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A Study of Evorpacept (ALX148) With Enfortumab Vedotin for Subjects With Urothelial Carcinoma (ASPEN-07)
AT148007 is a Phase 1, open-label, multicenter, safety, pharmacokinetic, pharmacodynamic study of ALX148 in combination with enfortumab vedotin and/or other anticancer therapies in subjects with urothelial carcinoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
All
18 Years and over
Phase 1
NCT05524545
STU-2022-1097
Inclusion Criteria:
• Histologically confirmed, unresectable locally advanced or metastatic urothelial carcinoma.
• Must have received prior treatment with an immune checkpoint inhibitor (CPI).
• Subjects must have received prior treatment with platinum-containing chemotherapy.
• Subjects must have had progression or recurrence of urothelial cancer.
• Subjects must have measurable disease according to RECIST (Version 1.1).
• Adequate bone marrow function.
• Adequate renal function.
• Adequate liver function.
• Adequate Eastern Cooperative Oncology Group (ECOG) performance status.
Exclusion Criteria:
• Preexisting sensory or motor neuropathy Grade ≥2.
• Presence of symptomatic or uncontrolled central nervous system (CNS) metastases.
• Prior treatment with enfortumab vedotin or other monomethylauristatin (MMAE)-based antibody-drug conjugate (ADCs)
• Prior treatment with any anti-CD47 or anti-signal regulatory protein-α (SIRPα) agent.
• Known active keratitis or corneal ulcerations. Subjects with superficial punctate keratitis are allowed if the disorder is being adequately treated.
• History of uncontrolled diabetes mellitus within 3 months of the first dose of study drug.
Drug: Evorpacept, Drug: Enfortumab Vedotin
Bladder Cancer, Urothelial Carcinoma, Urinary Bladder
UT Southwestern
Percutaneous Intervention Versus Observational Trial of Arterial Ductus in Low Weight Infants (PIVOTAL)
Patent Ductus Arteriosus is a developmental condition commonly observed among preterm infants. It is a condition where the opening between the two major blood vessels leading from the heart fail to close after birth. In the womb, the opening (ductus arteriosus) is the normal part of the circulatory system of the baby, but is expected to close at full term birth. If the opening is tiny, the condition can be self-limiting. If not, medications/surgery are options for treatment. There are two ways to treat patent ductus arteriosus - one is through closure of the opening with an FDA approved device called PICCOLO, the other is through supportive management (medications). No randomized controlled trials have been done previously to see if one of better than the other. Through our PIVOTAL study, the investigators aim to determine is one is indeed better than the other - if it is found that the percutaneous closure with PICCOLO is better, then it would immediately lead to a new standard of care. If not, then the investigators avoid an invasive costly procedure going forward.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Emilie.Vannguyen@UTSouthwestern.edu
Sushmita Yallapragada
ALL
7 Days to 32 Days old
NA
NCT05547165
STU-2022-1102
Inclusion Criteria:
• EPIs born between 22-weeks+0 days (220/7 wks) and 27-weeks+6 days (276/7 wks) gestation, inclusive
• Admitted to a study NICU
• Birth weight ≥700-grams
• Mechanically ventilated at time of consent and randomization
• HSPDA ("PDA Score" ≥6) noted on echocardiogram (ECHO)
• Randomization is able to be performed within 5 days of the qualifying ECHO and when infant is 7-32 days postnatal
Exclusion Criteria:
Clinical Exclusion Criteria
• Life-threatening congenital defects (including congenital heart disease such as aortic coarctation or pulmonary artery stenosis). PDA and small atrial/ventricular septal defects are permitted;
• Congenital lung abnormalities, (e.g. restrictive lung disease);
• Pharyngeal or airway anomalies (tracheal stenosis, choanal atresia);
• Treatment for acute abdominal process (e.g., necrotizing enterocolitis);
• Infants with planned surgery;
• Active infection requiring treatment;
• Chromosomal defects (e.g., Trisomy 18);
• Neuromuscular disorders;
• Infants whose parents have chosen to allow natural death (do not resuscitate order) or for whom limitation of intensive care treatment is being considered (e.g. severe intraventricular hemorrhage)
• Physician deems that the infant would not be a Percutaneous PDA Closure candidate due to clinical instability; however, if the infant's clinical status improves before 30-days postnatal and all inclusion criteria are still met, then the infant may be enrolled. ECHO-based Exclusion Criteria
• Pulmonary hypertension (defined by ductal right to left shunting for \>33% of the cardiac cycle) in which early PDA closure may increase right ventricular afterload and compromise pulmonary and systemic blood flow;
• Evidence of cardiac thrombus that might interfere with device placement;
• PDA diameter larger than 4 mm at the narrowest portion (consistent with FDA-approved instructions for Piccolo™ device use).
• PDA length smaller than 3 mm (consistent with FDA-approved instructions for Piccolo™ device use).
• PDA that does not meet inclusion requirements ("PDA Score" \<6).\* \* If a potential participant is found to have a PDA meeting eligibility requirements on a subsequent ECHO during the required period of 7 - 30 postnatal days of age, they may then be declared eligible to participate and enrolled, provided all other inclusion criteria are met and exclusion criteria are not met. Other Exclusion Criteria
• Parents or legal guardian do not speak English or Spanish
DEVICE: Percutaneous Patent Ductus Arteriosus Closure (PPC), COMBINATION_PRODUCT: Responsive Management Intervention, DIAGNOSTIC_TEST: Echocardiogram, cardiac
Ductus Arteriosus, Patent
PDA
Children’s Health
A Study of RGLS8429 in Patients With Autosomal Dominant Polycystic Kidney Disease
Primary Objectives - To assess the safety and tolerability of RGLS8429 - To assess the impact of RGLS8429 on ADPKD biomarkers Secondary Objectives - To assess the impact of RGLS8429 on height-adjusted total kidney volume (htTKV) - To characterize the pharmacokinetic (PK) properties of RGLS8429 - To assess the impact of RGLS8429 on renal function
Call 214-648-5005
studyfinder@utsouthwestern.edu, Luis.Madrigal@UTSouthwestern.edu
Ronak Lakhia
All
18 Years to 70 Years old
Phase 1
NCT05521191
STU-2022-0952
Key
• Male or female ADPKD patients, 18 to 70 years old
• Class 1C, 1D, or 1E Mayo Imaging Classification of ADPKD (based upon either the MRI obtained during screening, or a prior MRI obtained within 5 years of screening with documented Mayo classification)
• eGFR between 30 to 90 mL/min/1.73 m2
• Body mass index (BMI) 18 to 35 kg/m2
• Must understand and consent to the study procedures explained in the ICF and be willing and able to comply with the protocol Key
• Administration of tolvaptan in the 28 days before randomization
• Subject is mentally incapacitated or has significant emotional problems
• Any medical condition or social circumstance that, in the opinion of the Investigator, may make the subject unlikely to complete the study or comply with study procedures and requirements; or may pose a risk to the subject's safety
• History or presence of alcoholism or drug abuse within the past 2 years prior to screening
• Only one kidney or kidney transplant recipient
• Participation in another clinical trial and/or exposure to any investigational drug or approved therapy for investigational use within 28 days or 5 half-lives of the investigational drug's dosing, whichever is longer, prior to dosing. The 28-day or 5-half-life windows will be calculated from the date of the last dosing in the previous study to Day 1 of the current study.
Inclusion Criteria:
• Male or female ADPKD patients, 18 to 70 years old
• Class 1C, 1D, or 1E Mayo Imaging Classification of ADPKD (based upon either the MRI obtained during screening, or a prior MRI obtained within 5 years of screening with documented Mayo classification)
• eGFR between 30 to 90 mL/min/1.73 m2
• Body mass index (BMI) 18 to 35 kg/m2
• Must understand and consent to the study procedures explained in the ICF and be willing and able to comply with the protocol Key
Exclusion Criteria:
• Administration of tolvaptan in the 28 days before randomization
• Subject is mentally incapacitated or has significant emotional problems
• Any medical condition or social circumstance that, in the opinion of the Investigator, may make the subject unlikely to complete the study or comply with study procedures and requirements; or may pose a risk to the subject's safety
• History or presence of alcoholism or drug abuse within the past 2 years prior to screening
• Only one kidney or kidney transplant recipient
• Participation in another clinical trial and/or exposure to any investigational drug or approved therapy for investigational use within 28 days or 5 half-lives of the investigational drug's dosing, whichever is longer, prior to dosing. The 28-day or 5-half-life windows will be calculated from the date of the last dosing in the previous study to Day 1 of the current study.
Drug: RGLS8429, Drug: Placebo
Autosomal Dominant Polycystic Kidney Disease, ADPKD, Polycystic Kidney, Autosomal Dominant
UT Southwestern
A Study of ACR-368 in Ovarian Carcinoma, Endometrial Adenocarcinoma, and Urothelial Carcinoma
This is an open label Phase 1b/2 study to evaluate the efficacy and safety of ACR-368 as monotherapy or in combination with ultralow dose gemcitabine in participants with platinum-resistant ovarian carcinoma, endometrial adenocarcinoma, and urothelial carcinoma based on Acrivon's OncoSignature® test status.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Miller
ALL
18 Years and over
PHASE1
NCT05548296
STU-2023-0562
Inclusion Criteria:
General
• Participant must be able to give signed, written informed consent.
• Participant must have histologically confirmed, locally advanced (i.e., not amenable to curative surgery and/or radiation therapy) or metastatic cancer that has progressed during or after at least 1 prior therapeutic regimen.
• Participant must have at least 1 measurable lesion per RECIST v1.1 criteria (by local Investigator) (Eisenhauer, 2009) in a baseline tumor imaging that has been obtained within 28 days of the treatment start. Participant must have radiographic evidence of disease progression based on RECIST v1.1 criteria following the most recent line of treatment. Biochemical recurrence (eg, cancer antigen \[CA-125\] in ovarian carcinoma) only is not considered as disease progression.
• Participant must be willing to provide tissue from a newly obtained tumor biopsy from an accessible tumor lesion not previously irradiated after written informed consent. Newly obtained is defined as a specimen taken after written informed consent is obtained, during the 28-day Screening period.
• Participant must be willing to provide an archival tumor tissue block or at least 20 unstained slides, if available.
• Participant must have stabilized or recovered (Grade 1 or baseline) from all prior therapy related toxicities, except as follows:
• Alopecia is accepted.
• Endocrine events from prior immunotherapy stabilized at ≤ Grade 2 due to need for replacement therapy are accepted (including hypothyroidism, diabetes mellitus, or adrenal insufficiency).
• Neuropathy events from prior cytotoxic therapies stabilized at ≤ Grade 2 are accepted.
• Participant must have an Eastern Cooperative Oncology Group Performance Status 0 or 1.
• Participant must have an estimated life expectancy of longer than 3 months.
• Participant must have adequate organ function at Screening, defined as:
• Absolute neutrophil count \> 1500 cells/µL without growth factor support within 1 week prior to obtaining the hematology values at Screening.
• Hemoglobin ≥ 9.0 g/dL without transfusion or growth factor support within 2 weeks prior to obtaining the hematology values at Screening.
• Platelets ≥ 100,000 cells/µL without transfusion within 1 week prior to obtaining the hematology values at Screening.
• Calculated creatinine clearance ≥ 30 mL/min as calculated by the Cockcroft Gault formula.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN); ≤ 5 × ULN if liver metastases are present.
• Total bilirubin ≤ 1.5 × ULN not associated with Gilbert's syndrome. If associated with Gilbert's syndrome ≤ 3 x ULN is acceptable.
• Serum albumin ≥ 3 g/dL.
• Participant must have adequate coagulation profile as defined below if not on anticoagulation. If subject is receiving anticoagulation therapy, then subject must be on a stable dose of anticoagulation for ≥ 1 month:
• Prothrombin time within 1.5 x ULN.
• Activated partial thromboplastin time within 1.5 x ULN. Tumor Specific Inclusion Criteria For Ovarian Carcinoma:
• Participant must have histologically documented, advanced metastatic and/or unresectable) platinum resistant high-grade serous/endometrioid ovarian, primary peritoneal, or fallopian tube cancer. Platinum-resistant disease is defined as progression or relapse within 6 months after the completion of platinum-based therapy. a. Carcinosarcoma is eligible.
• Participant must have received at least 1 but no more than 6 prior lines of systemic therapy, including at least 1 line of therapy containing platinum derivative and taxane, and single-agent therapy must be appropriate as the next line of treatment:
• Participant must have had prior bevacizumab or did not receive bevacizumab based on Investigator judgment (see Section 2.1.1).
• Participants with or without documented test results assessing alterations in the DNA repair pathway genes, eg, Breast Cancer gene 1 (BRCA1), BRCA2, and homologous recombination deficiency, at Screening are eligible. Subjects with known BRCA mutated tumors should have received a PARP inhibitor maintenance or treatment.
• Participant will be enrolled regardless of tumoral folate receptor alpha (FRα) expression status. FRα expression status will be collected for retrospective analysis, if the information is available. For Endometrial Carcinoma
• Participant must have histologically documented, high-grade endometrial adenocarcinoma.
• All Grade 3 International Federation of Gynecology and Obstetrics epithelial endometrial histological subtypes are eligible including: endometrioid, serous, and clear-cell carcinoma.
• Carcinosarcoma is eligible.
• Participant must have no more than 4 prior lines of therapy in the recurrent setting, including platinum-based chemotherapy for subtypes of endometrial adenocarcinoma where it is a standard of care. The four lines of therapies must not include more than 3 lines containing a cytotoxic regimen.
• Participant must have documented failure (includes treatment discontinuation related to toxicity) or ineligibility (based on Investigator judgement) for prior anti-programmed cell death protein 1/anti-programmed death- ligand 1 (anti-PD 1/anti-PD L1) based therapy for advanced/metastatic disease. Prior combination of PD 1/PD L1 inhibitor and vascular endothelial growth factor tyrosine kinase inhibitor (TKI) is acceptable.
• Prior neoadjuvant or adjuvant chemotherapy included in initial treatment are not considered first- or later-line treatment unless such treatments were completed less than 6 months prior to the current tumor recurrence. Prior treatment may include chemotherapy, chemotherapy/radiation therapy, and/or consolidation/maintenance therapy.
• Prior treatment with hormonal therapy or inhibitors of the mTOR or CDK4/6 pathways are not considered a line of therapy in any setting. For Urothelial Carcinoma
• Participant must have histologically documented, advanced (metastatic and/or unresectable) urothelial carcinoma. Variant histology is allowed as long as the tumor is predominantly urothelial.
• Participants must have:
• Received a platinum containing regimen (cisplatin or carboplatin) in the metastatic/locally advanced, neoadjuvant, or adjuvant setting. If platinum was administered in the adjuvant/neoadjuvant setting, participant must have progressed within 12 months of completion.
• Been exposed to or have been ineligible for checkpoint inhibitors (including PD-1 or PD-L1 inhibitors).
• Been exposed to or have been ineligible for enfortumab vedotin.
Exclusion Criteria:
General
• Participant with known symptomatic brain metastases requiring \> 10 mg/day of prednisolone (or its equivalent). Participants with previously diagnosed brain metastases are eligible if they have completed their treatment, have recovered from the acute effects of radiation therapy or surgery prior to the start of ACR-368 treatment, fulfill the steroid requirement for these metastases, and are neurologically stable based on central nervous system imaging ≥ 4 weeks after treatment.
• Participant had systemic therapy or radiation therapy within 2 weeks prior to the first dose of study drug.
• Participants has known human immunodeficiency virus, hepatitis B, or hepatitis C infection that is considered uncontrolled based on the criteria included in Appendix 2.
• Participant has a history of clinically meaningful coagulopathy, bleeding diathesis.
• Participant has cardiovascular disease, defined as:
• Uncontrolled hypertension defined as blood pressure \> 160/90 mmHg at Screening confirmed by repeat (medication permitted).
• History of torsades de pointes, significant Screening electrocardiogram (ECG) abnormalities, including ventricular rhythm disturbances, unstable cardiac arrhythmia requiring medication, pathologic symptomatic bradycardia, left bundle branch block, second degree atrioventricular (AV) block type II, third degree AV block, Grade ≥ 2 bradycardia, uncorrected hypokalemia not amenable to correction, congenital long QT syndrome, prolonged QT interval due to medications, corrected QT based on Fridericia's formula (QTcF) \> 450 msec (for men) or \> 470 msec (for women).
• Symptomatic heart failure (per New York Heart Association guidelines; (Caraballo, 2019), unstable angina, myocardial infarction, severe cardiovascular disease (ejection fraction \< 20%, transient ischemic attack, or cerebrovascular accident within 6 months of Day 1).
• Participant has a history of major surgery within 4 weeks of Screening.
• Participant has a history of bowel obstruction related to the current cancer or participant has signs or symptoms of intestinal obstruction, which include nausea, vomiting, or objective radiologic finding of bowel obstruction in the last 4 weeks before the start of the treatment.
• Participant has taken a prior cell cycle CHK1 inhibitor, including ACR-368 Tumor Specific Exclusion Criteria For Ovarian Carcinoma:
• Participant has non-epithelial carcinoma, clear-cell, mucinous, germ-cell, low-grade serous, or low-grade endometrioid carcinoma.
• Participant has a history of clinically meaningful ascites, defined as a history of paracentesis or thoracentesis within 4 weeks of Screening. Participant has a planned therapeutic paracentesis or thoracentesis between Screening and Cycle 1 Day 1 dosing.
• Participant has a history of active inflammatory bowel disease within 2 years prior to Screening.
• Participant has a history of bowel perforation, fistula, necrosis, or leak within 8 weeks of Screening. For Endometrial Adenocarcinoma:
• Participant has low-grade endometrioid carcinoma.
• Participant has mesenchymal tumors of the uterus.
• Participant has a history of clinically meaningful ascites, defined as a history of paracentesis or thoracentesis within 4 weeks of Screening. Participant has a planned therapeutic paracentesis or thoracentesis between Screening and Cycle 1 Day 1 dosing. For Urothelial Carcinoma:
• Participant has sarcoma, carcinosarcoma, melanoma, or lymphoma of the bladder.
• Participant has not received a previous platinum-based regimen.
• Participant has small cell or neuroendocrine histology.
DRUG: ACR-368, DRUG: Gemcitabine, DIAGNOSTIC_TEST: OncoSignature
Platinum-resistant Ovarian Cancer, Endometrial Adenocarcinoma, Urothelial Carcinoma, Corpus Uteri, Ovary
Urothelial Carcinoma, Bladder Cancer, Urinary Bladder Neoplasm, Urologic Neoplasm, Urogenital Neoplasm, Endometrial Cancer, Endometrial Neoplasm, Ovarian Cancer, Ovarian Neoplasm, Ultralow dose gemcitabine, Platinum-resistant Ovarian Carcinoma
UT Southwestern
Study of JANX007 in Subjects With Metastatic Castration-Resistant Prostate Cancer (ENGAGER-PSMA-01)
studyfinder@utsouthwestern.edu
MALE
18 Years to 100 Years old
PHASE1
NCT05519449
Inclusion Criteria:
* Male ≥18 years of age at the time of signing informed consent
* Histologically or cytologically confirmed adenocarcinoma of the prostate
* For Dose Escalation and Backfill: Having mCRPC that progressed after at least one novel anti-androgen therapy and at least one taxane containing regimen. Participants who have actively refused a taxane containing regimen or are medically unsuitable to receive taxane are eligible
* Adequate organ function
* For Monotherapy Expansion Part a: Have received ≤ 2 anti-androgen therapies in either the HSPC or CRPC setting and no more than 1 prior taxane regimen in the HSPC or CRPC setting. Participants who have actively refused a taxane regimen or are medically unsuitable to receive taxane are eligible.
* For Monotherapy Expansion Part b: Have received ≤ 2 anti-androgen therapies in either the HSPC or CRPC settings
* For Monotherapy Expansion Part d: Have received ≤ 1 anti-androgen therapy and a poly(ADP-ribose) polymerase (PARP) inhibitor for mCRPC and have progressed following treatment with the PARP inhibitor
* For Combination Expansion: Have received ≤ 1 anti-androgen therapy other than darolutamide in the HSPC setting and ≤ 1 taxane in the mCRPC setting. Participants who have actively refused a taxane regimen or are medically unsuitable to receive taxane are eligible.
Exclusion Criteria:
* Prior solid organ transplant
* Prior treatment with PSMA-targeted CAR-T cell therapy or PSMA-CD3, PSMA-CD28 or other CD3 T-cell engaging bispecific antibodies or radioligand therapy
* Clinically significant cardiovascular disease
* For Monotherapy Expansion Part a: Prior receipt of any treatment other than an ARPI or taxane in the mCRPC setting
* For Monotherapy Expansion Part b: Prior receipt of any treatment other than an anti-androgen therapy or prior receipt of a taxane containing regimen or more than 1 prior line of therapy for mCRPC
* For Monotherapy Part d: More than 1 prior line of therapy for mCRPC or prior receipt of any treatment other than an anti-androgen therapy and PARP inhibitor for mCRPC or prior receipt of a taxane in the mCRPC setting
* For Combination expansion: More than 1 prior line of therapy for mCRPC or prior receipt of any treatment other than a taxane for mCRPC or prior receipt of Darolutamide or prior receipt of a taxane for HSPC
* Active clinically significant infection (bacterial, viral, fungal, mycobacteria or other)
* Any medical condition or clinical laboratory abnormality likely to interfere with assessment of safety or efficacy of study treatmentMelpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
MELPIDA is proposed for the treatment of subjects with SPG50 and targets neuronal cells to deliver a fully functional human AP4M1 cDNA copy via intrathecal injection to counter the associated neuronal loss. Outcomes will evaluate the safety and tolerability of a single dose of MELPIDA, which will be measured by the treatment-associated adverse events (AEs) and serious adverse events (SAEs). Secondarily, the trial will explore efficacy in terms of disease burden assessments.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Sydney.Cooper@UTSouthwestern.edu
Susan Iannaccone
ALL
4 Months to 10 Years old
PHASE1
NCT05518188
STU-2022-0886
Inclusion Criteria:
• Age 4 months-10 years old
• Confirmed diagnosis of SPG50 disease by:
• Genomic DNA mutation analysis demonstrating homozygous or compound heterozygous, confirmed pathogenic variants in the AP4M1 gene
• Clinical history or examination features consistent with SPG50 and that include neurologic dysfunction
• Parent/legal guardian willing to provide written informed consent for their child prior to participation in the study
• Subject able to comply with all protocol requirements and procedures
• Ability to stand for more than 5 seconds OR
• Ability to take 5 steps independently or with a walker OR
• Modified Ashworth Scale score 2 or below (Ankles).
Exclusion Criteria:
• Inability to participate in study procedures (as determined by the site investigator)
• Presence of a concomitant medical condition that precludes lumbar puncture (LP) or use of anesthetics
• History of bleeding disorder or any other medical condition or circumstance in which lumbar puncture is contraindicated according to local institutional policy
• Inability to be safely sedated in the opinion of the clinical anesthesiologist
• Active infection, at the time of dosing, based on clinical observations
• Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer
• Inability of the patient to undergo MRI according to local institutional policy
• Inability of the patient to undergo any other procedure required in this study
• The presence of significant non-SPG50 related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study
• Have received an investigational drug within 30 days prior to screening or plan to receive an investigational drug (other than gene therapy) during the study.
• Enrollment and participation in another interventional clinical trial
• Contraindication to MELPIDA or any of its ingredients
• Contraindication to any of the immune suppression medications used in this study
• Clinically significant abnormal laboratory values (GGT, ALT, and AST, or total bilirubin \> 3 × ULN, creatinine ≥ 1.5 mg/dL, hemoglobin \[Hgb\] \< 6 or \> 20 g/dL; white blood cell \[WBC\] \> 20,000 per cmm) prior to gene replacement therapy.
BIOLOGICAL: MELPIDA
Spasticity, Muscle, Microcephaly, Intellectual Deficiency, Growth Retardation, SPG50, Spastic Paraplegia
Children’s Health
Molecular and Clinical Risk-Directed Therapy for Infants and Young Children With Newly Diagnosed Medulloblastoma
This is a multi-center, multinational phase 2 trial that aims to explore the use of molecular and clinical risk-directed therapy in treatment of children 0-4.99 years of age with newly diagnosed medulloblastoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
ALL
to 59 Months old
PHASE2
NCT05535166
STU-2023-0119
Inclusion Criteria - Screening Phase (All Patients)
* Participants with presumptive/suspected newly diagnosed medulloblastoma.
* Participant meets one of the following criteria at the time of screening:
* Age \< 36 months OR Age ≥ 36 months and \< 60 months with presumptive/suspected non-metastatic disease
* Participant must have adequate tumor tissue from primary tumor for central review of pathology and molecular classification by methylation and IHC
* Participant must be able to begin treatment as outlined in the protocol within 36 days of definitive surgery (day of surgery is Day 0). In case a second surgery is clinically indicated to remove the residual tumor prior to starting treatment, the second surgery will be considered as the definitive surgery (Day 0).
* Parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines.
Exclusion Criteria - Screening Phase
* Participants with other clinically significant medical disorders (i.e., serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with the study procedure.
Inclusion Criteria - Study Enrollment (All Patients)
* Participant must be \< 60 months of age at time of enrollment.
* Note: Each treatment stratum has additional specific age requirements
* Participant must have confirmation of newly diagnosed medulloblastoma per Central Review:
* Central review includes histopathology, IHC and St. Jude Clinical Genomic Methylation Profiling conducted on MLPNet. If tissue or the extracted DNA does not meet quality control criteria for methylation analysis or if methylation classifier is unable assign molecular group/subgroup within the assigned classifier (MLPNet) parameters, then IHC will be used to define molecular group of these cases. IHC cannot be used to determine molecular subgroup. Therefore, IHC defined SHH patients will be enrolled on Stratum S-1 under "SHH-NOS", and all NWNS and indeterminate molecular group will be enrolled on stratum N.
* Note: Diagnosis of medulloblastoma, as well as group and subgroup assignment, will be done by central pathology review at St. Jude only. No outside testing is allowed for trial enrollment.
* Participant must have disease staged by MRI of the brain and spine and by cytologic examination of CSF\* and be placed into the following categories:
* M0: no evidence of metastatic disease.
* must include a negative CSF cytology result
* M1: Tumor cells found in the CSF but no other evidence of metastasis
* M2: Intracranial tumor beyond the primary tumor site
* M3: Metastatic disease in the spine
* M4: Extraneural metastatic disease
* \*All participants are to undergo CSF cytologic examination regardless of presence or absence of gross metastatic disease unless procedure is medically contraindicated. CSF is to be obtained by lumbar puncture (LP) performed at least 10 days after surgery. If LP is medically contraindicated, ventricular CSF from a shunt or Ommaya reservoir may be used for staging but this is not the preferred option due to lower sensitivity. If LP is medically contraindicated and the patient doesn't have a shunt or reservoir for CSF sampling, the treating physician should reach out to PI or Co-PI regarding decision on enrollment to SJiMB21. The decision to enroll without CSF cytology will be made on case-by-case basis.
* Note: Participants who have M2 disease and positive CSF will be assigned to M3.
* Note: Participants will be assigned to the highest stage number for which they meet eligibility.
* Note: Treatment stratums may have additional stage requirements.
* Patient must have received no previous radiotherapy, chemotherapy, or other brain tumor-directed therapy other than corticosteroid therapy and surgery.
* Participant must have a Lansky performance score of \> 30 (except for patients with posterior fossa syndrome.
* Participant must have adequate organ function prior to study entry, as defined by:
* Absolute neutrophil counts (ANC) \>750/mm\^3
* Platelet count ≥ 50,000/mm\^3 without support of a platelet transfusion within 7 days
* Hemoglobin ≥8.0 g/dL (with or without support of a blood transfusion).
* Normal liver function as defined by Alanine aminotransferase (ALT) concentration ≤ 3 x 45 U/L and total bilirubin ≤ 3 x 1.0.
* Adequate renal function as defined by a serum creatinine concentration:
* Age - 0 to \<1year; Maximum Serum Creatinine (mg/dl) - Male 0.5; Female 0.5
* Age - 1 to \< 2years; Maximum Serum Creatinine (mg/dl) - Male 0.6; Female 0.6
* Age - 1 to \< 2yearsr; Maximum Serum Creatinine (mg/dl) - Male 0.8; Female 0.8
* Participant's parent or legal guardian has the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines.
Inclusion Criteria - Stratum S-2
* Participant must have confirmed diagnosis of the following medulloblastoma molecular group and subgroup per Central Review.
* Medulloblastoma SHH-2
* Participant must meet one of the following criteria at time of enrollment:
* Age \<36 months OR Age ≥ 36 months and \< 60 months with non-metastatic disease (M0) Inclusion Criteria - Stratum S-1
* Participant must have confirmed diagnosis of one of the following medulloblastoma molecular subgroups per Central Review.
* Medulloblastoma SHH-1
* Medulloblastoma SHH-3
* Medulloblastoma SHH-4
* Medulloblastoma SHH-NOS
* Includes medulloblastoma cases that could not be assigned to a molecular subgroup using the DNA methylation classifier, but which are in the SHH group and/or cases defined as SHH by IHC.
* Participant must be \< 36 months of age at time of enrollment
* Note: Patients who are \< 36 months of age, regardless of metastatic status (M0/M+), are eligible for enrollment on stratum S-1.
Inclusion Criteria - Stratum N
* Participant must have confirmed diagnosis of one of the following medulloblastoma molecular subgroups per Central Review.
* Medulloblastoma G3
* Medulloblastoma G4
* Medulloblastoma - Not classified into SHH (i.e., NWNS or indeterminate)
* Includes medulloblastoma cases that could not be assigned to a molecular group using the DNA methylation classifier but which are in the NWNS class and/or defined as NWNS by IHC.
* Participant must be \<36 months of age at time of enrollment
* All NWNS patients (M+ and M0) are eligible for enrollment in stratum N
Exclusion Criteria - All Patients
* CNS embryonal tumor other than medulloblastoma, for example, patients with diagnosis of Atypical Teratoid/Rhabdoid Tumor (ATRT), PNET, Pineoblastoma, Ependymoma, and ETMR are excluded.
* Participant with prior treatment for medulloblastoma, including:
* Radiotherapy
* Chemotherapy
* Cancer directed immunotherapy
* Targeted agents
* NOTE: Corticosteroid therapy is acceptable; prior treatment with chemotherapy, immunotherapy or targeted agents for non-cancer directed indications are acceptable as long as these have been stopped at least 14 days prior to start of therapy or 2 half-lives from last dose. (i.e., methotrexate for juvenile rheumatoid arthritis, JAK inhibitor therapy for eczema, etc.)
* Participant who is actively receiving any other investigational agents.
* Participant with other clinically significant medical disorders (i.e., serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or results.
PROCEDURE: Surgical resection, PROCEDURE: Ommaya/VPS, DRUG: Methotrexate, DRUG: Cisplatin, DRUG: Vincristine, DRUG: Cyclophosphamide, DRUG: Carboplatin, DRUG: Topotecan, DRUG: Etoposide, DRUG: Pegfilgrastim, DRUG: Filgrastim, RADIATION: Irradiation, OTHER: Educational and Media Intervention, OTHER: SOC, Educational and Media Intervention
Medulloblastoma, Brain and Nervous System
SJiMB21, Brain Cancer, Brain Tumors in Children, Medulloblastoma Sonic Hedgehog subgroup 1, Medulloblastoma Sonic Hedgehog subgroup 2, Medulloblastoma Sonic Hedgehog subgroup 3, Medulloblastoma Sonic Hedgehog subgroup 4, Medulloblastoma Sonic Hedgehog-not otherwise specified, Medulloblastoma G3, Medulloblastoma G4, Medulloblastoma indeterminate, MLPNet, Neural Net Classification Pipeline, Non-WNT non-SHH medulloblastoma, Posterior fossa syndrome, St. Jude Brain Tumor Studies, Treatment for Brain Tumors in Infants and Young Children, Untreated Childhood Medulloblastoma
Children’s Health
Reduced-dose Botox for Urgency Incontinence Among Elder Females (RELIEF)
The purpose of this study is to study the treatment of urgency urinary incontinence (UUI), specifically among women 70 years and older, by comparing reduced versus standard dose of onabotulinumtoxinA (BTX; trade name BOTOX(c)) injection in the bladder.
Call 214-648-5005
studyfinder@utsouthwestern.edu, JOSE.SANTOYO@UTSouthwestern.edu
Ramy Goueli
FEMALE
70 Years and over
PHASE1
NCT05512039
STU-2022-0938
Inclusion Criteria:
• Adult female at least 70 years old at date of enrollment
• Urgency urinary incontinence (urge incontinence \> stress incontinence per screening criteria)
• On average 2 or more urgency or insensible incontinence episodes per day per patient report
• Refractory urinary urgency incontinence, defined as
• Persistent symptoms despite trial of one or more conservative treatments (e.g. behavioral therapy, physical therapy, home Kegel exercises); participants not required to have attempted first line therapies if deemed not feasible or appropriate by provider with input of participant/caregiver.
• Persistent symptoms despite the use of anticholinergic and/or beta-3 agonist medication; or inability to tolerate medication due to side effects, or has a contraindication to taking medication, or is unable to afford the cost of the medication.
• Currently not on an anticholinergic or beta-3 agonist medication or is willing to stop medication for 3 weeks prior to completing baseline bladder tally, with plan to remain off medication through duration of the study. Currently not actively using sacral neuromodulation therapy (either has not tried, or unit has been off for 4 weeks prior to baseline bladder tally and will remain turned off for the duration of the study). It is permissible for participants to continue self-led conservative therapies during participation in the study, including Kegel exercises, avoidance of bladder irritants, and urge suppression.
• Willing and able to complete all study-related items, with assistance of caregiver(s) if needed.
• Demonstrates awareness of possible need for catheterization in event of post-injection urinary retention \& acknowledges risks of catheterization. Participant does not need to demonstrate ability to perform self-catheterization.
• Grossly neurologically normal on exam and no gross systemic neurologic conditions believed to affect urinary function. Patients with a diagnosis of Parkinson's disease or diabetes may be eligible provided they have a grossly normal neurologic exam and otherwise fulfill the inclusion/exclusion criteria.
Exclusion Criteria:
• Lack of capacity to provide consent. Will be assessed if needed per judgment of the site PI and study staff, with use of optional questionnaire.
• Baseline persistently elevated post-void residual \[PVR\] (\>150mL on 2 occasions in the 6 weeks prior to enrollment). If the PVR was obtained via bladder scanner with measurements differing by more than 100mL, or if there is concern about the accuracy of the scanner, it will be confirmed via catheterization which will be considered the gold standard.
• Need for BTX injection to take place in the Operating Room or under sedation. (Of note, for repeat injection under the protocol, patients may have OR injection if indicated due to pain with initial BTX injection.)
• Previous treatment with intravesical BTX in the last 12 months or use of sacral neuromodulation therapy within the past 4 weeks (unit may remain implanted, but should remain off for duration of the study).
• Untreated symptomatic urinary tract infection (UTI). Eligible once UTI treatment complete and symptoms resolved.
• Known bladder abnormality, including current or prior bladder malignancy, carcinoma in situ or untreatable cystitis (e.g. eosinophilic cystitis); prior major bladder surgery that would alter the detrusor muscle, such as augmentation cystoplasty; or hematuria that has not been evaluated.
• Neurogenic detrusor overactivity or neurologic disease that may impact bladder function, including stroke, multiple sclerosis, peripheral neuropathy, spinal cord injury. Conditions such as Parkinson's disease and diabetes are acceptable provided normal bladder emptying and grossly normal neurologic function.
• Concurrent BTX use for other indication, participants cannot exceed 300 units BTX in a 3 month period. Participants who may have conflict between study BTX administration and administration for other purposes may be excluded from participation if there is concern that study drug administration will be compromised. Concurrent use of BTX for another indication that would not exceed 300 units in a 3 month period, or that can have time of administration of the other BTX adjusted to avoid excessive dose, is acceptable; for instance, for migraines.
• Greater than stage 2 pelvic floor prolapse, uncorrected or persistent despite pessary use (leading edge of prolapse not greater than 1cm beyond the hymen). Ongoing pessary use is permissible. Patients may have had a prior repair for pelvic organ prolapse. (see chart review of recent exam or perform brief exam while collecting post-void residual)
• Planned prolapse or stress incontinence surgery; would defer enrollment to \>3 months post-operative.
• Allergy or intolerance to lidocaine or BTX.
• Participation in another research study that could conflict with the RELIEF study, in estimation of the site PI.
DRUG: Botox 50 Unit Injection, DRUG: Botox 100 Unit Injection
Overactive Bladder, Urinary Incontinence in Old Age, Urgency Urinary Incontinence, Urinary Bladder
Urinary Incontinence, Urgency Urinary Incontinence, Overactive Bladder
UT Southwestern; Parkland Health & Hospital System
Treatment of Obstructive Sleep Apnea With Personalized Surgery in Children With Down Syndrome (TOPS-DS) (TOPS-DS)
The overall objective of this randomized clinical trial is to test the effectiveness of a personalized approach to the surgical treatment of OSA in children with Down syndrome (DS).The estimated prevalence of obstructive sleep apnea (OSA) in children with DS ranges from 45-83%, compared to 1-6% in the general pediatric population. Untreated OSA in children has been associated with daytime sleepiness, cognitive or behavioral problems, and cardiovascular complications, all which are common in children with DS. Adenotonsillectomy (AT) is the first line treatment for OSA in children, however, most large studies of AT outcomes have excluded children with DS. Available evidence demonstrates that AT is far less effective in children with DS than in the general pediatric population, with 48 to 95% of children with DS having persistent OSA after AT. Medical treatments such as positive airway pressure (PAP) therapy are frequently inadequate or poorly tolerated in this population, so many children with DS and OSA remain untreated. Drug-induced sleep endoscopy (DISE) enables direct observation of the sites and patterns of obstruction during sedated sleep using a flexible endoscope passed through the nose into the pharynx. DISE was developed to guide surgical decisions in adult OSA, and in recent years has also been used to design personalized surgical interventions in children. Using this DISE Rating Scale, the investigators have demonstrated that children with DS are more prone to tongue base and supraglottic obstruction than non-DS children, suggesting the need for more personalized surgical treatments that are tailored to the common sources of obstruction in this population. Several small case series demonstrate that DISE-directed surgery can be effective in treating OSA in children with DS. However, because there have been few prospective studies and no randomized trials comparing different treatment options in this population, there remains uncertainty about whether such a personalized approach leads to superior outcomes compared to the first line AT. It is the investigators' hypothesis that personalized DISE-directed surgery that uses existing procedures to address specific fixed and dynamic anatomic features causing obstruction in each child with DS will be superior to the current first line approach of AT. This novel approach may improve OSA outcomes and reduce the burden of unnecessary AT or secondary surgery for persistent OSA after an ineffective AT.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Francesca.Chambers@UTSouthwestern.edu
Ron Mitchell
ALL
2 Years to 17 Years old
NA
NCT05508971
STU-2022-0838
Requirements to participate in study:
Child has a diagnosis of Down syndrome (Trisomy 21). Child has a diagnosis of moderate to severe OSA diagnosed by PSG (oAHI ≥ 5). Child age is 2.00 to 17.99 years of age. Caregiver can provide signed and dated consent and is 18 years of age or older at the time of consent.
Caregiver can speak, read, and write in English or Spanish. Caregiver is primary caretaker of the child. Child is not expecting their own child. Child is eligible for surgical treatment
Cannot participate in study if:
Child has history of previous tonsillectomy, tonsillotomy, or partial tonsillectomy.
Child has any contraindication to surgery (e.g. bleeding disorders). Child has significant cardiopulmonary comorbidity besides OSA requiring supplemental oxygen, subglottic or tracheal stenosis, tracheostomy dependence.
Caregiver is unwilling or unable to comply with study procedures. Child is or plans to have their own child.
PROCEDURE: DISE-Directed Surgery, PROCEDURE: Adenotonsillectomy
Obstructive Sleep Apnea, Down Syndrome
Children’s Health
A Study to Evaluate the Safety and Efficacy of CT1812 in Early Alzheimer's Disease
This is a multicenter randomized, double-blind, placebo-controlled Phase 2 study designed to evaluate the efficacy, safety, and tolerability of two doses of CT1812 compared to placebo in participants diagnosed with early Alzheimer's disease.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Matthew.Jones@UTSouthwestern.edu
Brendan Kelley
ALL
50 Years to 85 Years old
PHASE2
NCT05531656
STU-2024-0467
Inclusion Criteria:
• Ages 50-85 years.
• Diagnosis of either MCI due to AD or mild AD dementia.
• MMSE 20-30 (inclusive).
• Amyloid PET scan of the brain or CSF biomarkers consistent with AD.
• Neuroimaging (MRI) obtained during screening consistent with the clinical diagnosis of Alzheimer's disease, as based on central read.
Exclusion Criteria:
• Screening MRI of the brain indicative of significant abnormality.
• Clinically significant abnormalities in screening laboratory tests.
• Clinical or laboratory findings consistent with:
• Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal dementia, Huntington's disease, Creutzfeldt-Jakob Disease, Down syndrome, etc.).
• Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral sclerosis, etc.).
• Other infectious, metabolic or systemic diseases affecting the central nervous system (syphilis, present hypothyroidism, present vitamin B12, other laboratory values etc.)
• A participant known to be actively infected with hepatitis B or hepatitis C at screening. History of acute/chronic hepatitis B or C and/or carriers of hepatitis B (seropositive for hepatitis B surface antigen \[HbsAg\] or anti-hepatitis C \[HCV\] antibody). Participants who have evidence of resolved hepatitis infection (e.g., HCV RNA negative) may be considered following discussion with the Medical Monitor.
• A current DSM-V diagnosis of active major depression or GDS \> 6, schizophrenia, or bipolar disorder.
DRUG: CT1812, DRUG: Placebo
Early Alzheimer's Disease, Brain and Nervous System
Alzheimer's Disease
UT Southwestern
Add-on Reparixin in Adult Patients With ARDS
Study objectives 1. To characterize the efficacy of reparixin in ameliorating lung injury and systemic inflammation and expediting clinical recovery and liberation from mechanical ventilation in adult patients with moderate to severe ARDS (PaO2/FIO2 ratio ≤ 200). 2. To evaluate the safety of reparixin vs. placebo in patients enrolled in the study.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Emily.Melikman@UTSouthwestern.edu
Christopher Choi
ALL
18 Years and over
PHASE2
NCT05496868
STU-2023-0193
Inclusion Criteria:
• Signed Informed Consent, according to local guidelines and regulation.
• Male and female adults (\>18 years old).
• Mechanically ventilated (invasive) patients with PaO2/FIO2 ratio ≤200 in the presence of PEEP of ≥5 cmH20.
• Respiratory failure not fully explained by cardiac failure or fluid overload (if acute Congestive Heart Failure exacerbation is identified as part of the clinical picture this should be addressed effectively and as soon as possible before the patient can be enrolled).
• Bilateral radiologic opacities consistent with pulmonary edema on the frontal chest x-ray (CXR), or bilateral ground glass opacities on a chest computerized tomography (CT) scan.
• ≤48 hours from fulfilling above ARDS criteria.
• ≤7 days from hospital admission.
• Females of child-bearing potential who are sexually active must be willing not to get pregnant within 30 days after the last Investigational Medicinal Product (IMP) dose and must agree to at least one of the following reliable methods of contraception:
• Hormonal contraception, systemic, implantable, transdermal, or injectable contraceptives from at least 2 months before the screening visit until 30 days after the last IMP dose;
• A sterile sexual partner;
• Abstinence. Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year will be admitted. For all female subjects with child-bearing potential, pregnancy test result must be negative before first drug intake.
Exclusion Criteria:
• Moderate-severe chronic hepatic disease (as verified by relevant history, imaging, if pre-existent, and Child-Pugh score B-C).
• Severe chronic renal dysfunction: eGFR (MDRD) \< 30 mL/min/1.73m2 or End Stage Renal Disease on renal replacement therapy.
• Participation in another interventional clinical trial.
• Patients that are clinically determined to have a high likelihood of death within the next 24 hours based on PI's estimation.
• Evidence of anoxic brain injury
• Currently receiving ECMO or high frequency oscillatory ventilation.
• Anticipated extubation within 24 hours of enrollment.
• Active malignancy (with the exception of non-melanotic skin cancers).
• Hemodynamic instability (\>30% increase in vasopressor in the last 6 hours or norepinephrine \> 0.5 mcg/Kg/min).
• Evidence of gastrointestinal (GI) dysmotility e.g., due to acute pancreatitis or immediate post-op state, as demonstrated by persistent gastric distention, enteral feeding intolerability and/or persistent gastric residuals \>500 ml).
• Anticipated discharge from the hospital or transfer to another hospital within 72 hours of screening.
• Decision to withhold or withdraw life-sustaining treatment (patients may still be eligible however if they are committed to full support except cardiopulmonary resuscitation if cardiac arrest occurs).
• History of:
• Documented allergy/hypersensitivity to more than one medication belonging to the class of sulfonamides, such as sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or celecoxib (hypersensitivity to sulphanilamide antibiotics alone, e.g., sulfamethoxazole does not qualify for exclusion), and to the study product and/or its excipients.
• Lactase deficiency, galactosemia or glucose-galactose malabsorption.
• History of GI bleeding or perforation due to previous Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) therapy or recurrent peptic ulcer/haemorrhage.
• Hypersensitive to ibuprofen.
• Active bleeding (excluding menses) or bleeding diathesis including patients on chronically high doses of NSAIDs.
• Pregnant or lactating women.
• Women of childbearing potential and fertile men who do not agree to use at least one primary form of contraception during the study and up to 30 days after the last IMP dose.
DRUG: Reparixin 600mg, OTHER: Matching Placebo
Acute Respiratory Distress Syndrome, Adult, Lung/Thoracic
ARDS, Reparixin
UT Southwestern
Efficacy, Safety, and Pharmacokinetics of Leuprolide Mesylate in Subjects With Central Precocious Puberty
The study will evaluate if Leuprolide Mesylate is safe and effective in the treatment of subjects with central (gonadotropin-dependent) precocious puberty, when administered as two injections six months apart.
Call 214-648-5005
studyfinder@utsouthwestern.edu, colten.youngblood@childrens.com
Perrin White
ALL
2 Years to 9 Years old
PHASE3
NCT05493709
STU-2023-0726
Inclusion Criteria:
• Females aged 2 to 8 years (inclusive) or males aged 2 to 9 years (inclusive).
• Confirmed diagnosis of CPP within 12 months of Baseline Visit (Day 0) but have not received prior GnRHa treatment for CPP.
• Pubertal-type LH response at 60 minutes post GnRHa stimulation test before treatment initiation \> 5 mIU/mL.
• Clinical evidence of puberty, defined as Tanner stage ≥ 2 for breast development in females or testicular volume ≥ 4 mL in males.
• Willing and able to participate in the study.
• Difference between bone age (Greulich and Pyle method) and chronological age ≥ 1 year.
• Bone age \< 13 years for girls and \< 14 years for boys.
• Signed Institutional Review Board/Independent Ethics Committee (IRB/IEC)-approved informed consent form (ICF) by one or both parents (per IRB/IEC requirements), by the custodial parent(s) or by the legal guardian(s) (if required).
• Signed Assent by patients as per IRB/IEC requirements.
Exclusion Criteria:
• Gonadotropin-independent (peripheral) precocious puberty: extra pituitary secretion of gonadotropins or gonadotropin-independent gonadal or adrenal sex steroid secretion. This includes true CPP triggered by other conditions, such as congenital adrenal hyperplasia.
• Prior or current GnRH treatment for CPP.
• Non-progressing isolated premature thelarche.
• Presence of an unstable intracranial tumor or an intracranial tumor requiring neurosurgery or cerebral irradiation. Patients with hamartomas or adenomas not requiring surgery are eligible.
• Any other condition, chronic illness or treatment that, in the opinion of the Investigator, may interfere with growth or other study endpoints (e.g., chronic steroid use \[except mild topical steroids\], renal failure, diabetes, moderate to severe scoliosis, previously treated intracranial tumor).
• Prior or current therapy with medroxyprogesterone acetate, growth hormone or insulin-like growth factor-1 (IGF-1).
• Major medical or psychiatric illness that could interfere with study visits.
• Diagnosis of short stature (i.e., 2.25 standard deviations (SD) below the mean height for age).
• Positive urine pregnancy test.
• Known hypersensitivity to GnRH or related compounds.
• Any other medical condition or serious intercurrent illness that, in the opinion of the Investigator, may make it undesirable for the patients to participate in the study.
• Any other condition(s) which could significantly interfere with Protocol compliance.
• Treatment with an investigational product within 5 half-lives of that product in prior clinical studies before the baseline visit (Day 0).
• Known history of seizures, epilepsy, and/or central nervous system disorders that may be associated with seizures or convulsions.
• Prior (within 6 months of Baseline (Day 0)) or current use of medications that, per Investigator opinion, have been associated with seizures or convulsions.
DRUG: Leuprolide Mesylate, Subcutaneous injection of 42 mg Leuprolide
Puberty, Precocious, Central
Children’s Health
A Study to Give Treatment Inside the Eye to Treat Retinoblastoma
This phase II trial tests the safety and side effects of adding melphalan (by injecting it into the eye) to standard chemotherapy in early treatment of patients with retinoblastoma (RB). RB is a type of cancer that forms in the tissues of the retina (the light-sensitive layers of nerve tissue at the back of the eye). It may be hereditary or nonhereditary (sporadic). RB is considered harder to treat (higher risk) when there are vitreous seeds present. Vitreous seeds are RB tumors in the jelly-like fluid of the eye (called the vitreous humor). The term, risk, refers to the chance of the cancer not responding to treatment or coming back after treatment. Melphalan is in a class of medications called alkylating agents. It may kill cancer cells by damaging their deoxyribonucleic acid (DNA) and stopping them from dividing. Other chemotherapy drugs given during this trial include carboplatin, vincristine, and etoposide. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Adding melphalan to standard chemotherapy early in treatment may improve the ability to treat vitreous seeds and may be better than standard chemotherapy alone in treating retinoblastoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
ALL
up to 18 Years old
PHASE2
NCT05504291
STU-2023-0581
Inclusion Criteria:
* Patient must be \< 18 years of age at enrollment
* Patient must have newly diagnosed intraocular (localized) retinoblastoma and meet one of the following criteria:
* Unilateral Group D retinoblastoma with vitreous seeding; OR
* Bilateral retinoblastoma with worst eye Group D, with vitreous seeding present and the contralateral eye is Group A-C; OR
* Bilateral Group D retinoblastoma with at least one eye with vitreous seeding; OR
* Bilateral retinoblastoma with one Group D eye with vitreous seeding and one Group E eye where the Group E eye has been enucleated prior to any therapy. Note exclusion for high-risk features
* Bilateral retinoblastoma with one Group D eye with vitreous seeding and one Group E eye where the Group E eye has not been enucleated prior to any therapy at the discretion of the treating physician. Note exclusion for patients with evidence of metastatic or extra orbital spread
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\<16 years of age
* Peripheral absolute neutrophil count (ANC) \>= 750/uL (must be performed within 7 days prior to enrollment unless otherwise indicated)
* Platelet count \>= 75,000/uL (transfusion independent) (must be performed within 7 days prior to enrollment)
* A serum creatinine based on age/gender as follows (must be performed within 7 days prior to enrollment; must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment):
* 1 month to \< 6 months = 0.4 (male and female)
* 6 months to \< 1 year = 0.5 (male and female)
* 1 to \< 2 years = 0.6 (male and female)
* 2 to \< 6 years = 0.8 (male and female)
* 6 to \< 10 years = 1.0 (male and female)
* 10 to \< 13 years = 1.2 (male and female)
* 13 to \< 16 years = 1.5 (male) and 1.4 (female)
* \>= 16 years = 1.7 (male) and 1.4 (female) OR - a 24-hour urine Creatinine clearance \>= 70 mL/min/1.73 m\^2 OR - a glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
* Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* For patients \< 1 month of age, serum creatinine levels must be \< 1.5 x the treating institution's creatinine upper limit of normal (ULN) for patients \< 1 month of age or the creatinine clearance or radioisotope GFR must be \>= 70 mL/min/1.73 m\^2
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment; must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (must be performed within 7 days prior to enrollment; must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
Exclusion Criteria:
* Patients with evidence of metastatic or extra-orbital spread
* Patients must not have an invasive infection at time of protocol entry
* Patients must not have had any prior anti-cancer therapy other than cryotherapy and/or laser therapy (green or infrared) to the study eye(s) and non-study eye, including systemic chemotherapy, intra-arterial chemotherapy, radioactive plaque, brachytherapy, or radiation therapy.
* Note: A study eye is defined as being Group D with vitreous seeding. Patients may have had enucleation of one eye as long as the remaining eye is Group D with vitreous seeds
* Patients with bilateral disease who undergo enucleation of a Group E eye prior to initiation of therapy and show evidence of high-risk histopathology features in the enucleated eye. High-risk histopathology includes choroid involvement \>= 3 mm, post lamina optic nerve involvement, full thickness scleral invasion or optic nerve invasion to the cut end
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Etoposide, PROCEDURE: Examination Under Anesthesia, PROCEDURE: Magnetic Resonance Imaging, DRUG: Melphalan, PROCEDURE: Ultrasound Biomicroscopy, DRUG: Vincristine
Bilateral Retinoblastoma, Childhood Intraocular Retinoblastoma, Group D Retinoblastoma, Stage I Retinoblastoma, Unilateral Retinoblastoma, Eye and Orbit
Children’s Health
The GORE® VIAFORT Vascular Stent Iliofemoral Study
This study is a prospective, non-randomized, multicenter, single-arm, clinical study to evaluate the performance, safety and efficacy of the GORE® VIAFORT Vascular Stent for treatment of symptomatic iliofemoral venous obstruction.
Call 214-648-5005
studyfinder@utsouthwestern.edu, christian.marsh@UTSouthwestern.edu
Michael Siah
ALL
18 Years and over
NA
NCT05489588
STU-2023-1240
Preoperative
Inclusion Criteria:
* Patient is at least 18 years of age.
* Patient is willing and able to comply with all follow-up evaluations as well as any required medication or compression regimen.
* Patient is able to provide informed consent.
* One of the following: Clinical severity class of CEAP 'C' classification ≥3 or rVCSS pain score ≥2.
* Intention to treat the target areas with only the GORE® VIAFORT Vascular Stent.
* Estimated life expectancy ≥1 year.
* Patient is ambulatory (use of assistive walking device such as a cane or walker is acceptable).
* Patient has adequate inflow to the target lesion(s), per investigator/sub-investigator discretion, involving at least a patent femoral or deep femoral vein.
* Presence of non-malignant symptomatic unilateral iliofemoral venous obstruction.
Preoperative Exclusion Criteria:
* Patient has DVT in the target areas with symptom onset date greater than 14 days but less than or equal to 90 days prior to treatment.
* Patient is a pregnant or breastfeeding woman, or a woman planning to become pregnant through the 12-month visit.
* Patient has clinically significant (e.g., symptoms of chest pain, hemoptysis, dyspnea, hypoxia, etc.) pulmonary embolism (confirmed via Computed Tomography Angiography) at the time of enrollment.
* Patient has a known uncorrectable bleeding diathesis or active coagulopathy meeting the following definitions: uncorrected INR\>2 (not as a result of warfarin or DOAC therapy), OR platelet count \<50,000 or \>1,000,000 cells/mm3, OR white blood cell count \<3,000 or \>12,500 cells/mm3.
* Patient has impaired renal function (eGFR \<30 mL/min/1.73m2) or is currently on dialysis.
* Patient has uncorrected hemoglobin of \<9 g/dL.
* Patient has known history of antiphospholipid syndrome (APS) or patients with hypercoagulable states that are unwilling to take anticoagulant medications on a long-term basis.
* Patient has known homozygous inherited coagulation defect or Protein C/S deficiency.
* Patient has a planned surgical intervention (other than pre-stenting procedures such as thrombolysis or thrombectomy) within 30 days prior to or within 30 days after the planned study procedure.
* Patient has had or requires open deep venous surgery in the target limb.
* Patient is currently participating in another investigational drug or device study that has not completed the primary endpoint or that clinically interferes with the endpoints of this treatment, in the opinion of the investigator/sub-investigator. Observational studies are permitted.
* Patient has had a previous major (i.e., above the ankle) amputation of the target lower limb.
* Patient has known sensitivity to device materials or contraindication to antiplatelets, thrombolytics, anticoagulants (including patients with known prior instances of Heparin Induced Thrombocytopenia type 2 (HIT-2)), or iodinated contrast.
* Patient has had prior stenting or grafts in the target vessels.
* Patient has a known or suspected active systemic infection at the time of the index procedure. Patients with a chronic infection (e.g., HIV, hepatitis C) that is well controlled under their current treatment regimen may be eligible.
* Patient has known history of intravenous drug abuse within one year of treatment.
* Patient has significant peripheral arterial disease (chronic Rutherford Type 2 or greater, acute Rutherford Type IIa or greater).
* Patient has a BMI \>40.
* Patient is actively undergoing or plans to begin cancer treatment.
Intraoperative Inclusion Criteria:
* Presence of non-malignant unilateral obstruction of the common femoral vein, external iliac vein, and/or common iliac vein defined as occlusion or at least 50% reduction in target vessel lumen as measured by procedural IVUS and venogram.
* Patient can accommodate an appropriately sized GORE® VIAFORT Vascular Stent as per reference vessel diameter (see IFU), as determined by intraoperative IVUS post pre-dilation.
* Patient must have appropriate access vessels to accommodate the delivery sheath for the selected device size.
* Patient has adequate landing zones free from significant disease requiring treatment within the native vessels beyond the proximal and distal margins of the lesion.
* Patient has adequate inflow to the target lesion(s), per investigator/sub-investigator discretion, involving at least a patent femoral or deep femoral vein.
* Lesion can be traversed with a guidewire.
* Disease involves only unilateral iliofemoral venous segments with intent to stent all affected iliofemoral segments. Patients with disease extending into the inferior vena cava or contra-lateral iliofemoral veins who are anticipated to require endovascular or surgical treatment within 12 months after investigational device implant will be excluded.
* Patient does not have significant (i.e., \>20% residual thrombosis) acute thrombus within the target stent area at the time of investigational device placement. Patients with acute thrombus within the target stent area must have thrombus successfully treated prior to investigational device placement. Successful thrombus treatment is defined as reestablishment of antegrade flow with ≤20% residual thrombosis as confirmed by IVUS and venogram, AND freedom from bleeding, vascular injury, or hemodynamically significant pulmonary embolism. After successful thrombus treatment, investigational device placement can occur within the same procedure. DEVICE: GORE® VIAFORT Vascular Stent
Venous Thromboses, Venous Disease, Venous Leg Ulcer, Venous Stasis, Venous Ulcer, Venous Stenosis, Venous Occlusion, Vein Thrombosis, Vein Occlusion, Vein Disease, Cardiovascular
VIAFORT, Vein Stent, Venous Thrombosis, Venous Stenosis, Gore, Venous Occlusion
UT Southwestern
Safety, Efficacy, and Pharmacokinetics of Tafamidis in Patients with Transthyretin-mediated Amyloidosis Post Orthotopic Heart Transplantation
Transthyretin cardiac amyloidosis (ATTR-CA) is a relentlessly progressive disease that can progress to end stage heart failure, at which point recently approved transthyretin production silencing or structure stabilizing therapies provide no clinical benefit. For well-selected individuals, heart transplantation is an excellent therapeutic option to improve survival. Historically, concomitant liver transplantation has been used to halt the progression of non-cardiac transthyretin amyloidosis (ATTR) manifestations, especially for individuals with TTR genotypes associated with significant neuropathy. However, despite this, patients continue to experience progressive non-cardiac manifestations, particularly gastrointestinal and neuropathic, which can have a substantial influence on post-heart transplantation morbidity. Concomitant liver transplantation is also associated with substantial morbidity and its future therapeutic role is questionable with recently established therapies for ATTR. Therefore, there is a clear unmet need to determine the utility and safety of ATTR targeted therapies for patients with recent heart transplantation for end-stage ATTR-CA. The central hypothesis of this proposal is that in patients who have received a heart transplantation for end-stage ATTR-CA, tafamidis therapy will be efficacious and well-tolerated. We aim to determine the safety and efficacy of tafamidis in stable patients who have undergone heart or combined heart/liver transplantation for ATTR (wild-type or variant) cardiac amyloidosis. The proposed study will be a single-arm intervention clinical trial with tafamidis. Because of the efficacy of tafamidis for both variant ATTR-CA and wild-type ATTR-CA, there is no clinical equipoise for an inactive-comparator placebo arm. The primary endpoint of this study will be serial change in plasma transthyretin (TTR) levels from baseline to 12 months at 3-month intervals. The secondary endpoints of this study will include serial changes in neuropathy assessments, modified body mass indices, incident transplant-specific adverse events, and pharmacokinetics of tafamidis. Observations from this study will establish the role of tafamidis use for the management of ATTR in patients after transplantation for end-stage ATTR-CA.
Call 214-648-5005
studyfinder@utsouthwestern.edu, YAMEI.CHENG@UTSouthwestern.edu
Justin Grodin
ALL
18 Years to 90 Years old
PHASE4
NCT05489523
STU-2022-0583
Inclusion Criteria:
* Has received orthotopic heart transplantation for end-stage ATTRv or ATTRwt ≥12 months prior to screening. Concomitant hepatic and renal transplantation with adequate allograft function are included.
* Has a stable immunosuppressive regimen and ≤ 10 mg of prednisone (or equivalent) at time of enrollment.
* Has a Karnofsky performance status ≥ 70%
Exclusion Criteria:
* Has previously received inotersen within the past 180 days, patisiran within the past 90 days, tafamidis within the past 14 days, or diflunisal in the past 14 days.
* Participating in a clinical trial for ATTR targeted therapies.
* Has an estimated glomerular filtration rate (eGFR) ≤ 15 ml/min/1.73 m2
* Has known leptomeningeal or AL amyloidosis
* Has active post-transplant lymphoproliferative disease
* Excluding non-melanomatous skin cancers, has an active malignancy.
* Has active infection with hepatitis B, hepatitis C, human immunodeficiency virus, or cytomegalovirus (CMV). For CMV, donor/ recipient exposure status and prior treated CMV disease on stable doses of antiviral therapies are not excluded.
* Has cardiac allograft dysfunction defined by left ventricular ejection fraction (LVEF) \<50% by echocardiogram within the past 3 months
* Has been treated for acute cellular or antibody mediated rejection in the past 3 months
* Has criteria to meet International Society for Heart and Lung Transplantation standardized nomenclature for severe coronary allograft vasculopathy ("ISHLT CAV3") DRUG: Tafamidis 61 MG
Transthyretin Cardiac Amyloidosis, Heart
heart transplantation, transthyretin amyloidosis, ATTR, tafamidis
UT Southwestern
Subclinical Transthyretin Cardiac Amyloidosis in V122I TTR Carriers
Approximately 1.5 million of the 44 million Blacks in the United States are carriers of the valine-to-isoleucine substitution at position 122 (V122I) in the transthyretin (TTR) protein. Virtually exclusive to Blacks, this is the most common cause of hereditary cardiac amyloidosis (hATTR-CA) worldwide. hATTR-CA leads to worsening heart failure (HF) and premature death. Fortunately, new therapies that stabilize TTR improve morbidity and mortality in hATTR-CA, especially when prescribed early in the disease. However, hATTR-CA is often diagnosed at an advanced stage and conventional diagnostic tools lack diagnostic specificity to detect early disease. The overall objectives of this study are to determine the presence of subclinical hATTR-CA and to identify biomarkers that indicate amyloid progression in V122I TTR carriers. The central hypothesis of this proposal is that hATTR-CA has a long latency period that will be detected through subclinical amyloidosis imaging and biomarker phenotyping. The central hypothesis will be tested by pursuing 2 specific aims: Aim 1) determine the association of V122I TTR carrier status with CMRI evidence of amyloid infiltration; Sub-aim 1) determine the association of V122I TTR carrier status with cardiac reserve; Aim 2) determine the association between amyloid-specific biomarkers and V122I TTR carrier status; and Sub-aim 2) determine the association of amyloid-specific biomarkers with imaging-based parameters and evaluate their diagnostic utility for identifying subclinical hATTR-CA. In Aim 1, CMRI will be used to compare metrics associated with cardiac amyloid infiltration between a cohort of V122I TTR carriers without HF formed by cascade genetic testing and age-, sex-, and race-matched non-carrier controls. For Sub-Aim 1, a sub-sample of carriers and non-carrier controls enrolled in Aim 1 will undergo novel exercise CMRI to measure and compare cardiac systolic and diastolic reserve. Aim 2 involves measuring and comparing amyloid-specific biomarkers in V122I TTR carriers without HF with samples matched non-carriers (both from Aim 1) and individuals with symptomatic V122I hATTR-CA from our clinical sites. These biomarkers detect and quantify different processes of TTR amyloidogenesis and include circulating TTR, retinol binding protein 4, TTR kinetic stability, and misfolded TTR oligomers. Sub-aim 2 will establish the role of these biomarkers to detect imaging evidence of subclinical hATTR-CA disease.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Amy.Browning@UTSouthwestern.edu
Justin Grodin
ALL
30 Years to 80 Years old
NCT05489549
STU-2022-0404
(V122I TTR carriers (or matched non-carriers))
Inclusion Criteria:
* Men and women ages 30-80 who are V122I TTR carriers (or matched non-carriers) without history of HF (this will be assessed by study personnel) and defined as: a) No history of hospitalization within the previous 12 months for management of HF; b) Without an elevated B-type natriuretic peptide level ≥100 pg/mL or NT-proBNP ≥360 pg/mL within the previous 12 months; or c) No clinical diagnosis of HF from a treating clinician
* Signed informed consent
Exclusion Criteria:
* A self-reported history or clinical history of HF
* Other known causes of cardiomyopathy
* History of light-chain cardiac amyloidosis
* Prior type 1 myocardial infarction (non-ST segment elevation myocardial Infarction {NSTEMI} or ST-elevation myocardial infarction {STEMI})
* Cardiac transplantation
* Body weight \>250 lbs
* Estimated glomerular filtration rate ≤30 mL/min/1.73 m2
* Inability to safely undergo CMRI
(For participants with symptomatic V122I hATTR-CA, we will enroll probands with HF from Aim 1 or patients with suspected symptomatic V122I hATTR-CA from the three study sites.)
Inclusion Criteria:
* Men and women ages 30-80 who have symptomatic V122I hATTR-CA as determined by a history of HF (this will be assessed by study personnel) and defined as: a) History of hospitalization within the previous 12 months for management of HF; b) An elevated B-type natriuretic peptide level ≥100 pg/mL or NT-proBNP ≥360 pg/mL within the previous 12 months; or c) A clinical diagnosis of HF from a treating clinician.
* Have an established or suspected diagnosis of hATTR-CA based on either a) Biopsy confirmed by Congo red (or equivalent) staining with tissue typing with immunohistochemistry or mass spectrometric analysis or immunoelectron microscopy, OR b) positive technetium-99m (99mTc)-pyrophosphate or -bisphosphonate scan, combined with accepted laboratory criteria without abnormal M-protein.
* TTR gene sequencing that is pending or that is confirming the V122I variant
* Signed informed consent
Exclusion Criteria:
* Other known causes of cardiomyopathy
* History of light-chain cardiac amyloidosis
* Cardiac transplantation
* Liver transplantation
* Previous treatment with a TTR stabilizer (tafamidis, acoramidis) within the prior 14 days or TTR any silencer (inotersen, patisiran, eplontersen)
* Estimated glomerular filtration rate ≤30 mL/min/1.73 m2 Amyloidosis, Hereditary, Amyloidosis Cardiac, Amyloidosis, Familial, Transthyretin-Related (ATTR) Familial Amyloid Cardiomyopathy, Transthyretin Gene Mutation, Cardiovascular
Amyloidosis, Transthyretin Amyloidosis, V122I TTR, p.Val142Ile TTR, Cardiac magnetic resonance imaging
UT Southwestern
Heat Waves and the Elderly - Cooling Modalities
The purpose of this study is to assess how well cooling modalities work in reducing cardiovascular stress of the elderly to heat wave conditions
Call 214-648-5005
studyfinder@utsouthwestern.edu, Taysom.Wallace@UTSouthwestern.edu
Craig Crandall
ALL
65 Years and over
NA
NCT05484739
STU-2022-0625
Inclusion Criteria:
* 65 years of age or older
* Free of any significant underlying medical problems based upon a detailed medical history and physical exam
Exclusion Criteria:
* Known heart disease
* Other chronic medical conditions requiring regular medical therapy including cancer, diabetes, uncontrolled hypertension, and uncontrolled hypercholesterolemia etc;
* Abnormality detected on routine screening suggestive of provokable ischemia or previously undetected cardiac disease or resting left bundle branch block on screening electrocardiogram.
* Current smokers, as well as individuals who regularly smoked within the past 3 years
* Subject with a body mass index ≥31 kg/m2
* Pregnant individuals OTHER: Water Spray, OTHER: Fan, OTHER: Water Spray and Fan, OTHER: Control
Aging, Hyperthermia
aging, heat wave, cardiovascular, low-energy cooling
UT Southwestern
Study of Cabozantinib and Nivolumab in Metastatic Castration Resistant Prostate Cancer (CANOPY)
This is a multicenter, single-arm, two-stage open-label phase 2 study of the combination of cabozantinib + nivolumab in subjects with advanced castration-resistant prostate cancer (CRPC).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Qian Qin
MALE
18 Years and over
PHASE2
NCT05502315
STU-2023-0313
Inclusion Criteria:
Subjects must meet all of the following applicable inclusion criteria to participate in this study:
* Willing and able to provide, or have a legally authorized representative provide, written informed consent and HIPAA authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed. NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.
* Males 18 years of age and above.
* Histological or cytological proof of prostate adenocarcinoma or mixed adenocarcinoma/neuroendocrine tumors. Pure small cell of the prostate is not allowed.
* ECOG status of ≤ 2
* Progressive mCRPC as defined: 1) castrate levels of serum testosterone \< 50 ng/dL AND 2) progressive disease as defined by PSA or radiographic progression. Subjects with measurable and non-measurable disease (i.e., bone only metastases) are allowed. NOTE: ENROLLMENT of subjects with non-measurable disease (i.e., bone only metastases) will be capped at 50% of enrollment target (n=25).
* Must have exposure to one prior taxane (or be taxane ineligible or refuse taxane) AND one prior AR-targeting agent (for example, abiraterone, enzalutamide, apalutamide, darolutamide). Receipt of taxane or AR-targeting agent may be in the hormone sensitive or castration resistant setting. Subjects may have received more than 1 prior Androgen receptor signaling inhibitors (ARSI). Subjects may have had prior 177Lu-PSMA-617.
* Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
* Normal organ function with acceptable initial laboratory values within 14 days of treatment start:
* WBC: ≥ 2,500/mcL
* ANC: ≥ 1,500/mcL
* Hemoglobin: ≥ 9 g/dL (transfusions are permitted)
* Platelet count: ≥ 100,000/mcL
* Serum creatinine or calculated Creatinine Clearance: Serum creatinine ≤ 1.5 x ULN or calculated CrCl ≥ 30 mL/min as defined by Cockcroft-Gault equation
* Total Bilirubin: ≤ 1.5 x ULN (≤ 3 x ULN for subjects with documented Gilbert's disease)
* SGOT (AST): ≤ 3 x ULN
* SGPT (ALT): ≤ 3 x ULN
* Alkaline Phosphatase (ALP): ≤ 5 x ULN with documented bone metastases
* Serum Albumin: ≥ 2.8 g/dL
* Urine protein/creatinine ratio (UPCR): ≤ 2 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 2 g
* Subjects must agree to use a medically acceptable method of birth control as outlined in the protocol
* HIV-positive with negative viral loads on stable antiretroviral regimen will be considered eligible. Subjects must have CD4 count \> 350.
Exclusion Criteria:
Subjects meeting any of the criteria below may not participate in the study:
* Disease progression on prior checkpoint inhibitor treatment.
* Prior cabozantinib.
* Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
* Receipt of any type of cytotoxic, biologic or investigational systemic anti-cancer agent within 4 weeks before first dose of study treatment.
* Treatment with abiraterone, apalutamide, or darolutamide within 2 weeks of treatment initiation. Treatment with investigational prostate cancer directed therapy within 4 weeks of treatment initiation. Treatment with enzalutamide within 4 weeks of treatment initiation.
* Receipt of more than 1 line of chemotherapy (including both hormone sensitive and CRPC). First-generation anti-androgen use (such as bicalutamide) will not be tabulated as a line of therapy.
* Administration of a live, attenuated vaccine within 30 days prior to first dose of study treatment.
* Active autoimmune disease or condition requiring prednisone \>10 mg daily (or equivalent). Physiologic replacement is permitted. Topical, ocular, intra-articular steroids or inhaled corticosteroids are permitted.
* Imminent or established spinal cord compression based on clinical and/or imaging findings.
* Radiation therapy within 1 week of study treatment start.
* Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment.
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
* Malabsorption syndrome.
* Requirement for hemodialysis or peritoneal dialysis.
* History of solid organ or allogenic stem cell transplant.
* Active hepatitis B/C or positive TB test with active mycobacterial infection requiring systemic treatment.
* Active treatment (within 5 days of registration) with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
* Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose molecular weight heparins (LMWH).
* Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
* The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
* Cardiovascular disorders:
* Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
* Uncontrolled hypertension defined as sustained blood pressure (BP) \> 150 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment.
* Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of study treatment.
* Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation (see exclusion criterion above) for at least 1 week before first dose of study treatment.
* Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation
* The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
* Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.
* Clinically significant hematuria, hematemesis, or hemoptysis of \> 0.5 teaspoon (2.5ml) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose of study treatment.
* Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
* Lesions invading or encasing any major blood vessels.
* Other clinically significant disorders that would preclude safe study participation.
* Serious non-healing wound/ulcer/bone fracture.
* Uncompensated/symptomatic hypothyroidism.
* Moderate to severe hepatic impairment (Child-Pugh B or C).
* Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 2 weeks before first dose of study treatment. Minor surgeries within 10 days before first dose of study treatment. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
* Corrected QT interval calculated by Fridericia formula (QTcF) \>500 ms per electrocardiogram (ECG) within 14 days before first dose of study treatment \[add reference for Fridericia formula\]. NOTE: If a single ECG shows a QTcF with an absolute \>500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility.
* Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer or superficial bladder cancer.
* Known allergy to any of the compounds under investigation.
* Inability to swallow tablets. DRUG: Cabozantinib, DRUG: Nivolumab
Castration-Resistant Prostate Cancer, Metastatic Cancer, Prostate
Castration resistant prostate cancer, Immunotherapy, Targeted therapy, Bone metastases
UT Southwestern
Dose Escalation and Expansion Study of WTX-124 as Monotherapy and in Combination With Pembrolizumab (Pembro) in Patients With Selected Advanced or Metastatic Solid Tumors
A first-in-human, Phase I, open-label, multicenter study of WTX-124 administered as monotherapy and in combination with pembrolizumab to patients with advanced or metastatic solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Hans Hammers
ALL
18 Years to old
PHASE1
NCT05479812
STU20250072
Inclusion Criteria:
Each patient must meet all the following criteria to participate in the study:
• Has histological or cytological documentation of a solid tumor indication for which a CPI (e.g. anti-PD-(L)1 is indicated for all parts of the clinical study;
• Monotherapy Dose Escalation: Patients with relapsed/refractory locally advanced or metastatic solid tumors for which immunotherapy is approved, who have progressed on or are intolerant to standard therapy, including CPIs, or for whom no standard therapy with proven benefit exists. Combination Dose Escalation: Patients with relapsed/refractory locally advanced or metastatic solid tumors for which immunotherapy is approved, who have progressed on or are intolerant to standard therapy or for whom no standard therapy with proven benefit exists. Monotherapy Dose Expansion: * Arm A: Patients with relapsed advanced or metastatic RCC who have received no more than 4 prior lines of therapy in the advanced or metastatic setting * Arm B: Patients with relapsed advanced or metastatic cutaneous malignant melanoma who have received no more than 2 prior lines of therapy for BRAF V600 wild type and no more than 3 prior lines of therapy for BRAF V600 mutant melanoma. * Arm C: Patients with relapsed advanced or metastatic cSCC who have received no more than 1 prior line of therapy Combination Dose Expansion:
• Arm D: Patients with RCC who have received no more than 3 prior lines of therapy
• Arm E: Patients with cutaneous melanoma who may be naïve to all prior therapy for advanced or metastatic disease. For BRAF wild type melanoma, patients should have received no more than 2 prior lines of therapy. For BRAF V600 mutant disease, patients should have received no more than 3 prior lines of therapy.
• Arm F: Patients with PD-L1-positive NSCLC who have received no more than 3 prior lines;
• ≥18 years of age;
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
• Has at least 1 measurable lesion per RECIST 1.1(lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions);
• Agrees to undergo a pre-treatment and on-treatment biopsy of a primary or metastatic solid tumor lesion;
• Has adequate organ and bone marrow function;
• Willingness of men and women of reproductive potential to observe highly effective birth control for the duration of treatment and for 4 months following the last dose of study drug;
• Additional criteria may apply
Exclusion Criteria:
• Have a history of another active malignancy (a second cancer) within the previous 2 years except for localized cancers that are not related to the current cancer being treated, are considered cured, and, in the opinion of the Investigator, presents a low risk of recurrence. These exceptions include, but are not limited to, basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast;
• Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease;
• Have received prior IL-2-directed therapy;
• Have had an allogeneic tissue/solid organ transplant;
• Have known symptomatic brain metastases requiring steroids;
• Have significant cardiovascular disease;
• Have an active autoimmune disease that required systemic treatment in the past 2 years;
• Diagnosis of immunodeficiency, is on immunosuppressive therapy, or is receiving chronic systemic or enteric steroid therapy
• Major surgery (excluding placement of vascular access) within 2 weeks prior to the first dose of study drug;
• Investigational agent or anticancer therapy within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study drug;
• Has received prior radiotherapy within 2 weeks of start of study treatment. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease;
• Any unresolved toxicities from prior therapy greater than NCI CTCAE version 5.0 Grade 1 at the time of starting study drug with the exception of alopecia and Grade 2 prior platinum-therapy related neuropathy;
• Received a live or live-attenuated vaccine within 30 days of the first dose of study drug; Note: Administration of killed vaccines or other formats are allowed.
• Active, uncontrolled systemic bacterial, viral, or fungal infection;
• HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease;
• Active infection as determined by hepatitis B surface antigen and hepatitis B core antibody, or hepatitis B virus DNA by quantitative polymerase chain reaction (qPCR) testing;
• Active infection as determined by hepatitis C virus (HCV) antibody or HCV RNA by qPCR testing;
• Pregnant or lactating;
• History of hypersensitivity to any of the study drug components;
• Additional criteria may apply.
DRUG: WTX-124, DRUG: pembrolizumab
Metastatic Solid Tumor, Advanced Solid Tumor, Kidney, Lung/Thoracic, Melanoma, skin
WTX-124, pembrolizumab, Tumors, Cutaneous Malignant Melanoma, mRCC, Renal Carcinoma, IL-2, Cutaneous SCC (cutaneous squamous cell carcinoma), NSCLC (non-small cell lung cancer)
UT Southwestern
An Extension Study to Assess Long-Term Safety of Eplontersen in Adults With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM)
The purpose of this study is to evaluate the safety and tolerability of extended dosing with eplontersen in participants with ATTR-CM.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Therese.Vallina@UTSouthwestern.edu
Justin Grodin
ALL
18 Years and over
PHASE3
NCT05667493
STU-2023-0810
Inclusion Criteria:
• Satisfactory completion of Treatment Period and the End of Treatment Visit of the Index Study (ION-682884-CS2) OR diagnosis of ATTR-CM and satisfactory participation on ISIS 420915- CS101 study as judged by the Investigator and Sponsor.
• Investigator is willing to treat the participant with open-label eplontersen.
• Willingness to adhere to vitamin A supplementation per protocol.
Exclusion Criteria:
• Permanently discontinued study drug administration while participating in the Index Study (ION 682884-CS2) or IST (ISIS 420915-CS101 Study).
• Have any new condition or worsening of an existing condition that in the opinion of the Investigator or Sponsor would make the participant unsuitable for enrolment, or which could interfere with the participant participating in or completing the study, including the need for treatment with medications disallowed in the Index Study.
DRUG: Eplontersen
Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM), Cardiovascular
Amyloidosis
UT Southwestern
MASA Valve Early Feasibility Study (MVEFS)
The MASA Valve Early Feasibility Study (MVEFS) multi-site interventional clinical trial within the United States of America with each center following a common protocol.The objective of the trial is to evaluate the safety and probable benefit of MASA Valve in the indicated subset of patients requiring Right Ventricular Outflow Tract Reconstruction (RVOTR). As an early feasibility study, the purpose is determine the feasibility of success of the device in order to gather early data towards a future pivotal study and/or regulatory clearance submission.
Call 214-648-5005
studyfinder@utsouthwestern.edu, madison.munson@childrens.com
Karl Reyes
All
0 Years to 22 Years old
N/A
NCT05452720
STU-2023-0657
Inclusion Criteria:
• At least one of the following: Right Ventricular to Pulmonary Artery mean gradient > 35mm Hg, moderate or severe Pulmonary regurgitation (≥3+), or clinical indication for replacement of their native or prosthetic pulmonary valve with a prosthesis.
• Age < 22 years
• Patient is geographically stable and willing to return for 1 year follow-up for the trial.
• Patient's legal guardian should be willing to provide informed consent (IC) at the hospital location where they are being enrolled.
• The patient, and the patient's parent / legal representative where appropriate, and the treating physician agree that the subject will return for all required post-procedure follow up visits and the subject will comply with clinical investigation plan required follow-up visits.
Exclusion Criteria:
• Patient is in need of or has presence of a prosthetic heart valve at any other position
• Patient has a need for concomitant surgical procedures (non-cardiac)
• Patients with previously implanted pacemaker (including defibrillators) or mechanical valves
• Patient has an active bacterial or viral infection or requiring current antibiotic therapy (if temporary illness, patient may be a candidate 4 weeks after discontinuation of antibiotics)
• Patient has an active endocarditis
• Leukopenia, according to local laboratory evaluation of white blood cell count
• Acute or chronic anemia, according to local laboratory evaluation of hemoglobin Patients can be transfused to meet eligibility criteria
• Thrombocytopenia, defined as Platelet count < 150,000/mm3 Patients can be transfused to meet eligibility criteria
• Severe chest wall deformity, which would preclude placement of the PV conduit
• Known hypersensitivity to anticoagulants and antiplatelet drugs and to the device materials
• Immunocompromised patient defined as: autoimmune disease, patients receiving immunosuppressant drugs or immune stimulant drugs
• Patient has chronic inflammatory / autoimmune disease
• Need for emergency cardiac or vascular surgery or intervention
• Major or progressive non-cardiac disease (liver failure, renal failure, cancer) that has a life expectancy of less than one year
• Currently participating, or participated within the last 30 days, in an investigational drug or device study
• Alcohol or drug abuse as defined by DSM IV-TR criteria for substance abuse - this includes the illicit use of cannabis within the last 12 months
• Patient has medical, social or psychosocial factors that, in the opinion of the Investigator, could have impact on safety or compliance
Device: Surgical Right Ventricular Outflow Tract Reconstruction
Tetrology of Fallot, Pulmonary Stenosis, Truncus Arteriosus, Transposition of Great Vessels, Pulmonary Atresia, Ross Procedure
Right Ventricular Outflow Tract Reconstruction, Pulmonary Valve, MASA Valve, Pulmonary Valve Replacement
Children’s Health
A Study of LP-300 with Carboplatin and Pemetrexed in Never Smokers with Advanced Lung Adenocarcinoma (HARMONIC)
The goal of this clinical trial is to determine clinical advantages for LP-300 in combination with carboplatin and pemetrexed in the never smoker patient population. The primary objectives of this study are to determine progression-free survival (PFS) and overall survival (OS) in the study-defined patient population when LP-300 is co-administered with the standard of care chemotherapy drugs carboplatin and pemetrexed compared to carboplatin and pemetrexed alone. This has been designed as a multicenter, open label, phase II trial with 90 patients to be enrolled in the United States.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Jonathan Dowell
ALL
18 Years and over
PHASE2
NCT05456256
STU-2023-0857
Inclusion Criteria:
• Patients with confirmed histopathological diagnosis of inoperable advanced (Stage III or IV) primary adenocarcinoma (including bronchioalveolar cell carcinoma) of the lung with specific actionable genomic alterations (e.g., mesenchymal epithelial transition (MET) exon14 skipping mutations, anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR), neurotrophic tyrosine receptor kinase (NTRK) fusions, etc.). If pathological or radiological findings are inconclusive for a diagnosis of primary adenocarcinoma of the lung, additional studies must be performed to confirm primary lung versus metastatic adenocarcinoma. Patients with no known actionable genomic alterations are ineligible to enroll in the study.
• Locally advanced inoperable or metastatic lung cancer.
• Patients must be never smokers: a never smoker is an adult who has never smoked, or who has smoked less than 100 cigarettes (or equivalent in other products such as vapes, cigars, pipes, hookahs, and marijuana use) in his or her lifetime. Note: a patient with actionable genomic alteration(s) who is a former smoker may be enrolled if such a patient would ordinarily be treated with pemetrexed and carboplatin combination based on institutional standard clinical practice; consultation with the sponsor's Medical monitor would be required
• Patients who have received systemic treatment with tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer but have experienced disease progression, unacceptable TKI-related toxicities, or are unable to tolerate the further use of TKIs.
• Prior radiation therapy is allowed, provided (1) that at least one area of measurable tumor (by computed tomography (CT) scan with at least one target lesion) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 that has not been subject to prior irradiation, and (2) that any such therapy is completed and any radiation-induced sequelae are recovered at least 21 days before randomization.
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Patients who are at least 18 years of age.
• Patients with documented stable central nervous system (CNS) metastases with no cognitive deficits, or progressive sensory or motor deficits, or seizures during the last 21 days prior to enrollment are eligible. Patients must have discontinued anti-seizure medications and steroids at least 14 days prior to patient enrollment.
• Patients must have fully recovered from any prior major surgical or diagnostic staging procedure (e.g., thoracotomy, mediastinoscopy), and have a post-operative status of at least 30 days before enrollment.
• Patients must have adequate bone marrow, adequate hepatic function, and baseline creatinine levels documented by specific laboratory criteria within 21 days prior to enrollment, including the following: * White blood cell count ≥ 2 x 10\*9/L * Absolute neutrophil count (ANC) ≥ 1.5 x 10\*9/L * Hemoglobin ≥ 10 g/dL * Platelet count ≥ 100 x 10\*9/L * Total bilirubin \< 1.5 x the upper limit of normal (ULN). For patients with Gilbert's syndrome, total bilirubin \< 2.5 x ULN * Aspartate aminotransferase/ serum glutamic oxaloacetic transaminase (AST/SGOT) ≤ 2.5 x ULN * Alanine aminotransferase/ serum glutamic pyruvic transaminase (ALT/SGPT) ≤ 2.5 x ULN * Alkaline phosphatase ≤ 2.5 x ULN * Baseline serum creatinine level no greater than 1.5 mg/dL or 133 μmol/L. * Creatinine clearance ≥ 45 mL/min as calculated using the Cockcroft-Gault methodology (Cockcroft 1976) * Magnesium ≥ 1.7 mg/dL
• Female patients of child-bearing potential must have a negative pregnancy test and must agree to use an acceptable contraceptive method during the study and for 12 weeks after their last dose of study treatment. Male patients with partners of child-bearing potential must also agree to use an adequate method of contraception for the duration of the study and for 12 weeks after their last dose of study treatment. Note: a) A patient is considered of childbearing potential if she is biologically capable of having children and is sexually active. Medically acceptable contraceptives include: (1) surgical sterilization (such as a tubal ligation, hysterectomy, or vasectomy), (2) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (3) barrier methods (such as a condom or diaphragm) used with a spermicide (only if used in combination with another mentioned method), or (4) an intrauterine device (IUD). Contraceptive measures and other medications sold for emergency use after unprotected sex, are not acceptable methods for routine use. If a female patient becomes pregnant, study therapy must be discontinued immediately. Lastly, b) the period for use of contraception after last dose of pemetrexed or carboplatin should be determined by the domestic drug labels and/or institutional standard clinical practice. For S Korea, contraception is to be used for 6 months after the last dose.
• Patients must have been disease-free at least two years for other malignancies, excluding: * Curatively-treated basal cell carcinoma, * Ductal carcinoma in situ (DCIS) of the breast * Non-melanomatous carcinoma of the skin, or * Carcinoma in situ of the cervix.
• Be willing to provide an archival tumor tissue sample, if available. The archival sample must be from a tumor lesion that was not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. The sample must have been obtained less than 36 months prior to consent.
• Provide signed, written, Institutional Review Board (IRB) approved informed consent prior to any screening procedures.
Exclusion Criteria:
• Patients with small cell, squamous cell, large cell, undifferentiated, mesothelioma, or any form of mixed (e.g., small cell and adenocarcinoma or squamous and adenocarcinoma) histopathological diagnosis of primary lung cancer.
• Patients with metastatic adenocarcinoma arising from any primary site other than the lung.
• Patients who have received any prior investigational agents except for investigational TKI drugs. The minimum drug washout period for all TKIs, including approved and investigational, is ≥ 5 half-lives or 2 weeks, whichever is shorter.
• Patients who have received chemotherapy and/or immunotherapy but transitioned to a TKI with no evidence of disease progression will be allowed to enroll. Patients who experienced disease progression while on chemotherapy and/or immunotherapy will be ineligible for the trial.
• Patients taking medications that are sensitive substrates of CYP2C19 or P-gp transporters
• Patients with recent onset (within 6 months of randomization) of congestive heart failure (New York Heart Association Classification Class II or greater), angina pectoris, unstable angina pectoris, serious uncontrolled cardiac arrhythmias, myocardial infarction, stroke, or transient ischemic attacks.
• Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of \> 470 msec. (average of triplicate ECGs) at Screening and/or on C1D1 (pre- dose) except for a documented bundle branch block or unless secondary to pacemaker. In the case of a documented bundle branch block or a pacemaker, discussion with the Medical Monitor is required prior to enrollment.
• Patients with unstable CNS metastases (characterized by progressive sensory/motor impairment, cognitive/speech impairment, or seizure activity) within 21 days before enrollment.
• Patients who do not have at least one (1) measurable disease site that has not been previously irradiated.
• Patients who are known to be positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HbsAg) or hepatitis C virus (HCV).
• Patients with active infections, active interstitial lung disease, uncontrolled high blood pressure, uncontrolled diabetes mellitus, uncontrolled seizures (not due to CNS metastases) within the last 3 months, or other serious underlying medical condition.
• Patients with documented hypersensitivity to any of the study medications (LP-300, pemetrexed, carboplatin and/or excipients) or supportive agents that may be used.
• Patients who are pregnant or are breastfeeding.
• Patients who have undergone blood transfusions within 10 days before randomization.
• Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence to study requirements or confound the interpretation of study results.
• Patients who have a life expectancy of less than 3 months.
DRUG: LP-300, DRUG: Pemetrexed, DRUG: Carboplatin
Adenocarcinoma of Lung, Carcinoma, Non-Small-Cell Lung, Lung/Thoracic
never smoker, non smoker, EGFR, ALK, ROS, MET, tyrosine kinase inhibitor, TKI, pemetrexed, carboplatin, NSCLC, never-smoker, non-smoker, TK inhibitor, lung cancer
UT Southwestern; Parkland Health & Hospital System
A Study of TTI-101 as Monotherapy and in Combination in Participants With Locally Advanced or Metastatic, and Unresectable Hepatocellular Carcinoma
The primary objectives of Cohort A Phase 1b are to evaluate the safety and tolerability of TTI-101 orally administered as a single agent to participants with locally advanced or metastatic, and unresectable Hepatocellular Carcinoma (HCC) and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of TTI-101 as a single agent. The primary objectives of Cohort A Phase 2 are to evaluate the safety and tolerability of TTI-101 orally administered as a single agent at the RP2D to participants with locally advanced or metastatic, and unresectable HCC and to assess the preliminary efficacy of TTI-101 as a single agent in participants with locally advanced or metastatic, and unresectable HCC. The secondary objectives of Cohort A Phase 2 are to assess response, progression, survival, and pharmacokinetics. The primary objectives of Cohorts B and C Phase 1b are to evaluate the safety and tolerability of TTI-101 orally administered in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) to participants with locally advanced or metastatic, or unresectable HCC and to determine the MTD and/or RP2D of TTI-101 when used in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C). The primary objectives of Cohorts B and C Phase 2 are to evaluate the safety and tolerability of TTI-101 orally administered in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) at the RP2D to participants with locally advanced or metastatic, and unresectable HCC and to assess the preliminary efficacy of TTI-101 in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) to participants with locally advanced or metastatic, and unresectable HCC. The secondary objectives of Cohorts B and C Phase 2 are to assess response, progression, survival, and pharmacokinetics.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Hsieh
All
18 Years and over
Phase 1/Phase 2
NCT05440708
STU-2022-0622
Inclusion Criteria:
• Able to understand and willing to provide informed consent and able to comply with the study procedures and restrictions.
• Age ≥18 years at the time of informed consent.
• Have histologically or radiographically (Liver Imaging Reporting and Data Systems category 5) confirmed diagnosis of locally advanced or metastatic, and unresectable HCC. Participants without cirrhosis require histological confirmation.
• Cohorts A and B only: Willing to provide a representative fresh tumor tissue specimen prior to enrollment. The fresh tumor specimen must be obtained after progression on the prior therapy. No biopsy is required for participants in Cohort C.
• Measurable disease as per RECIST Version 1.1. Participants who received prior local therapy are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST Version 1.1.
• Able to swallow tablets.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has adequate hematologic and organ function as defined by the following local laboratory values at screening:
• Absolute neutrophil count (ANC) ≥1.5 × 10^9/L (1500/μL) without granulocyte colony-stimulating factor support.
• Lymphocyte count ≥0.5 × 10^9/L (500/μL).
• Platelet count ≥75 × 10^9/L (75,000/μL) without transfusion.
• Hemoglobin ≥90 g/L (9 g/dL). Participants may be transfused to meet this criterion.
• Serum albumin ≥28 g/L (2.8 g/dL).
• AST, ALT, and alkaline phosphatase (ALP) ≤5 × upper limit of normal (ULN).
• Serum bilirubin ≤2 mg/dL.
• Adequate renal function defined as either:
• creatinine clearance ≥40 mL/min calculated using the Cockcroft-Gault formula, or
• 24-hour urine collection.
• Prothrombin time/international normalized ratio (PT/INR) and activated partial thromboplastin time (aPTT) ≤2 × ULN, except for participants receiving anticoagulation therapy.
• Child-Pugh class A or B7 within 7 days prior to enrollment.
• Females of childbearing potential (ie, ovulating, premenopausal, and not surgically sterile) must:
• Have a negative serum pregnancy test at screening.
• Not be breastfeeding or lactating.
• Agree to use a highly effective method of birth control for the duration of the study and for at least 30 days after the last dose in the study. Effective forms of birth control include barrier methods used in conjunction with a spermicidal agent (according to standard local practices), nonhormonal intrauterine devices, or permanent sterilization.
• Males must:
• Agree to use a condom for at least 30 days after the last dose in the study even if vasectomized in order to prevent delivery of the drug via seminal fluid.
• Agree to abstain from sperm donation through 30 days after administration of the last dose of the study treatment.
• Unless surgically sterile, males with female partners of childbearing potential must agree to use 2 methods of acceptable birth control for at least 30 days after the last dose in the study. Effective forms of birth control include barrier methods used in conjunction with a spermicidal agent (according to standard local practices), nonhormonal intrauterine devices in female partners, or permanent sterilization. Cohort A:
• In addition to the general inclusion criteria, participants enrolled in Cohort A must have demonstrated objective progression on up to 3 prior lines of systemic antitumor drug therapy. Cohort B:
• In addition to the general inclusion criteria, participants enrolled in Cohort B must have demonstrated objective progression following at least 2 cycles of first-line anti-PD-1 or anti-PD-L1 monotherapy or combination therapy. Participants may have received no more than one line of prior therapy.
• Agree to use contraception as specified in the general inclusion criteria for at least 4 months following the last dose of pembrolizumab in accordance with the approved prescribing information. Cohort C:
• In addition to the general inclusion criteria, participants enrolled in Cohort C must be naïve to systemic treatment for locally advanced or metastatic, and unresectable HCC.
• Must have had an evaluation (gastroduodenoscopy) for the presence of varices within 6 months prior to initiation of bevacizumab therapy.
• Agree to use contraception as specified in the general inclusion criteria for at least 5 months after the last dose of atezolizumab and at least 6 months after the last dose of bevacizumab in accordance with the approved prescribing information.
Exclusion Criteria:
• Pregnant or breastfeeding.
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
• History of leptomeningeal disease.
• Previous treatment of the current malignancy with a signal transducer and activator of transcription (STAT) inhibitor.
• Previous therapy with:
• Standard therapy including chemotherapy, immunotherapy, biologic therapy, or any other anticancer therapy within 28 days (or 5 elimination half-lives for non-cytotoxics, whichever is shorter) of Cycle 1 Day 1 (6 weeks for nitrosoureas or mitomycin).
• Any investigational agent within 28 days (or 5 elimination half-lives for a non-cytotoxic investigational therapy, whichever is shorter) of Cycle 1 Day 1 or 5 half-lives for a small molecule/targeted therapy.
• Extensive prior radiotherapy to more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation within 5 years from enrollment.
• Herbal preparations are not allowed throughout the study. These herbal medications include but are not limited to St. John's wort, kava, ephedra (mahung), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Participants should stop using herbal medications 7 days prior to the first dose of study treatment.
• Is not fully recovered from all coronavirus disease 2019 (COVID-19)-related symptoms for 2 weeks prior to Cycle 1 Day 1, if previously tested positive for COVID-19.
• Ongoing toxicity (except alopecia) due to a prior therapy, unless returned to baseline or Grade 1 or less.
• Has had major surgery within 3 weeks prior to starting investigational product (IP) or has not recovered from major side effects due to surgery.
• Significantly impaired cardiac function such as unstable angina pectoris, congestive heart failure with New York Heart Association Class III or IV, myocardial infarction within the last 12 months prior to study entry; serious arrhythmia (including QTc prolongation of >470 ms and/or pacemaker) or prior diagnosis of congenital long QT syndrome or left ventricular ejection fraction <50% on screening echocardiogram.
• Pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Participants with indwelling catheters for control of effusions or ascites are allowed.
• History of cerebrovascular accident or stroke within the previous 2 years.
• History of hepatic encephalopathy.
• Uncontrolled or symptomatic hypercalcemia (ionized calcium >1.5 mmol/L, calcium >12 mg/dL, or corrected serum calcium >ULN).
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
• History of Grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition as TTI-101 (hydroxyl-naphthalene sulfonamides).
• Known active metastases in the central nervous system (unless stable by brain imaging studies for at least 1 month without evidence of cerebral edema and no requirements for corticosteroids or anticonvulsants).
• History of difficulty swallowing oral medications, malabsorption, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the IP.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Participants with chronic hepatitis B virus (HBV) infection, unless screening viral load <500 IU/mL on stable doses of antiviral therapy. Note: Participants with chronic hepatitis C virus (HCV) infection are allowed to enroll into the study but do not have a defined maximum viral load requirement for study entry. Participants with both HBV and HCV infection are excluded unless they have negative HCV ribonucleic acid (RNA).
• History of malignancy other than HCC within 3 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (eg, 5-year overall survival [OS] rate >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
• Has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate participation in the clinical study, or compromise compliance with the protocol such as:
• Chronic pancreatitis.
• Active untreated or uncontrolled fungal, bacterial, or viral infections (including COVID-19), sepsis, etc.
• Acute and chronic, active infectious disorders including viral and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy.
• Is unable to understand and to comply with study instructions and requirements. Cohort B: In addition to the general exclusion criteria, participants enrolled in Cohort B must fulfill the following additional exclusion criteria:
• Discontinued prior treatment with anti-PD-1 or anti-PD-L1 for any reason other than disease progression. Cohort C: In addition to the general exclusion criteria and Cohort B criteria, participants enrolled in Cohort C must fulfill the following additional exclusion criteria:
• Inadequately controlled arterial hypertension (defined as systolic blood pressure [BP] ≥150 mmHg and/or diastolic BP ≥100 mmHg), based on an average of ≥3 BP readings on ≥2 sessions.
• Participant has received prior systemic chemotherapy for locally advanced or metastatic and/or unresectable HCC. However, participant may have received either neo-adjuvant or adjuvant chemotherapy as long as it was completed at least 6 months prior to the first dose of study treatment.
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding and a prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment.
• Urine dipstick for proteinuria ≥2+ at screening. If a 24-hour urine collection shows <1 g of protein in 24 hours, the participant is eligible.
• Current or recent (within 10 days of first dose of study treatment) use of aspirin (>325 mg/day) or treatment with dipyridamole, ticlopidine, clopidogrel, and cilostazol.
• Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants. Prophylactic anticoagulants (eg, low-dose warfarin with target INR <1.5 × ULN or low-dose low molecular weight heparin) are allowed.
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 3 days prior to the first dose of bevacizumab.
• History of gastrointestinal perforation or evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
• Metastatic disease that involves major airways or blood vessels. Participants with portal or hepatic vein involvement are not excluded.
• Participant has experienced any of the following within 6 months prior to enrollment: arterial thromboembolic event (including myocardial infarction, coronary arterial disease, transient ischemic attack, stroke, etc), congestive heart failure, hemoptysis, or pulmonary embolism.
• Participant has experienced a fistula. Cohorts B and C: In addition to the general exclusion criteria and the cohort-specific criteria listed above, participants enrolled in Cohorts B and C must fulfill the following additional exclusion criteria:
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during pembrolizumab treatment or within 5 months after the last dose of pembrolizumab treatment.
• Active or history of immune-mediated disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
• Participants with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
• Participants with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (eg, participants with psoriatic arthritis are excluded) are eligible for the study provided all of the following conditions are met:
• Rash must cover <10% of body surface area.
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor α [TNF-α] agents) within 2 weeks prior to initiation of study treatment. Participants receiving low-dose corticosteroids (equivalent of prednisone 10 mg/day or lower) or who receive pulse corticosteroids due to intravenous (IV) contrast allergy are not excluded.
• Active tuberculosis.
• Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Participants receiving prophylactic antibiotics (eg, to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• Prior allogeneic stem cell or solid organ transplantation.
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
Drug: TTI-101, Drug: Pembrolizumab, Drug: Atezolizumab, Drug: Bevacizumab
Hepatocellular Carcinoma, Liver
Hepatocellular carcinoma, TTI-101, Pembrolizumab, Atezolizumab, Bevacizumab, revert
UT Southwestern; Parkland Health & Hospital System
Pathways Relating Amnestic MCI to a Mild Traumatic Brain Injury History (PATH)
This study will probe if the biological changes in amnestic mild cognitive impairment (aMCI) are related to a history of mild traumatic brain injury (mTBI) using high definition transcranial direct current stimulation (HD-tDCS) and blood-derived biomarker tools. Participants who Do as well as those who Do Not have a history of mTBI will be enrolled in the study.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Hannah.Cabrera@UTSouthwestern.edu
Christian LoBue
ALL
55 Years and over
PHASE2
NCT05446584
STU-2022-0591
Inclusion Criteria:
• Active diagnosis of amnestic mild cognitive impairment
• Presence of an mTBI history for the mTBI+ group; absence of an mTBI history for a control sample
• Female and male subjects
• All races/ethnicities
• Age 55 years and older
• Fluent in English
Exclusion Criteria:
• Mild traumatic brain injury within past year
• Lifetime history of moderate or severe brain injury
• Lifetime major neurologic syndromes (e.g., stroke, epilepsy, brain tumor)
• Lifetime major cardiovascular conditions (e.g., heart attack, heart failure)
• Current substance use disorder
• Current major psychiatric disorders (e.g., major depressive disorder, bipolar disorder)
• Current vision or hearing impairment that interferes with testing
• Any electronic and or metallic implants in the skull or brain
• Current medication use known to alter HD-tDCS reactivity
DEVICE: High Definition Transcranial Direct Current Stimulation
Mild Cognitive Impairment, Amnestic Mild Cognitive Disorder, Amnestic Mild Cognitive Impairment, Mild Traumatic Brain Injury, Concussion, Brain, Brain and Nervous System
MCI, TBI, memory, biomarker, Alzheimer
UT Southwestern; Parkland Health & Hospital System
Peanut Sublingual Immunotherapy (SLIT)-Tablet for Treatment of Peanut Allergy
This clinical research study investigates the safety, tolerability and efficacy of a peanut SLIT-tablet in adults, adolescents, and children with peanut allergy.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Kaylee.Lirely@Childrens.com
John Bird
ALL
4 Years to 65 Years old
PHASE1
NCT05440643
STU-2024-0597
KEY INCLUSION CRITERIA:
Subjects are eligible to be included in the trial only if all the following criteria apply:
* Part 1: Male or female aged 12 through 65 years (inclusive) on the day of enrollment Part 2: Male or female aged 4 through 65 years (inclusive) on the day of enrollment Part 3: Male or female aged 4 through 65 years (inclusive) on the day of randomization
* Documented clinical history of an IgE-mediated allergic reaction towards peanut- containing food
* Peanut-specific serum IgE ≥ 0.7 kU/L at screening measured at central laboratory
* Skin prick test to peanut ≥ 5 mm at screening
* Cohorts 1-8: Experience dose-limiting symptoms at the 10 mg, 30 mg or 100 mg challenge dose of peanut protein on screening DBPCFC Cohorts 9-10: Experience dose-limiting symptoms at the 1 mg or 3 mg challenge dose of peanut protein on the screening DBPCFC Part 3: Experience dose-limiting symptoms at the 3 mg, 10 mg, 30 mg or 100 mg challenge dose of peanut protein on screening DBPCFC
KEY EXCLUSION CRITERIA:
Subjects are excluded from the trial if any of the following criteria apply:
* Diagnosis or history of eosinophilic esophagitis
* Uncontrolled asthma as defined by the Asthma Control Test questionnaire with a score of 19 or below at enrollment (subjects with a diagnosis of asthma only)
* All subjects ≥ 5 years old with FEV1 or PEFR \< 70% of predicted value at enrollment Subjects 4 years old with a history of recurrent wheeze requiring inhaled corticosteroids for 2 consecutive weeks or more within 3 months prior to enrollment
* Up-dosing with any allergy immunotherapy product. Maintenance dose of any subcutaneous immunotherapy product other than peanut is allowed
* History of peanut oral immunotherapy within the last 12 months prior to visit 1
* Chronic or acute oral inflammation at enrollment
* History of cardiovascular disease, including uncontrolled or inadequately controlled hypertension
* Currently using any prohibited medication on the list of prohibited medication
* Part 1 and 2: Allergic symptoms in reaction to the placebo part of the screening DBPCFC Part 3: Dose-limiting allergic symptoms in reaction to the placebo part of the screening DBPCFC
* History of severe or life-threatening episode of anaphylaxis or anaphylactic shock within 60 days of the screening DBPCFC
* Part 1 and 2: Asthma according to below criteria:
* Severe asthma as per the current GINA guidelines
* Uncontrolled or poorly controlled asthma as per the current GINA guidelines
* Asthma that requires more than a daily dose above 800 µg of inhaled budesonide (or clinically comparable inhaled corticosteroids)
* History of 2 or more systemic corticosteroid courses within 6 months of screening
* Prior intubation/mechanical ventilation for asthma
* Emergency room visit or hospitalization for asthma in the 12 months prior to screening
* Any history of a life-threatening asthma attack
* Part 3: Asthma fulfilling the below criteria:
* History of 2 or more systemic corticosteroid courses within 6 months of screening
* Prior intubation/mechanical ventilation for asthma
* Emergency room visit or hospitalization for asthma in the 12 months prior to screening
* Any history of a life-threatening asthma attack
* (US only) Severe asthma as per the current GINA guidelines
* (US only) Uncontrolled or poorly controlled asthma as per the current GINA guidelines
* (US only) Asthma that requires more than a daily maintenance dose above 800 μg of inhaled budesonide (or clinically comparable inhaled corticosteroids)
BIOLOGICAL: Peanut SLIT-tablet, OTHER: Placebo
Peanut Allergy
Peanut allergy, Children, Adolescent, Adult
Children’s Health
Efficacy and Safety of Intravenous Efzofitimod in Patients With Pulmonary Sarcoidosis
This is a multicenter, randomized, double-blind, placebo-controlled, study comparing the efficacy and safety of intravenous (IV) efzofitimod 3 mg/kg and 5 mg/kg versus placebo after 48 weeks of treatment. This study will enroll adults with histologically confirmed pulmonary sarcoidosis receiving stable treatment with oral corticosteroid (OCS), with or without immunosuppressant therapy.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Fabiola.Gianella@UTSouthwestern.edu
Connie Hsia
All
18 Years to 75 Years old
Phase 3
NCT05415137
STU-2022-0975
Inclusion Criteria:
• Confirmed diagnosis of pulmonary sarcoidosis for at least 6 months, defined by the following criteria: documented histologically proven diagnosis of sarcoidosis by tissue biopsy and documented evidence of parenchymal lung involvement by historical radiological evidence
• Evidence of symptomatic pulmonary sarcoidosis, as demonstrated by the following criteria: Modified Medical Research Council (MRC) dyspnea scale grade of at least 1 and KSQ-Lung score ≤70
• Patients must be receiving treatment with OCS of ≥ 3 months with a starting dose between ≥ 7.5 and ≤ 25 mg/day.
• Body weight ≥ 40 kg and < 160 kg
Exclusion Criteria:
• Treatment with > 1 oral immunosuppressant therapy
• Treatment with biological immunomodulators, such as tumor necrosis factor-alpha (TNF-α) inhibitors or antifibrotics or interleukin inhibitors
• Likelihood of significant pulmonary fibrosis as shown by any 1 or more of the following: High resolution CT fibrosis > 20% within the last 12 months; FVC percent predicted (FVCPP) < 50% and KSQ-Lung score < 30
• Clinically significant pulmonary hypertension requiring treatment with vasodilators
• Patients with cardiac sarcoidosis, neurosarcoidosis, or renal sarcoidosis
• Clinically significant cutaneous and ocular sarcoidosis
• History of Addisonian symptoms that precluded previous OCS taper attempts
• Is an active, heavy smoker of tobacco/nicotine-containing products
• History of anti-synthetase syndrome or Jo-1 positive at baseline
Drug: Efzofitimod 3 mg/kg, Drug: Efzofitimod 5 mg/kg, Drug: Placebo
Pulmonary Sarcoidosis, Lung/Thoracic
Pulmonary Sarcoidosis, Sarcoidosis, Granuloma, Inflammation, Lymphoproliferative Disorders, Interstitial Lung Disease, Neuropilin-2, Steroids, Oral corticosteroids, Immunomodulatory, tRNA Synthetase, ATYR1923, KRP-R120, Efzofitimod, Fibrosis
UT Southwestern
Implantable Long-Acting Pre-Exposure Prophylaxis For MSM
The long-term goal of this project is to better understand factors at the patient and physician level that can be addressed to impact uptake of long-acting, implantable PrEP (LA-PrEP) products in the future and identify the training needs of physicians. This project specifically focuses on men who have sex with men (MSM) seen in primary care settings in Texas. The main objective of this project is to examine perspectives of MSM and physicians in Texas regarding LA-PrEP, including attitudes and barriers to use and implementation by interviewing patients and physicians from the same clinical practices.
studyfinder@utsouthwestern.edu
MALE
18 Years to 45 Years old
NCT05420207
Inclusion Criteria:
* Patients must meet the following criteria:
• be a patient of one of the practices where physicians have agreed to participate or have been seen for a primary care visit in the past 12 months in the Dallas Austin, or San Antonio metro areas;
• be aged 18-45;
• be assigned male sex at birth and report having one or more male sexual partners in the past year; and
• be HIV negative. * Physicians who are interested in participating must be a practicing primary care physician in the Dallas, San Antonio, or Austin metropolitan area and be willing to allow recruitment of patient participants from their practice.
Exclusion Criteria:
* Those individuals who speak a language other than English or Spanish will be excluded as well as those who present with a cognitive or other impairment that would prevent them for consenting to participate in the study. OTHER: No intervention
HIV Prevention
Pre Exposure Prophylaxis, HIV, MSM, Primary Care
Testing Cabozantinib With or Without Atezolizumab in Patients With Advanced Papillary Kidney Cancer, PAPMET2 Trial
This phase II trial compares the effect of atezolizumab in combination with usual treatment with cabozantinib to cabozantinib alone in patients with papillary renal cell carcinoma that has spread from where it first started (primary site) to other places in the body (metastatic). Papillary renal cell carcinoma (PRCC) is a type of kidney cancer that forms in the lining of the tiny tubes in the kidney that return filtered substances that the body needs back to the blood and remove extra fluid and waste as urine. Most papillary tumors look like long, thin finger-like growths under a microscope. It is also called papillary kidney cancer or PRCC. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the tumor and may interfere with the ability of tumor cells to grow and spread. Cabozantinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply and may also prevent the growth of new blood vessels that tumors need to grow. By these actions it may help slow or stop the spread of tumor cells. Combination therapy with atezolizumab and cabozantinib may shrink the tumor and allow a longer survival time in patients with metastatic renal cell carcinoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
ALL
18 Years and over
PHASE2
NCT05411081
STU-2023-0866
Inclusion Criteria:
* Participants must have a histologically confirmed diagnosis of metastatic papillary renal cell carcinoma (PRCC), either type 1 or type 2. (NOTE: A designation of type 1 or type 2 should be made by the local pathologist if possible but is not required). Mixed histologies which contain type 1 or type 2 along with any other RCC histology/histologies will be allowed provided that they contain a papillary component
* Participants must have measurable disease per RECIST 1.1 criteria. All measurable lesions must be assessed by CT or MRI within 28 days prior to registration. All non-measurable lesions must be assessed by CT or MRI, or nuclear medicine bone scan within 42 days prior to registration. The CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality. If there is clinical suspicion for bone metastases at the time of enrollment (at the discretion of the investigator), bone scan must be performed at baseline (within 42 days prior to registration)
* Participants with new or progressive brain metastases (active brain metastases) must not require immediate central nervous system (CNS) specific treatment at the time of study registration or anticipated during the first cycle of therapy. Patients with leptomeningeal disease are excluded from enrolling
* Participants with measurable disease, per RECIST version (v)1.1, must be present outside the CNS
* Participants must have no history of intracranial hemorrhage or spinal cord hemorrhage
* Participants must not have undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment
* Participants must not have ongoing requirements for corticosteroids as therapy for CNS disease
* Participants, if needed, must receive a stable dose of anti-convulsant therapy
* Participants must not have cavitating pulmonary lesions
* Participants must not have uncontrolled pleural effusions, pericardial effusions, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Participants with indwelling catheters (e.g., PleurX \[registered trademark\]) are allowed
* Participants must not have tumor invading the gastrointestinal (GI) tract or evidence of endotracheal or endobronchial tumor within 28 days prior to registration
* Participants must not have evidence of tumor invading or encasing any major blood vessels
* Participants must not have had major surgery within 28 days prior to registration, and participants must have recovered from any adverse effects of surgery
* Participants must not have had prior treatment with cabozantinib for any reason
* Participants must not have had prior treatment or adjuvant therapy with PD-1/PD-L1 checkpoint inhibitors for any reason within the past 6 months
* Participants must not have received more than one prior systemic therapy for advanced or metastatic renal cell carcinoma with the exception of another VEGF inhibitor Food and Drug Administration (FDA)-approved for advanced RCC (i.e., pazopanib, bevacizumab, sorafenib or axitinib). If a participant develops metastatic disease within six months of discontinuation of adjuvant therapy, this will constitute one prior systemic therapy for advanced or metastatic RCC. If a patient develops metastatic disease and more than six months has elapsed since discontinuation of adjuvant therapy, this will not constitute prior systemic therapy for advanced or metastatic RCC
* Participants must not take within 14 days prior to registration, nor plan to take while on protocol treatment, any strong CYP3A4 inhibitors (e.g. boceprevir, cobicistat, danoprevir, elvitegravir/RIT, fluvoxamine, indinavir, itraconazole, ketoconazole, lopinavir/RIT, nefazodone, nelfinavir, posaconazole, ritonavir, telaprevir, telithromycin, tipranavir/RIT, or voriconazole,); Please refer to https://drug-interactions.medicine.iu.edu/MainTable.aspx for the updated CYP3A4 inhibitors or inducers
* Participants must not take within 14 days prior to registration, nor plan to take while on protocol treatment, any strong CYP3A4 inducers (e.g. avasimibe, phenytoin, rifampin, rifabutin); Please refer to https://drug-interactions.medicine.iu.edu/MainTable.aspx for the updated CYP3A4 inhibitors or inducers
* Participants must complete all prior radiation therapy at least 14 days prior to registration. Participants must have recovered to =\< grade 1 from all associated toxicities at the time of registration unless the toxicity is determined to be not clinically significant by the registering investigator
* Participants must not be receiving or planning to receive any other investigational agents at time of registration
* Participants must not have been diagnosed with a clinically significant autoimmune disease, exceptions such as diabetes, eczema, and vitiligo are allowed. Other non-clinically significant autoimmune diseases are allowed if approved by the registering investigator
* Participants must not be on steroid doses \> 10 mg prednisone equivalent. Replacement steroid doses for adrenal insufficiency will be allowed. Also, short duration steroid therapy to prevent allergic reactions are acceptable (e.g. prior to CT imaging)
* Participants must be \>= 18 years of age
* Participants must have a complete physical examination and medical history within 28 days prior to registration
* Participants must have a Zubrod performance status of 0-2
* White blood count (WBC) \>= 2 x 10\^3/uL (within 28 days prior to registration)
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^3/uL (within 28 days prior to registration)
* Platelet count \>= 100 x 10\^3/uL (within 28 days prior to registration)
* Lymphocyte count \>= 0.5 x 10\^3/uL (within 28 days prior to registration)
* Hemoglobin (\>= 9 g/dL) (within 28 days prior to registration). Participants may be transfused to meet this criterion
* Total serum bilirubin =\< 1.5 x the institutional upper limit of normal (ULN) unless history of Gilbert's disease (within 28 days prior to registration). Participants with history of Gilbert's disease must have total bilirubin =\< 5 x institutional ULN
* Aspartate aminotransferase (AST) must be =\< 3 x the institutional ULN unless the liver is involved with the tumor, in which case serum transaminase (SGOT) must be =\< 5 x the institutional ULN (within 28 days prior to registration)
* Alanine aminotransferase (ALT), must be =\< 3 x the institutional ULN unless the liver is involved with the tumor, in which case serum transaminase (SGPT) must be =\< 5 x the institutional ULN (within 28 days prior to registration)
* Participants must have serum creatinine =\< 2 x the institutional ULN OR creatinine clearance (either measured or calculated) \> 30 mL/min and obtained within 28 days prior to registration
* Participants must not have any clinical evidence of congestive heart failure (CHF) (specifically, New York Heart Association \[NYHA\] class III \[moderate\] or class IV \[severe\]) at the time of registration
* Participants must not have known history of congenital long QT syndrome and must not have experienced unstable angina pectoris, clinically significant cardiac arrhythmias, or stroke (transient ischemic attack \[TIA\] or other ischemic event) within 90 days prior to registration
* Participants must not have experienced myocardial infarction or thromboembolic event requiring anticoagulation within 90 days of registration, unless clinically stable with ongoing medical management
* Participants must have urine protein \< 3+ within 28 days prior to registration. If urine protein is 3+ or greater, then urine protein by 24-hour collection must show less than 3 grams of protein
* Participants must have documented blood pressure of systolic blood pressure (SBP) \< 150 mm Hg or diastolic blood pressure (DBP) \< 100 mm Hg within 14 days prior to registration
* Participants with known human immunodeficiency virus (HIV) must be on effective anti-retroviral therapy at registration and have undetectable viral load within 6 months of registration
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy within 6 months prior to registration, if indicated
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load within 6 months prior to registration
* Participants must be able to take oral medications (i.e., swallow pills whole). Participants must not have gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures that could in the opinion of the treating investigator affect absorption, or active peptic ulcer disease. Participants with intractable nausea or vomiting are not eligible
* Participants must not have had any clinically-significant GI bleeding within 3 months prior to registration and participants must not have a GI disorder which (at the discretion of the investigator) bears a high risk of perforation or fistula (e.g. Crohn's disease)
* Participants must not have had hemoptysis of \>= (2.5 mL) of red blood, and do not demonstrate any other signs indicative of pulmonary hemorrhage within 3 months prior registration
* Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Participants must not be pregnant or nursing, due to VEGF therapy being toxic to embryogenesis. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
* Participants must not be on warfarin, at therapeutic doses. Low dose aspirin for cardio-protection (per local applicable guidelines) and low molecular weight heparin (LMWH) are allowed
* Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
* NOTE: For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
* As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system BIOLOGICAL: Atezolizumab, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, DRUG: Cabozantinib S-malate, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging
Metastatic Papillary Renal Cell Carcinoma, Stage IV Renal Cell Cancer AJCC v8, Kidney
UT Southwestern
Study to Assess Change in Disease Activity and Adverse Events of Ab Externo Approach for Glaucoma Gel Stent (XEN45) Implantation In Participants Aged 45 Years or Older With Open-Angle Glaucoma
Glaucoma is the second most common cause of blindness in the world, second only to cataracts. This study will assess how safe and effective a glaucoma gel stent is when implanted using the ab externo approach. Adverse events and intraocular pressure will be assessed. XEN45 is an approved device for the treatment of glaucoma implanted using the ab interno approach (inside the eye). XEN45 implanted using the ab externo approach (outside the eye) is being studied in this study. Approximately 65 participants aged 45 years or older with open-angle glaucoma will be enrolled in this study at approximately 22 sites in the United States. All participants will receive XEN45 implanted using the ab externo approach on Day 1 and will be followed for 12 months. Participants will attend regular visits during the study at a hospital or clinic. The safety and effect of the gel stent on your glaucoma will be checked by medical assessments and eye examinations.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Stephanie.Morales@UTSouthwestern.edu
Shivani Kamat
ALL
45 Years and over
PHASE3
NCT05411198
STU-2022-0962
Inclusion Criteria:
* Glaucoma in the study eye.
• Study eye diagnosed with open-angle glaucoma uncontrolled by medical therapy
• Study eye that meet at least one of the following criteria: * Failed one or more incisional intraocular glaucoma surgeries (e.g., glaucoma filtering surgery or tube shunt) (a minimum of approximately 15 subjects will be enrolled) * Failed one or more cilioablative procedures (e.g., cryotherapy, cyclodiode therapy) * Have neovascular glaucoma * Have any other condition (e.g., conjunctival scarring, uveitis) in which a conventional incisional glaucoma surgery like trabeculectomy would be more likely to fail than for a person with uncomplicated primary open-angle glaucoma (OAG). Note: To allow for a subgroup of participants who only have OAG uncontrolled by medical therapy (non-refractory glaucoma), a maximum of 10 participants who meet only criterion a (and not b) will be enrolled.
Exclusion Criteria:
* A lack of healthy conjunctiva showing free mobility (free of scarring or evidence of prior surgery) in the target area.
* Excessive intraoperative bleeding, such that visualization in the study eye is impaired.
* Any anatomy or finding in the study eye that limits the investigator's ability to visualize the anterior chamber, angle, or target area of the conjunctiva.
* Other surgical complication that in the opinion of the investigator could impede proper placement of the Gel Stent. DEVICE: XEN45 (Glaucoma Gel Stent)
Open-Angle Glaucoma
Open-Angle Glaucoma, Glaucoma, OAG, XEN45, Glaucoma Gel Stent, XEN45 Glaucoma Treatment System
UT Southwestern; Parkland Health & Hospital System
Clinical Trial to Evaluate the Safety and Efficacy of DWN12088 in Patients With IPF
This is a randomized, double-blinded, placebo-controlled multicenter study to evaluate the safety and efficacy of DWN12088 in patients with Idiopathic Pulmonary Fibrosis.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Maria.Goralski@UTSouthwestern.edu
John Fitzgerald
All
40 Years and over
Phase 2
NCT05389215
STU-2023-0864
Inclusion Criteria:
• Male or female patients aged ≥40 years based on the date of the written informed consent form
• Diagnosis of IPF as defined by American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines
• In a stable condition and suitable for study participation based on the results of medical history, physical examination, vital signs, 12-lead ECG, and laboratory evaluation
• Patients receiving local standard-of-care for IPF, defined as either pirfenidone or nintedanib, at a stable dose for at least 3 months prior to screening, or neither pirfenidone nor nintedanib. If the patients were on pirfenidone or nintedanib previously and have been off for at least 3 months prior to screening, they will be considered as not on any treatment for IPF
• Meeting all of the following criteria during the screening period:
• FVC ≥40% predicted of normal
• DLCO corrected for Hgb ≥25% and ≤80% predicted of normal.
• forced expiratory volume in the first second/FVC (FEV1/FVC) ratio ≥0.7 based on pre-bronchodilator value
Exclusion Criteria:
• Acute IPF exacerbation within 6 months prior to screening and/or during the screening period
• Patients who are unwilling to refrain from smoking within 3 months prior to screening and until the end of the study
• Female patients who are pregnant or nursing
• Abnormal ECG findings
• Use of any investigational drugs for IPF within 4 weeks prior to screening
Drug: DWN12088, Drug: Placebo
Idiopathic Pulmonary Fibrosis, Lung/Thoracic
UT Southwestern