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Phase 3 Efficacy Study With Concurrent Control of IT MELPIDA in SPG50.Concurrent Controls. (SPG50)
Phase 3, open-label study to assess the efficacy and safety of a single lumbar intrathecal administration of MELPIDA in individuals with Hereditary Spastic Paraplegia Type 50 (SPG50).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Sydney.Cooper@UTSouthwestern.edu
Susan Iannaccone
ALL
4 Months to 72 Months old
PHASE3
NCT06692712
STU20252205
Inclusion:
For the treatment group
* Male and females between the ages of 4 months to 72 months at the time of screening.
* Molecularly-confirmed diagnosis of SPG50 (confirmed by a CLIA certified, CE-marked, or equivalent lab): Genomic DNA mutation analysis demonstrating bi-allelic pathogenic or likely pathogenic variants in the AP4M1 gene.
* Subjects must have features of neurologic dysfunction by clinical history and physical examination.
* Stable doses of concomitant medications such as anti-spasticity medications, anti-seizure medications, behavioral management medications, sleep medications, and special diets, supplements, or nutritional support for at least 3 months prior to Screening. If recent changes (\< 3 months) in medications, the subject may be allowed per Investigator judgement.
* Parent/legal guardian willing to provide written informed consent for their child prior to participation in the study,
* Subjects and caregivers must demonstrate the ability to travel to the study center. For the 30 days post treatment subjects must reside within 100 miles (approximately 160 km) of the clinical site.
For the control group
* Male and females between the ages of 4 to 72 months at the time of screening.
* A molecularly confirmed diagnosis of SPG47, SPG50 or SPG52 (confirmed by a CLIA certified, CE-marked, or equivalent lab). Genomic DNA mutation analysis demonstrating bi-allelic pathogenic variants in the AP4B1, AP4M1, or AP4S1 gene,
* Subjects must have features of neurologic dysfunction by clinical history and physical examination.
* 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.
* Subjects and caregivers must demonstrate the ability to travel to the study center.
Exclusion
For the treatment group
* Loss of one of the 8 major motor milestones within the last 12 months. Milestones defined as:
* #24: Sit on mat: Maintain, arms free, 3 seconds
* #44: 4 Point: Crawls or hitches forward 1.8m (6')
* #53: Standing: Maintains, arms free, 3 seconds
* #67: Standing: 2 hands held: walks forward 10 steps
* #69: Standing: Walks forward 10 steps
* #84: Standing: Holding 1 rail: walks up 4 steps, holding 1 rail, alternating feet
* #85: Standing: Holding 1 rail: walks down 4 steps, holding 1 rail, alternating feet
* #88: Standing on 15cm (6") step: Jumps off, both feet simultaneously
* Inability to participate in the clinical evaluation as determined by the principal investigators.
* Clinically significant abnormal laboratory values (hemoglobin \< 6 or \> 20 g/dL; white blood cell \> 20,000 per cmm, platelets count \< 100,000 per cmm; INR \> ULN; GGT, ALT, and AST or total bilirubin \> 1.5 × ULN, creatinine ≥ 1.5 mg/dL) prior to gene replacement therapy.
* Presence of a concomitant medical condition (eg, scoliosis or bleeding disorder) that precludes a lumbar puncture or use of anesthetics for sedated procedures.
* Documented cardiomyopathy or significant congenital heart abnormalities.
* History of severe/life-threatening allergic reaction to sirolimus, tacrolimus, corticosteroids, or gadolinium.
* Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer, or interactions with the immunosuppressive agents.
* Any item which would exclude the subject from being able to undergo MRI according to local institutional policy, or any other procedure.
* The presence of significant AP-4 related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study.
* Recent or planned elective surgical procedures (within 6 months) that would confound the scientific rigor or interpretation of results of the study.
* Failure to obtain appropriate informed consent.
* Reason to believe that the subject or parents of the subject will not comply with the study procedures outlined in the study protocol.
* 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 90 days before first visit (screening).
For the control group
* Loss of one of the 8 major motor milestones within the last 12 months. Milestones defined as:
* #24: Sit on mat: Maintain, arms free, 3 seconds
* #44: 4 Point: Crawls or hitches forward 1.8m (6')
* #53: Standing: Maintains, arms free, 3 seconds
* #67: Standing: 2 hands held: walks forward 10 steps
* #69: Standing: Walks forward 10 steps
* #84: Standing: Holding 1 rail: walks up 4 steps, holding 1 rail, alternating feet
* #85: Standing: Holding 1 rail: walks down 4 steps, holding 1 rail, alternating feet
* #88: Standing on 15cm (6") step: Jumps off, both feet simultaneously
* Inability to participate in the clinical evaluation as determined by the principal investigators.
* Any other situation that would exclude the subject from undergoing any other procedure required in this study.
* The presence of significant AP-4 related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study.
* Recent or planned elective surgical procedures that would confound the scientific rigor or interpretation of results of the study.
* Failure to obtain appropriate informed consent.
* Reason to believe that the subject or parents of the subject will not comply with the study procedures outlined in the study protocol.
* Have received an investigational drug within 30 days prior to screening or plans to receive an investigational drug (other than gene therapy) during the study.
* Enrollment and participation in another interventional clinical trial 90 days before first visit (screening).
GENETIC: MELPIDA
Hereditary Spastic Paraplegia Type 50
SPG50, Spastic Paraplegia, Gene Therapy, Phase 3
Children’s Health
A Study to Learn More About the Effects and Safety of Felzartamab Infusions in Adults With Kidney Transplants Who Have Antibody-Mediated Rejection (AMR) (TRANSCEND)
In this study, researchers will learn more about the use of felzartamab in kidney transplant patients who have antibody-mediated rejection, also known as AMR. Kidney transplants can save lives for people with kidney failure. But even after a successful transplant, the body's immune system can sometimes attack the new kidney. Antibody-mediated rejection (AMR) is when a person's immune system attacks a transplanted organ, like a new kidney. In the person receiving the transplant, their immune system creates specific antibodies. Antibodies are proteins that help the body fight infections. In people with AMR, these antibodies mistakenly see the new organ as a threat and damage its blood vessels. This can cause the new organ to fail. In this study, researchers will learn more about how a study drug called felzartamab affects people with AMR. Felzartamab is a monoclonal antibody, which means it is an antibody made in a laboratory. Felzartamab can target immune cells that produce antibodies, helping to lower their buildup in the kidneys. The main goal of this study is to compare how felzartamab works in participants with kidney transplants who experience AMR compared to a placebo. A placebo is something that looks like the study drug but does not contain any medicine. A placebo is also given in the same way as the study drug. All participants in this study will have active AMR or AMR that has lasted for at least 6 months after their kidney transplant. The main question that researchers want to answer is: • How many participants have biopsy results showing that their transplanted kidney tissue looks normal or near normal after 24 weeks of treatment? Researchers will also learn about: * How long it takes before the participants' disease gets worse * How long the participants' urine protein levels stay low * Kidney biopsy scores to check for blood vessel inflammation at 6 months and 1 year * How many people have no blood vessel inflammation at these times * Changes in donor deoxyribonucleic acid (DNA) levels in blood from the start of treatment * Biopsy test scores for signs of rejection and inflammation at 6 months and 1 year * Changes in kidney function from the start of treatment * How many people have biopsy results showing their kidney tissue looks normal again * How long the transplanted kidney keeps working * How many participants have medical problems during the study * How many participants show signs of another type of kidney transplant rejection called T-cell-mediated rejection (TCMR) at Week 24 and Week 52 * How do results from vital signs, electrocardiograms (ECGs), and blood and urine tests change over time * How felzartamab is processed by the body * How many participants develop antibodies against felzartamab in the blood The study will be done as follows: * Participants will be screened to check if they can join the study. This will take up to 42 days. * There will be 2 parts in this study. * Part A of the study is "double blind." This means that neither the participants, study doctor, or site staff know if the participants received the study drug or a placebo. During Part A, participants will be randomized to receive up to 9 doses of either felzartamab or placebo. * Part B of the study is "open label." This means that the participants, study doctor, and site staff know which study drug the participant is receiving. During Part B, all participants from Part A will receive up to 9 doses of felzartamab. * All doses will be given through an "intravenous" infusion. This means it will be given into a vein. The dose the participants receive will depend on their body weight. * Part A will last up to 24 weeks. Part B will last up to 28 weeks. In total, participants will have up to 21 study visits and will be in the study for about 1 year.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Elaine.Bonilla@UTSouthwestern.edu
David Wojciechowski
ALL
18 Years to 75 Years old
PHASE3
NCT06685757
STU20250439
Key
• Intravenous or subcutaneous immunoglobulin (IVIg or subcutaneous immunoglobulin \[SCIg\]) or PLEX.
• Complement system inhibitors (e.g., eculizumab).
• Proteasome inhibitors (e.g., bortezomib).
• Tocilizumab.
• Any B cell-depleting therapy (including anti-Cluster of Differentiation 20 \[CD20\] agents \[e.g., rituximab\]) within 3 months prior to randomization.
• Any other investigational agent within 3 months or 5 half-lives (whichever is longer) of randomization. Note: Other protocol-defined inclusion/exclusion criteria apply.
Inclusion Criteria:
* Active or chronic active AMR (biopsy-confirmed) without TCMR per central reading, as defined by the Banff 2022 criteria.
* Kidney transplant at least 6 months prior to Screening visit (recipients of either living or deceased donors).
* Donor-specific antibody (DSA): Human leukocyte antigen (HLA) Class I and/or II antigen-specific DSA-positive (preformed and/or de novo DSA) as determined by the local laboratory's definition of positivity using singleantigen bead-based assays within 3 months prior to randomization.
Key Exclusion Criteria:
* Transplant: Blood type (ABO)-incompatible transplant.
* History of multiple organ transplants including en bloc and dual kidney transplants.
* Acute, rapid decline in renal function, defined as a participant likely to require renal replacement therapy within the subsequent 30 days as determined by the Investigator.
* Treatment: Prior AMR/TCMR treatment (with the exception of corticosteroids) within 3 months prior to randomization is excluded as listed below. Participants who received any of these treatments between 3 and 6 months prior to randomization must have both a renal biopsy (IC3) and DSA testing at least 6 weeks after completing (or stopping) treatment in order to confirm continuing AMR and to determine eligibility:
• Intravenous or subcutaneous immunoglobulin (IVIg or subcutaneous immunoglobulin \[SCIg\]) or PLEX.
• Complement system inhibitors (e.g., eculizumab).
• Proteasome inhibitors (e.g., bortezomib).
• Tocilizumab.
• Any B cell-depleting therapy (including anti-Cluster of Differentiation 20 \[CD20\] agents \[e.g., rituximab\]) within 3 months prior to randomization.
• Any other investigational agent within 3 months or 5 half-lives (whichever is longer) of randomization. Note: Other protocol-defined inclusion/exclusion criteria apply.
DRUG: Felzartamab, DRUG: Placebo
Antibody-mediated Rejection
AMR, Felzartamab, Kidney Transplant
UT Southwestern
PTM-101 in Pancreatic Ductal Adenocarcinoma (PDAC)
This is a multi-center, non-randomized, single-arm, open-label, phase Ib, dose escalation/dose expansion study of PTM-101 when combined with neoadjuvant chemotherapy for the treatment of treatment-naïve subjects with borderline resectable and locally advanced pancreatic ductal adenocarcinoma (PDAC).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Patricio Polanco
ALL
18 Years to old
PHASE1
NCT06673017
STU20251994
Inclusion Criteria:
* Imaging consistent with primary borderline resectable or locally advanced PDAC. PDAC may be confirmed by histology/cytology either at study-mandated laparoscopy or by prior biopsy/cytology
* Indicated for laparoscopy
* No prior therapy of any kind for PDAC
* Acceptable laboratory values
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
* Ability to provide informed consent
* No symptomatic pancreatitis
* No other active medical issues which would confound interpretation of safety monitoring, efficacy results or prevent the subject from study participation
* Subjects with childbearing potential must agree to use adequate contraception throughout study participation
Exclusion Criteria:
* Active non-pancreatic cancer that currently requires treatment or is being treated; diagnosis of another malignancy within the past 2 years. This criterion excludes a history of carcinoma in situ of the cervix, superficial non-melanoma skin cancers, or superficial bladder cancer that has been adequately treated, or stage 1 prostate cancer that does not require treatment or requires only treatment with luteinizing hormone-releasing hormone agonists or antagonists if initiated at least 30 days prior to screening). Other potentially indolent cancers may be considered.
* Contraindications or allergies to paclitaxel, PLGA (poly(lactic-co-glycolic ) acid), or contraindications to implantation of PTM-101 or chemotherapies in protocol (e.g., FOLFIRINOX, gemcitabine, nab-paclitaxel)
* Known history of human immunodeficiency virus (HIV) or active viral hepatitis
* Active ongoing infection or autoimmune disease which may preclude laparoscopy, placement of PTM-101, administration of chemotherapy or surgical resection of pancreatic tumor
* Inability to comply with activities and therapeutic interventions as outlined in the schedule of events
* Currently enrolled in another investigational drug or device trial
* Women who are pregnant or breastfeeding or who plan to become pregnant or breastfeed; men who plan to donate sperm or conceive a child
* Any other medical or surgical conditions, including prior abdominal surgery, that would preclude safe laparoscopy or implantation in the opinion of the investigator DRUG: PTM-101
Pancreatic Ductal Adenocarcinoma, Borderline Resectable Pancreatic Adenocarcinoma, Locally Advanced Pancreatic Adenocarcinoma, Pancreatic Cancer
UT Southwestern
A Study of Amivantamab in Combination With Lazertinib, or Amivantamab in Combination With Platinum-Based Chemotherapy, for Common Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) (COPERNICUS)
The primary purpose of the study is to assess how well amivantamab in combination with lazertinib or in combination with chemotherapy works (antitumor activity) in participants with epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC; that is one of the major types of lung cancer).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Sawsan Rashdan
ALL
18 Years to old
PHASE2
NCT06667076
STU-2024-1175
Inclusion Criteria:
* Have histologically or cytologically confirmed advanced or metastatic non-small cell lung cancer (NSCLC) that is not amenable to curative intent therapy
* Epidermal growth factor resistance-mutation (EGFRm) must be an Ex19del or Ex21 L858R substitution, as detected by food and drug administration (FDA)-approved or other validated test in a clinical laboratory improvement amendments (CLIA)-certified laboratory (sites in the US), or an accredited local laboratory (sites outside of the US) in accordance with site standard of care. In the European union (EU), the local test must be Conformité Européenne (CE)-marked or an in-house laboratory-developed test from health institutions in the EU in accordance with Article 5(5) of the in vitro diagnostic regulations (IVDR ) 2071/746, as amended
* Have at least 1 measurable lesion, according to RECIST version (v)1.1, that has not been previously irradiated
* Any toxicities from prior systemic anticancer therapy must have resolved to national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 5.0 grade 1 or baseline level (except for alopecia \[any grade\], grade \<=2 peripheral neuropathy, or grade \<=2 hypothyroidism stable on hormone replacement)
* Have an eastern cooperative oncology group (ECOG) performance status of 0 to 1
Exclusion Criteria:
* Medical history of active interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis. Participants with medical history of radiation pneumonitis, including radiation pneumonitis which required steroid treatment, should consult with the medical monitor and eligibility be assessed on a case-by-case basis
* Had major surgery excluding placement of vascular access or tumor biopsy or had significant traumatic injury within 4 weeks before the first dose of anticancer treatments or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study
* Participant has uncontrolled tumor-related pain (symptomatic lesions amenable to palliative radiotherapy should be treated prior to first dosing)
* Received an investigational treatment that has not been cleared (based on at least 5 half lives of any pharmaceutical treatment) before the planned first dose of study treatment or is currently enrolled in an investigational study
* Has a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment could likely interfere with any study endpoints of safety or the efficacy of the study treatment(s) DRUG: Amivantamab, DRUG: Lazertinib, DRUG: Chemotherapy: Pemetrexed, DRUG: Chemotherapy: Carboplatin
Carcinoma, Non-Small-Cell Lung, Lung/Thoracic
UT Southwestern; Parkland Health & Hospital System
A Study of Vosoritide in Children With Noonan Syndrome With Inadequate Growth During or After Human Growth Hormone Treatment
The purpose of this study in children with Noonan syndrome is to evaluate the effect of 3 doses of vosoritide on growth as measured by AGV after 6 months of treatment. The long-term efficacy and safety of vosoritide at the therapeutic dose will be evaluated up to FAH.
Call 214-648-5005
studyfinder@utsouthwestern.edu, colten.youngblood@childrens.com
Nadia Merchant
ALL
3 Years to 11 Years old
PHASE2
NCT06668805
STU-2024-0821
Inclusion Criteria:
• Participants must be ≥ 3 years old, and \< 11 years old (females) or \< 12 years old (males), at the time of signing the informed consent form
• A genetically confirmed diagnosis of Turner syndrome, SHOX deficiency or Noonan syndrome.
• A height assessment corresponding to a height Z-score of ≤ -1.28 SDs (below the 10th percentile for height) in reference to the general population of the same age and sex.
• Tanner Stage 1, at time of signing the ICF.
• Previous or current hGH treatment for short stature associated with their condition.
• Inadequate growth confirmed with an AGV that is less than age- and sex-matched average stature AGV determined using median heights from CDC growth charts
Exclusion Criteria:
• Participants with Turner syndrome known to have Y-chromosome material unless they have undergone gonadectomy and have fully external female genitalia.
• Diagnosis of systemic disease or condition that may cause short stature other than Turner syndrome, SHOX deficiency, or Noonan syndrome, eg, renal, neoplastic, pulmonary, cardiac, gastrointestinal, immunologic and metabolic disease.
• Bone age advanced beyond chronological age by more than 2 years.
• Uncorrected congenital heart disease which places the participant at increased risk of an adverse cardiac outcome in the setting of hypotension,
• Have an unstable condition likely to require surgical intervention during the study.
• Evidence of decreased growth velocity (AGV \< 1.5 cm/year) as assessed over a period of at least 6 months and growth plate closure assessed using bilateral lower extremity X-rays.
• Previous limb-lengthening surgery, or planned or expected to have limb lengthening surgery during the study period.
• Planned or expected bone-related surgery (ie, surgery involving disruption of bone cortex, excluding tooth extraction), during the study period.
DRUG: Vosoritide Injection
Noonan Syndrome
Short Stature, Musculoskeletal Diseases, Bone Diseases, Developmental Endocrine System Diseases Natriuretic Peptide, C-Type
Children’s Health
A Study of Amivantamab and mFOLFOX6 or FOLFIRI Versus Cetuximab and mFOLFOX6 or FOLFIRI as First-line Treatment in Participants With KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer (OrigAMI-2)
The purpose of this study is to compare how long the participants are disease-free (progression-free survival) when treated with amivantamab and chemotherapy with 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, oxaliplatin (mFOLFOX6) or 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride (FOLFIRI) versus cetuximab and mFOLFOX6 or FOLFIRI in adult participants with Kirsten rat sarcoma viral oncogene homolog (KRAS)/ Neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) wild type (WT) unresectable or metastatic left-sided colorectal cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
ALL
18 Years to old
PHASE3
NCT06662786
STU20240010
Inclusion Criteria:
* Have histologically or cytologically confirmed adenocarcinoma of the left-sided colorectal cancer. Participants must have unresectable or metastatic disease
* Determined to have Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type (WT) tumor by local and/or central testing (if available)
* Must agree to the submission of fresh tumor tissue
* Have measurable disease according to RECIST v1.1
* Has not received any prior systemic therapy for unresectable or metastatic colorectal cancer (CRC). Prior adjuvant/neoadjuvant therapy in the non-metastatic disease is permitted. However, the last course of adjuvant or neoadjuvant chemotherapy must have concluded greater than (\>) 12 months prior to CRC recurrence/metastases
* Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1
Exclusion Criteria:
* Has medical history of (noninfectious) interstitial lung disease (ILD) /pneumonitis/pulmonary fibrosis or has current ILD/pneumonitis/pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening
* Has known allergies, hypersensitivity, or intolerance to excipients of any of the following: (a) amivantamab or cetuximab, (b) any component of mFOLFOX6 and, (c) any component of FOLFIRI
* Has a prior or concurrent second malignancy other than the disease under study or one whose natural history or treatment is likely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
* Participant with known mismatch repair deficiency (dMMR)/ high microsatellite instability (MSI-H) status and human epidermal growth factor receptor 2 (HER2)-positive/amplified tumor
* Has prior exposure to any agents that target epidermal growth factor receptor (EGFR), mesenchymal epithelial transition (MET) or vascular endothelial growth factor (VEGF) BIOLOGICAL: Amivantamab, BIOLOGICAL: Cetuximab, DRUG: 5-fluorouracil, DRUG: Leucovorin calcium/Levoleucovorin, DRUG: Oxaliplatin, DRUG: Irinotecan Hydrochloride
Colorectal Neoplasms, Colon, Rectum
UT Southwestern
HIV+ Deceased Donor Heart Transplant Study for HIV+ Recipients
This will be a prospective single-center interventional trial to compare the outcomes of HIV-positive heart transplant recipients by the HIV status of the donor; HIV-positive vs. HIV-negative and learn whether heart organ transplantation from HIV+ deceased donors is as safe and effective in HIV+ recipients as transplants from HIV- deceased donors. Patient will undergo standard evaluation for eligibility of transplantation by the primary heart transplant team. If patient meets eligibility criteria, they will be informed about the study and consent will be obtained. Informed consent will be obtained in a private clinic or inpatient hospital room in a confidential setting. HIV-positive or HIV-negative offers will be made by Organ Procurement and Transplantation Network (OPTN) (serving as a means of "natural randomization" and this information will also be collected, along with the information regarding any information for primary offer declines from the patients as well as other clinical indications to decline an organ offer. As a result of this, there will be two main groups in the study participants that will undergo analysis: 1. patients/recipients that are HIV+ who receive an organ from an HIV+ donor (HIV D+/R+ group) 2. patients/recipients that are HIV+ who receive an organ from an HIV negative donor (HIV D-/R+ group) Only study participants will be able to receive organ offers from both HIV-positive and HIV-negative organ donors whichever is available first regardless of HIV status. This is the only study intervention. Baseline visit parameters will be obtained during a routine heart transplant visit. There will be no additional procedures or blood collection after the baseline study visit. Study data will be collected from chart review of routine post-transplant follow-up visits at weeks 52 (1 year), 104 (2 years), and 152 (3 years) after the transplant.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Ricardo.LaHoz@UTSouthwestern.edu
Ricardo La Hoz
ALL
18 Years to old
NA
NCT06659952
STU-2024-0777
Inclusion Criteria:
All individuals with advanced heart failure and HIV infection who meet the study inclusion and exclusion criteria will be eligible for participation in the study.
* Participant meets the standard criteria for heart transplant at the local center.
* Participant is able to understand and provide informed consent.
* Participant meets with an independent advocate per the HOPE Act Safeguards and Research Criteria.
* Documented HIV infection (by any licensed assay, or documented history of detectable HIV-1 RNA).\*
* Participant is ≥ 18 years old.
* Opportunistic complications: if prior history of an opportunistic infection, the participant has received appropriate therapy and has no evidence of active disease. Medical record documentation should be provided whenever possible.\*
* CD4+ (cluster of differentiation 4+) T-cell count: ≥ 200/μL within 16 weeks of transplant.\*
* HIV-1 RNA is below 50 copies RNA/mL.\*/\*\* Viral blips between 50-400 copies will be allowed as long as there are not consecutive measurements \> 200 copies/mL. \*\*Organ recipients who are unable to tolerate ART due to organ failure or recently started Antiretroviral Therapy (ART) may have detectable viral load and still be eligible if a safe and effective antiretroviral regimen to be used by the recipient after transplantation is described.
* Participant is willing to comply with all medications related to their transplant and HIV management.
* For participants with a history of aspergillus colonization or disease, no evidence of active disease.
* The participant must have or be willing to start seeing a primary medical care provider with expertise in HIV management.
* Agreement to use contraception; according to the FDA Office of Women's Health (http://www.fda.gov/birthcontrol), there are a number of birth control methods that are more than 80% effective. Female participants of child-bearing potential must consult with their physician and determine the most suitable method(s) from this list to be used from the time that study treatment begins until after study completion.
* Participant is not suffering from significant wasting (e.g. body mass index \< 21) thought to be related to HIV disease.
Exclusion Criteria:
Individuals who meet any of these criteria are not eligible for enrollment as study participants:
* Participant has a history of progressive multifocal leukoencephalopathy (PML) or primary central nervous system (CNS) lymphoma.\*
* Participant is pregnant or breastfeeding. (Note: Participants who become pregnant post-transplant will continue to be followed in the study and will be managed per local site practice. Women that become pregnant should not breastfeed.)
* Past or current medical problems or findings from medical history, physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study. OTHER: HIV-positive heart transplant
HIV Infection, Advanced End Stage Heart Failure
HIV positive donor, HIV positive recipient, Heart transplant
UT Southwestern
Testing a Standardized Approach to Surgery and Chemotherapy for Type I Pleuropulmonary Blastoma or the Addition of an Anti-cancer Drug, Topotecan, to the Usual Treatment for Types II and III Pleuropulmonary Blastoma
This phase III trial tests how well surgery plus chemotherapy compared to surgery alone works in treating patients with type I pleuropulmonary blastoma (PPB), and tests how well surgery plus standard chemotherapy with the addition of topotecan works compared to surgery plus standard chemotherapy alone in treating patients with type II and III PPB. Historically, most children with type I PPB had surgery and approximately 40% of children with type I PPB received chemotherapy following their surgery, usually for 22-42 weeks. There has not been a consistent standard for which children with type I PPB receive chemotherapy after surgery. For patients whose tumor has been removed completely with surgery, observation without chemotherapy may work as well as giving chemotherapy after surgery in preventing a return of the PPB tumor. The standard chemotherapy for patients with types II or III PPB in the United States is four cycles of IVADo (ifosfamide, vincristine, dactinomycin, and doxorubicin) followed by 8 cycles of IVA (ifosfamide, vincristine and dactinomycin). Ifosfamide is in a class of medications called alkylating agents. It works by slowing or stopping the growth of tumor cells in the body. Vincristine is in a class of medications called vinca alkaloids. It works by stopping tumor cells from growing and dividing and may kill them. Dactinomycin is a type of antibiotic that is only used in cancer chemotherapy (antineoplastic antibiotic). It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill tumor cells. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's DNA and may kill tumor cells. It also blocks a certain enzyme needed for cell division and DNA repair. Topotecan is in a class of medications called topoisomerase I inhibitors. It works by interfering with tumor cell DNA which kills them. Giving topotecan in addition to standard IVADo and IVA chemotherapy regimens may shrink the cancer as well as or better than the standard therapy or could decrease the chance the tumor spreads while causing fewer side effects.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Avanthi Shah
ALL
to 21 Years old
PHASE3
NCT06647953
STU20250654
Inclusion Criteria:
* 21 years of age or younger
* Newly diagnosed PPB. Note that patients with known germline DICER1 variant or mosaicism with a large, solid unresectable thoracic mass with imaging features characteristic for Type II or III PPB are eligible without histologic confirmation of the diagnosis if a biopsy of the mass is not considered safe or feasible
* Individuals are eligible based on institutional diagnosis of Type I, Ir, II or III PPB diagnosed within 60 days prior to enrollment. Children with Type II or III PPB at risk for clinical decompensation may receive protocol therapy while awaiting rapid central pathology review. Children with Type I or Ir PPB will be assigned to chemotherapy vs. observation based on imaging and central pathology review diagnosis. Type I and Ir patients should not begin chemotherapy prior to return of central pathology results
* For patients with Type II or III PPB (within 7 days prior to enrollment): A serum creatinine based on age/sex as follows:
* Age: 1 month to \< 6 months - Maximum Serum Creatinine (mg/dL): 0.4 (Male), 0.4 (Female)
* Age: 6 months to \< 1 year - Maximum Serum Creatinine (mg/dL): 0.5 (Male), 0.5 (Female)
* Age: 1 to \< 2 years - Maximum Serum Creatinine (mg/dL): 0.6 (Male), 0.6 (Female)
* Age: 2 to \< 6 years - Maximum Serum Creatinine (mg/dL): 0.8 (Male), 0.8 (Female)
* Age: 6 to \< 10 years - Maximum Serum Creatinine (mg/dL): 1 (Male), 1 (Female)
* Age: 10 to \< 13 years - Maximum Serum Creatinine (mg/dL): 1.2 (Male), 1.2 (Female)
* Age: 13 to \< 16 years - Maximum Serum Creatinine (mg/dL): 1.5 (Male), 1.4 (Female)
* Age: ≥ 16 years - Maximum Serum Creatinine (mg/dL): 1.7 (Male), 1.4 (Female) OR - A 24 hour urine creatinine clearance ≥ 60 mL/min/1.73 m\^2 OR - A glomerular filtration rate (GFR) ≥ 60 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 with Type II or III PPB (within 7 days prior to enrollment): Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
* For patients with Type II or III PPB (within 7 days prior to enrollment): Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) ≤ 135 U/L
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* Shortening fraction of ≥ 27% by echocardiogram, or ejection fraction of ≥ 50% by radionuclide angiogram (within 21 days prior to start of protocol therapy)
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible as long as they are NOT receiving anti-retroviral agents that are strong inhibitors or inducers of CYP3A4
Exclusion Criteria:
* Administration of prior PPB-directed chemotherapy is an exclusion criterion. Prior treatment for another malignancy is not an exclusion criterion
* Patients with known Charcot-Marie-Tooth disease
* 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, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, BIOLOGICAL: Dactinomycin, DRUG: Dexrazoxane, DRUG: Doxorubicin, PROCEDURE: Echocardiography Test, DRUG: Ifosfamide, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan, OTHER: Patient Observation, PROCEDURE: Positron Emission Tomography, DRUG: Topotecan, PROCEDURE: Ultrasound Imaging, DRUG: Vincristine
Pleuropulmonary Blastoma, Lung/Thoracic
Children’s Health
A Phase 2 Study of JNT-517 in Adolescent Participants With Phenylketonuria
The goal of this Phase 2, randomized study is to assess the safety, tolerability, and pharmacokinetics (PK) of oral JNT-517 in adolescents (12 to less than 18 years of age) with PKU. Participants will receive either JNT-517 or placebo and will be blinded to their treatment assignment. Participants will have a 4 in 5 (or 80%) chance of receiving JNT-517. The study will last for up to 63 days including a Screening period, Treatment period and Follow-up period for safety. Participants will: * Take 75 mg JNT-517 or a placebo BID (2x per day) for 28 days * Visit the clinic or have a mobile health nurse visit your home for checkups and tests * Collect urine sample at home and bring to clinic on specified days * Keep a food diary 3 days before each study visit
Call 214-648-5005
studyfinder@utsouthwestern.edu, Juana.Luevano@UTSouthwestern.edu
Markey McNutt
ALL
12 Years to 17 Years old
PHASE2
NCT06637514
STU20240016
Key
• Males and females 12 to less than 18 years of age, inclusive on Day 1.
• Clinical diagnosis of PKU.
• Ability to swallow tablets.
• Average of 2 plasma Phe levels during the Screening period greater than 360 μM and no plasma Phe level less than 300 μM.
• Body weight equal or greater than 45 kg and body mass index less than 40 kg/m2.
• Females of childbearing potential must practice sexual abstinence or agree to use 2 highly effective contraceptive methods.
• Capable of giving signed informed consent (emancipated minors) or parent/legal guardian to provide informed consent and the participant to give assent and confirm ability to comply with study procedures. Key
• Any acute or chronic medical condition that would prevent the participant from complying with the procedures or place the participant at risk if they participate in the study.
• Positive for hepatitis B or C or human immunodeficiency virus.
• Any history of malignancy in the last 5 years, excluding nonmelanoma skin cancer.
• Any history of liver disease.
• Any history of cataracts or more than minimal cataracts observed during the Screening ophthalmologic examination.
• Any surgical or medical conditions that may affect study drug absorption, distribution, metabolism, or excretion.
• Creatinine clearance less than 90 mL/min by Cockcroft-Gault formula.
• History of drug or alcohol abuse in the last year
• Current, recent, or suspected infection within 14 days of Screening of SARS CoV 2/COVID 19.
• Participation in another investigational drug trial within 30 days or, if known 5 half-lives of investigational drug (whichever is longer).
• Unable to tolerate oral medication.
• Allergy to JNT-517 or any component of the investigational product.
• Received greater than 50 mL of blood or plasma within 30 days of Screening or greater than 500 mL of blood or plasma within 60 days of Screening.
Inclusion Criteria:
• Males and females 12 to less than 18 years of age, inclusive on Day 1.
• Clinical diagnosis of PKU.
• Ability to swallow tablets.
• Average of 2 plasma Phe levels during the Screening period greater than 360 μM and no plasma Phe level less than 300 μM.
• Body weight equal or greater than 45 kg and body mass index less than 40 kg/m2.
• Females of childbearing potential must practice sexual abstinence or agree to use 2 highly effective contraceptive methods.
• Capable of giving signed informed consent (emancipated minors) or parent/legal guardian to provide informed consent and the participant to give assent and confirm ability to comply with study procedures. Key
Exclusion Criteria:
• Any acute or chronic medical condition that would prevent the participant from complying with the procedures or place the participant at risk if they participate in the study.
• Positive for hepatitis B or C or human immunodeficiency virus.
• Any history of malignancy in the last 5 years, excluding nonmelanoma skin cancer.
• Any history of liver disease.
• Any history of cataracts or more than minimal cataracts observed during the Screening ophthalmologic examination.
• Any surgical or medical conditions that may affect study drug absorption, distribution, metabolism, or excretion.
• Creatinine clearance less than 90 mL/min by Cockcroft-Gault formula.
• History of drug or alcohol abuse in the last year
• Current, recent, or suspected infection within 14 days of Screening of SARS CoV 2/COVID 19.
• Participation in another investigational drug trial within 30 days or, if known 5 half-lives of investigational drug (whichever is longer).
• Unable to tolerate oral medication.
• Allergy to JNT-517 or any component of the investigational product.
• Received greater than 50 mL of blood or plasma within 30 days of Screening or greater than 500 mL of blood or plasma within 60 days of Screening.
DRUG: JNT-517 Tablet, OTHER: Placebo, DRUG: JNT-517 Tablet
Phenylketonuria (PKU), Other Endocrine System
PKU
UT Southwestern; Children’s Health
APVO436 Phase 1b/2 Study in Patients With Newly Diagnosed AML
A multi-center, open-label, dose-finding study of five dose levels of APVO436 in combination with venetoclax and azacitidine (ven/aza) in adult patients with newly diagnosed, CD123+ AML.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years to old
PHASE1
NCT06634394
STU-2024-1192
Inclusion Criteria:
* 1. Age ≥18 years. 2. Patient must have confirmation of AML based on 2016 World Health Organization (WHO) criteria and not been previously treated.
• Patients must have CD123-positive AML as confirmed by local flow cytometry (or immunohistochemistry \[IHC\]). Confirmation at diagnosis is acceptable.
• Patient must be considered ineligible for induction therapy defined by at least one of the following:
• ≥75 years of age
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or 3
• Cardiac disorder (e.g., congestive heart failure requiring treatment, ejection fraction ≤ 50%, or chronic stable angina)
• Pulmonary disorder (e.g., DLCO ≤65% or FEV1 ≤65%)
• Creatinine clearance 30-45 mL/min based on Cockcroft-Gault or Modified of Diet in Renal Disease (MDRD) formular
• Hepatic disorder with total bilirubin between 1.5 and 3 times the ULN 5. Patient must have a projected life expectancy of ≥12 weeks
Exclusion Criteria:
• Patient has received treatment with the following:
• A hypomethylating agent, venetoclax, and/or chemotherapeutic agent for AML, myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), or myelodysplastic/myeloproliferative neoplasms (MPS/MPN)
• CAR-T cell therapy or history of allogeneic hematopoietic stem cell transplant (HSCT)
• Experimental therapies for MDS or AML
• Patient is currently participating in another interventional research study.
• Patient has history of MPN including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation, or AML with BCR-ABL1 translocation.
• Patient has acute promyelocytic leukemia.
• Patient has a current autoimmune disorder requiring immunosuppressive therapy such as systemic (oral or IV) steroid therapy \>10 mg methylprednisolone daily or its equivalent
• Patient is receiving concurrent corticosteroid therapy as an anticancer drug (any dose).
• Patient has known active CNS involvement with AML. Patients who received intrathecal chemotherapy for prophylaxis of AML in the CNS prior to enrollment may enroll in this study.
• Creatinine clearance \<30ml/min based on Cockcroft-Gault or MDRD formular.
• Bilirubin of \>3xULN in the absence of Gilbert's Syndrome.
• AST and/or ALT \>3 times the ULN.
DRUG: APVO436, DRUG: Venetoclax, DRUG: Azacitidine
Acute Myeloid Leukemia (AML), Myeloid and Monocytic Leukemia
Acute Myeloid Leukemia
UT Southwestern
Neonatal Platelet Transfusion Threshold Trial (NeoPlaTT)
The objective of the NeoPlaTT trial is to test whether, among extremely preterm infants born at 23 0/7 to 26 6/7 weeks' gestation, a lower platelet transfusion threshold, compared to a higher threshold, improves survival without major or severe bleeding up to 40 0/7 weeks' postmenstrual age (PMA).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Arpineh.Chavez@UTSouthwestern.edu
Vishal Kapadia
ALL
1 Hour to 48 Hours old
NA
NCT06676904
STU20250417
Inclusion Criteria:
* Gestational age of 23 0/7 to 26 6/7 weeks
* Postnatal age of \< 48 hours
Exclusion Criteria:
* Comfort care or withdrawal of care planned
* Neonatal alloimmune thrombocytopenia or suspected/confirmed congenital platelet or bleeding disorder
* Receipt of platelet transfusion
* No receipt of Vitamin K
* Parents/guardian decline consent PROCEDURE: Higher Platelet Transfusion Threshold, PROCEDURE: Lower Platelet Transfusion Threshold
Thrombocytopenia, Neonatal, Platelet Transfusion, Infant, Newborn, Diseases, Infant, Extremely Low Birth Weight, Infant, Small for Gestational Age, Thrombosis
platelet transfusion, neonatal, thrombosis
UT Southwestern; Children’s Health; Parkland Health & Hospital System
A Long-Term Study of JNT-517 in Participants With Phenylketonuria
The goal of this Phase 3, open-label study is to evaluate the long-term safety of JNT-517 in pediatric and adult participants with Phenylketonuria (PKU) after completion of either Study JNT517-101 (NCT05781399) or JNT517-201 (NCT06637514) as well as participants who have not participated in a prior JNT-517 study. In this trial, all participants will receive JNT-517 using age- and weight-banded dosing as outlined in the protocol, regardless of any dose received in a previous study.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Juana.Luevano@UTSouthwestern.edu
Markey McNutt
ALL
4 Years to old
PHASE3
NCT06628128
STU20250336
Key
• Diagnosis of phenylketonuria (ie, PAH deficiency) by either molecular testing or biochemical criteria consistent with the applicable regional guidelines.
• Participants 4 years of age and older, inclusive, at time of Screening.
• Not on pegvaliase within 4 weeks of Screening.
• Not on sepiapterin within 2 weeks of Screening.
• If on sapropterin or large neutral amino acids at Screening, must be on a stable dose for 4 weeks prior to Screening.
• Willing and able to maintain a diet consistent in Phe content from the Screening period through the duration of the study, unless otherwise directed by a dietician as allowed in the protocol.
• Body weight ≥ 12.5 kg.
• If female of childbearing potential:
• Must have a negative serum pregnancy test at Screening and a negative urine pregnancy test by Day 1.
• Must practice sexual abstinence, or if involved in any sexual intercourse that could lead to pregnancy, must agree to use 2 different contraceptive methods, where at least 1 method must be highly effective, from Screening until at least 30 days after the last study drug administration.
• Must refrain from donating ova during the course of the study and for 30 days after the last dose of the study drug.
• Is a female not of childbearing potential or postmenopausal, defined as follows:
• Has had surgical sterilization (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy).
• Has had amenorrhea for minimum of 1 year with confirmation by levels of follicle stimulating hormone testing.
• Has not achieved menarche (has not had first menstrual period). If a female achieves menarche during the study, she will need to follow the contraception requirement for females of childbearing potential.
• If male, must practice sexual abstinence, or if involved in any sexual intercourse that could lead to pregnancy, must agree to use 2 different contraceptive methods, where at least 1 method must be highly effective, from Day 1 until at least 30 days after the last study drug administration and must refrain from donating sperm during the course of the study and for 30 days after the last dose of the study drug. Note: No restrictions are required for males who have undergone a documented vasectomy at least 4 months prior to Screening. If the vasectomy procedure is not documented or was performed less than 4 months prior to Screening, males must follow the same contraception as for non-vasectomized participants.
• Capable of giving signed informed consent, or parent/legal guardian to provide informed consent and pediatric participant to give assent, and be able to comply with study procedures.
• Participants with psychiatric illness must be well-controlled for the last 3 months prior to screening visit and, if on medication, on stable medications for the last 3 months. Key
• Participation in this study is not considered safe and/or feasible in the opinion of the Investigator.
• Participants have not completed a previous JNT-517 study and are eligible for another active JNT-517 trial at the site, unless approval is obtained from the medical monitor.
• Any acute or chronic medical condition that would prevent the participant from complying with the procedures or place the participant at risk if they participate in the study.
• Positive for hepatitis B or C or human immunodeficiency virus.
• Any history of significant liver disease.
• Any history of cataracts or more than minimal cataracts observed during the Screening ophthalmologic examination.
• Any surgical or medical conditions that may affect study drug absorption, distribution, metabolism, or excretion.
• Estimated glomerular filtration rate \< 60 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2) by 2021 Chronic Kidney Disease Epidemiology Collaboration formula (participants aged 17 years or greater) or by Schwartz formula (participants aged 4 to 16 years of age).
• History of drug or alcohol abuse in the last year.
• Use of any medication that are inhibitors or inducers of cytochrome P450 (CYP)3A4 or inhibitors of the transporter P glycoprotein (P-gp) within 4 weeks prior to the first dose of study drug and unwilling and/or unable to avoid these medications throughout the treatment duration.
• Use of any medications that are a substrate of breast cancer resistance protein (BCRP), multidrug and toxin extrusion (MATE)1, MATE2-K, organic anion transporter 3 (OAT3), or CYP3A4 within 4 weeks prior to the first dose of study drug and unwilling and/or unable to avoid these medications throughout the treatment duration (Appendix A). CYP3A4 substrates may be allowed if reduction in exposure is not expected to impact safety of the participant after consultation with the Medical Monitor. NOTE: Participants of childbearing potential will be permitted to continue with estrogen- or progesterone based oral contraceptives, but must agree to use 2 other methods of contraception, where at least 1 must be highly effective, or must agree to sexual abstinence during the study.
• Current, recent, or suspected infection within 2 weeks of Screening of Severe Acute Respiratory Syndrome Coronavirus 2/Coronavirus Disease 2019 (SARS-CoV-2/COVID-19).
• Unable to tolerate oral medication or inability to swallow tablets.
• Allergy to JNT-517 or any component of the investigational product.
• Any of the following laboratory values at the Screening visit:
• Alanine aminotransferase or aspartate aminotransferase values ˃ 1.5 x the upper limit of normal (ULN).
• Total bilirubin ˃ULN unless history of Gilbert Syndrome and then total bilirubin \>4 milligrams per deciliter \[mg/dL\] is exclusionary.
• Hemoglobin ˂10.0 g/dL (˂100.0 grams per liter \[g/L\])
• White blood cell count ˃1 x ULN
• Platelet count ˂150 × 109/L (˂150,000/cubic millimeters\[mm\^3\])
• Participation in another investigational drug trial within 30 days (other than for JNT-517) or, if known 5 half-lives of investigational drug (whichever is longer).
Inclusion Criteria:
• Diagnosis of phenylketonuria (ie, PAH deficiency) by either molecular testing or biochemical criteria consistent with the applicable regional guidelines.
• Participants 4 years of age and older, inclusive, at time of Screening.
• Not on pegvaliase within 4 weeks of Screening.
• Not on sepiapterin within 2 weeks of Screening.
• If on sapropterin or large neutral amino acids at Screening, must be on a stable dose for 4 weeks prior to Screening.
• Willing and able to maintain a diet consistent in Phe content from the Screening period through the duration of the study, unless otherwise directed by a dietician as allowed in the protocol.
• Body weight ≥ 12.5 kg.
• If female of childbearing potential:
• Must have a negative serum pregnancy test at Screening and a negative urine pregnancy test by Day 1.
• Must practice sexual abstinence, or if involved in any sexual intercourse that could lead to pregnancy, must agree to use 2 different contraceptive methods, where at least 1 method must be highly effective, from Screening until at least 30 days after the last study drug administration.
• Must refrain from donating ova during the course of the study and for 30 days after the last dose of the study drug.
• Is a female not of childbearing potential or postmenopausal, defined as follows:
• Has had surgical sterilization (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy).
• Has had amenorrhea for minimum of 1 year with confirmation by levels of follicle stimulating hormone testing.
• Has not achieved menarche (has not had first menstrual period). If a female achieves menarche during the study, she will need to follow the contraception requirement for females of childbearing potential.
• If male, must practice sexual abstinence, or if involved in any sexual intercourse that could lead to pregnancy, must agree to use 2 different contraceptive methods, where at least 1 method must be highly effective, from Day 1 until at least 30 days after the last study drug administration and must refrain from donating sperm during the course of the study and for 30 days after the last dose of the study drug. Note: No restrictions are required for males who have undergone a documented vasectomy at least 4 months prior to Screening. If the vasectomy procedure is not documented or was performed less than 4 months prior to Screening, males must follow the same contraception as for non-vasectomized participants.
• Capable of giving signed informed consent, or parent/legal guardian to provide informed consent and pediatric participant to give assent, and be able to comply with study procedures.
• Participants with psychiatric illness must be well-controlled for the last 3 months prior to screening visit and, if on medication, on stable medications for the last 3 months. Key
Exclusion Criteria:
• Participation in this study is not considered safe and/or feasible in the opinion of the Investigator.
• Participants have not completed a previous JNT-517 study and are eligible for another active JNT-517 trial at the site, unless approval is obtained from the medical monitor.
• Any acute or chronic medical condition that would prevent the participant from complying with the procedures or place the participant at risk if they participate in the study.
• Positive for hepatitis B or C or human immunodeficiency virus.
• Any history of significant liver disease.
• Any history of cataracts or more than minimal cataracts observed during the Screening ophthalmologic examination.
• Any surgical or medical conditions that may affect study drug absorption, distribution, metabolism, or excretion.
• Estimated glomerular filtration rate \< 60 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2) by 2021 Chronic Kidney Disease Epidemiology Collaboration formula (participants aged 17 years or greater) or by Schwartz formula (participants aged 4 to 16 years of age).
• History of drug or alcohol abuse in the last year.
• Use of any medication that are inhibitors or inducers of cytochrome P450 (CYP)3A4 or inhibitors of the transporter P glycoprotein (P-gp) within 4 weeks prior to the first dose of study drug and unwilling and/or unable to avoid these medications throughout the treatment duration.
• Use of any medications that are a substrate of breast cancer resistance protein (BCRP), multidrug and toxin extrusion (MATE)1, MATE2-K, organic anion transporter 3 (OAT3), or CYP3A4 within 4 weeks prior to the first dose of study drug and unwilling and/or unable to avoid these medications throughout the treatment duration (Appendix A). CYP3A4 substrates may be allowed if reduction in exposure is not expected to impact safety of the participant after consultation with the Medical Monitor. NOTE: Participants of childbearing potential will be permitted to continue with estrogen- or progesterone based oral contraceptives, but must agree to use 2 other methods of contraception, where at least 1 must be highly effective, or must agree to sexual abstinence during the study.
• Current, recent, or suspected infection within 2 weeks of Screening of Severe Acute Respiratory Syndrome Coronavirus 2/Coronavirus Disease 2019 (SARS-CoV-2/COVID-19).
• Unable to tolerate oral medication or inability to swallow tablets.
• Allergy to JNT-517 or any component of the investigational product.
• Any of the following laboratory values at the Screening visit:
• Alanine aminotransferase or aspartate aminotransferase values ˃ 1.5 x the upper limit of normal (ULN).
• Total bilirubin ˃ULN unless history of Gilbert Syndrome and then total bilirubin \>4 milligrams per deciliter \[mg/dL\] is exclusionary.
• Hemoglobin ˂10.0 g/dL (˂100.0 grams per liter \[g/L\])
• White blood cell count ˃1 x ULN
• Platelet count ˂150 × 109/L (˂150,000/cubic millimeters\[mm\^3\])
• Participation in another investigational drug trial within 30 days (other than for JNT-517) or, if known 5 half-lives of investigational drug (whichever is longer).
DRUG: JNT-517
Phenylketonuria (PKU), Other Endocrine System
Phenylketonuria, PKU
UT Southwestern; Children’s Health
Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors
First in human study to evaluate the safety, tolerability, and pharmacokinetics (PK) of BBO-10203, a PI3Kα:RAS breaker, alone and in combination with other anti-cancer agents in patients with advanced solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nisha Unni
ALL
18 Years to old
PHASE1
NCT06625775
STU20250194
Inclusion Criteria:
* Locally advanced and unresectable or metastatic HER2-positive advanced breast cancer (aBC), HR-positive/HER2-negative advanced breast cancer, KRAS mutant advanced colorectal cancer (aCRC), or KRAS mutant advanced non-small cell lung cancer (aNSCLC)
* Measurable disease by RECIST v1.1 (except for HR-positive HER2-negative aBC where evaluable bone-only disease is permitted)
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
* Adequate LVEF assessed by ECHO or MUGA (BBO-10203 + Trastuzumab cohorts only)
* Stable brain metastases
* Patients with HER2-positive aBC: Must have had at least 2 prior lines of anti-HER2-directed therapy. Only 1 prior line is acceptable where there is no other regionally available standard of care (SoC)
* Monotherapy Cohort patients with HR-positive, HER2-negative aBC, KRAS mutant aCRC or aNSCLC: Must have progression on, or disease recurrence after at least one line of SOC treatment or in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from SoC therapy
* BBO-10203 + Fulvestrant combination cohort patients with HR-positive, HER2-negative aBC: confirmed PIK3CA mutation, must have been treated with a CDK4/6i
* BBO-10203 + Fulvestrant + ribociclib combination cohort patients with HR-positive, HER2-negative aBC: confirmed PIK3CA mutation, no prior systemic therapy in the aBC setting permitted
* BBO-10203 + FOLFOX + Bevacizumab combination cohort patients with KRAS mutant aCRC: One prior line of irinotecan-containing therapy for locally advanced or metastatic CRC is allowed but not required
Exclusion Criteria:
* Patients with KRAS mutant aCRC who have KRAS G12R mutation, BRAFV600E mutation, HER2amp, or dMMR/MSI-H tumors
* Patients with KRAS mutant aNSCLC who have KRAS G12R mutation, or tumors with other targetable driver mutations (eg, EGFR, anaplastic lymphoma kinase, ROS1/BRAF/RET/MET/EGFR exon20 insertion/NTRK/HER2)
* Patients with untreated and/or non-stable brain metastases
Other inclusion/exclusion criteria are specified in the protocol DRUG: BBO-10203, DRUG: Trastuzumab, DRUG: Fulvestrant, DRUG: Ribociclib, DRUG: FOLFOX, DRUG: Bevacizumab
Solid Tumor, Adult, Metastatic Breast Cancer, Advanced Breast Cancer, HER2 Mutation-Related Tumors, HER2-positive Metastatic Breast Cancer, KRAS Mutant Metastatic Colorectal Cancer, Metastatic Lung Cancer, Metastatic Colorectal Cancer, Advanced Lung Cancer, HR-positive, HER2-negative Advanced Breast Cancer, HER2-positive Advanced Breast Cancer, Breast - Female, Breast - Male, Colon, Lung/Thoracic, Rectum
BREAKER-101, BridgeBio Oncology Therapeutics, BBOT, Phase1, Phase 1a/1b, Trastuzumab, Breast, Colorectal, Non-Small Cell Lung Cancer, CRC, NSCLC, Metastatic Cancer, Advanced Cancer, HER2-positive, HR-positive, HR-positive, HER2-negative, HER2-negative
UT Southwestern
A Study of Bleeding and Treatment in Participants With Von Willebrand Disease
The purpose of this screening study is to accumulate information regarding bleeding events, quality of life, and the social and clinical impact of bleeds in participants with Von Willebrand Disease (VWD). Data from this study will be used to establish baseline bleeding and treatment rates in a population of participants with VWD and act as comparator data for future clinical study outcomes.(e.g. Velora Pioneer)
Call 214-648-5005
studyfinder@utsouthwestern.edu, Ruth.Ikpefan@UTSouthwestern.edu
Yu-Min Shen
ALL
16 Years to old
NCT06610201
STU20250392
Inclusion Criteria:
• Has the ability to provide informed consent to participate in the study, in accordance with applicable regulations.
• Has an understanding, ability, and willingness to comply with Study procedures and restrictions.
• Is 16 years and \< 70 years at the time of screening.
• Weight 50 to 120 kg (±10%) at Screening and body mass index (BMI) \<38.5 kg/m\*2.
• Has Von Willebrand Disease: Type 1 VWD (including Type 1C VWD) or Type 2A VWD. All participants must have: Documented lab results confirming their diagnosis consistent with ISTH/ASH diagnostic guidelines; VWF Activity ≤30 IU/dL and FVIII activity ≤70 IU/dL during Screening.
• Has symptomatic disease as defined by a history of bruising or bleeding events, with an expected minimum of 3 bleeding episodes (including heavy menstrual bleeding) per year that require treatment to control bleeding symptoms, and/or has recurrent and ongoing episodes of heavy menstrual bleeding at the time of enrollment.
Exclusion Criteria:
• Has a history of clinically significant hypersensitivity associated with monoclonal antibody therapies.
• Has a personal history of venous or arterial thrombosis or thromboembolic disease, except for catheter-associated, superficial vein thrombosis events.
• Has a high-risk thrombophilia: Homozygous Factor V Leiden (FVL), compound heterozygous FVL/prothrombin gene mutation, antithrombin \<50%, congenital protein C and protein S deficiency with levels \<50%.
• Requires ongoing hemostatic (bleed-prophylaxis) treatment to prevent bleeding
• Has other known severe bleeding disorder(s) other than VWD.
• Planned major surgery during the study period.
• Has other conditions that substantially increase the risk of thrombosis either individually or in combination, at the discretion of the Investigator, including but not limited to: significant family history; BMI \>30 and ≤38.5 kg/m² (moderately obese, adjusted for ethnicity and increased central adiposity); reduced mobility; active malignancy; major surgery within 6 weeks preceding Screening; or postpartum within 12 weeks preceding Screening.
• Is pregnant or plans to become pregnant within the next 6 months following informed consent sign off.
• Has clinically significant cardiovascular disease including, but not limited to: NYHA Class III or IV heart failure, coronary artery disease, uncontrolled arrythmia, moderate to severe valvular heart disease, peripheral vascular disease, and ischemic stroke.
• Has other combinations of conditions that substantially increase the risk of cardiovascular events at the discretion of the Investigator including, but not limited to, smoking, uncontrolled hyperlipidemia, and uncontrolled hypertension.
• Has any concurrent disease, treatment, medication (including but not limited to ongoing anticoagulation, antiplatelet therapy, or non-steroidal anti-inflammatory drugs or other drugs that affect hemostasis), condition, medication, or abnormality in clinical laboratory tests which may impact on the participant's bleeding symptoms or affect their ability to complete the study, in the Investigator's opinion.
• Has received any investigational product within 30 days prior to Screening. If the participant was enrolled and dosed in Velora Pioneer (study HMB-002-102; NCT06754852), they must have completed their End of Study Visit.
OTHER: Clinical outcomes of patients with VWD, Type 1, OTHER: Clinical outcomes of patients with VWD, Type 2A, Type 2M, Type 2N, or Type 3
Von Willebrand Disease (VWD), Von Willebrand Disease (VWD), Type 1, Von Willebrand Disease (VWD), Type 2, Von Willebrand Disease (VWD), Type 3, Von Willebrand Disease, Type 2A, Von Willebrand Disease, Type 2M, Von Willebrand Disease, Type 2N
Von Willebrand Disease (VWD), Prospective Study, Type 1 VWD, Type 2 VWD, Type 3 VWD, Prophylaxis, Von Willebrand Factor (VWF)
UT Southwestern
Radiotherapy in Combination With Checkpoint Inhibition for Patients With Metastatic Kidney Cancer (SPARK)
To evaluate the impact of combining innate immune system activation (with IMSA101) with antigen release (through SAbR/PULSAR) on limited progressing lesions during ongoing adaptive immune system activation (with maintenance Nivo).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Raquibul Hannan
ALL
18 Years to old
PHASE2
NCT06601296
STU-2024-0919
Inclusion Criteria:
* Patients must have metastatic ccRCC.
* Patients must have oligoprogression defined as progression in ≤5 lesions.
* All oligoprogression lesions must be suitable for radiation.
* Patients must have at least one site of disease that can be safely injected with IMSA101.
* Karnofsky Performance Status (KPS) of at least 50%.
* Age ≥ 18 years.
* Patients must have adequate organ and marrow function within 14 days prior to study entry.
* All IMDC risk categories are allowed.
Exclusion Criteria:
* Patients with progressive ultracentral/central chest lesions will be excluded DRUG: IMSA101
Metastatic Renal Cell Carcinoma ( mRCC), OligoProgressive Metastatic Disease, Kidney
renal, kidney, mrcc, metastatic, cancer, STING, PULSAR, SABr, SPARK, nivolumab, IMSA 101
UT Southwestern
A Study of Pembrolizumab (MK-3475) With or Without Intismeran Autogene (V940) in Participants With Non-small Cell Lung Cancer (V940-009/INTerpath-009)
The goal of this study is to learn if people who receive intismeran autogene and pembrolizumab after surgery are cancer-free longer than people who receive placebo and pembrolizumab. Researchers want to know if giving intismeran autogene and pembrolizumab after surgery can help prevent the cancer from coming back in people with non-small cell lung cancer (NSCLC) whose tumors did not respond completely to treatment before surgery (neoadjuvant treatment).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Nelson
ALL
18 Years to old
PHASE3
NCT06623422
STU20250085
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has histologically/cytologically confirmed diagnosis of previously untreated and pathologically confirmed resectable clinical Stage II, IIIA, or IIIB (N2) non-small cell lung cancer (NSCLC) \[American Joint Committee on Cancer (AJCC) 8th Edition\]
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before the first dose of study intervention
* Participants who have not achieved a pathological complete response (pCR) following completion of neoadjuvant chemotherapy and pembrolizumab followed by surgery will be eligible
* Confirmation that epidermal growth factor receptor (EGFR)-directed therapy is not indicated as primary therapy (documentation of absence of tumor-activating EGFR mutations \[eg, DEL19 or L858R\])
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on anti-retroviral therapy (ART)
* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Diagnosis of small cell lung cancer (SCLC) or, for mixed tumors, presence of small cell elements, or has a neuroendocrine tumor with large-cell components, or a sarcomatoid carcinoma, or a pancoast tumor
* Documentation by local test report indicating presence of anaplastic lymphoma kinase (ALK) gene rearrangements
* Received prior neoadjuvant therapy for their current NSCLC diagnosis
* Received prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti-programmed cell-death ligand 2 (PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein \[CTLA-4\], OX-40, CD137)
* Received prior systemic anticancer therapy including investigational agents other than what is specified in this protocol
* Received prior treatment with a cancer vaccine
* Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention BIOLOGICAL: Pembrolizumab, DRUG: Cisplatin, DRUG: Carboplatin, DRUG: Pemetrexed, DRUG: Gemcitabine, DRUG: Paclitaxel, BIOLOGICAL: Intismeran autogene, OTHER: Placebo
Carcinoma, Non-Small-Cell Lung, Lung/Thoracic
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2), Individualized neoantigen therapy (INT)
UT Southwestern
A Study With NKT3964 for Adults With Advanced/Metastatic Solid Tumors
The goal of the Dose Escalation phase of the study is to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity to determine the preliminary recommended dose for expansion (RDE) of NKT3964 in adults with advanced or metastatic solid tumors. The goal of the Expansion phase of the study is to evaluate the preliminary anti-tumor activity of NKT3964 at the RDE based on objective response rate (ORR) and determine the preliminary recommended Phase 2 dose (RP2D).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Miller
ALL
18 Years to old
PHASE1
NCT06586957
STU20252305
Inclusion Criteria:
\- Must have a pathologically confirmed advanced and unresectable or metastatic solid tumor listed below with documented disease progression on last standard treatment. Part 1 only: subjects must be refractory to, or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
Dose Escalation:
• Ovarian cancer
• Endometrial cancer (only endometrioid subtype will require CCNE1 amplification)
• Gastric, gastroesophageal junction (GEJ) or esophageal adenocarcinoma with CCNE1 amplification
• Small cell lung cancer (SCLC)
• Triple-negative breast cancer (TNBC; HER2, estrogen receptor and progesterone receptor negative)
• HR+ (includes estrogen-receptor or progesterone-receptor) and HER2- breast cancer (must have progressed following treatment with a CDK4/6 inhibitor, and is not suitable for endocrine therapy \[ET\])
• Other solid tumors with CCNE1 amplification Dose Expansion: Part 2A: HR+ and HER2- breast cancer that is locally advanced and unresectable (Stage III) or metastatic (Stage IV); previously treated with ≥1 line of standard of care (SOC) including CDK4/6 inhibitor plus ET and not suitable for further ET. Subjects must have progressed after receiving therapy for ≥3 months in the metastatic setting or for ≥6 months in the adjuvant setting. Subjects must have received ≤2 lines of systemic cytotoxic therapy (chemotherapy or cytotoxic antibody drug conjugate \[ADC\]) in the metastatic setting.. Part 2B: Advanced platinum-based-chemotherapy resistant or refractory epithelial ovarian/fallopian/primary peritoneal carcinoma or clear cell ovarian cancer (defined as recurrence ≤6 months after completing platinum-based regimen) with progression on at least one platinum containing therapy and previously treated with ≤4 prior lines of systemic therapy administered for advanced/metastatic disease and with CCNE1 amplification. Part 2C: Advanced unresectable or metastatic gastric, GEJ or esophageal adenocarcinoma with progression on at least one systemic therapy and previously treated with ≤3 prior lines of systemic therapy administered for advanced/metastatic disease, with CCNE1 amplification as determined by NGS by local liquid or tissue test. Part 2D: Advanced endometrial adenocarcinoma or uterine papillary serous carcinoma previously treated with ≤4 prior lines of systemic therapy administered for advanced/metastatic disease with CCNE1 amplification. Part 2E: Advanced/recurrent uterine carcinosarcoma previously treated with 1 prior platinum-based chemotherapy regimen and ≤3 prior lines of systemic therapy. Prior bevacizumab or PARP inhibitors are allowed and must be at least 3 weeks prior to the start of study drug. * Have adequate organ function * Subjects with female reproductive organs must be surgically sterile, post-menopausal, or must be willing to use highly effective method(s) of contraception * Ability to swallow oral medications. * Consent to provide archived tumor tissues and paired tumor biopsy at pretreatment
Exclusion Criteria:
* Locally advanced solid tumor that is a candidate for curative treatment through radical surgery and/or radiotherapy, or chemotherapy.
* History of another malignancy with exceptions
* History of lymphohistiocytic or lymphoid hyperplasia; hemophagocytic lymphohistiocytosis.
* Failed to recover from effects of prior anticancer treatment therapy to baseline or Grade ≤ 1 severity (per CTCAE)
* Clinically significant cardiovascular event within 6 months prior to start of NKT3964 treatment
* Known active CNS metastases and/or carcinomatous meningitis
* Active interstitial lung disease currently requiring treatment
* History of uveitis, retinopathy or other clinically significant retinal disease
* Active or chronic corneal disorders, other active ocular conditions requiring ongoing therapy, or any clinically significant corneal disease
* Active wound healing from major surgery within 1 month or minor surgery within 10 days before the first dose of NKT3964.
* Known human immunodeficiency virus (HIV), active hepatitis B or C infection
* Prior investigative treatment with a selective or nonselective CDK2 inhibitor or degrader
* Childs-Pugh class B or C cirrhosis or any other clinically significant liver disorder
* Palliative radiation therapy within 14 days or other radiation therapy within 4 weeks prior to C1D1 DRUG: NKT3964
Solid Tumor, Advanced Solid Tumor, Solid Tumor, Adult, Metastatic Tumor, Ovarian Cancer, Ovarian Neoplasms, Ovarian Carcinoma, Metastatic Ovarian Carcinoma, Endometrial Neoplasms, Endometrial Diseases, Metastatic Endometrial Cancer, Triple Negative Breast Cancer, Metastatic Endometrial Carcinoma, Advanced Endometrial Carcinoma, Advanced Ovarian Carcinoma, Gastric Cancer, Advanced Gastric Carcinoma, Metastatic Gastric Cancer, Metastatic Gastric Carcinoma, Small Cell Lung Cancer, Small Cell Lung Carcinoma, Triple Negative Breast Neoplasms, Platinum-resistant Ovarian Cancer, Platinum-Refractory Ovarian Carcinoma, CCNE1 Amplification, Hormone Receptor Negative Breast Carcinoma, Human Epidermal Growth Factor 2 Negative Carcinoma of Breast, Progesterone-receptor-positive Breast Cancer, Breast - Female, Breast - Male, Lung/Thoracic, Ovary
CDK 2 Inhibitor, CDK 4 Inhibitor, CDK 6 Inhibitor, CDK2 Degrader, Protein Degrader, PROTAC
UT Southwestern
A Randomized, Phase 2/3 Study to Investigate the Efficacy and Safety of RP2 in Combination With Nivolumab in Immune Checkpoint Inhibitor-Naïve Adult Patients With Metastatic Uveal Melanoma (RP2-202)
The purpose of this study is to measure the clinical benefits of the combination of RP2 and nivolumab as compared with the combination of nivolumab and ipilimumab in patients with metastatic uveal melanoma who have not been treated with immune checkpoint inhibitor therapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Sanjay Chandrasekaran
ALL
PHASE2
NCT06581406
STU20240015
Key
Inclusion Criteria:
* Patients who are 18 years of age or older at the time of signed informed consent.
* Patients with confirmed diagnosis of metastatic Uveal melanoma not amenable to surgical resection.
* Has at least 1 measurable and injectable tumor of ≥ 1 cm in longest diameter (≥ 1.5 cm in the shortest axis for a lymph node \[LN\]) that is amenable to serial RP2 injections.
* Must be willing to provide tumor biopsy samples.
* LDH ≤ 2 × upper limit of normal (ULN).
* Has adequate hematologic, hepatic and renal function
* Prothrombin time (PT) ≤ 1.5 × ULN (or international normalization ratio \[INR\] ≤ 1.3) and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
* Life expectancy of \> 6 months as estimated by the Investigator.
Key Exclusion Criteria:
* Any exposure to immune checkpoint inhibitor (ICIs) since the time of first being diagnosed with uveal melanoma.
* Known acute or chronic Hepatitis B or C infection or human immunodeficiency virus (HIV) infection or any other uncontrolled infection.
* Current active significant herpetic infections or prior complications of HSV-1 infection.
* Any central nervous system (CNS) involvement of melanoma, including carcinomatous meningitis.
* Major surgery ≤ 2 weeks prior to the first dose of study intervention.
* Any bleeding, thrombotic and/or other event that places the patient at an unacceptable risk of complications of intratumoral therapy.
* Active, known, or suspected autoimmune disease requiring systemic treatment.
* Prior treatment with an oncolytic virus.
* Requires intermittent or chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir).
* Systemic anticancer therapy or prior radiotherapy within 2 weeks of the first dose.
* Has received Investigation agent within 4 weeks or 5 half-lives (whichever longer) prior to the first dose.
* Conditions requiring treatment with immunosuppressive doses (\> 10 mg per day of prednisone or equivalent) of systemic corticosteroids other than for corticosteroid replacement therapy within 14 days after enrollment.
Additional inclusion/ exclusion criteria are outlined in the study protocol BIOLOGICAL: RP2, BIOLOGICAL: Ipilimumab, BIOLOGICAL: Nivolumab
Metastatic Uveal Melanoma, Melanoma, skin
Metastatic, Uveal, Melanoma, Nivolumab, Ipilimumab, Randomized, Immune checkpoint inhibitor-naïve, RP2, Oncolytic viruses, HSV-1
UT Southwestern
Testing Olaparib for One or Two Years, With or Without Bevacizumab, to Treat Ovarian Cancer
This phase III trial compares the effect of olaparib for one year versus two years, with or without bevacizumab, for the treatment of BRCA 1/2 mutated or homologous recombination deficient stage III or IV ovarian cancer. Olaparib is a polyadenosine 5'-diphosphoribose polymerase (PARP) enzyme inhibitor and may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving olaparib for one year with or without bevacizumab may be effective in treating patients with BRCA 1/2 mutated or homologous recombination deficient stage III or IV ovarian cancer, when compared to two years of olaparib.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Jayanthi Lea
ALL
18 Years to old
PHASE3
NCT06580314
STU20250304
Inclusion Criteria:
* Patients with newly diagnosed, pathologically confirmed, Federation of Gynecology and Obstetrics (FIGO) stage III or IV ovarian cancer of the following types:
* High grade serous
* High grade endometrioid, and/or
* Other epithelial ovarian cancer with BRCA1/2 deleterious alteration (germline or somatic)
* Submission of pathology report is required
* Ovarian cancer = ovarian, fallopian, or primary peritoneal cancer
* Patients must have:
* Documented variant (tumor or germline) in BRCA1 or BRCA2 that is predicted to be pathogenic or suspected pathogenic (deleterious alteration)
* Submission of testing report is required. OR
* BRCA 1/2 wildtype AND known HRD deficient tumor determined by any commercial or academic, Clinical Laboratory Improvement Act (CLIA)-certified laboratory (e.g., Myriad MyChoice©)
* Submission of testing report is required
* Patient must have undergone cytoreductive surgery (primary or interval)
* Patients must have completed first line platinum-based therapy prior to registration:
* Platinum based chemotherapy course must have consisted of a minimum of 4 treatment cycles and a maximum of 9, although it is strongly recommended that patients receive at least 6 cycles unless medically contraindicated
* For those receiving less than 6 cycles of platinum-based therapy, the reason for this must be documented and could include hematologic toxicity or non-hematologic toxicities directly related to therapy
* Intravenous, intraperitoneal, or neoadjuvant platinum-based chemotherapy is allowed; for weekly therapy, three weeks are considered one cycle
* Patients must not have received an investigational agent during their first line course of chemotherapy
* Patients must have, in the opinion of the investigator, no clinical evidence of disease progression following completion of this chemotherapy course (partial or complete response to platinum-based chemotherapy)
* Patients with treated brain metastases are eligible if follow up brain imaging after central nervous system (CNS) directed therapy shows no evidence of progression following completion of this chemotherapy course (partial or complete response to platinum-based chemotherapy)
* Patients must be randomized at least 3 weeks and no more than 12 weeks after their last dose of chemotherapy (last dose is the day of the last infusion of platinum agent)
* No previous treatment with a PARP inhibitor, including olaparib, niraparib, and rucaparib
* Age ≥ 18
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
* Not pregnant and not nursing
* Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3
* Platelets ≥ 100,000 cells/mm\^3
* Hemoglobin ≥ 9 g/dl
* Creatinine clearance (CrCL) of \> 30 mL/min by the Cockcroft-Gault formula
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x institutional ULN may be enrolled)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional ULN
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* No active infection requiring parental antibiotic(s)
* No current evidence of intra-abdominal abscess, abdominal/pelvic fistula (not diverted), gastrointestinal perforation, gastrointestinal (GI) obstruction, and/or need for drainage nasogastric or gastrostomy tube
* No current inability to swallow orally administered medication
* No history of myelodysplastic syndrome and/or acute myeloid leukemia
* No history of allogeneic bone marrow transplant
* No concomitant use of strong or moderate CYP3A inducers
* No known hypersensitivity to olaparib or any of the excipients of the product BIOLOGICAL: Bevacizumab, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, DRUG: Olaparib
Fallopian Tube Endometrioid Adenocarcinoma, Fallopian Tube High Grade Serous Adenocarcinoma, FIGO Stage III Ovarian Cancer 2014, FIGO Stage IV Ovarian Cancer 2014, Ovarian Carcinoma, Ovarian High Grade Endometrioid Adenocarcinoma, Ovarian High Grade Serous Adenocarcinoma, Primary Peritoneal Endometrioid Adenocarcinoma, Primary Peritoneal High Grade Serous Adenocarcinoma, Ovary
UT Southwestern; Parkland Health & Hospital System
The Modulatory Effect of Female Sex Hormones on Spinal Neuroplasticity (TMSpine)
The goal of this project is to test our central hypothesis that the spinal cord neuroplasticity in females will be modulated by the level of estradiol concentration. under aim 1 we will determine the influence of estradiol fluctuations on spinal circuit excitability post afferent (sensory) mediated subthreshold motor priming in young healthy females and males. We will use an established repetitive peripheral nerve electrical stimulation with a stimulation intensity below the motor threshold to prime the spinal motor circuits. under aim 2 we seek to characterize the input output property of spinal circuit excitability after descending drive (motor) mediated priming in young healthy male participants. in aim 3 we will examine the influence of estradiol fluctuations on descending drive mediated motor priming in young healthy females.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Yu-Chen.Chung@UTSouthwestern.edu
Yasin Dhaher
ALL
18 Years to 39 Years old
NCT06656819
STU-2020-0738
FEMALES
Inclusion Criteria:
* Ages 18-39 years
* Eumenorrheic (regular monthly cycles of 24-35 days)
* Moderately active (less than 7 hours of vigorous physical activity per week)
* History of pregnancy is allowed if patient is in post-lactation phase
Exclusion Criteria:
* History of musculoskeletal or orthopedic injury of the spine, hip, knee, ankle or foot
* History of neurological injury of the peripheral or central nervous system
* Current smoker
* History of disordered eating
* History of stress fracture in the lower limb
* History of a connective tissue disorder (Marfan's syndrome, Ehlers-Danlos disease)
* Pacemaker, metal implants in the head and spine region
* Pregnancy
* On a hormonal contraceptive regimen (oral, transdermal or vaginal)
* History of menstrual dysfunction (primary or secondary amenorrhea, oligomenorrhea, anovulatory cycles, polycystic ovarian disease)
* Started or stopped taking oral contraceptives within the previous 6 months
* Exercise vigorously more than 7 hours per week or currently participating in competitive level sports.
MALES
Inclusion Criteria:
* Ages 18-39
* Moderately active (less than 7 hours of vigorous physical activity per week)
Exclusion Criteria:
* History of musculoskeletal or orthopedic injury of the spine, hip, knee, ankle or foot
* History of neurological injury of the peripheral or central nervous system
* Current smoker
* History of disordered eating
* History of stress fracture in the lower limb
* History of a connective tissue disorder (Marfan's syndrome, Ehlers-Danlos disease)
* Pacemaker, metal implants in the head and spine region DEVICE: Magstim Rapid2
Healthy
UT Southwestern
A Trial to Evaluate the Safety and Activity of Fruquintinib in Minority Populations With Advanced, Previously Treated Colorectal Cancer
High blood pressure (hypertension) is a known side effect of the treatment with fruquintinib. Current research does not provide a clear answer whether minority groups such as Black/African American and/or Hispanic/Latino with refractory metastatic colorectal cancer (mCRC) have a bigger risk of higher blood pressure after treatment with fruquintinib. The main aim of this study is to learn how often adults of a minority group experience hypertension after they have been treated with fruquintinib for refractory mCRC. Other aims are to learn how safe fruquintinib is and how well it is tolerated by participants. Participants will receive fruquintinib in 4-week treatment cycles until their condition worsens, they do no longer tolerate the treatment or stop the treatment for other reasons. After the last treatment, participants will be checked upon every 3 months until study completion.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nilesh Verma
ALL
18 Years to old
PHASE4
NCT06562543
STU-2024-0987
Inclusion Criteria:
• Provide written (or electronic) informed consent.
• Male or female aged more than or equal to (≥)18 years.
• Presence of histologically and/or cytologically documented metastatic colorectal adenocarcinoma. Rat sarcoma virus (RAS) status for each participant must be documented.
• Have been previously treated with standard approved therapies: * Fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, * An anti-vascular endothelial growth factor (VEGF) biological therapy (e.g., bevacizumab, aflibercept, ramucirumab \[regorafenib is NOT an anti-VEGF biologic\]), and * If RAS wild-type and medically appropriate, an anti-epidermal growth factor receptor (EGFR) therapy (e.g., cetuximab, panitumumab). * If known microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumor and medically appropriate, a programmed cell death protein 1 (PD1) inhibitor.
• Self-identify as Black and/or African American or Hispanic and/or Latino or as both.
• Body weight ≥40 kilograms (kg).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at screening.
• Have assessable disease according to RECIST version 1.1, assessed locally.
• In participants of childbearing potential, agreement to use highly effective form(s) of contraception, which results in a low failure rate (less than \[\<\]1 percent \[%\] per year) when used consistently and correctly, starting during the screening period, continuing throughout the entire trial period, and for 2 weeks after taking the last dose of the trial intervention. Such methods include oral (PO) hormonal contraception (combined estrogen/progestogen or progestogen-only) associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system (IUS), bilateral tubal ligation, vasectomized partner, or true sexual abstinence in line with the preferred and usual lifestyle of the participant. Those assigned male sex at birth must always use a condom.
Exclusion Criteria:
• Absolute neutrophil count (ANC) \<1.5 times 10\^9 per liter (10\^9/L), platelet count \<100 times 10\^9/L, or hemoglobin \<9.0 grams per deciliter (g/dL). Blood transfusion within 1 week prior to enrollment for the purpose of increasing the likelihood of eligibility is not allowed.
• Serum total bilirubin more than (\>)1.5 times the upper limit of normal range (ULN). Participants with previously documented Gilbert syndrome and bilirubin \<2 times ULN are eligible.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.5 times ULN in participants without hepatic metastases; ALT or AST \>5 times ULN in participants with hepatic metastases.
• Creatinine clearance \<30 milliliters per minute (mL/min). Creatinine clearance can either be measured in a 24-hour urine collection or estimated by the Cockcroft-Gault equation. Where available and appropriate, other formulae may be used to estimate clearance after consultation with the trial medical monitor.
• Urine dipstick or urinalysis with protein ≥2 positive or 24-hour urine protein ≥1.0 gram per 24 hours (g/24 hours). Participants with 1+ positive proteinuria must undergo a 24-hour urine collection to assess urine protein level.
• Uncontrolled hypertension, defined as systolic BP ≥140 millimeter of mercury (mmHg) and/or diastolic blood pressure (BP) ≥90 mmHg despite optimal medical management. The participant must have BP below both limits. Repeated assessments are permitted.
• International normalized ratio (INR) \>1.5 times ULN or activated partial thromboplastin time (aPTT) \>1.5 times ULN, unless the participant is currently receiving or intended to receive anticoagulants for prophylactic purposes.
• History of or active gastric/duodenal ulcer or ulcerative colitis, active hemorrhage of an unresected gastrointestinal tumor, history of perforation or fistulas, or any other condition that could, in the investigator's judgment, result in gastrointestinal hemorrhage or perforation within the 6 months prior to screening.
• History or presence of hemorrhage from any other site (e.g, hemoptysis or hematemesis) within 2 months prior to screening.
• History of a thromboembolic event, including deep vein thrombosis, pulmonary embolism, or arterial embolism within 6 months prior to screening.
• Stroke and/or transient ischemic attack within 12 months prior to screening.
• Clinically significant cardiovascular disease, including but not limited to, acute myocardial infarction or coronary artery bypass surgery within 6 months prior to enrollment, severe or unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, ventricular arrhythmias requiring treatment, or left ventricular ejection fraction \<50% by echocardiogram.
• QT interval, corrected using the Fridericia method (QTcF) \>480 milliseconds or any factors that increase the risk of QT interval, corrected based on the patient's heart rate (QTc) prolongation or risk of arrhythmic events such as hypokalemia, congenital long QT syndrome, or family history of long QT syndrome.
• Systemic antineoplastic therapies (except for that described in exclusion criterion no. 15) or any investigational therapy within 2 weeks prior to the first dose of the trial intervention, including chemotherapy, radical radiotherapy, hormonotherapy, biotherapy, and immunotherapy.
• Systemic small molecule targeted therapies (e.g., tyrosine kinase inhibitors \[TKIs\]) within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of the trial intervention.
• Palliative radiotherapy for bone metastasis/lesion within 2 weeks prior to the initiation of the trial intervention.
• Brachytherapy (i.e., implantation of radioactive seeds) within 60 days prior to the first dose of the trial intervention.
• Surgery or invasive procedure (i.e., a procedure that includes a biopsy; central venous catheter placement is allowed) within 14 days prior to the first dose of the trial intervention or unhealed surgical incision.
• Any unresolved toxicities from previous antitumor treatments greater than NCI CTCAE, version 5.0, Grade 1 (except for alopecia or neurotoxicity Grade less than or equal to \[≤\]2).
• Known human immunodeficiency virus infection.
• Known history of active viral hepatitis. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load had to be undetectable on suppressive therapy, if indicated. Participants with hepatitis C virus (HCV) infection who are currently on treatment are eligible if they have an undetectable HCV viral load.
• Clinically uncontrolled active infection requiring intravenous (IV) antibiotics.
• Tumor invasion of a large vascular structure (e.g., pulmonary artery or superior or inferior vena cava).
• Those who are currently pregnant or lactating.
• Brain metastases and/or spinal cord compression untreated with surgery and/or radiotherapy, and without clinical imaging evidence of SD for 14 days or longer; participants requiring steroids within 4 weeks prior to the start of the trial intervention are to be excluded.
• Other malignancy, except for non-melanoma skin cancer, in situ cervical carcinoma, or bladder carcinoma (tumor in situ and T1) that had been adequately treated during the 5 years prior to screening. Participants with another primary malignancy that has been adequately treated may be included after consultation with the trial medical monitor.
• Inability to take medication PO, dysphagia, or an active gastric ulcer resulting from previous surgery (e.g., gastric bypass) or a severe gastrointestinal disease, or any other condition that investigators believe might affect absorption of the investigational medicinal product (IMP).
• Other disease, metabolic disorder, physical examination anomaly, abnormal laboratory result, or any other condition (e.g., current alcohol or drug abuse) that investigators suspect might prohibit use of the IMP, affect interpretation of trial results, or put the participant at undue risk of harm based on the investigator's assessment.
• Known hypersensitivity to fruquintinib or any of its inactive ingredients, including the azo dyes Tartrazine- Federal Food, Drug, and Cosmetic Act (FD\&C) Yellow 5 and Sunset yellow For Coloring Food (FCF)-FD\&C Yellow 6.
• Received prior fruquintinib.
• Live vaccine ≤28 days before the first dose of the trial intervention. Seasonal vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed.
• Use of strong inducers of cytochrome P450 3A4 (CYP3A4) within 2 weeks before the first dose of the trial intervention.
DRUG: Fruquintinib
Colorectal Cancer, Colon, Rectum
colorectal cancer, fruquintinib
UT Southwestern; Parkland Health & Hospital System
Phase 2 Study to Evaluate Safety and Efficacy of Cretostimogene Grenadenorepvec in High-Risk NMIBC
This is a Phase 2, Multi-Arm, Multi-Cohort, Open-Label Study to Evaluate the Safety and Efficacy of Cretostimogene Grenadenorepvec in Participants with High-Risk Non-Muscle-Invasive Bladder Cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Solomon Woldu
ALL
18 Years to old
PHASE2
NCT06567743
STU20250671
Cohort A Key
Inclusion Criteria:
* Pathologically confirmed BCG-naïve high-risk high-grade NMIBC (i.e., CIS with or without Ta/T1 disease or high-grade Ta/T1 papillary-only disease without CIS) within 90 days of treatment allocation.
* All visible disease must be resected, and all CIS resected or fulgurated, as feasible within 90 days prior to treatment allocation.
* Acceptable baseline organ function.
Cohort B Key Inclusion Criteria:
* Pathologically confirmed BCG-exposed high-risk high-grade NMIBC (i.e., CIS with or without Ta/T1 disease or high-grade Ta/T1 papillary-only disease without CIS) within 90 days of treatment allocation.
* All visible disease must be resected, and all CIS resected or fulgurated, as feasible within 90 days prior to treatment allocation.
* Acceptable baseline organ function.
Cohort CX Inclusion Criteria
* Pathologically confirmed high-risk high-grade BCG-unresponsive or BCG-exposed NMIBC (i.e., CIS with or without Ta/T1 disease or high-grade Ta/T1 papillary-only disease without CIS) within 90 days of treatment allocation.
* All visible disease must be resected, and all CIS resected or fulgurated, as feasible within 90 days prior to treatment allocation.
* Acceptable baseline organ function.
Key Exclusion Criteria (Both Cohorts):
* Current or past history of muscle-invasive, locally advanced or metastatic bladder cancer.
* High-grade urothelial carcinoma in the upper urinary tract or prostatic urethra within 24 months or T2 in upper tract within 48 months or any history of locally advanced/ nodal or metastatic disease in the upper urinary tract.
* Significant immunodeficiency.
* Pregnant or breastfeeding.
* Cohort CX Only: serial intravesical gemcitabine within 24 months DRUG: Cretostimogene Grenadenorepvec
High-Risk Non-Muscle-Invasive Bladder Cancer
Bladder Cancer
UT Southwestern
A Trial to Evaluate Intravesical Nadofaragene Firadenovec Alone or in Combination With Chemotherapy or Immunotherapy in Participants With High-grade BCG Unresponsive Non-muscle Invasive Bladder Cancer (ABLE-22)
The pivotal phase 3 trial (rAd-IFN-CS 003) evaluating the efficacy of nadofaragene firadenovec showed that 55 (53.4%) of 103 subjects with CIS ± high-grade Ta/T1 achieved a complete response (CR) at 3 months. In this trial, the safety and efficacy of intravesical instillation of nadofaragene firadenovec alone or in combination with chemotherapy or immunotherapy will be evaluated in participants with NMIBC CIS (± high-grade Ta/T1).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Solomon Woldu
ALL
18 Years to old
PHASE3
NCT06545955
STU20250195
Inclusion Criteria:
* Diagnosed, as documented, with carcinoma in situ (CIS) ±Ta/T1 high-grade disease.
* For T1 disease biopsies should contain muscle fibres.
* Unresponsive to ≥2 courses of Bacillus Calmette-Guerin (BCG) therapy within the last 12 months. BCG-unresponsive refers to participants with high-grade non-muscle invasive bladder cancer (NMIBC) who are unlikely to benefit from and who will not be receiving further intravesical BCG. The term "BCG-Unresponsive" includes participants who did not respond to BCG treatment and have a persistent high-grade recurrence within 12 months after BCG was initiated, and those who despite an initial complete response to BCG, relapse with CIS within 12 months of their last intravesical treatment with BCG or relapse with high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG. The following criteria define the participants who may be included in the trial:
* Have received at least 2 courses of BCG within a 12 month period - defined as at least 5 of 6 induction BCG instillations and at least 2 of 3 instillations of maintenance BCG, or at least 2 of 6 instillations of a second induction course, where maintenance BCG is not given.
o Exception: those who have T1 high-grade disease at 1st evaluation after induction BCG alone (at least 5 of 6 doses) may qualify in the absence of disease progression
* At the time of tumour recurrence, participants with CIS alone or high-grade Ta/T1 with CIS should be within 12 months of last exposure to BCG
* No maximum limit to the amount of BCG administered
* All visible papillary tumours must be resected and those with persistent T1 disease on transurethral resection of bladder tumour (TURBT) should undergo an additional re-TURBT within 14 to 70 days prior to beginning trial treatment. Obvious areas of CIS should also be fulgurated
* Eastern Cooperative Oncology Group (ECOG) status ≤2
* Aged ≥18 years at the time of consent
* Available for the whole duration of the trial
* Life expectancy \>2 years, in the opinion of the investigator
* Absence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra. Freedom from upper tract disease (if clinically indicated) as indicated by no evidence of upper tract tumour by either intravenous pyelogram, retrograde pyelogram, computed tomography (CT) scan with or without urogram, or magnetic resonance imaging (MRI) with or without urogram performed within 6 months of enrolment. Absence of locally advanced disease as assessed by CT scan or MRI
* Participants who elect not to undergo cystectomy
* Participants with prostate cancer on active surveillance at low risk for progression are permitted to be included into the trial at the discretion of the investigator
* Females of reproductive potential must have a negative highly sensitive urine or serum pregnancy test upon entry into this trial and be willing to use highly effective contraception during treatment with the investigational medicinal product and for 6 months following the last dose. Otherwise, female participants must be post-menopausal (no menstrual period for a minimum of 12 months, as confirmed by follicle-stimulating hormone levels) or surgically sterile
* Male subjects must be willing to use a male condom and effective contraception during sex throughout the treatment period and for 3 months following the last dose.
Exclusion Criteria:
* Current or previous evidence of muscle-invasive (muscularis propria) or metastatic disease presented at the screening visit. Examples of increased risk of muscle-invasive disease include but are not limited to:
* Presence of lymphovascular invasion and / or micropapillary, sarcomatoid, plasmacytoid and / or neuroendocrine disease as shown in the histology of the biopsy sample
* Participants with CIS+T1 disease accompanied by the presence of hydronephrosis secondary to the primary tumour
* Current systemic therapy for bladder cancer other than investigational medicinal products used in randomisation arm
* Current or prior investigational treatment for BCG-unresponsive NMIBC or any other investigational drug (drug used in a clinical trial, i.e drug used in a Ferring sponsored non interventional study does not apply) within 1 month prior to screening
* Current or prior pelvic external beam radiotherapy within 2 years of screening
* Prior treatment with nadofaragene firadenovec at any time
* Prior systemic therapy for bladder cancer at any time
* Prior intravesical chemotherapy for the treatment of BCG-unresponsive NMIBC DRUG: Nadofaragene Firadenovec, DRUG: Gemcitabine, DRUG: Docetaxel, DRUG: Pembrolizumab
Non-muscle Invasive Bladder Cancer With Carcinoma in Situ
UT Southwestern
Zanubrutinib, Bendamustine, Rituximab Prev. Untreated WM (ZEBRA)
The purpose of this study is to determine the very good partial response (VGPR) or better rate in participants with Waldenström macroglobulinemia (WM). The names of the study drugs involved in this study are as follows: zanubrutinib, bendamustine, and rituximab.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Larry Anderson
ALL
18 Years to old
PHASE2
NCT06561347
STU20251632
Inclusion Criteria:
* Clinicopathological diagnosis of waldenström macroglobulinemia (WM) per the second international workshop on waldenström macroglobulinemia (IWWM2) criteria
* Presence of any MYD88 and CXCR4 mutation status, including MYD88 L265P mutation plus CXCR4 wild type, MYD88 L265P mutation plus CXCR4 mutation, or MYD88 wild type
* Meeting criteria for treatment per IWWM2 criteria. At least one of the following:
* Constitutional Symptoms (at least one of the following)
* Recurrent fever
* Night sweats
* Fatigue
* Weight loss
* Progressive or symptomatic lymphadenopathy or splenomegaly
* Hemoglobin ≤ 10 g/dL
* Platelet count ≤ 100 k/uL
* Hyperviscosity syndrome
* Symptomatic peripheral neuropathy
* Systemic amyloidosis
* Renal insufficiency
* Symptomatic cryoglobulinemia or cold agglutinemia
* Treatment naive; must have not received any prior systemic therapy for WM
* Participants with suspected or symptomatic hyperviscosity (e.g. nosebleeds, headaches, blurred vision) must undergo plasmapheresis prior to treatment initiation.
* Adults age ≥18
* ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
* Women of childbearing potential: Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or practice complete abstinence1 from heterosexual intercourse during treatment and for at least 1 week after the last dose of zanubrutinib or at least 12 months after the last dose of rituximab, whichever is later. FCBP must be referred to a qualified provider of contraceptive methods if needed. Also, FCBP must have a pregnancy check with a negative serum pregnancy test obtained 28 days prior to and confirmed by C1D1.
* Men must agree to use a condom during sexual contact with a female of childbearing potential (FCBP) even if they have had a successful vasectomy 1) while participating in the study; and 2) for at least 1 week following the last dose of zanubrutinib.
* Participants must meet the following organ and marrow function as defined below:
* Absolute neutrophil count ≥500/mcL believed to be caused by WM bone marrow involvement. Growth factors are not permitted \<14 days prior to C1D1.
* Platelets ≥30,000/mcL believed to be caused by WM bone marrow involvement. Platelet transfusions are not permitted \<14 days prior to C1D1.
* Hemoglobin ≥ 7 g/dL. RBC transfusions are not permitted \<14 days prior to C1D1.
* Total bilirubin ≤ 1.5 X institutional ULN, or ≤3 x institutional ULN with documented liver metastases and/or Gilbert's Disease
* AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal, or ≤5 X institutional ULN with documented liver metastases
* Creatinine clearance ≥30 mL/min using the Cockcroft-Gault formula
* Able to adhere to the study visit schedule and other protocol requirements.
* Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
* Any serious medical condition, laboratory abnormality, uncontrolled intercurrent illness, or psychiatric illness/social condition that would prevent the participant from signing the informed consent form
* Female participants who are pregnant, breastfeeding, or planning to become pregnant or breastfeed while enrolled in this study
* Participants with known CNS involvement by WM
* Participants with known history of Human Immunodeficiency Virus (HIV)
* Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection based on criteria below:
* Hepatitis B virus (HBV): Patients with positive hepatitis B surface antigen (HBsAg) are excluded. Patients with positive hepatitis B core antibody (antiHBc) and negative HBsAg require hepatitis B polymerase chain reaction (PCR) evaluation before enrollment. Patients who are hepatitis B PCR positive will be excluded.
* Hepatitis C virus (HCV): positive hepatitis C antibody. If positive hepatitis C antibody result, patient will need to have a negative result for hepatitis C ribonucleic acid (RNA) before enrollment. Patients who are hepatitis C RNA positive will be excluded.
* Concurrent systemic immunosuppressant therapy. Systemic steroids at doses \<20mg prednisone per day are permitted.
* Active and/or ongoing autoimmune anemia and/or autoimmune thrombocytopenia (eg, idiopathic thrombocytopenia purpura).
* Concurrent administration of warfarin or warfarin derivatives.
* Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
* Active uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the Investigator and the Sponsor makes it undesirable for the patient to participate in the trial. Screening for chronic conditions is not required. Active uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the Investigator and the Sponsor makes it undesirable for the patient to participate in the trial. Screening for chronic conditions is not required.
* Major surgery within 4 weeks of first dose of study drug.
* History of severe bleeding disorder such as hemophilia A, hemophilia B, or history of spontaneous bleeding requiring blood transfusion or other medical intervention. History of stroke or intracranial hemorrhage within 6 months before first dose of study drug.
* Participants with inability to swallow pills.
* Inability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of the study participation.
* Any uncontrolled or significant cardiovascular disease defined as:
* Unstable angina within 3 months before screening, or
* History of myocardial infarction within 6 months prior to planned start of zanubrutinib, or
* Previously documented left ventricular ejection fraction (LVEF) by any method of ≤ 45% in the 12 months prior to planned start of zanubrutinib; assessment of LVEF via echocardiogram or multigated acquisition (MUGA) scan during Screening should be performed in selected patients as medically indicated, or
* Any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or
* Uncontrolled or symptomatic arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes)
* Participants with a known hypersensitivity to any of the excipients of Zanubrutinib, Rituximab, or Bendamustine.
* Participants with a history of non-compliance to medical regimens, which will render the administration of study drug hazardous or obscure the interpretation of toxicity or AEs.
* Prior malignancy within the past 3 years, except for curatively treated basal or squamous cell skin cancer, non-muscle-invasive bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score 6 prostate cancers.
* Severe or debilitating pulmonary disease.
* Ongoing alcohol or drug addiction or any psychiatric condition(s) which would compromise ability to comply with study procedures.
* Ongoing use of a strong CYP3A inducer. DRUG: Zanubrutinib, DRUG: Bendamustine, DRUG: Rituximab
Waldenström Macroglobulinemia, Non-Hodgkins Lymphoma
MW, Untreated
UT Southwestern
A Study Investigating Subcutaneously Administered Pozelimab in Combination With Cemdisiran or Cemdisiran Alone in Adult Participants With Geographic Atrophy (SIENNA)
This study is researching experimental (study) drugs called pozelimab and cemdisiran. The study is focused on participants who have Geographic Atrophy (GA) caused by Age-related Macular Degeneration (AMD). Geographic atrophy is a medical term that refers to later-stage cases of AMD which is an eye condition affecting central vision (what one sees straight ahead). The purpose of this study is to evaluate the progression rate of Geographic Atrophy in eyes of patients treated with cemdisiran alone or in combination with pozelimab compared to those treated with placebo. The study is looking at several other research questions, including: * What side effects may happen from taking the study drug(s) * How much study drug(s) are in the blood at different times * Whether the body makes antibodies against the study drug(s) (which could make the study drug(s) less effective or could lead to side effects)
Call 214-648-5005
studyfinder@utsouthwestern.edu, Juan.Mo@UTSouthwestern.edu
Yu-Guang He
ALL
50 Years to 85 Years old
PHASE3
NCT06541704
STU-2024-0904
Key
• Study eye with diagnosis of GA of the macula secondary to AMD as described in the protocol
• Total GA area in the study eye measuring between ≥2.5 mm\^2 and ≤17.5 mm\^2 as described in the protocol
• BCVA of 55 letters or better using ETDRS charts (20/80 Snellen equivalent) in the study eye as described in the protocol
• Sufficiently clear ocular media, adequate pupillary dilation and fixation to permit quality fundus imaging in the study eye as described in the protocol
• Willing and able to comply with clinic visits and study-related procedures, including completion of the full series of meningococcal vaccinations and pneumococcal vaccination required per protocol Key
• GA in either eye due to causes other than AMD, such as Stargardt disease, cone rod dystrophy or toxic maculopathies like hydroxychloroquine maculopathy
• History or current evidence of Macular Neovascularization (MNV) and/or exudation or Peripapillary Choroidal Neovascularization (PPCNV) in either eye as described in the protocol
• Prior or current Intravitreal (IVT) treatment of any kind for any indication in study eye or fellow eye, except approved or investigational IVT complement inhibitor therapy or anti-VEGF therapy, as long as last dose was ≥6 months prior to randomization
• Prior intraocular surgery except cataract extraction or minimally invasive glaucoma surgery in study eye as long as date of these procedures was ≥3 months prior to randomization
• Comorbid progressive ocular condition (eg, diabetic retinopathy, macular edema, uncontrolled glaucoma, full thickness macular hole) in study eye that could affect central vision and confound study
• Any ophthalmologic condition that reduces the clarity of the media and that, in the opinion of the investigator interferes with ophthalmologic examination of the study eye (e.g., advanced cataract or corneal abnormalities) as described in the protocol Systemic Exclusion criteria
• History or current use of systemic complement inhibitor therapy within 6 months prior to randomization as described in the protocol
• History of solid organ or bone marrow transplantation
• Use of chronic (\>14 days) systemic corticosteroids (oral or parenteral, ≥20 mg oral prednisone or equivalent) within the previous 30 days prior to the first screening visit as described in the protocol
• Current or prior use of systemic immunosuppressive therapy other than corticosteroids within 12 months prior to randomization or the likelihood of treatment with any such agent during the study inclusive of the screening period as described in the protocol
• Not meeting meningococcal or pneumococcal vaccination requirements as described in the protocol
• Carrier of Neisseria meningitidis based on culture collected during screening
• Has a hemoglobin A1C ≥ 8.0% during screening as described in the protocol NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply
Inclusion Criteria:
• Study eye with diagnosis of GA of the macula secondary to AMD as described in the protocol
• Total GA area in the study eye measuring between ≥2.5 mm\^2 and ≤17.5 mm\^2 as described in the protocol
• BCVA of 55 letters or better using ETDRS charts (20/80 Snellen equivalent) in the study eye as described in the protocol
• Sufficiently clear ocular media, adequate pupillary dilation and fixation to permit quality fundus imaging in the study eye as described in the protocol
• Willing and able to comply with clinic visits and study-related procedures, including completion of the full series of meningococcal vaccinations and pneumococcal vaccination required per protocol Key
Exclusion Criteria:
• GA in either eye due to causes other than AMD, such as Stargardt disease, cone rod dystrophy or toxic maculopathies like hydroxychloroquine maculopathy
• History or current evidence of Macular Neovascularization (MNV) and/or exudation or Peripapillary Choroidal Neovascularization (PPCNV) in either eye as described in the protocol
• Prior or current Intravitreal (IVT) treatment of any kind for any indication in study eye or fellow eye, except approved or investigational IVT complement inhibitor therapy or anti-VEGF therapy, as long as last dose was ≥6 months prior to randomization
• Prior intraocular surgery except cataract extraction or minimally invasive glaucoma surgery in study eye as long as date of these procedures was ≥3 months prior to randomization
• Comorbid progressive ocular condition (eg, diabetic retinopathy, macular edema, uncontrolled glaucoma, full thickness macular hole) in study eye that could affect central vision and confound study
• Any ophthalmologic condition that reduces the clarity of the media and that, in the opinion of the investigator interferes with ophthalmologic examination of the study eye (e.g., advanced cataract or corneal abnormalities) as described in the protocol Systemic Exclusion criteria
• History or current use of systemic complement inhibitor therapy within 6 months prior to randomization as described in the protocol
• History of solid organ or bone marrow transplantation
• Use of chronic (\>14 days) systemic corticosteroids (oral or parenteral, ≥20 mg oral prednisone or equivalent) within the previous 30 days prior to the first screening visit as described in the protocol
• Current or prior use of systemic immunosuppressive therapy other than corticosteroids within 12 months prior to randomization or the likelihood of treatment with any such agent during the study inclusive of the screening period as described in the protocol
• Not meeting meningococcal or pneumococcal vaccination requirements as described in the protocol
• Carrier of Neisseria meningitidis based on culture collected during screening
• Has a hemoglobin A1C ≥ 8.0% during screening as described in the protocol NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply
DRUG: Pozelimab, DRUG: Cemdisiran, DRUG: Placebo
Age-related Macular Degeneration (AMD), Geographic Atrophy (GA)
GA secondary to AMD
UT Southwestern
A Phase 2, Open-Label Study to Evaluate the Safety and Effects of HLX-1502 in Patients With Neurofibromatosis Type 1 (INSPIRE-NF1)
The trial will be an open label, single arm, phase 2 study to assess the tolerability and efficacy of HLX-1502 in participants with NF1 that are 16 years or older in age with progressive and/or symptomatic PN. This study will also investigate the safety and efficacy of HLX-1502 in a small cohort of 12 to 15 year olds.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
ALL
12 Years to old
PHASE2
NCT06541847
STU20251825
Inclusion Criteria:
• All participants must have a diagnosis of NF1 based on the 2021 revised consensus criteria.
• Participants must have PN(s) that are progressive OR are causing significant morbidity, such as (but not limited to) head and neck lesions that are compromising the airway or great vessels, brachial or lumbar plexus lesions that are causing nerve compression and loss of function, lesions causing significant disfigurement (e.g., orbital lesions), lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions. Participants with paraspinal PN will be eligible for this trial. Histologic confirmation of tumor is not necessary but should be considered if there are clinical or radiographic findings concerning for malignant transformation of a PN.
• Measurable Disease: Participants must have measurable PN(s) amenable to volumetric MRI analysis. For the purpose of this study, the target lesion must be seen on at least 3 consecutive MRI slices and the field of view must contain the entire tumor of interest. Tumors must be at least 3 mL in volume (most PN 3 cm in longest diameter will meet this criteria). If the tumor is \< 3 cm in longest diameter, the participant may still be eligible. Central review of the MRI of the target PN is required prior to enrollment to ensure that the tumor is measurable and amenable to volumetric analysis.
• Age: Participants must be ≥ 12 years of age at the time of study entry. Note: Although prior MEKi therapy is not a requirement, patients should be counseled on the availability of FDA-approved MEKi therapies prior to enrollment.
• Weight ≥ 42 kg.
• Performance Level: Participants must have a Lansky (12-15 years of age) or Karnofsky (16+ years of age) score ≥ 50%.
• Organ Function Requirements: Adequate Bone Marrow Function, Adequate Renal Function, Adequate Liver Function, Normal pancreatic function: amylase and lipase levels ≤ 1.5 x ULN. Blood pressure within upper limit of normal as defined below based on the average of the 2nd and 3rd of a total of 3 consecutive measurements, 5 minutes apart. Antihypertensives are permissible to achieve blood pressure within ULN, however must be on stable antihypertensive regimen with no adjustments within 14 days of enrollment.
• Sexually active women of childbearing potential and fertile male participants and their partners must agree to use effective methods of contraception e.g., hormonal oral contraception, injectables, intrauterine device, surgical sterilization including vasectomy, or hormonal implant with barrier methods (male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment. Barrier methods alone are insufficient. True sexual abstinence or evidence of surgical sterility (e.g. vasectomized partner, post-hysterectomy, menopause with last menstrual period \>=12 months prior to screening visit) are acceptable method of birth control. Persons of childbearing potential will be given a pregnancy test within 14 days prior to first dose of study treatment and must have a negative urine or serum pregnancy test.
• The participant is not planning to undergo surgery or other interventions/ treatments for the target lesion, except protocol specified therapy, for the duration of the study.
• The participant or the participant's legal authorized representative is able to understand the informed consent form describing the risks of the study and voluntarily signs the informed consent document.
• In the opinion of the investigator, the participant is willing and able to attend study visits, comply with the study procedures as specified in the protocol, and comply with the administration of the study drug.
Exclusion Criteria:
• Prior treatment with HLX-1502 for a PN.
• The participant has used any of the following systemic medications/ therapies within the specified period prior to enrollment: MEK-inhibitors, other drugs in the TKI class, HLX-1502, Participants may have received treatment for a PN or other tumor/malignancy but must have fully recovered to baseline or CTCAE ≤ Grade 1 from acute toxicities from prior therapies except alopecia, Myelosuppressive chemotherapy, Hematopoietic growth factors, Biologic (anti-neoplastic agent), Investigational Drugs, Any other systemically administered anti-neoplastic agent and Radiation therapy.
• Evidence of an NF1-related tumor such as optic pathway or other low-grade glioma, high-grade glioma, malignant peripheral nerve sheath tumor, or other cancer/tumor requiring treatment with chemotherapy, biologic therapy, surgery or radiation therapy.
• Participants with high-grade glioma, malignant peripheral nerve sheath tumor, or other malignancy who received treatment in the last 12 months. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that have undergone potentially curative therapy. If the investigator has any clinical concerns for ANNUBP/Atypical Neurofibroma or MPNST, a biopsy sample must be taken prior to study confirming eligibility.
• Dental braces or prosthesis that interfere with volumetric analysis of the neurofibroma(s).
• Surgery: Any major surgery within 12 weeks before starting the Treatment Period or foreseen during participation in the trial, any minor surgeries within 1 month before first dose of study treatment and Participants must have complete wound healing from major surgery or minor surgery before the first dose of study treatment. Participants with clinically relevant ongoing complications from prior surgery are not eligible.
• Cataracts noted on ophthalmologic exam.
• Cardiovascular disorders.
• Other clinically significant disorders that would preclude safe study participation, including active infection, a known history of HIV seropositivity or known immunodeficiency or Known history of Hepatitis B or Hepatitis C.
• Participants who require treatment with a drug that is a substrate of CYP1A2, CYP2C8, UGT1A1, UGT1A3 with a narrow therapeutic index during protocol therapy.
• Known severe sensitivity to HLX-1502 or any excipient of HLX-1502 or history of allergic reactions attributed to compounds of similar chemical or biologic composition to HLX-1502.
• Known severe sensitivity to FD\&C Yellow No. 5.
• Participants receiving therapeutic anticoagulation with vitamin K antagonist.
• Participants presently with iron deficiency and/or actively receiving iron replacement or requiring treatment with copper or zinc for any indication at study baseline.
• Pregnant or breast-feeding women.
• Unable or unwilling to swallow tablets.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter ingestion and/or the absorption of HLX-1502.
• Participants who have other medical, social or concurrent challenges that are likely to negatively impact their ability to meet all of the trial obligations and therefore may increase the risk of safe participation in the study.
DRUG: HLX-1502
Neurofibromatosis Type 1, Brain and Nervous System
Neurofibromatosis Type 1, Plexiform Neurofibroma, pediatric
UT Southwestern; Children’s Health
Triptorelin for the Prevention of Ovarian Damage in Adolescents and Young Adults With Cancer
This phase III trial compares the effect of giving triptorelin vs no triptorelin in preventing ovarian damage in adolescents and young adults (AYAs) with cancer receiving chemotherapy with an alkylating agents. Alkylating agents are part of standard chemotherapy, but may cause damage to the ovaries. If the ovaries are not working well or completely shut down, then it will be difficult or impossible to get pregnant in the future. Triptorelin works by blocking certain hormones and causing the ovaries to slow down or pause normal activity. The triptorelin used in this study stays active in the body for 24 weeks or about 6 months after a dose is given. After triptorelin is cleared from the body, the ovaries resume normal activities. Adding triptorelin before the start of chemotherapy treatment may reduce the chances of damage to the ovaries.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Ksenya Shliakhtsitsava
FEMALE
to 39 Years old
PHASE3
NCT06513962
STU20250281
Inclusion Criteria:
* \< 40 years of age at the time of enrollment
* Patient must be a post-menarchal female and report that their initial menstrual period occurred \> 6 months prior to enrollment. (Current menstrual status is not part of the inclusion criteria.)
* Newly diagnosed with first cancer, exclusive of breast cancer.
* Note: Apart from breast carcinoma, other tumor types originating in the breast are permitted (e.g., sarcoma, lymphoma).
* Planned treatment must include one or more of the following alkylating agents delivered with curative intent: cyclophosphamide, ifosfamide, procarbazine, chlorambucil, carmustine (BCNU), lomustine (CCNU), melphalan, thiotepa, busulfan, nitrogen mustard.
* For patients \< 20 years of age at enrollment, the expected alkylator dose must be ≥ 4 g/m\^2 cumulative cyclophosphamide equivalent dose (CED). For patients ≥ 20 years of age at enrollment, any planned alkylator dose is permitted. Eligible patients must receive at least one of the alkylators that contribute to CED.
* All patients and/or their parents or legal guardians must sign a written informed consent.
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
Exclusion Criteria:
* Any planned radiation to the pelvis; or cranial radiation ≥ 30 gray (Gy) to the hypothalamus, inclusive of any total body irradiation (TBI).
* Planned bilateral oophorectomy. Note: A participant's desire to pursue alternative fertility preservation procedures (i.e., embryo, oocyte, or ovarian tissue cryopreservation) will be allowed (and in fact encouraged).
* Congenital syndromes associated with infertility and decreased ovarian reserve at baseline. For example: Turner's Syndrome, Fragile X premutation carriers, Down syndrome, etc.
* Pre-existing seizure disorder, congenital long QT syndrome, pseudotumor cerebri; history of pulmonary embolism, venous thrombosis, or myocardial infarction. Note: Contact study chairs if questions arise about other pre-existing conditions.
* Receipt of long acting (depot) GnRH agonists within 6 months before enrollment. In contrast, subcutaneous GnRH agonist used for oocyte retrieval is not an exclusion; oral and other hormonal contraceptive use is also not an exclusion. Note: Please see protocol for the concomitant therapy restrictions for patients during the study treatment period. See protocol for information about oral and other hormonal contractive use during the study treatment period.
* Prior receipt of systemic chemotherapy. However, steroids and intrathecal chemotherapy are permitted prior to study enrollment.
* Any prior radiation to the pelvis; or cranial radiation ≥ 30 Gy to the hypothalamus, inclusive of any total body irradiation (TBI).
* Patients who are pregnant are not eligible. A pregnancy test is required for female patients of childbearing potential.
* Lactating females who plan to breastfeed their infants for the duration of triptorelin therapy (24 weeks per dose).
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of triptorelin therapy (24 weeks per dose). OTHER: Best Practice, PROCEDURE: Biospecimen Collection, OTHER: Electronic Health Record Review, OTHER: Survey Administration, DRUG: Triptorelin Pamoate
Hematopoietic and Lymphatic System Neoplasm, Malignant Solid Neoplasm, Multiple
UT Southwestern; Children’s Health
Invert-Prospective Phase II Randomized Trial of Involved Nodal Versus Elective Neck RadioTherapy
To determine the risk of solitary elective volume recurrence following involved nodal radiotherapy (INRT) versus elective nodal irradiation (ENI)
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Sher
ALL
18 Years to 99 Years old
PHASE2
NCT06477692
STU-2024-0603
Inclusion Criteria:
* Pathologically-proven diagnosis of squamous cell carcinoma of the oropharynx, larynx, or hypopharynx. Squamous cell carcinoma of unknown primary is not allowed.
* Patients must have clinically or radiographically evident measureable disease at the primary site and/or nodal stations. Diagnostic lymph node excision (≤ 2 nodes) is also allowable.
* Patients may undergo a diagnostic or therapeutic transoral resection for a T1-2 tonsil or base of tongue cancer.
* Clinical stage I-IVB (AJCC, 7th edition); stages I-II glottic cancer are excluded
* Age ≥ 18 years.
* ECOG Performance Status 0-2
* All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
* A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria Has not undergone a hysterectomy or bilateral oophorectomy; or Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
* Neck CT and/or neck MRI, and PET-CT
* Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
* Distant metastasis.
* Inability to undergo either a diagnostic CT with contrast or simulation CT with contrast.
* Inability to undergo PET-CT.
* Stage I and II glottic carcinoma.
* Gross total excision of both the primary and nodal disease.
* Synchronous non-skin cancer primaries outside of the oropharynx, larynx, and hypopharynx except for low- and intermediate-risk prostate cancer and synchronous well-differentiated thyroid cancer; in the latter case, surgery may occur before or after treatment, provided all other eligibility criteria are met.
* Prior invasive malignancy with an expected disease-free interval of less than 3 years.
* Prior systemic chemotherapy for the study cancer; prior chemotherapy for a remote cancer is allowable.
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields.
* Subjects may not be receiving any other investigational agents.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to the chemotherapy agents in this study (if necessary).
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
* History of severe immunosuppression, including HIV, and organ or autologous or allogeneic stem cell transplant. DRUG: ENI using IMRT with or without chemotherapy, RADIATION: INRT, RADIATION: ENI
Head and Neck Cancer, Larynx, Lip, Oral Cavity and Pharynx
UT Southwestern; Parkland Health & Hospital System
Study of Navtemadlin add-on to Ruxolitinib in JAK Inhibitor-Naïve Patients With Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib (POIESIS)
This clinical trial is evaluating whether addition of navtemadlin to ruxolitinib treatment will provide more clinical benefit than ruxolitinib alone for patients with Myelofibrosis who have a suboptimal response to ruxolitinib treatment alone. Subjects will start by receiving ruxolitinib alone in the run-in period. Those who demostrate a suboptimal response from ruxolitinib alone will then be randomized 2:1 to receive navtemadlin or navtemadlin placebo as add-on treatment to their ongoing ruxolitinib. Randomized means that subjects will be assigned to a group by chance, like a flip of a coin. The study is blinded, meaning the subjects, doctors, central endpoint assessors and sponsor will not know which add on treatment (navtemadlin or navtemadlin placebo) the subject is receiving.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Clayton Jackson
ALL
18 Years to old
PHASE3
NCT06479135
STU20240013
Inclusion Criteria for Ruxolitinib Alone Period:
* Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by the treating physician according to the World Health Organization (WHO) criteria
* High, Intermediate-1, Intermediate-2 risk category International Prognosis System Score (IPSS)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
* JAK-inhibitor treatment naive
Exclusion Criteria for Ruxolitinib Alone Period:
* Prior Splenectomy
* Splenic irradiation within 3 months prior to the first dose
* Prior BCL-XL, BET, MDM2, PI3K, PIM, or XPO1 inhibitors therapy or p53-directed therapy
* Eligible for Bone Marrow Transplant
* Peripheral blood or bone marrow blast count ≥ 10 percent
Inclusion Criteria for Randomized Period:
* PMF, post-PV MF, or post-ET MF that is TP53WT as assessed by central testing
* ECOG performance status of 0 to 2
* Treatment with a stable dose of ruxolitinib
* Suboptimal response to run-in ruxolitinib treatment
Exclusion Criteria for Randomized Period:
* Elevated white blood cell count that doubles (or more) during ruxolitinib treatment and exceeds 50 × 10\^9/L
* Peripheral blood or bone marrow blast count ≥ 10 percent
DRUG: Navtemadlin, DRUG: Navtemadlin placebo, DRUG: Ruxolitinib
Myelofibrosis, Post-PV MF, Post-ET Myelofibrosis, Primary Myelofibrosis, MF, Leukemia, Other, Myeloid and Monocytic Leukemia
Navtemadlin, KRT-232, Ruxolitinib, POIESIS, TP53, Suboptimal response, Sub-optimal response
UT Southwestern
Trial of Transurethral Bulking Agent Injection Versus Single-Incision Sling for Stress Urinary Incontinence (BASIS)
This is a multicentered, double-blind, randomized controlled, surgical trial of 358 women with inadequate symptom relief of stress urinary incontinence (SUI) or stress predominant mixed urinary incontinence (MUI) after conservative care. The Primary Aim is to determine the comparative effectiveness (as defined by "much" or "very much" better on PGI-I) of transurethral bulking agent (TBA) \[for 1 or 2 injections in 12 months\] vs. single-incision sling (SIS) 12 months after treatment intervention in women with predominant stress urinary incontinence (SUI).
Call 214-648-5005
studyfinder@utsouthwestern.edu, AGNES.BURRIS@UTSouthwestern.edu
David Rahn
FEMALE
21 Years to old
NA
NCT06480227
STU-2024-1228
Inclusion Criteria:
* Women ≥ 21 years
* Bothersome SUI (PFDI-20 Q:#17 of somewhat, moderately or quite a bit) or stress predominant MUI (PFDI-20 Q:#16 \< Q:#17)50 for \> 3 months with well-controlled UUI on stable medication treatment through baseline and follow-up.
* A positive cough stress test or urodynamic SUI within the past 18 months.
* Normal voiding function as demonstrated by PVR \< 150 mL
* Candidate for either study procedure as determined by treating surgeon (i.e., failed or unable to perform conservative management for SUI including pelvic floor strengthening and failed or declines pessary option for SUI)
* Available for up to 3 years.
* Agrees to randomization.
Exclusion Criteria:
* Anterior/apical vaginal prolapse beyond the hymen (\>0 on POPQ) - Advanced prolapse may require additional surgery or potentially increase the risk of postoperative urinary obstruction and confound the results of the study.
* Urge-predominant mixed UI by UDI-6 despite stable therapy - Urge predominant UI would not be expected to improve after TBA or SIS and may bias results of interventions designed specifically for stress urinary incontinence.
* Planned hysterectomy, urethral or anterior/apical surgeries - additional surgery beyond TBA or SIS has potential to confound the results. Additionally, these procedures generally require general anesthesia and indwelling catheterization immediately post operatively. The impact of urethral instrumentation after TBA is unknown and could impact the efficacy of the urethral coaptation.
* Malignancy or history of radiation of the pelvis - The risk of foreign material rejection and mesh complications may be higher in women with pelvic radiation and other treatment for pelvic malignancy may impact primary outcomes.
* Pregnant, breast feeding or plans for pregnancy within 1 year - subsequent vaginal delivery and hormonal changes of breast feeding prior to primary outcome could impact the efficacy of either treatment.
* Incomplete emptying (PVR \> 150mL) - SUI surgery may increase the risk of urinary retention.
* Prior anti-incontinence procedure - the aim of the study is to identify the role of TBA and SIS in primary, uncomplicated SUI or stress predominant MUI management.
* Neurogenic bladder - the aim of the study is to identify the role of TBA and SIS in primary, uncomplicated SUI or stress predominant MUI management.
* Prior adverse reaction to synthetic mesh or polyacrylamide - to minimize risk of post procedure complications.
* Chronic bladder or pelvic pain conditions (e.g., Interstitial cystitis, painful bladder syndrome, fibromyalgia, chronic pelvic pain, etc.) - given the known risks of postoperative pain with SIS and higher risks of pain in those with baseline chronic pain, we aim to minimize post operative complications.
* Active 3rd line treatment for OAB/UUI with botulinum toxin, sacral neuromodulation stimulation (SNS) or percutaneous tibial nerve stimulation (PTNS) within 12 months or plan for 3rd line or new OAB/UUI treatment within 1 year of SUI surgery. For those on stable medication OAB/UUI treatment, participants should be on stable treatment for 3 months with adequate symptom control prior to baseline measures and plan to remain on stable therapy without 3rd line treatment plans within 1 year of SUI surgery. Those who have received 3rd line treatment (Botox. PTNS or SNS) should have a washout of 1yr from and no plans for restarting within the primary outcome timeframe of 1 year post procedure. Those using SNS for bowel leakage only and no UUI symptoms do not require minimum 3 months. Participants with MUI on OAB/UUI medication therapy will still need to have SUI worse than UUI at baseline. Randomization will be stratified based on presence of UUI treatment component.
* Active treatment for SUI with a pessary. For those using a pessary or other SUI support device, a 3-week washout period should occur prior to assessing baseline measures. DEVICE: Solyx Single-incision Sling, DEVICE: Bulkamid Transurethral Bulking Agent
Stress Urinary Incontinence, Urinary Incontinence, Mixed Urinary Incontinence
Urinary Incontinence, Pelvic Floor Disorders, Single Incision Sling, Transurethral Bulking Agent
UT Southwestern; Parkland Health & Hospital System