).
E 14. History or evidence of psychiatric, substance abuse (including IV substance abuse), or any other clinically significant disorder, condition, or disease (with the exception of those described above) that, in the opinion of the Investigator or the Medical Monitor, would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion.
E 15. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
E 16. Active, known, or suspected autoimmune disease requiring systemic treatment.
E 17. History of (noninfectious) pneumonitis that required steroids or has current pneumonitis.
E 18. Prior oncolytic virus therapy or other therapy given by intratumoral administration.
E 19. Requires chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir).
E 20. Has received a live vaccine within 28 days prior to the first dose of study treatment.
E 21. Systemic anticancer therapies within 5 half-lives or 4 weeks of the first dose, whichever is shorter.
E 22. Is currently participating in or has participated in a study of an investigational agent within 4 weeks prior to the first dose of study treatment.
E 23. Has received prior radiotherapy within 2 weeks of start of study treatment or has not recovered from radiotherapy.
E 24. Conditions requiring treatment with immunosuppressive doses (\> 10 mg per day of prednisone or equivalent) of systemic corticosteroids other than for corticosteroid replacement therapy 14 days before randomization.
Note: Patients who require a brief course (≤ 7 days) or corticosteroids (eg, as prophylaxis for imaging studies due to hypersensitivity to contrast agents) are not excluded. Physiologic replacement doses of systemic corticosteroids are permitted, only if the dose does not exceed 10 mg/day prednisone equivalent.
E 25. History of allergy or sensitivity to study drug components (VO, nivolumab, pembrolizumab, or relatlimab) or to cisplatin or carboplatin or paclitaxel (dependent on cohort) or prior monoclonal antibody treatment.
E 26. Treatment with botanical preparations (eg, herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to treatment.
E 27. Is a person who is deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily. BIOLOGICAL: Vusolimogene Oderparepvec, BIOLOGICAL: Nivolumab, BIOLOGICAL: Nivolumab + Relatlimab, BIOLOGICAL: Pembrolizumab, DRUG: Single-agent chemotherapy
Advanced Melanoma, Melanoma, skin
UT Southwestern
A Study of Valemetostat Tosylate in Combination With DXd ADCs in Subjects With Solid Tumors
This study will evaluate the safety, tolerability, and efficacy of valemetostat tosylate in combination with DXd ADC in patients with advanced solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Timothy Brown
ALL
18 Years to old
PHASE1
NCT06244485
STU20240005
Key Inclusion Criteria
All participants must meet all of the following criteria, as well as all criteria from the relevant sub-protocol to be eligible for enrollment:
* At least 18 years or the minimum legal adult age (whichever is greater) at the time the ICF is signed.
* Has at least 1 measurable lesion based on investigator imaging assessment (computed tomography or magnetic resonance imaging) using RECIST v 1.1 at Screening.
* Is willing to provide an adequate tumor sample.
* Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at Screening.
Additional Key Inclusion for Sub-Protocol A:
* Diagnosed with pathologically documented breast cancer that:
• Is unresectable or metastatic.
• Has progressed on and would no longer benefit from endocrine therapy in hormone receptor-positive subjects in the opinion of the investigator.
• Has been treated with at least 1 and at most 2 prior lines of chemotherapy in the recurrent or metastatic setting.
• Has a history of low HER2 expression, defined as IHC 2+ /ISH-negative or IHC 1+ (ISH-negative or untested). ), as classified by the American Society of Clinical Oncology/College of American Pathologists 2018 HER2 testing guidelines.
• Was never previously HER2-positive (IHC 3+ or IHC 2+/ISH+) on prior pathology testing (per American Society of Clinical Oncology/College of American Pathologists guidelines Additional Key Inclusion for Sub-Protocol B: • Gastric or GEJ adenocarcinoma that is (a) unresectable or metastatic or (b) has progressed on trastuzumab or approved trastuzumab biosimilar-containing regimen. Additional Key Inclusion for Sub-Protocol C: * Pathologically documented Stage IIIB, IIIC, or IV non-squamous NSCLC with or without AGA at the time of enrollment. * Must meet prior therapy requirements: * Participants without AGA: (a) received platinum-based chemotherapy in combination with α-PD-1/α -PD-L1 mAb as a prior line of therapy or (b) received platinum-based chemotherapy and α -PD-1/ α -PD-L1 mAb (in either order) sequentially as 2 prior lines of therapy. * Participants with AGA: (a) has been treated with at least 1 or 2 prior lines of applicable targeted therapy that is locally approved for participant's genomic alteration at the time of Screening, (b) participants who have received platinum-based chemotherapy as a prior line of cytotoxic therapy, (c) may have received α -PD-1/α -PD-L1 mAb alone or in combination with a cytotoxic agent Key Exclusion Criteria * Has previously been treated with any enhancer of zeste homolog inhibitors. * Uncontrolled or significant cardiovascular disease. * Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. * Has leptomeningeal carcinomatosis or metastasis. * Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses. * Current use of moderate or strong cytochrome P450 (CYP)3A inducers. * Systemic treatment with corticosteroids (\>10 mg daily prednisone equivalents). * History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs). * Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection requiring treatment with intravenous (IV) antibiotics, antivirals, or antifungals. * Female who is pregnant or breastfeeding or intends to become pregnant during the study. * Psychological, social, familial, or geographical factors that would prevent regular follow-up. Additional Key Exclusion for Sub-Protocol A: * Has previously received any anti-HER2 therapy in the metastatic setting. * Has received prior treatment with an antibody-drug conjugate that consists of an exatecan derivative that is a topoisomerase I inhibitor, including either as part of prior treatment history or within prior participation in a clinical study. Additional Key Exclusion for Sub-Protocol B: \* Participants who have received an antibody-drug conjugate consisting of an exatecan derivative that is a topoisomerase I inhibitor. Additional Key Exclusion for Sub-Protocol C: \* Has received any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I or TROP2-targeted therapy including Dato-DXD
• Is unresectable or metastatic.
• Has progressed on and would no longer benefit from endocrine therapy in hormone receptor-positive subjects in the opinion of the investigator.
• Has been treated with at least 1 and at most 2 prior lines of chemotherapy in the recurrent or metastatic setting.
• Has a history of low HER2 expression, defined as IHC 2+ /ISH-negative or IHC 1+ (ISH-negative or untested). ), as classified by the American Society of Clinical Oncology/College of American Pathologists 2018 HER2 testing guidelines.
• Was never previously HER2-positive (IHC 3+ or IHC 2+/ISH+) on prior pathology testing (per American Society of Clinical Oncology/College of American Pathologists guidelines Additional Key Inclusion for Sub-Protocol B: • Gastric or GEJ adenocarcinoma that is (a) unresectable or metastatic or (b) has progressed on trastuzumab or approved trastuzumab biosimilar-containing regimen. Additional Key Inclusion for Sub-Protocol C: * Pathologically documented Stage IIIB, IIIC, or IV non-squamous NSCLC with or without AGA at the time of enrollment. * Must meet prior therapy requirements: * Participants without AGA: (a) received platinum-based chemotherapy in combination with α-PD-1/α -PD-L1 mAb as a prior line of therapy or (b) received platinum-based chemotherapy and α -PD-1/ α -PD-L1 mAb (in either order) sequentially as 2 prior lines of therapy. * Participants with AGA: (a) has been treated with at least 1 or 2 prior lines of applicable targeted therapy that is locally approved for participant's genomic alteration at the time of Screening, (b) participants who have received platinum-based chemotherapy as a prior line of cytotoxic therapy, (c) may have received α -PD-1/α -PD-L1 mAb alone or in combination with a cytotoxic agent Key Exclusion Criteria * Has previously been treated with any enhancer of zeste homolog inhibitors. * Uncontrolled or significant cardiovascular disease. * Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. * Has leptomeningeal carcinomatosis or metastasis. * Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses. * Current use of moderate or strong cytochrome P450 (CYP)3A inducers. * Systemic treatment with corticosteroids (\>10 mg daily prednisone equivalents). * History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs). * Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection requiring treatment with intravenous (IV) antibiotics, antivirals, or antifungals. * Female who is pregnant or breastfeeding or intends to become pregnant during the study. * Psychological, social, familial, or geographical factors that would prevent regular follow-up. Additional Key Exclusion for Sub-Protocol A: * Has previously received any anti-HER2 therapy in the metastatic setting. * Has received prior treatment with an antibody-drug conjugate that consists of an exatecan derivative that is a topoisomerase I inhibitor, including either as part of prior treatment history or within prior participation in a clinical study. Additional Key Exclusion for Sub-Protocol B: \* Participants who have received an antibody-drug conjugate consisting of an exatecan derivative that is a topoisomerase I inhibitor. Additional Key Exclusion for Sub-Protocol C: \* Has received any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I or TROP2-targeted therapy including Dato-DXD
DRUG: Valemetostat tosylate, DRUG: T-DXd, DRUG: Dato-DXd
Advanced Solid Tumor, Breast - Female, Breast - Male, Lung/Thoracic, Other
Advanced Solid Tumor, Valemetostat tosylate, DXD Antibody-drug Conjugates
UT Southwestern
A Phase 2 Study Evaluating Safety and Tolerability of RCT2100 (CFTR mRNA) in Healthy Participants and in Participants With CF
This is the first-in-human study with RCT2100 and is designed to provide safety and tolerability data for future clinical studies.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Maria.Mcleod@UTSouthwestern.edu
Raksha Jain
ALL
18 Years to 60 Years old
PHASE2
NCT06237335
STU-2024-0519
Part 1 Major
Inclusion Criteria:
* Healthy, adult, male or female, 18-55 years of age, inclusive, at screening.
* Body weight greater than or equal to 50 kg and body mass index (BMI) between 16-32 kg/m2, inclusive
* The participant has a forced expiratory volume in one second (FEV1) of at least 80% predicted
* The participant is considered by the investigator to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead ECG results, and physical examination findings at screening.
* Understands the study procedures in the informed consent form (ICF), and is willing and able to comply with the protocol.
Part 1 Major Exclusion Criteria:
* History or presence of clinically significant medical, surgical, clinical laboratory, or psychiatric condition or disease.
* The participant has supine blood pressure (BP) \>150 mm Hg (systolic) or \>90 mm Hg (diastolic), following at least 5 minutes of supine rest.
* The participant has abnormal clinical laboratory tests at screening, as assessed by the study-specific laboratory.
* The participant is a smoker or has used nicotine or nicotine-containing products 6 weeks before the first dose of study drug. Former smokers with greater than 10 pack years of smoking history are excluded.
Part 2 Major Inclusion Criteria:
* Confirmed diagnosis of CF
* Forced expiratory volume in 1 second ≥50% and ≤100% of predicted mean value for age, sex, and height
* a) Not eligible for CFTR modulators based on having mutations of CFTR gene on both alleles that are not responsive to CFTR modulator therapy OR
* b) Eligible for CFTR modulators (based on local prescribing information) but not using CFTR modulators due to intolerance or contraindications
Part 2 Major Exclusion Criteria:
* Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15)
* An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for sinopulmonary disease within 4 weeks before the first dose of study drug
* Lung infection with organisms associated with a more rapid decline in pulmonary status
* Arterial oxygen saturation on room air less than 94% at screening
* Treatment with a CFTR modulator (Kalydeco, Trikafta, Symdeko, Orkambi, or Alyftrek) within 12 weeks of Screening
Other protocol defined Inclusion/Exclusion criteria may apply.
Part 3 Major Inclusion Criteria:
* Confirmed diagnosis of CF
* Forced expiratory volume in 1 second ≥50% and ≤100% of predicted mean value for age, sex, and height
* a) Not eligible for CFTR modulators based on having mutations of CFTR gene on both alleles that are not responsive to CFTR modulator therapy OR
* b) Eligible for dual or triple CFTR modulators (based on local prescribing information) but not using CFTR modulators due to intolerance or contraindications
Part 3 Major Exclusion Criteria:
* Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15)
* An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for sinopulmonary disease within 4 weeks before the first dose of study drug
* Lung infection with organisms associated with a more rapid decline in pulmonary status
* Arterial oxygen saturation on room air less than 94% at screening
* Treatment with a CFTR modulator (Kalydeco, Trikafta, Symdeko, Orkambi, or Alyftrek) within 12 weeks of Screening
Other protocol defined Inclusion/Exclusion criteria may apply. DRUG: RCT2100, OTHER: Placebo, DRUG: RCT2100, DRUG: RCT2100, DRUG: Ivacaftor, DRUG: RCT2100
Cystic Fibrosis, Lung/Thoracic
Cystic Fibrosis, CF, mRNA
UT Southwestern
Escitalopram in Asthma Patients With Frequent Exacerbation
Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), such as escitalopram are widely used for mood and anxiety disorders. However, they have also been explored, with promising findings, for a variety of disorders outside of psychiatry. Clinical studies of SSRIs in depressed people with asthma were associated with decreased asthma exacerbations and improvement in asthma control. In this study, the number of asthma exacerbations will be assessed as the primary outcome measure in patients using escitalopram vs. placebo.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Reagan.Volzer@UTSouthwestern.edu
Edson Brown
ALL
18 Years to 75 Years old
PHASE2
NCT06216535
STU-2023-0494
Inclusion Criteria:
* Moderate to severe persistent asthma
* Treatment with medium to high dose ICS and LABA therapy
* Three or more severe asthma exacerbations (requiring ≥ 3 days of systemic corticosteroids) in the past year
* Age 18-75 years old, male or female sex, English or Spanish speaking
* Participants will be required to be clinically stable with no recent exacerbations, infections or changes in asthma controller therapy for at least 4 weeks before study entry
* Biologic therapy for asthma (e.g., omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, tezepelumab) will be allowed if started at least 6 months prior to randomization
Exclusion Criteria:
* Current substance use disorder and/or current tobacco use or greater than 10 pack-years lifetime use
* A current MDD episode as well as bipolar disorder, schizophrenia, or schizoaffective disorder
* Vulnerable populations including intellectual disability or other severe cognitive impairment, inmates, pregnant or nursing women or women of childbearing age who will not use UT Southwestern IRB-approved methods of birth control or abstinence during the study
* Currently taking an antidepressant (antidepressants that are not SSRIs nor SNRIs prescribed for an indication other than depression at subtherapeutic doses are acceptable)
* High risk for suicide defined as \> 1 past suicide attempts or any attempt within the past 12 months
* Severe or life-threatening medical illness that would make completion of study unlikely or clinically significant laboratory or ECG findings at baseline DRUG: Escitalopram, DRUG: Placebo
Asthma
Escitalopram, SSRI, Adults
UT Southwestern; Parkland Health & Hospital System
Trial of Naltrexone/Bupropion for the Treatment of Methamphetamine Use Disorder
The primary objective of this study is to evaluate the efficacy of extended release naltrexone plus bupropion XL (XR-NTX/BUP-XL) compared to matched injectable and oral placebo (iPLB/oPLB) in reducing methamphetamine (MA) use in individuals with moderate or severe methamphetamine use disorder (MUD) seeking to stop or reduce MA use.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Teresa.Slettebo@UTSouthwestern.edu
Manish Jha
ALL
18 Years to 65 Years old
PHASE3
NCT06233799
STU-2024-0033
Inclusion Criteria:
• Is 18 to 65 years of age;
• Meets DSM-5 criteria for moderate or severe MUD (4 or more criteria);
• Is interested in reducing or stopping MA use;
• Is able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study;
• Self-reports MA use on 18 or more days in the 30-day period prior to consent using the Timeline Followback (TLFB);
• Provides at least 2 urine samples positive for MA out of up to 3 tests, which will occur at least 2 days apart within a 10-day period;
• If assigned as female at birth and/or currently has a uterus, is not pregnant, agrees to use acceptable birth control methods, and have periodic urine pregnancy testing done during participation in the study unless documentation of hysterectomy provided;
• Is not physically dependent on opioids and meets subjective and objective measures of being opioid-free prior to naltrexone injection per study medical clinician's determination, including, if clinically required, a negative naloxone challenge;
• Is willing to comply with all study procedures and medication instructions;
• Agrees to use a smartphone app (downloaded for free to own device or on a study provided smartphone device) to take daily videos of medication dosing.
Exclusion Criteria:
• Has an acute medical or psychiatric disorder that would, in the judgment of the study medical clinician, make participation difficult or unsafe;
• Has suicidal or homicidal ideation that requires immediate attention;
• Has a history of epilepsy, seizure disorder, or head trauma with neurological sequelae (e.g., loss of consciousness that required hospitalization); current anorexia nervosa or bulimia; or any other conditions that increase seizure risk in the opinion of the study medical clinician;
• Has evidence of second or third degree heart block, atrial fibrillation, atrial flutter, prolongation of the QTc, or any other finding on the screening ECG that, in the opinion of the study medical clinician, would preclude safe participation in the study;
• Has Stage 2 hypertension as determined by the study medical clinician (e.g., greater than or equal to 160/100 in 2 out of 3 readings during screening);
• Has any elevated bilirubin test value per laboratory criteria OR any other liver function test (LFT) value \> 5 times the upper limit of normal per laboratory criteria;
• Has a platelet count \<100 x 10exp3/microliter;
• Has a body habitus that precludes gluteal intramuscular injection of XR-NTX in accordance with the administration equipment (needle) and procedures;
• Has a known allergy or sensitivity to bupropion, naloxone, naltrexone, PLG (polyactideco-glycolide), carboxymethylcellulose or any other component of the XR-NTX diluents;
• Has been in a prior study of pharmacological or behavioral treatment for MUD within 6 months of study consent;
• Has taken an investigational drug in another study within 30 days of study consent;
• Has been prescribed and taken naltrexone or bupropion within 30 days of study consent;
• Is concurrently enrolled in formal behavioral or pharmacological Substance Use Disorder (SUD) treatment services;
• Is receiving ongoing treatment with tricyclic antidepressants, xanthines (i.e., theophylline and aminophylline), systemic corticosteroids, nelfinavir, efavirenz, chlorpromazine, MAOIs, central nervous system stimulants (e.g., Adderall, Ritalin, etc.), or any medication that, in the judgment of the study medical clinician, could interact adversely with study medications;
• Has a current pattern of alcohol, benzodiazepine, or other sedative hypnotic use which would preclude safe participation in the study as determined by the study medical clinician;
• Requires treatment with opioid-containing medications (e.g., opioid analgesics) during the study period;
• Has a surgery planned or scheduled during the study period;
• Is currently in jail, prison or any inpatient overnight facility as required by court of law or have pending legal action or other situation (e.g., unstable living arrangements) that could prevent participation in the study or in any study activities;
• If assigned as female at birth and/or currently has a uterus, is currently pregnant, breastfeeding, or planning on conception.
DRUG: extended-release naltrexone (XR-NTX), DRUG: extended release bupropion (BUP-XL) tablets (BUP-XL), DRUG: iPLB, DRUG: oPLB
Methamphetamine-dependence, Methamphetamine Abuse, Psychiatric Disorders
UT Southwestern