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406 Study Matches
NP-G2-044 as Monotherapy and Combination Therapy in Patients With Advanced or Metastatic Solid Tumor Malignancies
Multicenter, open-label study in patients with advanced or metastatic solid tumor malignancies to evaluate the safety, tolerability, and preliminary anti-tumor efficacy, PK, and pharmacodynamics of continuously dosed NP-G2-044 monotherapy and NP-G2-044 in combination with anti-PD-1 therapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Sanjay Chandrasekaran
ALL
18 Years and over
PHASE1
NCT05023486
STU-2022-0778
Inclusion Criteria:
• Male or female ≥18 years of age;
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
• Life expectancy of \> 6 months;
• Abilty to swallow capsules and tablets;
• Adequate organ and bone marrow function, defined by the following: ANC \>1500 cells/μL; Hemoglobin \>9.0 g/dL; Platelet count \>100,000 cells/μL; Total bilirubin ≤1.5 mg/dL; Albumin ≥3.0 g/dL; Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase ≤2.5 × upper limit of normal (ULN); Creatinine clearance ≥50 mL/min; and Prothrombin time and partial thromboplastin time ≤1.5 × ULN.
• Female patients of childbearing potential must have a negative serum or urine pregnancy test at Screening and within 24 hours (if urine test) or 72 hours (if serum test) before the first dose of NP-G2-044. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required and must be negative for the patient to be eligible; Note: A woman is considered to be childbearing potential unless she is postmenopausal (≥1 year without menses and confirmed with a follicle-stimulating hormone \[FSH\] test) or surgically sterilized via bilateral oophorectomy, hysterectomy, bilateral tubal ligation, or successful Essure® placement with a documented confirmation test at least 3 months after the procedure.
• Male patients must be surgically sterile or willing to use a highly effective double-barrier contraception method (eg, male condom with diaphragm or male condom with cervical cap) upon study entry, while on NP-G2-044, and for a period of at least 4 months following the last dose of NP-G2-044; and
• Able to understand and voluntarily sign a written informed consent form (ICF) and willing and able to comply with protocol requirements. Inclusion Criteria for NP-G2-044 Monotherapy: Patients must meet all the following criteria to receive NP-G2-044 monotherapy in the study:
• Have a histopathologically confirmed advanced or metastatic solid tumor malignancy for which standard therapies are no longer effective, not tolerated or ineligible for the patient to receive;
• Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.;
• For monotherapy expansion cohort A (after the Mono-RP2D has been identified), patients must have:
• Gynecologic malignancies including ovarian, endometrial/uterine, fallopian tube, cervical, vulvar, and vaginal cancers; or
• Epidermal growth factor receptor (EGFR)-high (2+ or 3+ staining per DAKO criteria or genomic sequencing data showing 3 or more copies of the EGFR gene) triple-negative breast cancer (TNBC).
• For Monotherapy Expansion Cohort B, patient must have advanced or metastatic solid tumors malignancy Inclusion Criteria for NP-G2-044 Combination Therapy Patients must meet 1 of the following criteria to receive NP-G2-044 in combination with anti-PD-1 therapy in the study:
• Have initiated anti-PD-1 therapy in accordance with the package insert and have been receiving the anti-PD-1 therapy for ≥3 months (with therapy currently ongoing) and have stable disease, or had an initial period of stable disease and now have an initial scan demonstrating progressive disease per RECIST 1.1. or Have discontinued prior anti-programmed death-1/programmed death ligand-1 (PD- \[L\]1) therapy and are now eligible for de novo NP-G2-044 plus standard of care anti-PD 1 therapy.
Exclusion Criteria:
• Received chemotherapy or radiotherapy within 4 weeks or 5 half-lives, whichever is shorter, of the first dose of NP-G2-044; Note: Prior immunotherapy is allowed for patients receiving NP-G2-044 monotherapy.
• Unresolved toxicities from previous anti-cancer therapy, defined as toxicities (other than NCI CTCAE v5.0 Grade ≤2 alopecia or neuropathy) not yet resolved to NCI CTCAE v5.0 Grade ≤1; Note: Patients who experienced a Grade ≥3 anti-PD-1-related AE per NCI CTCAE v5.0 are excluded unless recovered and reviewed by the Novita Medical Monitor or designee.
• Receiving any other investigational agent(s) or have received an investigational agent within 4 weeks of the first dose of NP-G2-044; Note: Patients who have progressed on NP-G2-044 treatment prior to this study are not eligible
• Known untreated brain metastases or treated brain metastases that have not been radiographically and clinically stable (ie, not requiring steroids) ≥4 weeks prior to study enrollment;
• QTc by Fridericia method \>470 msec or electrocardiogram (ECG) with evidence of clinically meaningful conduction abnormalities or active ischemia as determined by the Investigator;
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, hypertension, unstable angina pectoris, cardiac arrhythmia, autoimmune or inflammatory diseases, or psychiatric illness/social situations that would limit compliance with study requirements;
• Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during the study or within 90 days after dosing of NP-G2-044;
• Received prior allogenic hematopoietic stem cell transplantation or allogenic bone marrow transplantation;
• Received prior solid organ transplantation;
• Ongoing immunosuppressive therapy (≥10 mg/day of prednisone or its equivalent);
• Requires the use of a strong inhibitor or inducer of cytochrome P450 (CYP)3A4, CYP1A2, or CYP2D6 during the study;
• History of clinically meaningful gastrointestinal bleeding, intestinal obstruction, or gastrointestinal perforation within 6 months of study enrollment; or
• Excluded by the Sponsor due to medical history, physical examination findings, clinical laboratory results, prior medications, or other entrance criteria.
DRUG: NP-G2-044 Monotherapy, DRUG: Anti-PD-1 Therapy, DRUG: NP-G2-044 Combination therapy
Advanced or Metastatic Solid Tumor Malignancies, Breast - Female, Cervix, Other Female Genital
Advanced or Metastatic Solid Tumor Malignancies
UT Southwestern
[18F]PT2385 PET/CT in Patients with Renal Cell Carcinoma
This is an exploratory study to assess \[18F\]PT2385 Positron Emission Tomography/Computed Tomography (PET/CT) in patients with renal cell carcinoma (RCC). This is an open-label, nontherapeutic trial. The main objective is to correlate hypoxia-inducible factor-2alpha (HIF2α) levels as determined by an investigational \[18F\]PT2385 PET/CT scan with the levels on subsequently obtained tissue by HIF2α immunohistochemistry (IHC). There will be three cohorts. The first pre-surgical cohort will have \[18F\]PT2385 PET/CT prior to nephrectomy. The uptake and retention on Positron Emission Tomography (PET), quantified as standardized uptake value (SUV) max and mean, abbreviated SUV henceforth will be correlated with HIF2α levels by IHC on the primary tumor. The second cohort will comprise patients with metastatic clear cell renal carcinoma (ccRCC). SUV will be correlated with HIF2α levels measured by IHC on a biopsy sample from a metastasis. Both low- and high-avidity sites will be biopsied and tracer uptake correlated with HIF2α IHC. A third cohort will include patients with Von Hippel-Lindau (VHL) syndrome and any of the following disease manifestations - RCC, central nervous system (CNS) hemangioblastoma, and/or pancreatic neuroendocrine tumor(s). Investigational imaging will evaluate HIF2α expression within a tumor type and across different tumor types. A biopsy is encouraged but not mandatory for this cohort.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
James Brugarolas
ALL
18 Years and over
PHASE1
NCT04989959
STU-2021-0592
Inclusion Criteria:
* Ability to understand and the willingness to sign a written informed consent that includes study interventions (PET/CT and, if cohort 2, mandatory biopsy).
* Ability to lie still for a 30- to 60-minute PET/CT scan.
* One of the following:
• Cohort 1. Patients with suspected RCC planned for surgery.
• Cohort 2. Patients with metastatic ccRCC or VHL syndrome and RCC. Biopsy is required (planned resection for treatment reasons of a metastatic site is acceptable in lieu of the biopsy).
• Cohort 3. Patients with VHL syndrome with RCC, CNS hemangioblastoma, and/or pancreatic neuroendocrine tumor(s) planning to start belzutifan. * Patients with liver dysfunction will be considered "patients of special interest," and enrollment is allowed with or without criteria outlined for Cohorts 1-3. Liver dysfunction is defined clinically and is typically supported by abnormalities in imaging or laboratory studies (alanine / aspartate amino-transferase, bilirubin, alkaline phosphatase, or international normalized range (INR) for prothrombin time). * Women of child-bearing potential must agree to undergo and have documented a negative pregnancy test on the day of \[18F\]PT2385 administration. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or 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).
Exclusion Criteria:
* Uncontrolled severe and irreversible intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.
* Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
* Claustrophobia or other contraindications to PET/CT.
* Subjects must not weigh more than the maximum weight limit for the table for the PET/CT scanner where the study is being performed (\>200 kilograms or 440 pounds).
* For cohort 2 patients, lack of suitable sites for mandatory biopsy. For example, patients with metastatic disease restricted to the lungs that would require percutaneous biopsies with associated risk of bleeding and pneumothorax will be excluded. DRUG: [18F]PT2385, PROCEDURE: Positron Emission Tomography/Computed Tomography, PROCEDURE: Biopsy
Renal Cell Carcinoma, Clear Cell Renal Cell Carcinoma, Kidney
UT Southwestern; Parkland Health & Hospital System
Testing Combination Erdafitinib and Enfortumab Vedotin in Metastatic Bladder Cancer After Treatment With Chemotherapy and Immunotherapy
This phase Ib trial evaluates the best dose, potential benefits, and/or side effects of erdafitinib in combination with enfortumab vedotin in treating patients with bladder cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and possesses genetic alterations in FGFR2/3 genes. Erdafitinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal FGFR protein that signals cancer cells to multiply. This may help keep cancer cells from growing and may kill them. Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of cancer cells. Enfortumab attaches to a protein called nectin-4 on cancer cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Giving erdafitinib in combination with enfortumab vedotin may shrink or stabilize metastatic bladder cancer with alterations in FGFR 2/3 genes.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Waddah Arafat
ALL
18 Years and over
PHASE1
NCT04963153
STU-2023-0272
Inclusion Criteria:
* Patients must have histologically or cytologically documented locally advanced (T4b, any N; or any T, N 2-3) or metastatic (M1, Stage IV; or metastatic recurrence after locoregional treatment) urothelial carcinoma (including renal pelvis, ureters, urinary bladder, urethra). Patients with mixed histologies are required to have a dominant transitional cell pattern
* Patients who had disease progression during or following treatment with at least one platinum-containing regimen (e.g., gemcitabine and cisplatin \[GC\], methotrexate, vinblastine, doxorubicin and cisplatin \[MVAC\], carboplatin and gemcitabine \[Carbo-Gem\]) and an immune checkpoint inhibitor (PD-1/ PD-L1 inhibitor including but not limited to: atezolizumab, pembrolizumab, durvalumab, avelumab, and nivolumab)
* Received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease
* Or received neo/adjuvant platinum-containing therapy for localized muscle-invasive UC, with recurrence/progression =\< 12 months following completion of therapy
* Patients who received immune checkpoint inhibitor therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during therapy or within 12 months of therapy completion are eligible. This criterion does not apply if the checkpoint inhibitor is contraindicated
* Patients with metastatic urothelial carcinoma who are cisplatin-ineligible and progressed on upfront immune checkpoint inhibitor; or ineligible/refused immune checkpoint inhibitor therapy will be eligible for this trial
* Patient who received prior antibody drug conjugate such as sacituzumab govitecan are allowed
* Patients must have measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Previously irradiated lesions cannot be counted as target lesions unless there has been demonstrated progression in the lesion since radiotherapy and no other lesions are available for selection as target lesions
* Patients must have FGFR2/3 activating alterations identified by tumor tissue or plasma ctDNA profiling using a Clinical Laboratory Improvement Act (CLIA) certified College of American Pathologists (CAP) accredited platform
* Age \>= 18 years, for ability to comply with protocol
* Because no dosing or adverse event data are currently available on the use of erdafitinib in combination with enfortumab vedotin in patients \< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
* Absolute neutrophil count \>= 1,500/mcL (within 14 days prior to beginning trial treatment)
* Platelets \>= 100,000/mcL (within 14 days prior to beginning trial treatment)
* Hemoglobin \>= 9 g/dL (within 14 days prior to beginning trial treatment)
* Measured or calculated creatine clearance (CrCl) \>= 30 ml/min (glomerular filtration rate \[GFR\] can also be used in place of creatinine CrCl) (within 14 days prior to beginning trial treatment)
* Total bilirubin =\< 1.5 x ULN (institutional upper limit of normal) OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 x ULN (within 14 days prior to beginning trial treatment)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 x institutional ULN (=\< 5 x ULN for subjects with liver metastasis) (within 14 days prior to beginning trial treatment)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression (CNS metastases have been clinically stable for at least 4 weeks prior to screening and baseline scans show no evidence of new or enlarged metastasis)
* Patients with a history of prostate cancer (T2NXMX or lower with Gleason score =\< 7) treated with definitive intent (surgically or with radiation therapy) at least 1 year prior to study entry are eligible, provided that the subject is considered prostate cancer-free and the following criteria are met:
* Patients who have undergone radical prostatectomy must have undetectable prostate specific antigen (PSA) for \> 1 year and at screening
* Patients who have had radiation must have a PSA doubling time \> 1 year (based on at least 3 values determined \>1 month apart) and a total PSA value that does not meet Phoenix criteria for biochemical recurrence (i.e., \< 2.0 ng/mL above nadir)
* Patients with untreated low-risk prostate cancer (Gleason score =\< 6) on active surveillance with PSA doubling time \>1 year (based on at least 3 values determined \> 1 month apart) are also eligible
* Patients who have undergone an ophthalmologic examination and have no active eye disease which would be likely to increase the risk of eye toxicity
* The effects of erdafitinib and enfortumab vedotin on the developing human fetus are unknown. For this reason and because FGFR inhibitors and humanized antibody-drug conjugate (ADC) agents are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 3 months after completion of erdafitinib and enfortumab vedotin administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 5 months after completion of erdafitinib and enfortumab vedotin administration
* Ability to understand and willingness to sign a written informed consent document
Exclusion Criteria:
* Patients who have had chemotherapy, targeted therapies, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (including ongoing sensory or motor neuropathy of grade 2 or higher) (i.e., have residual toxicities \> grade 1 or returned to baseline) with the exception of alopecia. Subjects with =\< grade 2 immunotherapy- related hypothyroidism or panhypopituitarism may be enrolled when well-maintained/controlled on a stable dose of hormone replacement therapy (if indicated). Subjects with ongoing \>= grade 3 immunotherapy-related hypothyroidism or panhypopituitarism are excluded. Subjects with ongoing immunotherapy related colitis, uveitis, myocarditis, or pneumonitis or subjects with other immunotherapy related adverse events (AEs) requiring high doses of steroids (\> 20 mg/day of prednisone or equivalent) are excluded
* Patients who have previously received enfortumab vedotin or other MMAE-based ADCs
* Patients who have had prior treatment with an FGFR inhibitor
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to erdafitinib and enfortumab vedotin
* Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
* Patients with a history of any corneal or retinal abnormality likely to increase the risk of eye toxicity
* Patients with uncontrolled intercurrent illness and currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of starting treatment. Routine antimicrobial prophylaxis is permitted
* Patients with psychiatric illness/social situations that would limit compliance with study requirements
* Subjects who have received radiotherapy within 2 weeks prior to start of treatment. Subject must have recovered adequately from the toxicity from the intervention prior to starting study treatment
* Patients with uncontrolled diabetes. Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) \>= 8% or HbA1c 7% to \< 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained
* Subjects who have received major surgery within 4 weeks prior to start of treatment. Subject must have recovered adequately from complications from the intervention prior to starting study treatment
* Subjects who have received a prior allogeneic stem cell or solid organ transplant
* Has persistent phosphate level \> ULN during screening (within 14 days of treatment and prior to cycle 1 day 1) and despite medical management
* Has a history of or current uncontrolled cardiovascular disease including:
* Unstable angina, myocardial infarction, or known congestive heart failure class II-IV within the preceding 12 months; cerebrovascular accident or transient ischemic attack within the preceding 3 months
* Any of the following: sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes, cardiac arrest, Mobitz II second degree heart block or third degree heart block; known presence of dilated, hypertrophic, or restrictive cardiomyopathy
* Corrected QT interval (QTc) prolongation as confirmed by triplicate assessment at screening (Fridericia;QTc \> 480 milliseconds)
* Subjects with a history of another invasive malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Subjects with nonmelanoma skin cancer or carcinoma in situ of any type (if complete resection was performed) are allowed PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, DRUG: Enfortumab Vedotin, DRUG: Erdafitinib, PROCEDURE: Multigated Acquisition Scan
Locally Advanced Bladder Urothelial Carcinoma, Locally Advanced Renal Pelvis Urothelial Carcinoma, Locally Advanced Ureter Urothelial Carcinoma, Locally Advanced Urethral Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma, Metastatic Bladder Urothelial Carcinoma, Metastatic Renal Pelvis Urothelial Carcinoma, Metastatic Ureter Urothelial Carcinoma, Metastatic Urethral Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Recurrent Bladder Urothelial Carcinoma, Recurrent Renal Pelvis Urothelial Carcinoma, Recurrent Ureter Urothelial Carcinoma, Recurrent Urethral Urothelial Carcinoma, Recurrent Urothelial Carcinoma, Stage IIIB Bladder Cancer AJCC v8, Stage IV Bladder Cancer AJCC v8, Stage IV Renal Pelvis Cancer AJCC v8, Stage IV Ureter Cancer AJCC v8, Stage IV Urethral Cancer AJCC v8, Gall Bladder, Other Urinary, Urinary Bladder
UT Southwestern
Motor Network Physiology
The brain networks controlling movement are complex, involving multiple areas of the brain. Some neurological disorders, like Parkinson's disease (PD) and essential tremor (ET), cause abnormalities in these brain networks. Deep brain stimulation is a treatment that is used to treat these types of neurological diseases and is thought to help patients by modulating brain networks responsible for movement. Levodopa medication is also used to modulate this brain networks in patients with PD. The overall objective is to develop a unified theory of basal ganglia thalamocortical (BGTC) circuit dynamics that accounts for disease symptomatology, movement, and their inter-relationship. The underlying hypothesis, is that the rigidity and bradykinesia of PD are fundamentally related to excessive functional coupling across nodes in the BGTC motor circuit impeding effective information flow. In this research, the investigator will take advantage of the unique opportunity provided by awake deep brain stimulation surgery to learn more about how the brain functions in a diseased state and how deep brain stimulation changes these networks to make movement more normal. The investigator will simultaneously assess cortical and subcortical electrophysiology in relation to clinical symptoms and behavioral measures and in response to deep brain stimulation, cortical stimulation, and pharmacologic therapy in patients undergoing Deep Brain Stimulation (DBS) implantation surgery.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Sahil.Chilukuri@UTSouthwestern.edu
Nader Pouratian
ALL
18 Years to 89 Years old
NA
NCT04957095
STU-2021-0376
Inclusion Criteria:
* Diagnosis of Parkinson's disease who have been recommended to undergo deep brain stimulation for management of their movement disorder
* Preoperative MRI without evidence of cortical or subdural adhesions or vascular abnormalities
* Willingness and ability to cooperate during conscious operative procedure for up to 40 minutes
Exclusion Criteria:
* Patients with recent use (within one week) of anticoagulant or antiplatelet agents
* Neurocognitive testing indicating amnestic cognitive deficits DRUG: Apomorphine Injectable Solution, OTHER: Subcortical Stimulation
Parkinson Disease, Essential Tremor, Brain and Nervous System
deep brain stimulation, levodopa medication, motor cortex, basal ganglia, thalamus
UT Southwestern
Olanzapine Versus Megestrol Acetate for the Treatment of Loss of Appetite Among Advanced Cancer Patients
This phase III trial compares the effects of olanzapine versus megestrol acetate in treating loss of appetite in patients with cancer that has spread to other places in the body (advanced). Olanzapine may stimulate and increase appetite. This study aims to find out if olanzapine is better than the usual approach (megestrol acetate) for stimulating appetite and preventing weight loss.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Namrata Peswani
ALL
18 Years and over
PHASE3
NCT04939090
STU-2021-1170
Inclusion Criteria:
* Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)
* Diagnosis of advanced cancer
* Patient-reported 2-month weight loss of at least 5 pounds (2.3 kilograms) and/or physician-estimated caloric intake of less than 20 calories/kilogram of body weight per day
* The patient must perceive loss of appetite and/or weight as a problem; and have an appetite score of 4 or worse on the "Please rate your appetite…." question that requires a patient response on a 0-10 numeric rating scale
* Not receiving ongoing tube feedings or parenteral nutrition at the time of registration
* Not currently using systemic adrenal steroids (with the exception of short-term dexamethasone within 3 days of chemotherapy for control of chemotherapy side effects)
* No use of androgens, progesterone analogs, or other appetite stimulants within the past month
* Patient should not have poorly controlled hypertension or congestive heart failure at registration
* Patient should not have an obstruction of the alimentary canal, malabsorption, or intractable vomiting (defined as vomiting more than 3 times per day over the preceding week)
* Not currently using olanzapine for another medical condition or had previously used olanzapine for chronic nausea or for any pre-existing psychotic disorder
* Patient should not have had a previous blood clot at any time in the past
* No history of poorly controlled diabetes
* No symptomatic leptomeningeal disease or known brain metastases as these patients may have difficulty taking oral medications
* No history of hypersensitivity to olanzapine or megestrol acetate
* No COVID-19 infection in the past that, in the opinion of the treating physician, had left patients with compromised taste, which has not resolved at the time of registration
* Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done =\< 14 days prior to registration is required
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
* Estimated life expectancy of 3 months or longer
* Serum creatinine =\< 2.0 mg/dL
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 3 x upper limit of normal (ULN)
* Fasting glucose \< 140 mg/dL
* Granulocytes \> 1000/hpf
* No treatment with another antipsychotic agent, such as risperidone, quetiapine, clozapine, butyrophenone within 30 days of enrollment
* In order to complete the mandatory patient-completed measures, participants must be able to speak and/or read English or Spanish. Sites seeking to enroll Spanish-speaking patients should have access to Spanish speaking staff on site or through the use of a translation service to be able to conduct the informed consent discussion in Spanish, and to conduct the weekly phone calls
Exclusion Criteria:
* Psychiatric illness which would prevent the patient from giving informed consent
* Medical condition such as uncontrolled infection (including human immunodeficiency virus \[HIV\]), uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
* Patients who cannot swallow oral formulations of the agents
* Patients with impaired decision-making capacity (such as with a diagnosis of dementia or memory loss) are not eligible for this study
* No presence of a hormone-sensitive tumor, such as breast, endometrial, or prostate cancer (this exclusion criterion is intended to circumvent any confounding antineoplastic effects of megestrol acetate) DRUG: Olanzapine, DRUG: Megestrol Acetate, OTHER: Questionnaire Administration
Advanced Malignant Solid Neoplasm, Anorexia, Hematopoietic and Lymphoid Cell Neoplasm, Anklylosing Spondylitis, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Carcinoid Tumor, Cardiovascular, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Eye and Orbit, Gall Bladder, Head and Neck, Heart, Hodgkins Lymphoma, Ill - Defined Sites, Kaposis sarcoma, Kidney, Larynx, Leukemia, Not Otherwise Specified, Leukemia, Other, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Lymphoid Leukemia, Lymphoma, Melanoma, skin, Multiple Myeloma, Mycosis Fungoides, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Nose, Other, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Psychiatric Disorders, Rectum, Sarcoma, Small Intestine, Soft Tissue, Stomach, Throat, Thyroid, Unknown Sites, Urinary Bladder, Uterine (Endometrial), Vulva
UT Southwestern
Outpatient Treatment With Anti-Coronavirus Immunoglobulin (OTAC)
The primary objective of the Outpatient Treatment with Anti-Coronavirus Immunoglobulin (OTAC) (INSIGHT 012) trial is to compare the safety and efficacy of a single infusion of anti-COVID-19 hyperimmune intravenous immunoglobulin (hIVIG) versus placebo among adults with recently diagnosed severe acute respiratory syndrome - coronavirus 2 (SARS-CoV2) infection who do not require hospitalization. The primary endpoint of this double-blind randomized trial is a five-category ordinal outcome that assesses the participant's clinical status seven days after the infusion of hIVIG or placebo. 1. Asymptomatic and no limitations in usual activity due to COVID-19 2. Mild COVID-19 illness or minor limitations to usual activity 3. Moderate COVID-19 illness and with major limitations to usual activity 4. Severe COVID-19 or serious disease manifestation from COVID-19 5. Critical illness from COVID-19 or Death Two strata of participants will be identified for analysis purposes. Stratum 2 will be participants who receive direct-acting antivirals (DAAs) or other anti-SARS-CoV2 agents that are approved/available and recommended for use as part of standard of care (SOC), estimated to be about 20% of participants. Stratum 1 will be participants who do not receive this agents, estimated to be about 80% of participants.
Call 214-648-5005
studyfinder@utsouthwestern.edu, TIANNA.PETERSEN@UTSouthwestern.edu
Mamta Jain
ALL
18 Years and over
PHASE3
NCT04910269
STU-2021-0399
Inclusion Criteria:
* Clinical risk based on age ≥ 55 years or an adult (age ≥ 18 years) with an immunosuppressed condition.
* Positive test for SARS-CoV-2 within ≤5 days (if \>1 test, the first positive is within ≤5 days). Tests may include an institutional-based nucleic acid amplification test (NAAT), or any protocol-approved rapid test.
* Within ≤5 days from symptom onset, if symptomatic from current SARS-CoV-2 infection.
* Agrees to not participate in another clinical trial for the treatment or management of SARS-CoV-2 infection through Day 7, or until hospitalized or significant disease progression if prior to Day 7 (defined by ordinal category 4 or 5).
* Participant provides written informed consent prior to study procedures, and understands and agrees to adhere to planned study procedures through Day 28.
Ongoing immunosuppressive condition or immunosuppressive treatment, includes:
• Steroids equivalent to prednisone \> 10 mg/day for at least the last 28 days
• Rheumatologic or autoimmune disorder treated with a biologic or non-biologic immunosuppressive therapy
• Antirejection medicine after solid organ or stem cell transplantation
• Cancer treatment with systemic chemotherapy, biologic and/or cell-based therapy in the last 12 months
• Primary or acquired severe B- or T-lymphocyte immune dysfunction
• HIV infection
• Splenectomy or functional asplenia
Exclusion Criteria:
* Asymptomatic and had prior symptoms from the current infection that have now resolved (for \>24 hours).
* Asymptomatic and has received a vaccination for COVID-19 (≥1 dose).
* Undergoing evaluation for possible admission to hospital for medical management (this does not include evaluation of possible hospitalization for public health purposes).
* Evidence of pneumonia and/or hypoxia due to COVID-19 (NOTE: chest imaging is not required, but if available it should not show new infiltrates suggestive of pneumonia; hypoxia is defined by new oxygen supplementation or increase above pre-illness level).
* Prior receipt of immunoglobulin product or passive immune therapy for SARS-CoV-2 in the past 90 days (i.e., convalescent plasma, SARS-CoV-2 monoclonal antibodies, or any IVIG).
* Any of the following thrombotic or procoagulant conditions or disorders:
• acute coronary syndrome, cerebrovascular syndrome, pulmonary embolism, or deep venous thrombosis within 28 days of randomization.
• prothrombin gene mutation 20210, homozygous Factor V Leiden mutations, antiphospholipid syndrome, or a deficiency in antithrombin III, protein C, or protein S. * History of hypersensitivity to blood, plasma or IVIG excipients. * Known immunoglobulin A (IgA) deficiency or anti-IgA antibodies. * In the opinion of the investigator, any condition for which participation would not be in the best interest of the participant or that could prevent or confound protocol assessments.
BIOLOGICAL: Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG), OTHER: Placebo
COVID, SARS-CoV2 Infection, Covid19
immunotherapy, hIVIG, early treatment
UT Southwestern; Parkland Health & Hospital System
PROGRESS: Management of Moderate Aortic Stenosis by Clinical Surveillance or TAVR (PROGRESS)
This study objective is to establish the safety and effectiveness of the Edwards SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA Transcatheter Heart Valve systems in subjects with moderate, calcific aortic stenosis. Following completion of enrollment, subjects will be eligible for enrollment in the continued access phase of the trial.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Ruth.Ikpefan@UTSouthwestern.edu
Anthony Bavry
ALL
65 Years and over
NA
NCT04889872
STU-2024-0557
Key
• 65 years of age or older at time of randomization
• Moderate aortic stenosis
• Subject has symptoms or evidence of cardiac damage/dysfunction
• The subject or subject's legal representative has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent. Key
• Native aortic annulus size unsuitable for the THV
• Anatomical characteristics that would preclude safe transfemoral placement of the introducer sheath or safe passage of the delivery system
• Aortic valve is unicuspid or non-calcified
• Bicuspid aortic valve with an aneurysmal ascending aorta \> 4.5 cm or severe raphe/leaflet calcification
• Pre-existing mechanical or bioprosthetic aortic valve
• Severe aortic regurgitation
• Prior balloon aortic valvuloplasty to treat severe AS
• LVEF \< 20%
• Left ventricular outflow tract calcification that would increase the risk of annular rupture or significant paravalvular leak post-TAVR
• Cardiac imaging evidence of intracardiac mass, thrombus, or vegetation
• Coronary or aortic valve anatomy that increases the risk of coronary artery obstruction post-TAVR
Inclusion Criteria:
• 65 years of age or older at time of randomization
• Moderate aortic stenosis
• Subject has symptoms or evidence of cardiac damage/dysfunction
• The subject or subject's legal representative has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent. Key
Exclusion Criteria:
• Native aortic annulus size unsuitable for the THV
• Anatomical characteristics that would preclude safe transfemoral placement of the introducer sheath or safe passage of the delivery system
• Aortic valve is unicuspid or non-calcified
• Bicuspid aortic valve with an aneurysmal ascending aorta \> 4.5 cm or severe raphe/leaflet calcification
• Pre-existing mechanical or bioprosthetic aortic valve
• Severe aortic regurgitation
• Prior balloon aortic valvuloplasty to treat severe AS
• LVEF \< 20%
• Left ventricular outflow tract calcification that would increase the risk of annular rupture or significant paravalvular leak post-TAVR
• Cardiac imaging evidence of intracardiac mass, thrombus, or vegetation
• Coronary or aortic valve anatomy that increases the risk of coronary artery obstruction post-TAVR
DEVICE: SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA
Aortic Stenosis, Calcific, Aortic Valve Stenosis, Cardiovascular
Transcatheter aortic valve replacement (TAVR), SAPIEN 3, SAPIEN 3 Ultra, SAPIEN 3 Ultra RESILIA, Moderate aortic stenosis, Aortic stenosis, Transcatheter heart valve
UT Southwestern
TReatment for ImmUne Mediated PathopHysiology (TRIUMPH)
TReatment for ImmUne Mediated PathopHysiology (TRIUMPH) is a multi-center, three arm, randomized, controlled trial of immunosuppressive therapy for children with acute liver failure. The study will determine if suppressing inflammatory responses with either corticosteroids or equine anti-thymocyte globulin therapy improves survival for children with this rare, life-threatening condition.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Evelyn.Rojo@UTSouthwestern.edu
Norberto Rodriguez-Baez
ALL
1 Year to 18 Years old
PHASE2
NCT04862221
STU-2022-0154
Inclusion Criteria:
• Patient with liver injury of ≤ 6 weeks duration resulting in an international normalized ratio (INR) of ≥ 1.5 and \< 2.0 (not corrected by vitamin K) with evidence of hepatic encephalopathy (HE) or INR ≥ 2.0 without evidence of HE.
• Age is greater than or equal to 1 year and less than 18 years of age.
• Patient or their legally authorized representative(s) (LAR) must consent (and assent, if applicable) to be in the study and must have signed and dated an approved informed consent form which conforms to federal and institutional guidelines.
• Females of reproductive potential should not plan on conceiving children during the study and must agree to use a medically accepted form of contraception.
Exclusion Criteria:
• Evidence of active infection with Hepatitis A, B, C, E or evidence of acute herpes simplex virus (HSV) or adenovirus infection
• Travel within the past 3 months to an area highly endemic for Hepatitis E
• Diagnosis of hemophagocytic lymphohistiocytosis (HLH) Note: Patients with a history of consanguinity and/or central nervous system (CNS) dysfunction that is exaggerated compared to the degree of liver dysfunction (as judged by the site investigator) will not be enrolled until results of rapid genetic testing are available. Turn-around time for genetic testing results is estimated to be 72-96 hours.
• Aplastic anemia as defined by standardized criteria \[1\] diagnosed prior to enrollment
• Diagnosis of autoimmune Hepatitis (AIH)
• Diagnosis of acute Wilson disease
• Diagnosis of inborn error of metabolism Note: Suspicion of metabolic disease is not an exclusion for entry into the Trial.
• Diagnosis of acute drug or toxin-induced liver injury
• History of recreational drug use within the past 4 weeks
• Therapy with an immunosuppressive agent, including chemotherapy, biological therapies or an experimental drug or device within the past 6 weeks
• Liver injury due to ischemia
• Liver dysfunction diagnosed more than 6 weeks prior to screening
• History of allergy to horse dander
• Sepsis
• Imminent risk of death as judged by the clinical site investigator, including but not limited to; signs of cerebral herniation at the time of enrollment and presence of intractable arterial hypotension
• Solid organ or stem cell transplant recipient
• Pregnant or breast-feeding at the time of proposed study entry
• Clinical AIDS or HIV positive
• History of any form of malignant neoplasm and/or tumors treated within five years prior to study entry (other than non-melanoma skin cancer or in situ cervical cancer) or where there is current evidence of recurrent or metastatic disease
• Received a live-virus vaccine within 4 weeks of study entry
• Patients with positive respiratory secretion testing for respiratory viral infection including SARS-CoV-2, influenza and respiratory syncytial virus only if they also have declining respiratory function
• Psychiatric or addictive disorders that would preclude obtaining informed consent/assent
• Patient is unwilling or unable to adhere with study requirements and procedures
• Currently receiving other experimental therapies
DRUG: High-dose methylprednisolone, DRUG: Equine anti-thymocyte globulin, DRUG: Prednisolone, DRUG: Placebo for prednisolone, DRUG: Placebo for infusions, DRUG: Diphenhydramine, DRUG: Methylprednisolone
Acute Liver Failure, Fulminant Hepatic Failure, Hepatic Encephalopathy, Acute Liver Injury, Immune Dysregulation, Liver
hepatic insufficiency, liver diseases, liver failure, anti-thymocyte agents
Children’s Health
APOLLO: A Randomized Phase II Double-Blind Study of Olaparib Versus Placebo Following Curative Intent Therapy in Patients With Resected Pancreatic Cancer and a Pathogenic BRCA1, BRCA2 or PALB2 Mutation
This phase II trial investigates how well the addition of olaparib following completion of surgery and chemotherapy works in treating patients with pancreatic cancer that has been surgically removed (resected) and has a pathogenic mutation in BRCA1, BRCA2, or PALB2. Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep tumor cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Timothy Brown
ALL
18 Years and over
PHASE2
NCT04858334
STU-2023-0968
Inclusion Criteria:
* STEP 0 (PRE-REGISTRATION) INCLUSION CRITERIA
* Patient must be \>= 18 years of age on day of consent
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Patient must have a diagnosis of pancreatic cancer and have successfully undergone a curative intent surgical resection and must have no evidence of recurrent disease as determined by the investigator
* NOTE: This includes patients with adenocarcinoma, acinar carcinoma, squamous cell carcinoma adenosquamous and variants thereof. Patients with neuroendocrine tumors are excluded from enrolling
* Patient must (1) be planning to receive, (2) be receiving or (3) have received at least three combined months (i.e., 12 weeks) of perioperative (neoadjuvant, adjuvant or a combination of both) systemic, multi-agent chemotherapy. Patients may have had up to 6 months of perioperative systemic therapy as deemed appropriate by their primary treating medical team (patients can have received radiation or chemoradiation in addition to this 6 month course)
* Patient must be no more than 12 weeks from their most recent treatment (this may be chemotherapy, radiotherapy or surgery)
* Patient must have a known pathogenic or likely pathogenic germline or somatic mutation in BRCA1, BRCA2, or PALB2, as determined by a Clinical Laboratory Improvement Amendments (CLIA) certified or equivalently-accredited laboratory. Mutations must be considered pathogenic or likely pathogenic by a reference database such as ClinVar or OncoKb.org
* STEP 1 (RANDOMIZATION) INCLUSION CRITERIA
* Patient must have met the eligibility criteria outlined above
* Patient must have undergone at least 3 combined months (i.e., 12 weeks) of perioperative (neoadjuvant, adjuvant or a combination of both) systemic, multi-agent chemotherapy. Patients may have had up to 6 months of perioperative systemic therapy as deemed appropriate by their primary treating medical team (patients can have received radiation or chemoradiation in addition to this 6 months course)
* Central expert reviewer must have determined the patient eligible for randomization after review of local genetic testing reports
* If mutation in BRCA1, BRCA2 or PALB2 was identified in tumor tissue and the patient has not previously undergone germline testing, the patient must agree to undergo germline testing
* Patient must have no evidence of recurrent or metastatic pancreatic cancer at the time of randomization as documented by baseline scans obtained =\< 4 weeks prior to Step 1 randomization
* Patient must not have previously had evidence of progressive pancreatic cancer while receiving platinum-based therapy
* Patient must be \>= 21 days (three weeks) from their last treatment (including chemotherapy radiotherapy or surgery) but =\< 84 days (twelve weeks) from their last treatment at the time of Step 1 randomization. Patients who have received neoadjuvant and/or adjuvant radiotherapy are eligible
* Patient must have recovered from any adverse events due to prior anti-cancer therapy (i.e., have no residual toxicities \> grade 1 with the exception of alopecia and/or neuropathy)
* Patient must not be receiving any other investigational agents at the time of Step 1 randomization and while on protocol treatment
* Patient must not have any history of allergic reactions attributed to compounds of similar chemical or biological composition to olaparib
* Patient must not have any personal history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
* Patient must not have any uncontrolled gastrointestinal disorder that would, in the opinion of the investigator, interfere with the ingestion or absorption of olaparib
* Patient must not be pregnant or breast-feeding due the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to Step 1 randomization to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for 6 months after the last dose of protocol treatment for female patients and for 3 months after the last dose of protocol treatment for male patients. Patients must also not donate sperm while on protocol treatment and for 3 months after the last dose of protocol treatment. Patients must also not breast-feed while on protocol treatment and for 1 month after the last dose of protocol treatment
* Leukocytes \>= 3,000/mcL (obtained =\< 28 days prior to Step 1 randomization)
* Absolute neutrophil count \>= 1,500/mcL (obtained =\< 28 days prior to Step 1 randomization)
* Platelets \>= 100,000/mcL (obtained =\< 28 days prior to Step 1 randomization)
* Hemoglobin \>= 9.0 g/dL with no blood transfusion in the past 28 days (obtained =\< 28 days prior to Step 1 randomization)
* Total bilirubin =\< 1.5 institutional upper limit of normal (ULN) except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome may enroll if direct bilirubin =\< 2.5 x ULN of the direct bilirubin (obtained =\< 28 days prior to Step 1 randomization)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 institutional ULN (obtained =\< 28 days prior to Step 1 randomization)
* Creatinine =\< 1.5 institutional ULN OR calculated Cockcroft Gault creatinine clearance \> 50 mL/min/1.73 m\^2 (obtained =\< 28 days prior to Step 1 randomization)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patient must not have resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g. unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT \[QTc\] prolongation \> 500 ms, electrolyte disturbances, etc.) or have congenital long QT syndrome
* Concomitant use of known potent CYP3A4/5 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir is prohibited
* Patients who are being actively treated for an ongoing concurrent malignancy are ineligible, with the exception of those receiving adjuvant hormone therapies and those receiving topical therapies for skin cancers
* Patient must not have, in the opinion of the investigator, any other concurrent medical condition that would prevent the patient from complying with the study procedures
* Patient must not be considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent
* Patient must have the ability to understand and the willingness to sign a written informed consent document, or have legally authorized representative provide authorization to participate
* Patient must not have had major surgery within 2 weeks prior to Step 1 randomization and patients must have recovered from any effects of any major surgery PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, DRUG: Olaparib, DRUG: Placebo Administration
Pancreatic Acinar Cell Carcinoma, Pancreatic Adenosquamous Carcinoma, Pancreatic Squamous Cell Carcinoma, Resectable Pancreatic Acinar Cell Carcinoma, Resectable Pancreatic Adenocarcinoma, Resectable Pancreatic Adenosquamous Carcinoma, Resectable Pancreatic Carcinoma, Pancreas
Adjuvant, Resected Pancreatic cancer, Pancreatic adenocarcinoma, BRCA1, BRCA2, BRCA1 mutation, BRCA2 mutation, PALB2 PALB2 mutation, PARP inhibitor, PARP, Olaparib
UT Southwestern; Parkland Health & Hospital System
CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma
This phase I/II trial evaluates the best dose, side effects and possible benefit of CBL0137 in treating patients with solid tumors, including central nervous system (CNS) tumors or lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Drugs, such as CBL0137, block signals passed from one molecule to another inside a cell. Blocking these signals can affect many functions of the cell, including cell division and cell death, and may kill cancer cells.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
ALL
12 Months to 21 Years old
PHASE1
NCT04870944
STU-2023-0600
Inclusion Criteria:
* Parts A and B: Patients must be \>= 12 months and =\< 21 years of age at the time of study enrollment
* Patients must have had histologic verification of malignancy at original diagnosis or relapse, except in patients with diffuse intrinsic brain stem tumors, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers, including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
* Part A: Patients with relapsed or refractory solid tumors or lymphoma, including patients with CNS tumors or known CNS metastases (including untreated or progressive) are eligible
* Part B: Patients with progressive or recurrent DIPG (diagnosed by biopsy or imaging characteristics) and other H3 K27-altered DMG previously treated with radiation therapy
* Part A: Patients must have either measurable or evaluable disease
* Part B: Patients must have measurable disease
* Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
* Patients must have a performance status corresponding to Easter Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age. Patients must have a Karnofsky or Lansky score \>= 50%
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
* Solid tumor patients: \>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
* Anti-cancer agents not known to be myelosuppressive (eg, not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
* Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid. Patients with CNS tumors receiving corticosteroids must have been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell Infusions (with or without total body irradiation \[TBI\]):
* Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \>= 84 days after infusion and no evidence of graft versus host disease (GVHD)
* Autologous stem cell infusion including boost infusion: \>= 30 days
* Cellular therapy: \>= 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.)
* Radiation therapy \[XRT\]/external beam irradiation including protons: \>= 14 days after local XRT; \>= 150 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, I-131 metaiodobenzylguanidine \[131I MIBG\]): \>= 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have received prior exposure to CBL0137
* For patients with solid tumors without known bone marrow involvement:
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
* For patients with solid tumors without known bone marrow involvement:
* Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a creatinine based on age/sex as follows (performed within 7 days prior to enrollment unless otherwise indicated):
* Age: Maximum serum creatinine (mg/dL)
* 1 to \< 2 years: 0.6 (male); 0.6 (female)
* 2 to \< 6 years: 0.8 (male); 0.8 (female)
* 6 to \< 10 years: 1 (male); 1 (female)
* 10 to \< 13 years: 1.2 (male); 1.2 (female)
* 13 to \< 16 years: 1.5 (male); 1.4 (female)
* \>= 16 years: 1.7 (male); 1.4 (female)
* Patients with solid tumors:
* Bilirubin (sum of conjugated + unconjugated or total) =\< 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with solid tumors:
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L (performed within 7 days prior to enrollment unless otherwise indicated)
* Shortening fraction of \>= 27% by echocardiogram (performed within 7 days prior to enrollment unless otherwise indicated) or
* Ejection fraction of \>= 50% by gated radionuclide study (performed within 7 days prior to enrollment unless otherwise indicated)
* Corrected QT (QTC) \< 480 msec (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with seizure disorder may be enrolled if seizures well controlled without the use of enzyme-inducing anti-convulsant agents. Well controlled is defined by no increase in seizure frequency in the prior 7 days
* Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]5) resulting from prior therapy must be =\< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
* Patients have consented to receive a central venous catheter prior to the administration of CBL0137. A central line is required for CBL0137 administration
Exclusion Criteria:
* Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control
* Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Patients who are currently receiving another investigational drug are not eligible
* Patients who are currently receiving other anti-cancer agents are not eligible (except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)
* Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
* Patients who are receiving drugs that are strong inducers or inhibitors of CYP3A4, CYP2B6 (e.g., carbamazepine) and CYP1A2 (e.g., ciprofloxacin, enoxacin, fluvoxamine, smoking) are not eligible. These agents are to be avoided for 7 days prior to the start of CBL0137 and for the duration of the protocol therapy. Sensitive substrates of CYP2D6 (e.g., atomoxetine, desipramine, dextromethorphan, eliglustat, nebivolol, nortriptyline, perphenazine, tolterodine, R-venlafaxine) should also be avoided for the duration protocol therapy
* Patients who are receiving drugs associated with a known risk of Torsades de Pointes (TdP) are not eligible. Drugs associated with known risk of Torsades de Pointes (TdP) are to be avoided for 7 days prior to the start of CBL0137 and for duration of the protocol therapy
* Patients with known peripheral vascular disease are excluded
* Patients with a history of pro-thrombotic disorder are not eligible
* Patients who have an uncontrolled infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspirate, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Echocardiography, DRUG: FACT Complex-targeting Curaxin CBL0137
Diffuse Midline Glioma, H3 K27-Altered, Metastatic Malignant Neoplasm in the Central Nervous System, Recurrent Diffuse Intrinsic Pontine Glioma, Recurrent Diffuse Midline Glioma, H3 K27-Altered, Recurrent Lymphoma, Recurrent Malignant Solid Neoplasm, Recurrent Primary Malignant Central Nervous System Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Primary Malignant Central Nervous System Neoplasm, Bones and Joints, Brain and Nervous System, Lymphoma
Children’s Health
CHIlled Platelet Study "CHIPS" (CHIPS)
A phase 3 randomized partial blind storage duration ranging study in patients undergoing complex cardiac surgery that will compare the transfusion of cold stored platelets to standard room temperature stored platelets. The primary objective is to establish that cold stored platelets have a non-inferiority (or superiority) to room temperature platelets.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Erryn.Hopson@UTSouthwestern.edu
Philip Greilich
All
0 Days to 84 Years old
Phase 3
NCT04834414
STU-2021-0445
Inclusion Criteria:
• Viable neonates ≥ 3 kg at time of enrollment (as defined in Section 4.1) OR age greater than 28 days and less than 85 years of age at time of consent; AND
• Planned complex cardiac surgery with planned use of cardiopulmonary bypass, with an expectation of bleeding requiring platelet transfusion.
Exclusion Criteria:
• Expected order for washed or volume reduced platelets
• Patient with known anti-platelet antibodies
• Platelet transfusion refractoriness due to anti-HLA antibodies
• Known or suspected pregnancy
• Previously randomized in this study
• Conscious objection or unwillingness to receive blood products
• Known IgA deficiency
• Known congenital platelet disorder
• Known congenital bleeding disorder
• Planned post-operative extracorporeal membrane oxygenation (ECMO), ventricular assist device (VAD), and/or continuous renal replacement therapy (CRRT)/ hemodialysis
• Patients intended to receive whole blood either intra-operative or post-operative for bleeding
• Platelet transfusion (of any type) within 24 hours prior to the date of surgery
• Pre-operative thrombocytopenia, defined as platelet count <75x10(9)/L, based on the most recent labs completed within 72 hours prior to the date of surgery.
Biological: Cold Stored Platelets, Biological: Room Temperature Platelets
Acute Blood Loss, Cardiovascular
platelets, cold-stored platelets, bleeding, hemostasis, complex cardiac surgery
UT Southwestern; Children’s Health; Parkland Health & Hospital System
A Trial of Robotic Versus Open Hysterectomy Surgery in Cervix Cancer (ROCC)
This is a randomized controlled trial to compare survival for patients who undergoe robotic assisted laparoscopy versus open hysterectomy and lymph node assessment for the treatment of early stage cervical cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Elizabeth Stock
FEMALE
18 Years and over
NA
NCT04831580
STU-2022-0545
Inclusion Criteria:
• Patient must have histologically confirmed adenocarcinoma (usual/classic/NOS), squamous cell carcinoma, adenosquamous carcinoma (Including glassy cell)
• Patient must be FIGO Stage IA2, IBI, IB2 (2018 staging) without evidence of definitive parametrial, vaginal, nodal or distant metastases on exam or imaging. Patients with tumor size less than or equal to 4 cm confirmed on MRI prior to randomization are eligible.
• Patient must have uterine size \<12 cm AND felt to be appropriate for vaginal delivery of the specimen per investigator.
• Patient must be suitable surgical candidate with preoperative assessments such as labs and EKG performed per institutional standard and agree to be randomized to undergo open or robotic radical (or simple) hysterectomy. NOTE: Simple hysterectomy will be allowed in patients who meet the following criteria:
• pelvic MRI must demonstrate a maximal tumor size of 2 cm or less AND
• less than 50% stromal invasion on MRI if tumor present or less than 10 mm of stromal invasion if an excisional (cold knife or LEEP) has been performed. Submission of source documents in the GOG Partners Source Document Portal will be required prior to randomization for review and confirmation of simple hysterectomy being met (see Section 6.0 for instructions).
• Patient must be age 18 years or older.
• Patient must have ECOG performance status 0-1.
• Patient must have a negative urine pregnancy test within 30 days of surgery in pre-menopausal women.
• Patient must have signed an approved informed consent and authorization permitting the release of personal health information.
Exclusion Criteria:
• Patients with any tumor histology other than those listed above, specifically excluding the following histologies: neuroendocrine, other adenocarcinoma (gastric type, endometrioid, clear cell, serous, signet ring, minimal deviation)
• Patients with FIGO stage 1A1, IB3, II-IV (2018 staging).
• Patient with inability to receive an MRI.
• Patients with a tumor size greater than 4cm or on MRI confirmed prior to randomization are excluded. Patients with definite evidence of vaginal/parametrial involvement on MRI are excluded; if MRI findings are not definitive, then clinical examination must also not reveal parametrial or vaginal extension).
• Patients with evidence of metastatic disease (imaging or histologically positive lymph nodes).
• Patients with a history of prior pelvic or abdominal radiotherapy.
• Patients with a prior malignancy \< 5 years from enrollment with the exception of non-melanoma skin cancer.
• Patients who are unable to withstand prolonged lithotomy or steep trendelenberg.
• Patient compliance and geographic proximity that do not allow adequate follow-up.
• Patients with poorly controlled HIV with CD4 counts \<500.
DEVICE: da Vinci, OTHER: open surgery
Cervical Cancer, Cervix
UT Southwestern; Parkland Health & Hospital System
Doravirine Versus Integrase Inhibitors on Backbone of Emtricitabine and Tenofovir Alafenamide in HIV
This research application will explore the impact of the Non-nucleoside reverse transcriptase inhibitor (NNRTI) doravirine in the setting of established Nucleoside reverse transcriptase inhibitors (NRTIs) backbone \[Tenofovir alafenamide (TAF) / Emtricitabine (FTC) as a possible therapeutic strategy to minimize the detrimental impact of ART-related toxicities on metabolism and instigators of atherosclerosis. Given the possible favorable role of NNRTI in pathogenesis of HIV-related dyslipidemia and cardiovascular disease (CVD), this research will provide mechanistic insights into HIV pathogenesis and safety data regarding doravirine (DOR). These data may promote DOR as a robust "HDL friendly" and "metabolism friendly", therapeutic agent that may attenuate morbidity in chronic treated HIV infection. Towards this aim, the investigators will study DOR-related effects on HDL (HDL-C levels and function) and ex vivo assays that determine key molecular determinants of atherogenesis.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Theodoros.Kelesidis@UTSouthwestern.edu
Theodoros Kelesidis
MALE
18 Years to 70 Years old
EARLY_PHASE1
NCT04820933
STU-2023-0724
Inclusion Criteria:
* 18 years of age or older
* Cases: Chronically infected and on anti-retroviral therapy with suppressed viremia for at least 3 months (viral RNA \<50 copies per ml)
* On stable antiretroviral therapy for \>6 months with Genvoya (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg; E/C/F/TAF) 2) Biktarvy (bictegravir 50 mg/ emtricitabine 200 mg/tenofovir alafenamide 25 mg; B/F/TAF).
* Dyslipidemia (Defined based on use of lipid lowering medications or abnormal baseline lipids (total cholesterol, triglycerides, high density lipoprotein): Rationale: Enrolling participants with dyslipidemia will determine whether switching from TAF/FTC/integrase inhibitor regimen to TAF/FTC/doravirine regimen will directly improve the lipids over 3 months within the same participant.
* Adequate renal function determined by the Cockcroft-Gault formula for creatinine clearance (\>60 mL/min/1.73 m2
* Able and willing to provide written consent
Exclusion Criteria:
* • Pregnancy
* Hepatitis; no evidence of acute hepatitis in the prior 30 days
* History of severe renal impairment (eGFR \< 30 ml/min/1.73 m2)
* History of severe or recent cardiac event
* Current alcoholism or IV drug abuse
* Use of systemic immunomodulatory medications (e.g. steroids) within 4 weeks of enrollment
* Anemia precluding safe donation of blood (For men, anemia is typically defined as hemoglobin level of less than 13.5 gram/100 ml and in women as hemoglobin of less than 12.0 gram/100 ml).
* Use of any investigational products within 4 weeks of enrollment
* Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study requirements. Such conditions may include, but are not limited to, current or recent history of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, or cerebral disease.
* Subjects who are on medications that are strong inducers of CYP3A (as these may decrease the efficacy of Stribild or Genvoya). Examples include phenobarbital, phenytoin, carbamazepine, and rifampin.
* Subjects who are on medications that are cleared by CYP3A and that may be toxic with elevated drug levels (examples include Cisapride, ergotamine, Pimozide, Lurasidone, Lovastatin, and Simvastatin). DRUG: Doravirine 100 Mg
HIV I Infection, Cardiovascular Risk Factor, Lipid Metabolism Disorders, Heart, Other
HIV, Antiretroviral therapy, Cardiovascular disease
UT Southwestern; Parkland Health & Hospital System
A Study to Evaluate DAY101 in Pediatric and Young Adult Patients With Relapsed or Progressive Low-Grade Glioma and Advance Solid Tumors (FIREFLY-1)
FIREFLY-1 is a Phase 2, multi center, open-label study to evaluate the safety and efficacy of oral pan-RAF inhibitor DAY101 in pediatric, adolescent, and young adult patients with recurrent or progressive low-grade glioma or an advanced solid tumor harboring a known BRAF alteration.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
All
6 Months to 25 Years old
Phase 2
NCT04775485
STU-2022-0878
Inclusion Criteria:
• Age 6 months to 25 years with:
• Arms 1 & 2: a relapsed or progressive LGG with documented known activating BRAF alteration
• Arm 3: locally advanced or metastatic solid tumor with documented known or expected to be activating RAF fusion
• Confirmation of histopathologic diagnosis of LGG and molecular diagnosis of activating BRAF alteration
• Must have received at least one line of systemic therapy and have evidence of radiographic progression
• Must have at least 1 measurable lesion as defined by RANO (Arms 1 & 2) or RECIST v1.1 (Arm 3) criteria
Exclusion Criteria:
• Patient's tumor has additional previously-known activating molecular alterations
• Patient has symptoms of clinical progression in the absence of radiographic progression
• Known or suspected diagnosis of neurofibromatosis type 1 (NF-1)
• Other inclusion/exclusion criteria as stipulated by protocol may apply
Drug: DAY101
Low-grade Glioma, Advanced Solid Tumor, Brain and Nervous System
Children’s Health
DALY II USA/ MB-CART2019.1 for DLBCL
DALY II USA is a phase II, multi-center, single arm study to evaluate the efficacy, safety, and pharmacokinetics of zamtocabtagene autoleucel (MB-CART2019.1) in patients with relapsed and/or refractory diffuse large B cell lymphoma (DLBCL) after receiving at least two lines of therapy. Additional cohorts include subjects with B-cell primary or secondary central nervous system (CNS) lymphoma (PCNSL) and (SCNSL), mantle cell lymphoma (MCL) and Richter's transformation (RT) after receiving at least one line of therapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Farrukh Awan
ALL
18 Years and over
PHASE2
NCT04792489
STU-2022-0110
Inclusion Criteria:
* Histologically confirmed B-cell non-Hodgkin's lymphoma:
* DLBCL DLBCL or associated subtype, defined by WHO 2016 classification:
* DLBCL not otherwise specified (NOS)
* High-grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements
* High-grade B cell lymphoma (NOS)
* Primary mediastinal (thymic) large B cell lymphoma
* Transformed lymphoma (e.g., transformed follicular, or marginal zone lymphoma, follicular lymphoma (FL Grade 3)
* CNS Cohort only: B-cell primary or secondary central nervous system lymphoma (PCNSL or SCNSL)
* Mantle Cell Lymphoma (MCL) Cohort: Histologically confirmed MCL determined by overexpression of cyclin D1 or presence of t(11;14) (q13; q32) translocation
* Richter's Transformation (RT) Cohort: Histologically confirmed Richter's transformation (RT) to a diffuse large B-cell lymphoma (DLBCL) subtype from underlying CLL (clonally related)
* Relapsed or refractory disease is defined for DLBCL (and associated subtypes) population as failure of 2 or more lines of chemotherapy including rituximab or equivalent and anthracycline and either having failed autologous stem cell transplant (ASCT), or ineligible, not intended for or not consenting to ASCT
* Chemotherapy-refractory disease is defined as persistent disease after last line of therapy or relapsed or persistent disease after prior ASCT for lymphoma
* Disease relapse in subjects without prior ASCT is defined as relapse of disease after the last dose of most recent therapy regimen
* CNS Cohort: Subjects with relapsed/refractory PCNSL that have failed (or unable to tolerate) at least first-line therapy.
* No contraindications for MRI evaluation
* CNS Cohort: Subjects with SCNSL must have relapsed or refractory disease after having received at least one prior line of systemic therapy
* Prior lines of systemic therapy should include an anti-CD20 monoclonal antibody and anthracycline containing chemotherapy regimen and/or with or without an autologous stem cell transplant
* No contraindications for MRI evaluation
* MCL Cohort: Subjects with relapsed/refractory disease after at least one prior systemic treatment, that must include:
* Cytotoxic rituximab-based chemotherapy regimen (eg, rituximab bendamustine, R-CHOP, R-DHAP, R-ARA-C) AND
* BTK inhibitor
* RT Cohort: Subject must have relapsed/refractory disease after at least one prior systemic treatment following Richter's Transformation
* Age ≥18 years
* Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening. ECOG performance status of 2 at screen is allowed if the decrease in performance status is due to lymphoma
* Measurable disease according to Lugano 2014 criteria for assessing FDG-PET/CT in systemic lymphoma (Cheson et al, 2014). Measurable disease according to IPCG criteria will be assessed by brain/spine MRI for CNS disease
* Subject must have a tumor biopsy sample (at least 16 unstained slides of tissue or tissue block) from the most recent relapse available prior to MB-CART2019.1 infusion. If medically not feasible to obtain a biopsy from the most recent relapse and for cases when the amount of tissue is limited, the sponsor should be consulted, to confirm adequacy of the sample for study required analyses
* No clinical suspicion of central nervous system (CNS) lymphoma (not applicable to CNS cohort)
* If the subject has history of CNS disease (not applicable to CNS cohort), then he/she must have no signs or symptoms of CNS disease, have no active disease on magnetic resonance imaging (MRI), have no large cell lymphoma present in cerebral spinal fluid (CSF), regardless of the number of white blood cells (WBCs)
* If has history of cerebral vascular accident (CVA), the CVA event must be greater than 12 months prior to leukapheresis. Any neurological deficits must be stable
* A creatinine clearance (as estimated by direct urine collection or Cockcroft-Gault Equation) \> 45mL/min
* Cardiac ejection fraction (EF) ≥ 45% as determined by an echocardiogram (ECHO) or Multigated Radionuclide Angiography (MUGA)
* Resting O2 saturation \>90% on room air
* Serum alanine aminotransferase (ALT) / aspartate aminotransferase (AST)\<5 times the Upper Limit of Normal (ULN) for age
* Total bilirubin \<1.5 mg/dl, except in individuals with Gilbert's syndrome
* Absolute neutrophil count (ANC) \> 1000/μL
* Absolute lymphocyte count \> 100/μL
* Platelet count \> 50,000/µL
* Estimated life expectancy of more than 3 months other than primary disease
Exclusion Criteria:
* Primary CNS lymphoma (not applicable to CNS cohort)
* Richter's transformed DLBCL arising from chronic lymphocytic leukemia (CLL) (not applicable to RT cohort)
* Unable to give informed consent
* Known history of infection with human immunodeficiency virus (HIV) or active hepatitis B (HBsAg positive). If there is a history of treated hepatitis B or hepatitis C, the viral load must be quantitative polymerase chain reaction (PCR) negative; antiviral prophylaxis is required if HBsAg negative and anti-HBc positive
* Known history of infection with hepatitis C virus (anti-HCV positive) unless viral load is undetectable per quantitative PCR and/or nucleic acid testing.
* Pharmacologically uncontrolled seizures.
* Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis, or other immunologic or inflammatory disease
* Presence of CNS disorder that, in the judgment of the investigator, may impair the ability to evaluate neurotoxicity. For CNS Cohort:
* Midline shift on MRI
* Abnormal high CSF opening pressure and or CSF protein \>150 mg/dL Recent (within 3 months) whole brain radiotherapy (WBRT)
* Active systemic fungal, viral, or bacterial infection
* Pregnant or breast-feeding woman
* Previous or concurrent malignancy with the following exceptions:
* Adequately treated basal cell or squamous cell carcinoma (adequate wound healing required prior to study entry)
* In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 2 years prior to the study
* Adequately treated breast or prostate carcinoma on hormonal therapies such as Lupron or tamoxifen and in clinical remission of ≥ 2 years
* A primary malignancy which has been completely resected / treated with curative intent and in complete remission of ≥ 2 years
* Severely immunocompromised subjects e.g., due to current treatment of non-neurologic autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus).
* Medical condition requiring prolonged use of systemic corticosteroids equivalent to prednisone \>10 mg/day. For CNS cohort: Up to 2 mg/day dexamethasone (or equivalence) may be allowed at any time, higher doses allowed up to 7 days prior to apheresis or after apheresis until lymphodepletion.
* History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment
* Concurrent radiotherapy (normal tissue sparing palliative radiotherapy allowed up to time of lymphodepletion). For systemic therapy, at least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed at the time of scheduled leukapheresis.
* Baseline dementia that would interfere with therapy or monitoring, determined using Immune Effector Cell-Associated Encephalopathy (ICE) Assessment at baseline
* History of severe immediate hypersensitivity reaction to any of the agents used in this study
* Refusal to participate in additional lentiviral gene therapy LTFU protocol
* Prior CAR-T therapy for any indication or systemic gene modifying therapy for B-cell lymphoma
* Prior allogeneic stem cell transplant for any indication
* Prior BITE antibodies for cancer therapy
* Prior T cell receptor-engineered T cell therapy BIOLOGICAL: zamtocabtagene autoleucel (MB-CART2019.1), DRUG: Cyclophosphamide, DRUG: Fludarabine, DRUG: Bendamustine
Refractory Diffuse Large B Cell Lymphoma (DLBCL), Relapsed Diffuse Large B Cell Lymphoma, High Grade B-cell Lymphoma (HGBCL), Primary Mediastinal B-cell Lymphoma (PMBCL), Transformed Lymphoma, Central Nervous System Lymphoma, Mantle Cell Lymphoma (MCL), Richter Transformation, Non-Hodgkins Lymphoma
CD19/CD20-directed CAR-T Cells, Zamtocabtagene autoleucel, B-Cell Non-Hodgkin Lymphoma, Primary Central Nervous System Lymphoma, Secondary Central Nervous System Lymphoma, NHL, PCNSL, SCNSL, Chimeric Antigen Receptor, CAR, CAR-T Cell, Autologous T Cell Therapy, Central Nervous System Neoplasms, Lymphoma, Lymphoma, Non-Hodgkin, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, MCL, RT, CLL, Immunotherapy, T cells, T cell infusion
UT Southwestern
Study With ABBV-CLS-484 in Participants With Locally Advanced or Metastatic Tumors
The study will assess the safety, PK, PD, and preliminary efficacy of ABBVCLS-484 as monotherapy and in combination with a PD-1 targeting agent or with a or a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). The trial aims to establish a safe, tolerable, and efficacious dose of ABBVCLS-484 as monotherapy and in combination. The study will be conducted in three parts. Part 1 Monotherapy Dose Escalation, Part 2 Combination Dose Escalation and Part 3 Dose Expansion (Monotherapy and Combination therapy). Part 1, ABBV-CLS-484 will be administered alone in escalating dose levels to eligible subjects who have advanced solid tumors. Part 2, ABBV-CLS-484 will be administered at escalating dose levels in combination with a PD-1 targeting agent or with a VEGFR TKI to eligible subjects who have advanced solid tumors. Part 3, ABBV-CLS-484 will be administered alone as a monotherapy at the determined recommended dose in subjects with locally advanced or metastatic, relapsed or refractory head and neck squamous cell carcinoma (HNSCC), relapsed or refractory non-small cell lung cancer (NSCLC), and advanced clear cell renal cell carcinoma (ccRCC). ABBV-CLS-484 will also be administered at the determined recommended dose in combination with a PD-1 targeting or with a VEGFR TKI agent in subjects with locally advanced or metastatic, HNSCC, NSCLC, MSI-H tumors refractory to PD-1/PD-L1, and advanced ccRCC.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Hans Hammers
ALL
18 Years and over
PHASE1
NCT04777994
STU-2023-0762
Inclusion Criteria:
* Must weigh at least 35 kilograms (kg).
* An Eastern Cooperative Oncology Group (ECOG) performance status \<= 2.
* Life expectancy of \>= 12 weeks.
* Laboratory values meeting protocol criteria.
* QT interval corrected for heart rate \< 470 msec (using Fridericia's correction), and no clinically significant electrocardiographic findings.
* Measurable disease defined by RECIST 1.1 criteria.
For Monotherapy and Combination Dose Escalation:
* Participants with histologically or cytologically proven metastatic or locally advanced tumors, for which no effective standard therapy exists, or where standard therapy has failed. Participants must have received at least 1 prior systemic anticancer therapy for the indication being considered.
For Monotherapy Dose Expansion only:
* Participants must have received at least 1 prior line containing PD-1/PD-L1 targeted therapy with a best response by RECIST v1.1 of CR/PR/stable (any duration) or stable disease (for greater than 6 months); AND
* Must have been previously treated with 1 or more prior lines of therapy in the locally advanced or metastatic setting with the following tumor types:
* Relapsed/refractory HNSCC
* Relapsed/refractory NSCLC
* Advanced ccRCC
For PD-1 Targeting Agent Combination Dose Expansion only:
* For the following tumor types, subject must have received at least 1 prior line containing PD-1/PD-L1 targeted therapy with response by RECIST v1.1 of CR/PR (any duration) or stable disease (for greater than 6 months):
* Relapsed HNSCC
* Relapsed NSCLC
* Relapsed Advanced ccRCC
* For the following tumor types, subject must have received at least 1 prior line containing PD-1/PD-L1 targeted therapy and have had disease progression with PD-1/PD-L1 targeted therapy:
* Locally Advanced or metastatic MSI-H tumors
For VEGFR TKI Combination Dose Expansion only:
* Relapsed advance ccRCC with no more than 1 prior VEGFR TKI
* Participants no recent history of hemorrhage, including hemoptysis, hematemesis, or melena
* Participants with poorly controlled hypertension are excluded.
Exclusion Criteria:
* Untreated brain or meningeal metastases (i.e., subjects with history of metastases are eligible provided they do not require ongoing steroid treatment and have shown clinical and radiographic stability for at least 28 days after definitive therapy)
* Unresolved Grade 2 or higher toxicities related to previous anticancer therapy except alopecia.
* Unresolved Grade 2 or higher peripheral neuropathy.
* History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
* Recent history (within 6 months) of congestive heart failure (defined as New York Heart Association, Class 2 or higher), ischemic cardiovascular event, pericarditis, or clinically significant pericardial effusion or arrythmia.
* Recent history (within 6 months) of Childs-Pugh B or C classification of liver disease.
* History of clinically significant medical and/or psychiatric conditions or any other reason that, in the opinion of the investigator, would interfere with the subject's participation in this study or would make the subject an unsuitable candidate to receive study drug.
* History of uncontrolled, clinically significant endocrinopathy.
* Known gastrointestinal disorders making absorption of oral medications problematic; subject must be able to swallow capsules.
* If treated with a PD-1/aPD-L1 targeting or other immune-oncology agents in the past, excluded if had prior pneumonitis, prior Grade 3 or higher immune mediated toxicity, hypersensitivity to administered drug or drug related toxicity requiring discontinuation.
* Active autoimmune disease requiring systemic treatment in past 2-years (exceptions for endocrinopathies, vitiligo or atopic conditions).
* History of solid organ transplant or allogeneic stem cell transplant.
* History of other malignancy, with the following exceptions:
* No known active disease present within \>= 3 years before first dose of study treatment and felt to be at low recurrence by investigator.
* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
* Adequately treated carcinoma in situ without evidence of disease.
* History of interstitial lung disease or pneumonitis.
* Major surgery \<= 28 days prior to first dose of study drug
* Known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection per local testing practices. DRUG: ABBV-CLS-484, DRUG: Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI), DRUG: Programmed Cell Death-1 (PD-1) Inhibitor
Advanced Solid Tumor Cancer, Cervix, Colon, Kidney, Lung/Thoracic, Ovary
Cancer, Tumor, anti-PD-1, ABBV-CLS-484, clear cell renal cell carcinoma (ccRCC), head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), relapsed or refractory (R/R), Microsatellite instability - high tumors (MSI-H), Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)
UT Southwestern
VITAS: Atezolizumab in Combination With Chemotherapy for Pediatric Relapsed/Refractory Solid Tumors
This trial is a multi-center, non-randomized, open-label Phase I/II study evaluating the feasibility and efficacy of vincristine, irinotecan, temozolomide, and atezolizumab in children with relapsed/refractory solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Arhanti Sadanand
ALL
6 Months to 30 Years old
PHASE1
NCT04796012
STU-2021-0606
Inclusion Criteria:
• Signed informed consent
• Relapsed or refractory solid tumor after at least one prior course of therapy.
• Hodgkin lymphoma or non-Hodgkin lymphoma are not permitted.
• Patients with CNS malignancy or asymptomatic CNS metastases may be enrolled, provided all of the following criteria are met. * No metastatic or primary disease affecting the brainstem, midbrain, pons, or cerebellum, or within 10 mm of optic nerve * No history of leptomeningeal disease * No history of intracranial or spinal cord hemorrhage * No evidence of progression of neurologic deficit, in the investigator's judgment, within 7 days prior to initiation of study medications.
• Must have histologically confirmed rhabdomyosarcoma (RMS) for RMS efficacy cohort.
• Age ≥ 6 months and ≤ 30 years
• Lansky Performance Status (patients \< 16 years old) or Karnofsky Performance Status (patients ≥ 16 years old) ≥ 50
• Ability to comply with the study protocol, in the investigator's judgment
• For RMS efficacy cohort, disease must be measurable as defined by RECIST v1.1.
• For the feasibility cohort, disease must be evaluable, but patients enrolled in the feasibility cohort will be prospectively assessed for measurable disease, RMS patients will also be included in the RMS efficacy cohort.
• Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation.
• Availability of a tumor specimen suitable for determination of PD-L1 status, either from initial diagnosis or from a recurrence.
• For PD-L1 staining to be performed at the central site, a formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 15 slides containing unstained, freshly cut, serial sections must be available along with an associated pathology report prior to study enrollment.
• Patients for whom the required number of slides are not available may still be eligible to enroll on study with PI approval
• For the RMS efficacy cohort, it will be required that at least 8 of 17 patients have PD-L1(+) tumor. PD-L1 status will be determined at time of enrollment for all patients. When the maximum allowable number of PD-L1(-) patients has been enrolled and treated on study, PD-L1 positivity will be required for all further enrolled patients.
• Staining will be performed in the central site CAP/CLIA-certified laboratory using the 22c3 antibody for immunohistochemical analysis
• PD-L1(+) status will be defined as staining on ≥1% of tumor cells or ≥1% of stroma.
• For the feasibility cohort, PD-L1 positivity is not required but will be performed centrally in all cases for exploratory biomarker studies.
• Adequate organ and marrow function as defined by the following laboratory values obtained within 21 days prior to initiation of study medication.
• For patients without known bone marrow involvement: * Absolute neutrophil count ≥ 1.0 x 10\^9 / L (1000/µL) without granulocyte colony-stimulating factor support (≥14 days after the last dose of a long-acting growth factor such as pegfilgrastim, or 7 days after short-acting growth factor) * Platelet count ≥ 75 x 10\^9 / L (75,000/µL) without transfusion in the last 7 days
• Patients with known bone marrow metastatic disease will be eligible for the study if they meet the following criteria: * Patients with documented liver metastases: AST and ALT ≤ 5 x ULN * Patients with documented liver or bone metastases: ALP ≤ 5 x ULN * Absolute neutrophil count (ANC) ≥ 750/mm\^3 * Platelet count ≥ 50,000/mm\^3 (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions) * These patients will not be evaluable for hematologic toxicity. At least 4 of 6 patients in the feasibility cohort must be evaluable for hematologic toxicity. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity.
• Total bilirubin ≤1.5 x upper limit of normal (ULN) for age (Patients with known Gilbert disease: serum bilirubin ≤ 3 x ULN)
• AST (SGOT) and ALT (SPGT) ≤ 2.5 x ULN for age
• Serum albumin ≥ 25 g/L (2.5 g/dL)
• Creatinine ≤ 1.5 x ULN for age or creatinine clearance (or radioisotope glomerular filtration rate) ≥ 70 mL/min/1.73 m2
• Left ventricular ejection fraction ≥ 50% or shortening fraction ≥ 30%
• Hemoglobin ≥ 90 g/L (9 g/dL)
• Patients may be transfused to meet this criterion.
• For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• Negative HIV and hepatitis B surface antigen (HBsAg) tests at screening
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below:
• Women must remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for 5 months after the final doses of atezolizumab, vincristine, and temozolomide. Women must refrain from donating eggs during this same period.
• A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus), regardless of sexual orientation or marital status.
• Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception.
• For men who are not surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
• With a female partner of childbearing potential who is not pregnant, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of less 1% per year during the treatment period and for 5 months after the final doses of atezolizumab, irinotecan, and temozolomide. Men must refrain from donating sperm during this same period.
• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception
Exclusion Criteria:
• Pregnancy or breast-feeding:
• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of study treatment
• Women of childbearing potential must have a negative serum pregnancy test result within 21 days prior to initiation of study treatment.
• Medical conditions that are excluded:
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Guillain-Barré syndrome, multiple sclerosis, or Kawasaki syndrome with the following exceptions: * Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study. * Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study. * Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met at study initiation: (1) Rash must cover less 10% of body surface area, (2) Disease is well controlled at baseline and requires only low-potency topical corticosteroids, (3) No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
• Uncontrolled or symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected serum calcium \> ULN)
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) * Patients with indwelling catheters (e.g., PleurX®) are allowed.
• Uncontrolled tumor-related pain * Patients requiring pain medication must be on a stable regimen at study entry for at least 2 weeks. Intermittent use of as-needed medication is allowed during this period.
• Clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (at the discretion of the treating physician)
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan * History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
• History of severe asthma or uncontrolled asthma
• Dyspnea at rest or requirement for supplemental oxygen
• Uncontrolled seizures. Patients taking a stable dose of anticonvulsants (for 2 weeks) are permitted, as long as they are not strong inducers or inhibitors of CYP3A4.
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications in the opinion of the treating investigator
• Washout periods from prior therapies:
• Myelosuppressive chemotherapy or radiotherapy within 21 days prior to starting study treatment. * Subjects must have recovered from all acute prior treatment-related toxicities to grade 1 or baseline (excluding alopecia and clinically stable toxicities requiring ongoing medical management, such as hypothyroidism).
• Non-myelosuppressive cancer therapy, such as kinase inhibitors, within 7 days prior to study treatment.
• Treatment with monoclonal antibodies with long half-lives, within 3 half-lives prior to study treatment.
• Treatment with targeted cellular therapies within 28 days prior to starting study treatment.
• Major surgical procedure, other than for diagnosis, within 30 days prior to initiation of study treatment, or anticipation of the need for a major surgical procedure during the first four cycles of the study. * Biopsy tissue collection or placement of a vascular access device is permitted if the site has healed prior to initiation of study medications. * For patients with CNS disease, no neurosurgical resection, brain biopsy, or stereotactic/whole-brain radiation within 30 days prior to Cycle 1, Day 1
• Treatment with a live, attenuated vaccine within 30 days prior to initiation of study treatment, or anticipation of the need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
• Treatment with investigational therapy within 21 days prior to initiation of study treatment or concurrent participation with another investigational agent
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-agents) within 2 weeks prior to initiation of study treatment, or anticipation of the need for systemic immunosuppressive medication during study treatment, with the following exceptions: * Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Principal Investigator confirmation has been obtained. * Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study. * Patients with CNS disease can be receiving concurrent treatment with corticosteroids with approval from the Principal Investigator. Patients must be receiving a stable or decreasing dose for ≥ 5 days prior to the baseline MRI scan and at the time of drug initiation. The Principal Investigator should be informed when steroid doses are increased because of declining patient status.
• Use of strong CYP3A4 inhibitors or inducers or strong UGT1A1 inhibitors within 12 days of Cycle 1, Day 1.
• Treatment with high-dose chemotherapy and hematopoietic stem-cell rescue within 3 months prior to initiation of study drug
• Treatment with herbal cancer therapy within 1 week prior to initiation of study medications.
• Treatment with a long-acting hematopoietic growth factor (such as pegfilgrastim) within 2 weeks prior to initiation of study medications, or a short-acting hematopoietic growth factor (such as G-CSF) within 1 week prior to initiation of study medications.
• Prior treatments:
• Prior allogeneic stem cell or solid organ transplantation
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies to include all anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\] within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• Subjects must not have previously progressed while receiving regimens that include irinotecan or temozolomide. Patients who have received irinotecan or temozolomide and did not progress while on these medications are eligible.
• Known ongoing or untreated infection, including, but not limited to bacteremia, active tuberculosis, or severe pneumonia
• Active tuberculosis
• Current treatment with anti-viral therapy for HBV
• Active hepatitis C
• Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study
• Known allergy or hypersensitivity to any component of the study medications
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
DRUG: Atezolizumab, DRUG: Vincristine, DRUG: Irinotecan, DRUG: Temozolomide
Solid Tumor, Rhabdomyosarcoma, Brain and Nervous System, Colon, Lymphoma, Soft Tissue
Relapsed solid tumor, Refractory solid tumor, Rhabdomyosarcoma
UT Southwestern; Children’s Health
Diuretic Tuner Clinical Decision Support
This purpose of this study is to determine the effectiveness of a mobile phone application in helping to control body swelling in patients with kidney problems. The application will help in the day to day adjustments in diuretic medication dosing. Participants in this study will have an application loaded on to their mobile phone by the study team and be taught how to use it over a 2 hour visit. Participants will need to check their blood pressure and weight daily and enter this information into the mobile phone application every day. Participants will need to follow daily instructions in their medication dosing provided by the application. There will be periodic blood testing. This will happen at 2 weeks, 90 days, and up to 4 other times if necessary. At the end of the study there is a 2 hour study visit during which participants will answer a survey. The total length of the study is 90 days.
Call 214-648-5005
studyfinder@utsouthwestern.edu, KSAMBANDAM@UTSouthwestern.edu
Kamalanathan Sambandam
All
18 Years and over
N/A
NCT04759274
STU-2020-1124
Inclusion Criteria:
• The presence of nephrotic range proteinuria (> 3 g/d proteinuria by 24hr urine protein, 24hr urine albumin, spot urine protein/creatinine ratio, or spot urine albumin/creatinine ratio) or stage 4 or 5 chronic kidney disease (estimated glomerular filtration rate < 30 mL/min/1.73 m2 by Modification of Diet in Renal Disease equation) PLUS
• Clinical signs of hypervolemia present (lower extremity edema, ascites, or pleural effusions) with an estimated dry weight (defined as edema-free weight without orthostatic hypotension) 5 lbs less than enrollment body weight
Exclusion Criteria:
• Weight < 100 lbs or > 300 lbs.
• Autonomic insufficiency resulting in orthostatic hypotension at screening
• Hypokalemia at enrollment (defined as serum potassium < 3.5 mmol/L)
• Moderate to severe hyponatremia at enrollment (defined as serum sodium < 130 mmol/L)
• Serum creatinine > 6 mg/dL or > 1.5 times baseline
• Patients who are unable or unwilling to measure their home blood pressures and weights
• Patients without a working phone number and smart phone device
• Expectation that the patient will require dialysis initiation within < 3 months
• Expected lifespan of < 6 months
• The presence of a medical condition that would interfere with effectively using the Diuretic Tuner (dementia, illiteracy, or blindness)
• Pregnant patients
• Prisoners
Device: Diuretic Tuner
Edema, Hypervolemia, Chronic Kidney Diseases, Nephrotic Syndrome, Kidney
UT Southwestern; Parkland Health & Hospital System
LEGEND Study: EG-70 in NMIBC Patients BCG-Unresponsive and High-Risk NMIBC Incompletely Treated With BCG or BCG-Naïve
This study will evaluate the safety and efficacy of intravesical administration of EG-70 in the bladder and its effect on bladder tumors in patients with NMIBC. This study study consists of two phases; a Phase 1 dose-escalation to establish safety and recommended the phase 2 dose, followed by a Phase 2 study to establish how effective the treatment is. The Study will include patients with NMIBC with Cis for whom BCG therapy is unresponsive and patients with NMIBC with Cis who are BCG-naïve or inadequately treated.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yair Lotan
ALL
18 Years and over
PHASE1
NCT04752722
STU-2021-0254
Inclusion Criteria:
BCG-unresponsive Patients:
• BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without coexisting papillary Ta/T1 tumors who are ineligible for or have elected not to undergo cystectomy, and have experienced CIS disease within 12 months of treatment where: adequate BCG regimen consists of at least 2 courses of BCG where the first course (induction) must have included at least 5 or 6 doses and the second course may have included a re-induction (at least 2 treatments) or maintenance (at least 2 doses), and Cis must be documented or indicated by pathology Phase 2 Only:
• BCG-Naïve or BCG-incompletely treated Patients with CIS or BCG-unresponsive, HG Ta/T1 papillary disease without CIS: -NMIBC with current Cis of the bladder, with or without coexisting papillary Ta/T1 NMIBC tumor(s), who are ineligible for or have elected not to undergo cystectomy, where: either: cohort 2a) no treatment with BCG but may have previously been treated with at least 1 dose of intravesical chemotherapy following transurethral resection of bladder tumor (TURBT) and Cis must be documented or cohort 2b) indicated by pathology incomplete BCG treatment (at least 1 dose and less than the 5+2 doses required for adequate dosing per Cohort 1) or cohort 3) patients who are BCG-unresponsive following adequate treatment, with HG Ta/T1 papillary disease without CIS. All Patients:
• Patients who have previously been treated with a checkpoint inhibitor and failed treatment are eligible for inclusion 30 days post-treatment (Phase 1) or 3 months post-treatment (Phase 2).
• Male or non-pregnant, non-lactating female, 18 years or older.
• Women of childbearing potential must have a negative pregnancy test at Screening.
• Female patients of childbearing potential must be willing to consent to using highly effective birth control methods; Male patients are required to utilize a condom for the duration of the study treatment through 3 months post-dose.
• In Phase 2, for patients with T1 lesions may be eligible after repeat TURBT if pathology shows non-invasive (Ta or less) or no disease.
• Performance Status: Eastern Cooperative Oncology Group 0, 1, and 2.
• Hematologic inclusion: a. Absolute neutrophil count \>1,500/mm3. b. Hemoglobin \>9.0 g/dL. c. Platelet count \>100,000/mm3.
• Hepatic inclusion: a. Total bilirubin must be ≤1.5 x the upper limit of normal (ULN). b. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤2.5 x ULN.
• Adequate renal function with creatinine clearance \>30 mL/min
• Prothrombin time and partial thromboplastin time ≤1.25 x ULN or within the therapeutic range if on anticoagulation therapy.
• Must have satisfactory bladder function with ability to retain study drug for 60 minutes.
Exclusion Criteria:
• Active malignancies (i.e., progressing or requiring treatment change in the last 24 months). Exceptions allowed under Sponsor review.
• Concurrent treatment with any chemotherapeutic agent.
• History of partial cystectomy.
• Treatment with last therapeutic agent (including intravesical chemotherapy post-TURBT) within 30 days of Screening (prior to the screening biopsy).
• Patients who have received systemic immunosuppressive medication including high-dose corticosteroids.
• History of severe asthma or other respiratory diseases.
• History of unresolved vesicoureteral reflux or an indwelling urinary stent.
• History of unresolved hydronephrosis due to ureteral obstruction.
• Participation in any other research protocol involving administration of an investigational agent within 30 Days prior to screening or any prior treatment of NMIBC with any investigational gene or immunotherapy agent.
• History of external beam radiation to the pelvis or prostate brachytherapy within the last 12 months.
• History of interstitial lung disease and/or pneumonitis in patients who have previously received a PD-1 or PD-L1 inhibitor therapy.
• Evidence of metastatic disease.
• History of difficult catheterization that in the opinion of the Investigator will prevent administration of EG-70.
• Active interstitial cystitis on cystoscopy or biopsy.
• Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
• Known human immunodeficiency virus, Hepatitis B, or Hepatitis C infection.
• Significant cardiovascular risk (e.g., coronary stenting within 8 weeks, myocardial infarction within 6 months).
• Hypersensitivity to any of the excipients of the study drug.
DRUG: EG-70 (phase 1), DRUG: EG-70 (phase 2)
Superficial Bladder Cancer, Non-muscle Invasive Bladder Cancer With Carcinoma in Situ, Urinary Bladder
Non-muscle invasive bladder cancer (NMIBC), Bacillus calmette- guerin (BCG) failure, BCG unresponsive, NMIBC, Bladder Cancer, LEGEND Study, EG-70, High-risk NMIBC, BCG-naïve, Incomplete BCG treatment, Carcinoma in situ (Cis), BCG-exposed
UT Southwestern
Ferric Citrate and Chronic Kidney Disease in Children (FIT4KID)
We will conduct a 12-month, double-blind, randomized, placebo-controlled trial to assess the effects of therapy with ferric citrate (FC) on changes in intact FGF23 levels (iFGF23, primary endpoint) in 160 pediatric patients (80 in each of the two arms) aged 6-18 years of either sex with chronic kidney disease (CKD) stages 3-4 and age-appropriate normal serum phosphate levels. Participants will be randomized to one of the two groups: 1) FC or 2) FC placebo. Participants will be recruited from 20 core clinical sites.
Call 214-648-5005
studyfinder@utsouthwestern.edu, melaku.lemma@childrens.com
Raymond Quigley
ALL
6 Years to 18 Years old
PHASE2
NCT04741646
STU-2020-1055
Inclusion Criteria:
• Ages 6 to 18 years (inclusive);
• Estimated Glomerular Filtration Rate (GFR) of 15-59 ml/min per 1.73 m2 by modified Chronic Kidney disease in Children (CKiD) under 25 (U25) formula;56
• Serum phosphate \<=5.9 mg/dl;
• Serum ferritin \<500 ng/ml and TSAT \<50%;
• For those patients treated with growth hormone, calcitriol, nutritional vitamin D, iron, and/or erythropoiesis-stimulating agents (ESAs) such treatments must have stable dosing for at least 2 weeks prior to screening;
• Able to swallow tablets;
• Able to eat at least two meals a day;
• In the opinion of the investigator, willing and able to follow the study treatment regimen and comply with the site investigator's recommendations.
Exclusion Criteria:
• Patients currently treated with phosphate binders.
• History of allergy to all ingredients (including non-medical ingredients) in both products (i.e. investigational product and placebo)
• Current intestinal malabsorption, documented in the medical record; disease, inflammatory bowel syndrome, and/or Crohn's Disease.
• Anticipated initiation of dialysis or kidney transplantation within 6 months
• Current or planned future systemic immunosuppressive therapy
• Prior solid organ transplantation
• Receipt of bone marrow transplant within two years of screening
• Current pregnancy, lactation or female subjects who have reached menarche, unless using highly-effective contraception as outlined in section 7.1.1 of Protocol
• Patients participating in other interventional study (observational study participation permitted)
• Poor adherence to medical treatments in the opinion of the investigator
• Cystinosis
• Fanconi syndrome
• Hemochromatosis or laboratory tests indicating possible hemochromatosis or other iron overload (primary or secondary) syndrome
DRUG: Ferric Citrate, DRUG: Placebo
Chronic Kidney Diseases, Kidney
Pediatric, CKD, Phosphate Binder
Children’s Health
Efficacy and Safety of Nemtabrutinib (MK-1026) in Participants With Hematologic Malignancies (MK-1026-003)
The purpose of this study is to evaluate the safety and efficacy of nemtabrutinib (formerly ARQ 531) in participants with hematologic malignancies of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Richter's transformation, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and Waldenström's macroglobulinemia (WM).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Farrukh Awan
ALL
18 Years and over
PHASE2
NCT04728893
STU-2023-0815
Inclusion Criteria:
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days before C1D1 (the first dose of study treatment)
* Has a life expectancy of at least 3 months, based on the investigator assessment
* Has the ability to swallow and retain oral medication
* 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
* Has adequate organ function
* Male participants agree to refrain from donating sperm and agree to either remain abstinent from penile-vaginal intercourse as their preferred and usual lifestyle OR agree to use contraception, during the intervention period and for at least the time required to eliminate the study intervention after last dose of study intervention
* Female participants assigned female sex at birth who are not pregnant or breastfeeding are eligible to participate if not a participant of childbearing potential (POCBP), or if a POCBP they either use a contraceptive method that is highly effective OR remain abstinent from penile-vaginal intercourse as their preferred and usual lifestyle during the intervention period and for at least to eliminate study intervention after the last dose of study intervention
* Participants with Human immunodeficiency virus (HIV) are eligible if they meet all of the following: the CD4 count is \>350 cells/uL at screening, the HIV viral load is below the detectable level, are on a stable ART regimen for at least 4 weeks prior to study entry, and are compliant with their ART
Part 1 and Part 2 (Cohorts A to C and J)
* Has a confirmed diagnosis of Chronic lymphocytic leukemia/ Small lymphocytic lymphoma (CLL/SLL) with
* At least 2 lines of prior therapy (Part 1 only)
* Part 2 Cohort A: CLL/SLL participants who are relapsed or refractory to prior therapy with a covalent, irreversible Bruton's tyrosine kinase inhibitor (BTKi), and a B-cell lymphoma 2 inhibitor (BCL2i). CLL participants must have received and failed, been intolerant to, or determined by their treating physician to be a poor phosphoinositide 3-kinase inhibitor (PI3Ki) candidate or ineligible for a PI3Ki per local guidelines
* Part 2 Cohort B: CLL/SLL participants who are relapsed or refractory following at least 1 line of prior therapy and are BTKi treatment naive
* Part 2 Cohort C: CLL/SLL participants with 17p deletion or tumor protein p53 (TP53) mutation who are relapsed or refractory following at least 1 line of prior therapy
* Part 2 Cohort J: CLL/SLL participants whose disease relapsed or was refractory to prior therapy with a covalent/irreversible BTKi and BCL2i. NOTE: As of Protocol Amendment 09, at least 10 CLL/SLL participants whose disease relapsed or was refractory to prior therapy with a covalent/irreversible BTKi, BCL2i and noncovalent/reversible BTKi (all three classes of therapies are required) will be enrolled into Cohort J
* Has active disease for CLL/SLL clearly documented to initiate therapy
* For SLL participants in Part 2: Has evaluable core or excisional lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy or bone marrow aspirate at Screening (optional for participants enrolling in Part 1)
Part 2 (Cohorts D to G)
\- Has a confirmed diagnosis of and meets the following prior therapy requirements:
* Participants with Richter's transformation who are relapsed or refractory following at least 1 line of prior therapy (Cohort D)
* Participants with pathologically confirmed Mantle-cell lymphoma (MCL), documented by either overexpression of cyclin D1 or t (11;14), who are relapsed or are refractory to chemoimmunotherapy and a covalent irreversible BTKi (Cohort E)
* Participants with Marginal zone lymphoma (MZL) (including splenic, nodal, and extra nodal MZL) who are relapsed or refractory to at least one prior line of systemic therapy including an anti-CD20-based regimen
* Participants with Follicular lymphoma (FL) who are relapsed or refractory to chemoimmunotherapy and immunomodulatory agents (such as lenalidomide based regimen) (Cohort G)
* Have measurable disease defined as at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral Computed tomography (CT) scan
* Has a lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy or bone marrow aspirate (Cohort D) at Screening
Part 2 (Cohort H): confirmed diagnosis of Waldenström's macroglobulinemia (WM); participants who are relapsed or refractory to standard therapies for WM including chemoimmunotherapy and a covalent irreversible BTKi
* Has active disease defined as 1 of the following: systemic symptoms, physical findings, laboratory abnormalities, coexisting disease
* Has measurable disease, satisfying any of the following: at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan (minimum measurement must be \>15 mm in the longest diameter or \>10 mm in the short axis); IgM ≥450 mg/dL; or bone marrow infiltration of 10%
* Has fresh bone marrow aspirate or a lymph node biopsy for biomarker analysis at Screening or a lymph node biopsy from an archival
Exclusion Criteria:
* Has active HBV/HCV infection (Part 1 and Part 2)
* Has a history of malignancy ≤3 years before providing documented informed consent. Participants with basal cell carcinoma of skin, squamous cell carcinoma of skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potential curative therapy are not excluded. Participants with low-risk, early-stage prostate cancer (T1-T2a, Gleason score ≤6, and prostate-specific antigen \<10 ng/mL) either treated with definitive intent or untreated in active surveillance with SD are not excluded
* Has active central nervous system (CNS) disease
* Has an active infection requiring systemic therapy
* Has received prior systemic anti-cancer therapy within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibody) before C1D1
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
* Has any clinically significant gastrointestinal abnormalities that might alter absorption
* History of severe bleeding disorders DRUG: Nemtabrutinib
Hematologic Malignancies, Waldenstroms Macroglobulinaemia, Non-Hodgkins Lymphoma, Chronic Lymphocytic Leukaemia, Other Hematopoietic
UT Southwestern
The Pediatric Acute Leukemia (PedAL) Screening Trial - A Study to Test Bone Marrow and Blood in Children With Leukemia That Has Come Back After Treatment or Is Difficult to Treat - A Leukemia & Lymphoma Society and Children's Oncology Group Study
This study aims to use clinical and biological characteristics of acute leukemias to screen for patient eligibility for available pediatric leukemia sub-trials. Testing bone marrow and blood from patients with leukemia that has come back after treatment or is difficult to treat may provide information about the patient's leukemia that is important when deciding how to best treat it, and may help doctors find better ways to diagnose and treat leukemia in children, adolescents, and young adults.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kathleen Ludwig
ALL
up to 22 Years old
PHASE1
NCT04726241
STU-2022-0170
Inclusion Criteria:
* Patients must be less than 22 years of age at the time of study enrollment
* Patient must have one of the following at the time of study enrollment:
* Patient has known or suspected relapsed/refractory (including primary refractory) AML as defined in protocol
* This includes isolated myeloid sarcoma
* Patient has known or suspected relapsed/refractory (including primary refractory) myeloid leukemia of Down syndrome (ML-DS)
* Patient has known or suspected relapsed ALL as defined in protocol that meets one of the following criteria:
* Second or greater B-ALL medullary relapse, excluding KMT2Ar
* Any first or greater B-ALL medullary relapse involving KMT2Ar
* Any first or greater T-ALL medullary relapse with or without KMT2Ar
* Patient has known or suspected relapsed/refractory (including primary refractory) mixed phenotype acute leukemia (MPAL) as defined in protocol
* Patient has known or suspected de novo or relapsed/refractory (including primary refractory) treatment-related AML (t-AML)
* Patient has known or suspected de novo or relapsed/refractory (including primary refractory) myelodysplastic syndrome (MDS) or treatment-related myelodysplastic syndrome (t-MDS)
* Note: Relapsed/refractory disease includes stable disease, progressive disease, and disease relapse.
* Patient has known or suspected de novo or relapsed/refractory (including primary refractory) juvenile myelomonocytic leukemia (JMML)
* Note: Relapsed/refractory disease includes stable disease, progressive disease, and disease relapse.
* 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
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Acute Myeloid Leukemia Post Cytotoxic Therapy, Juvenile Myelomonocytic Leukemia, Mixed Phenotype Acute Leukemia, Myelodysplastic Syndrome, Myelodysplastic Syndrome Post Cytotoxic Therapy, Myeloid Leukemia Associated With Down Syndrome, Leukemia, Other, Myeloid and Monocytic Leukemia
Children’s Health
ACCEL Absorbable Hemostat
The ACCEL® Absorbable Hemostat Powder Clinical IDE Trial is designed as a prospective, multi-center, randomized, non-inferiority, controlled pivotal clinical trial to evaluate the safety and efficacy of the ACCEL® Absorbable Hemostat Powder as compared to gelatin sponge, for achieving hemostasis in subjects undergoing cardiovascular, liver, or soft tissue surgery, when control of oozing to moderate bleeding by standard surgical techniques is ineffective and/or impractical.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Haley.Mathis@UTSouthwestern.edu
Lynn Huffman
ALL
22 Years and over
NA
NCT04728087
STU-2021-1224
Inclusion Criteria:
Pre-Surgery:
• Subject is greater than or equal to 22 years old
• Subject is undergoing a cardiovascular surgery, liver surgery or soft tissue surgical procedure
• Subject is willing and able to provide appropriate (Institutional Review Board (IRB) approved) informed consent.
• The subject is willing and able to comply with the requirements of the protocol, including follow-up evaluations and schedule.
• The subject is willing to be treated with ACCEL® Absorbable Hemostat Powder
• The subject is willing to be treated with a commercially available absorbable gelatin sponge During Surgery:
• Subject has not received blood transfusions between screening and application of investigational product or commercially available absorbable gelatin sponge
• There is an estimated TBS surface area of ≤ 60 cm2
• Visual observation of oozing (0.01 g/10s ˂ Flow ˂ 0.04 g/10s), mild (0.04 g/10s ≤ Flow ˂ 0.32 g/10s), or moderate (0.32 g/10s ≤ Flow ˂ 1.01 g/10s) bleeding as validated and when control by conventional surgical techniques, including but not limited to suture, ligature and cautery, is ineffective and/or impractical
• There is an absence of intra-operative complications other than bleeding, which, in the opinion of the Investigator, may interfere with the assessment of efficacy or safety
• There has been no intra-operative use of adjunct hemostat(s) on the target bleeding site identified for application of the study treatment
Exclusion Criteria:
Pre-Surgery:
• The subject is pregnant (verified in a manner consistent with institution's standard of care)
• Subject is lactating
• Subject is currently participating in another investigational device or drug trial or has participated in one in the past 4 weeks (prior to surgery) or is planning to participate in another research study involving any investigational product within 4 weeks after surgery
• Subject is a prisoner, a minor or unable to adequately give informed consent due to mental or physical condition
• Subject has medical, social, or psychosocial issues that the Investigator believes could impact the subject's safety or compliance with study procedures
• Subject has a known allergy to potatoes
• Subject has a known allergy to porcine collagen/gelatin
• Subject has a religious or other objection to porcine products
• Subject is unwilling to receive blood products
• Subject has history of heparin-induced thrombocytopenia (only for cardiovascular subjects where heparin use is required)
• Subject with a baseline abnormality of INR \> 2.5 or an aPTT\> 100 seconds during screening that is not explained by current drug treatment (e.g. heparin, warfarin, etc.).
• Subjects with platelets \< 100 X 109 PLT/L during screening
• Subject with Aspartate Aminotransferase (AST) or Alanine aminotransferase (ALT) \> 3 X upper limit normal range during screening, except for subjects undergoing liver resection surgery or with a diagnosis of liver metastases where there is no upper limit normal for these analytes due to the nature of their disease
• Subject is unwilling or unable to return for the required follow-up after surgery During Surgery:
• Subject has an operative bleeding site which the surgeon is unable or unwilling to control with a hemostatic agent
• Extracorporeal cardiopulmonary bypass circuits or blood salvage circuits are to be used during or after identification of the TBS.
• There has been intra-operative use of thrombin on the patient.
DEVICE: ACCEL® Absorbable Hemostat Powder, DEVICE: Gelfoam® (Absorbable Gelatin Sponge, Pfizer Manufacturer Part Number 0342-01)
Hemostasis, Cardiovascular, Head and Neck, Liver, Other
UT Southwestern
Prediction of Neoadjuvant Chemotherapy Response Using Contrast-Enhanced Ultrasound in Patients With Locally Advanced Breast Cancer
This phase II/III trial studies if contrast-enhanced ultrasounds using a contrast dye, perflutren lipid microspheres (Definity), can predict the response to chemotherapy by estimating the pressure in the cancer in patients with breast cancer that has spread to nearby tissues and lymph nodes (locally advanced). The efficacy of cancer therapy is affected by the pressure in the cancer. Definity is a contrast dye used to create better images during ultrasounds. The purpose of this trial is to determine if a special kind of ultrasound, called contrast-enhanced ultrasound, an experimental imaging test, can detect pressures in cancer to determine the response to neoadjuvant chemotherapy in patients with breast cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Basak Dogan
FEMALE
21 Years and over
PHASE2
NCT04715958
STU-2020-0620
Inclusion Criteria:
* Provide signed and dated informed consent form
* Willing to comply with all study procedures and be available for the duration of the study
* At least 21 years old
* Be diagnosed with breast cancer (T1 or greater LABC, any N and M0)
* Be scheduled for neoadjuvant chemotherapy
* Be medically stable
* Be conscious and able to comply with study procedures
* If a female of child-bearing potential, must have a negative urine pregnancy test
Exclusion Criteria:
* Males
* Females who are pregnant or nursing
* Patients with other primary cancers requiring systemic treatment
* Patients with any distal metastatic disease
* Patients undergoing neoadjuvant endocrine therapy
* Patients who are medically unstable, patients who are seriously or terminally ill, and patients whose clinical course is unpredictable. For example:
* Patients on life support or in a critical care unit;
* Patients with unstable occlusive disease (e.g., crescendo angina);
* Patients with clinically unstable cardiac arrhythmias, such as recurrent ventricular tachycardia;
* Patients with uncontrolled congestive heart failure (New York Heart Association \[NYHA\] Class IV);
* Patients with recent cerebral hemorrhage;
* Patients who have undergone surgery within 24 hours prior to the study sonographic examination
* Patients with known hypersensitivity or allergy to any component of Definity
* Patients with unstable cardiopulmonary conditions or respiratory distress syndrome
* Patients with uncontrollable emphysema, pulmonary vasculitis, pulmonary hypertension or a history of pulmonary emboli PROCEDURE: Contrast-Enhanced Ultrasound, DRUG: Perflutren Lipid Microspheres, PROCEDURE: Ultrasound
Anatomic Stage III Breast Cancer AJCC v8, Locally Advanced Breast Carcinoma, Breast - Female
UT Southwestern; Parkland Health & Hospital System
Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis (TETON)
Study RIN-PF-301 is designed to evaluate the superiority of inhaled treprostinil against placebo for the change in absolute forced vital capacity (FVC) from baseline to Week 52.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Maria.Goralski@UTSouthwestern.edu
Traci Adams
ALL
40 Years and over
PHASE3
NCT04708782
STU-2022-0821
Inclusion Criteria:
• Subject gives voluntary informed consent to participate in the study.
• Subject is ≥40 years of age, inclusive, at the time of signing informed consent.
• The subject has a diagnosis of IPF based on the 2018 ATS/ERS/JRS/ALAT Clinical Practice Guideline (Raghu 2018) and confirmed by central review of high-resolution computed tomography (HRCT) (performed within the previous 12 months), and if available, surgical lung biopsy.
• FVC ≥45% predicted at Screening.
• Subjects on pirfenidone or nintedanib must be on a stable and optimized dose for ≥30 days prior to Baseline. Concomitant use of both pirfenidone and nintedanib is not permitted.
• Women of childbearing potential must be non-pregnant (as confirmed by a urine pregnancy test at Screening and Baseline) and non-lactating, and will abstain from intercourse (when it is in line with their preferred and usual lifestyle) or use 2 medically acceptable, highly effective forms of contraception for the duration of the study, and at least 30 days after discontinuing study drug.
• Males with a partner of childbearing potential must use a condom for the duration of treatment and for at least 48 hours after discontinuing study drug.
• In the opinion of the Investigator, the subject is able to communicate effectively with study personnel, and is considered reliable, willing, and likely to be cooperative with protocol requirements, including attending all study visits.
Exclusion Criteria:
• Subject is pregnant or lactating.
• Subject has primary obstructive airway physiology: FEV1/FVC \<0.70 at Screening.
• The subject has shown intolerance or significant lack of efficacy to a prostacyclin or prostacyclin analogue that resulted in discontinuation or inability to effectively titrate that therapy.
• The subject has received any PAH-approved therapy, including prostacyclin therapy (epoprostenol, treprostinil, iloprost, or beraprost; except for acute vasoreactivity testing), IP receptor agonists (selexipag), endothelin receptor antagonists, phosphodiesterase type 5 inhibitors (PDE5-Is), or soluble guanylate cyclase stimulators within 60 days prior to Baseline. As needed use of a PDE5-I for erectile dysfunction is permitted, provided no doses are taken within 48 hours of any study-related efficacy assessments.
• Use of any of the following medications: azathioprine (AZA), cyclosporine, mycophenolate mofetil, tacrolimus, oral corticosteroids (OCS) \>20 mg/day or the combination of OCS+AZA+N-acetylcysteine within 30 days prior to Baseline; cyclophosphamide within 60 days prior to Baseline; or rituximab within 6 months prior to Baseline.
• The subject is receiving \>10 L/min of oxygen supplementation by any mode of delivery at rest at Baseline.
• Exacerbation of IPF or active pulmonary or upper respiratory infection within 30 days prior to Baseline. Subjects must have completed any antibiotic or steroid regimens for treatment of the infection or acute exacerbation more than 30 days prior to Baseline to be eligible. If hospitalized for an acute exacerbation of IPF or a pulmonary or upper respiratory infection, subjects must have been discharged more than 90 days prior to Baseline to be eligible.
• Uncontrolled cardiac disease, defined as myocardial infarction within 6 months prior to Baseline or unstable angina within 30 days prior to Baseline.
• In the opinion of the Investigator, the subject has any condition that would interfere with the interpretation of study assessments or would impair study participation or cooperation.
• Use of any other investigational drug/device or participation in any investigational study in which the subject received a medical intervention (ie, procedure, device, medication/supplement) within 30 days prior to Screening. Subjects participating in non-interventional, observational, or registry studies are eligible.
• Life expectancy \<6 months due to IPF or a concomitant illness.
• Acute pulmonary embolism within 90 days prior to Baseline.
DRUG: Placebo, DRUG: Inhaled Treprostinil, DEVICE: Treprostinil Ultrasonic Nebulizer
Idiopathic Pulmonary Fibrosis, Interstitial Lung Disease
Treprostinil, IPF, ILD
UT Southwestern
Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial
The dose escalation phase of this trial identifies the safety, side effects and best dose of ceralasertib (AZD6738) when given in combination with trastuzumab deruxtecan (DS-8201a) in treating patients with solid tumors that have a change (mutation) in the HER2 gene or protein and have spread to other places in the body (advanced). The dose expansion phase (phase Ib) of this trial compares how colorectal and gastroesophageal cancers with HER2 mutation respond to treatment with a combination of ceralasertib and trastuzumab deruxtecan versus trastuzumab deruxtecan alone. Ceralasertib may stop the growth of tumor cells and may kill them by blocking some of the enzymes needed for cell growth. Trastuzumab deruxtecan is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers deruxtecan to kill them. Ceralasertib and trastuzumab deruxtecan may be safe, tolerable and effective in treating patients with advanced solid tumors expressing the HER2 protein or gene.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
ALL
18 Years and over
PHASE1
NCT04704661
STU-2023-0128
Inclusion Criteria:
* DOSE-ESCALATION PHASE: Must have histologically confirmed advanced solid tumor including but not restricted to breast cancer, gastric or gastroesophageal cancer, colon cancer, endometrial cancer, salivary gland tumors, and hepatobiliary tumors
* DOSE-EXPANSION PHASE: Must have histologically confirmed advanced/metastatic gastroesophageal cancer (cohort A) or colorectal cancer (cohort B)
* DOSE-EXPANSION PHASE: Patients must have a biopsiable lesion and provide consent for on treatment biopsy
* Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of AZD6738 in combination with DS-8201a in patients \< 18 years of age, children are excluded from this study
* Patients must have HER2-positive or HER2-expressing tumors determined by a Clinical Laboratory Improvement Act (CLIA)-certified laboratory. As a rule, for HER2 immunohistochemistry (IHC) scoring system trastuzumab for gastric cancer (TOGA) criteria used for gastric/gastroesophageal junction (GEJ) cancers will be employed (Note: in escalation phase, for breast cancer patients that are included, breast cancer criteria can be used). Specific requirement of HER2 status is outlined below:
* HER2 expression (1-3+) by IHC locally and confirmed centrally OR
* HER2 expression (1-3+) by IHC tested centrally OR
* HER2 amplification based on fluorescence in situ hybridization (FISH) or next generation sequencing
* Must have received at least one line of systemic chemotherapy for either locally advanced or metastatic disease and should have either progressed on this therapy or been intolerant to this therapy
* For tumors where anti-HER2 therapy is standard of care, patients must have progressed on at least 1 line of anti-HER2 therapy if eligible. For patients where DS8201a is approved as standard of care, prior treatment with DS8201a is not allowed
* Must have unresectable, advanced/metastatic disease
* Must have at least 1 measurable lesion on CT scan per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Patient without measurable but evaluable disease are allowed for dose-escalation phase
* Must be willing and able to provide an adequate archival tumor sample available to confirm HER2 status by Central Laboratory (if local testing is used for enrollment), else must be willing and able to provide an adequate archival tumor sample for HER2 testing centrally
* Must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
* Must have life expectancy of at least 3 months
* Must have left ventricular ejection fraction (LVEF) \>= 50% within 28 days before enrollment (study drug treatment) by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan
* Must have a negative pregnancy test (if female)
* Platelets \>= 100,000/mcL (within 14 days before enrollment)
* No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment
* Hemoglobin \>= 9.0 g/dL (within 14 days before enrollment)
* Absolute neutrophil count \>= 1,500/mcL (within 14 days before enrollment)
* No administration of granulocyte colony-stimulating factor (G-CSF) is allowed within 1 week prior to screening assessment
* Creatinine clearance \> 45/mL/min (using the Cockcroft-Gault equation) (within 14 days before enrollment)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x institutional upper limit of normal (ULN) (within 14 days before enrollment)
* Total bilirubin =\< 1.5 x ULN if no liver metastases or \< 3 x ULN with Gilbert's Syndrome or liver metastases at baseline (within 14 days before enrollment)
* Leukocytes \>= 3,000/mcL (within 14 days before enrollment)
* Albumin \> 2.5 g/dL (GEJ patients only) (within 14 days before enrollment)
* International normalized ratio (INR) and either partial thromboplastin time (PTT) or activated (a)PTT =\< 1.5 x ULN (within 14 days before enrollment)
* Must have adequate treatment washout period before study treatment, defined as: Major surgery (\>= 4 weeks), radiation therapy (\>= 3 weeks; in case of palliative radiation \>= 2 weeks), systemic therapy (\>= 3 weeks; in case of investigational drug use \>= 2 weeks or 5 half-lives, whichever is longer)
* Patients who are human immunodeficiency virus (HIV) positive may participate IF they meet the following eligibility requirements:
* They must be stable on their anti-retroviral regimen, and they must be healthy from an HIV perspective
* They must have a CD4 count of greater than 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count \< 200 cells/mcl over the past 2 years, unless it was deemed related to THE CANCER AND/OR CHEMOTHERAPY-induced bone marrow suppression
* For patients who have received chemotherapy in the past 6 months, a CD4 count \< 250 cells/mcl during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy
* They must have an undetectable viral load and a CD4 count \>= 250 cells/mcL within 7 days of enrollment
* They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months. HIV-infected patients should be monitored every 12 weeks for viral load and CD4 counts
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Subjects with clinically inactive brain metastases may be included. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole-brain radiation therapy and study treatment
* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (CNS) specific treatment is not required and is unlikely to be required for at least 4 weeks (or scheduled assessment after the first cycle of treatment), and a risk-benefit analysis (discussion) by the patient and the investigator favors participation in the clinical trial
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* HER2 antibody conjugated to a topoisomerase 1 inhibitor agents as well as AZD6738 are known to be teratogenic; thus, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 7 months (women of childbearing potential \[WOCBP\] only) after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of study drug administration
* Women of non-child-bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone \[FSH\] \> 40 mIU/mL and estradiol \< 40 pg/mL \[\< 147 pmol/L\] is confirmatory) are eligible. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for women of child-bearing potential if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method
* Male subjects must not freeze or donate sperm starting at screening and throughout the study period, and at least 6 months after the final study drug administration. Preservation of sperm should be considered prior to enrolment in this study
* Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration
* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible
Exclusion Criteria:
* Patients with a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. Patient using e-cigarettes/vaping are also excluded
* Patients with a medical history of myocardial infarction within 6 months before enrollment (study treatment), symptomatic congestive heart failure (New York Heart Association Class II to IV, corrected QT interval (Fridericia's formula-corrected QT interval \[QTcF\]) prolongation to \> 470 ms (females) or \> 450 ms (males) as corrected by Framingham's formula
* Patients with spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms
* Patients with multiple primary malignancies within 2 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other curatively treated solid tumors
* Patients with a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product
* Patients with an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
* Patients with substance abuse or any other medical conditions that would increase the safety risk to the subject or interfere with participation of the subject or evaluation of the clinical study in the opinion of the investigator
* Patients with a concomitant medical condition that would increase the risk of toxicity in the opinion of the investigator
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities grade \>1) with the exception of alopecia. Subjects with chronic grade 2 toxicities may be eligible per discretion of the investigator after discussion with study principal investigator (PI) (e.g., grade 2 chemo-induced neuropathy).
* Any previous treatment with an ATR inhibitor
* Patients with any clinically apparent pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease \[COPD\], restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (i.e., Rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy
* Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
* Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
* Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir). The required washout period prior to starting study treatment is 2 weeks. Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents
* Patients with a pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART). (Drainage and CART are not allowed within 2 weeks prior to screening assessment)
* Patients with previous allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
* Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable within the last 28 days as long as they are not within 1 week prior to screening assessment)
* Patients at risk of brain perfusion problems, e.g., medical history of carotid stenosis or pre-syncopal or syncopal episodes, history of transient ischemic attacks (TIAs)
* Uncontrolled hypertension (grade 2 or above) requiring clinical intervention
* Patients with relative hypotension (\< 90/60 mm Hg) or clinically relevant orthostatic hypotension, including a fall in blood pressure of \> 20 mm Hg
* Patients who have received corticosteroids (at a dose \> 10 mg prednisone/day or equivalent) for any reason within 2 weeks prior to first dose
* Patients with uncontrolled intercurrent illness
* Patients with psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded from this study because DS-8201a is a HER2 antibody conjugated to a topoisomerase 1 inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with DS-8201a, breastfeeding should be discontinued if the mother is treated with DS-8201a. These potential risks may also apply to AZD6738
* Patients cannot be receiving chloroquine or hydroxychloroquine. Patients receiving these drugs must have a washout period of \> 14 days before enrollment/randomization PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, DRUG: Ceralasertib, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, PROCEDURE: Multigated Acquisition Scan, PROCEDURE: Positron Emission Tomography, BIOLOGICAL: Trastuzumab Deruxtecan
Advanced Breast Carcinoma, Advanced Colon Carcinoma, Advanced Colorectal Carcinoma, Advanced Endometrial Carcinoma, Advanced Gastric Carcinoma, Advanced Gastroesophageal Junction Adenocarcinoma, Advanced Malignant Solid Neoplasm, Advanced Salivary Gland Carcinoma, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Clinical Stage III Gastric Cancer AJCC v8, Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage IV Gastric Cancer AJCC v8, Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8, HER2-Positive Breast Carcinoma, Malignant Hepatobiliary Neoplasm, Metastatic Breast Carcinoma, Metastatic Colon Carcinoma, Metastatic Colorectal Carcinoma, Metastatic Endometrial Carcinoma, Metastatic Gastric Carcinoma, Metastatic Gastroesophageal Junction Adenocarcinoma, Metastatic Malignant Solid Neoplasm, Metastatic Salivary Gland Carcinoma, Stage III Colon Cancer AJCC v8, Stage III Colorectal Cancer AJCC v8, Stage III Major Salivary Gland Cancer AJCC v8, Stage III Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8, Stage IV Colon Cancer AJCC v8, Stage IV Colorectal Cancer AJCC v8, Stage IV Major Salivary Gland Cancer AJCC v8, Stage IV Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8, Unresectable Breast Carcinoma, Unresectable Colon Carcinoma, Unresectable Colorectal Carcinoma, Unresectable Endometrial Carcinoma, Unresectable Gastric Carcinoma, Unresectable Gastroesophageal Junction Adenocarcinoma, Unresectable Malignant Solid Neoplasm, Unresectable Salivary Gland Carcinoma, Colon, Esophagus, Rectum
UT Southwestern; Parkland Health & Hospital System
POCUS: Hemostatic Potential and Joint Health in Patients With Severe Hemophilia A on Novel Replacement Therapies
This is a prospective, randomized control trial in which each patient will be randomly assigned to receive either extended half-life factor VIII based replacement therapy or non-FVIII based replacement therapy, which are both standard of care treatment for persons with Hemophilia A.
Call 214-648-5005
studyfinder@utsouthwestern.edu, lindsey.hartland@childrens.com
Jessica Garcia
ALL
up to 17 Years old
PHASE4
NCT04690322
STU-2020-1378
Inclusion Criteria:
* Subjects with moderate hemophilia A (baseline factor VIII activity 1-5%) or severe hemophilia A (baseline factor VIII activity \<1%) on prophylactic standard half-life FVIII infusions OR subjects with moderate or severe hemophilia A who have not started prophylactic treatment
* Less than 18 years of age
Exclusion Criteria:
* Subjects with documented FVIII inhibitor
* Subjects with a history of ≥ 2 target joints
* Subjects with a history of synovectomy
* Currently using medications known to impact bone and mineral metabolism (e.g., bisphosphonates, corticosteroids, estrogen, testosterone, calcitonin, thyroid hormone therapy);
* Disease states known to affect bone integrity (e.g., primary hyperparathyroidism, Paget's disease, clinically significant liver disease) DRUG: Eloctate, DRUG: Adynovate, DRUG: Emicizumab
Hemophilia A, Factor VIII, Bones and Joints, Other Hematopoietic
Children’s Health
Ultra-fractionated Radiotherapy for Rectal Cancer
The rationale of this clinical trial is to assess the feasibility of selective non-operative management for locally advanced rectal cancer using dose-escalated ultra-fractionated short course radiation therapy interdigitated with chemotherapy. We believe delivering short course radiotherapy over a prolonged interval, at escalated doses and with concurrent chemotherapy may be feasible and allow for improved clinical response.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nina Sanford
ALL
18 Years and over
PHASE1
NCT04677413
STU-2020-1394
Inclusion Criteria:
• At least 18 years of age. Both men and women and members of all races and ethnic groups will be included.
• Willing and able to provide written informed consent
• Pathologic diagnosis of rectal adenocarcinoma
• T3-4 and/or N+ disease per AJCC 8th edition
• No prior treatment for rectal adenocarcinoma
• Eastern Cooperative Group (ECOG) performance status of 0-2.
• Laboratory values supporting acceptable organ and marrow function within 30 days of eligibility confirmation. Defined as follows: * WBC ≥ 3,000/mL; * ANC WBC ≥ 1,000/mL; * PLT ≥ 75,000/mL; * T Bili ≤ 1.5 x upper limit of normal (ULN); * AST/ALT ≤ 2.5 x ULN; * Creatinine not above ULN, or creatinine clearance \>50 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal.
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) starting with the first dose of study therapy through 90 days after the last dose of study drugs. 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, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
Exclusion Criteria:
• Distant nodal disease (retroperitoneal nodes) including inguinal nodes, or any metastatic disease by CT.
• Prior RT to the pelvis.
• Uncontrolled comorbid illness or condition including congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric illness that would limit compliance with the study requirements.
• Psychiatric illness/social situations that would limit consenting and compliance with study requirements.
• Participants who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
RADIATION: Ultrafractionated radiotherapy for rectal cancer
Rectal Cancer, Rectum
Rectal Cancer,T3-4 or N+
UT Southwestern; Parkland Health & Hospital System
A Study of a New Way to Treat Children and Young Adults With a Brain Tumor Called NGGCT
This phase II trial studies the best approach to combine chemotherapy and radiation therapy (RT) based on the patient's response to induction chemotherapy in patients with non-germinomatous germ cell tumors (NGGCT) that have not spread to other parts of the brain or body (localized). This study has 2 goals: 1) optimizing radiation for patients who respond well to induction chemotherapy to diminish spinal cord relapses, 2) utilizing higher dose chemotherapy followed by conventional RT in patients who did not respond to induction chemotherapy. Chemotherapy drugs, such as carboplatin, etoposide, ifosfamide, and thiotepa, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays or high-energy protons to kill tumor cells and shrink tumors. Studies have shown that patients with newly-diagnosed localized NGGCT, whose disease responds well to chemotherapy before receiving radiation therapy, are more likely to be free of the disease for a longer time than are patients for whom the chemotherapy does not efficiently eliminate or reduce the size of the tumor. The purpose of this study is to see how well the tumors respond to induction chemotherapy to decide what treatment to give next. Some patients will be given RT to the spine and a portion of the brain. Others will be given high dose chemotherapy and a stem cell transplant before RT to the whole brain and spine. Giving treatment based on the response to induction chemotherapy may lower the side effects of radiation in some patients and adjust the therapy to a more efficient one for other patients with localized NGGCT.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
ALL
3 Years to 29 Years old
PHASE2
NCT04684368
STU-2021-0638
Inclusion Criteria:
* Patients must be \>= 3 years and \< 30 years at the time of study enrollment
* Patients must be newly diagnosed with localized primary CNS NGGCT of the suprasellar and/or pineal region by pathology and/or serum or cerebrospinal fluid (CSF) elevation of AFP above institutional normal or \> 10 ng/mL or human chorionic gonadotropin (hCG) beta \> 100 mIU/mL as confirmed by Rapid Central Marker Screening Review on APEC14B1-CNS. Suprasellar, pineal and bifocal tumors are included. (CSF tumor markers and cytology must be within 31 days prior to enrollment and start of protocol therapy \[repeat if necessary\]. Serum tumor markers, AFP and hCGbeta must be within 7 days prior to enrollment and start of protocol therapy \[repeat if necessary\]). Basal ganglia or other primary sites are excluded
* Patients with any of the following pathological elements are eligible: endodermal sinus (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma and mixed germ cell tumor (GCT) (i.e., may include some pure germinoma) if malignant elements listed above are present. Patients with only mature teratoma are excluded. Patients with pure germinoma admixed with mature teratoma are excluded (would be eligible for pure germinoma protocols)
* Patients must have a cranial MRI with and without gadolinium at diagnosis/prior to enrollment. If surgical resection is performed, patients must have pre-operative and post operative brain MRI with and without gadolinium. The post operative brain MRI should be obtained within 72 hours of surgery. If patient has a biopsy only, post-operative brain MRI is recommended but not required (within 31 days prior to study enrollment and start of protocol therapy )
* Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to enrollment. Spine MRI with and without gadolinium is recommended (within 31 days prior to study enrollment and start of protocol therapy)
* Lumbar CSF must be obtained prior to study enrollment unless medically contraindicated. If a patient undergoes surgery and lumbar CSF cytology cannot be obtained at the time of surgery, then it should be performed at least 10 days following surgery and prior to study enrollment. False positive cytology can occur within 10 days of surgery
* Patients must have RAPID CENTRAL TUMOR MARKER REVIEW CSF tumor markers obtained prior to enrollment unless medically contraindicated. Ventricular CSF obtained at the time of CSF diversion procedure (if performed) is acceptable for tumor markers but lumbar CSF is preferred. In case CSF diversion and biopsy/surgery are combined, CSF tumor markers should be collected first
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL (within 7 days prior to enrollment)
* Platelet count \>= 100,000/uL (transfusion independent) (within 7 days prior to enrollment)
* Hemoglobin \>= 8.0 g/dL (may receive red blood cell \[RBC\] transfusions) (within 7 days prior to enrollment)
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
* Age: Maximum serum creatinine (mg/dL)
* 3 to \< 6 years: 0.8 (male), 0.8 (female)
* 6 to \< 10 years: 1 (male), 1 (female)
* 10 to \< 13 years: 1.2 (male), 1.2 (female)
* 13 to \< 16 years: 1.5 (male), 1.4 (female)
* \>= 16 years: male (1.7), 1.4 (female)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (within 7 days prior to enrollment)
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* Central nervous system function defined as:
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
* Patients must not be in status epilepticus, coma or assisted ventilation prior to study enrollment
* Protocol therapy must begin within 31 calendar days of definitive surgery or clinical diagnosis, whichever is later. If a biopsy only was performed, the biopsy date will be considered the date of definitive surgery. For patients who have a biopsy or incomplete resection at diagnosis followed by additional surgery, the date of the last resection will be considered the date of definitive surgery.
* 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
* NEUROCOGNITIVE FUNCTION AND QUALITY OF LIFE ASSESSMENT:
* English-, Spanish-, or French- speaking
* Note: Patients who speak a language other than English, Spanish, or French will be allowed to participate in ACNS2021 but will not complete the neurocognitive and quality of life assessments
* No known history of neurodevelopmental disorder prior to diagnosis of NGGCT (e.g., Down syndrome, fragile X, William syndrome, intellectual disability). Patients with NF1 will be allowed to participate
* Additional eligibility criteria for the COG Standardized Neuropsychological Battery only: must be at a site that has a psychologist to administer the battery
* Note: If not eligible for the COG Standardized Battery, patients should still complete the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2), Pediatric Quality of Life Inventory (PedsQL), Adaptive Behavior Assessment System Third Edition (ABAS-3), and Behavior Assessment System for Children, Third Edition (BASC-3) questionnaires
Exclusion Criteria:
* Patients with tumors located outside the ventricles (i.e., basal ganglia, thalamus)
* Patients with only mature teratoma and non-elevated markers upon tumor sampling at diagnosis
* Patients who have received any prior tumor-directed therapy for their diagnosis of NGGCT other than surgical intervention and corticosteroids
* Patients with metastatic disease (i.e., MRI evaluation, lumbar CSF cytology or intraoperative evidence of dissemination)
* Female patients who are pregnant, since fetal toxicities and teratogenic effects have been noted for several of the study drugs
* Note: Serum and urine pregnancy tests may be falsely positive due to HCGbeta-secreting germ cell tumors. Ensure the patient is not pregnant by institutional standards
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Etoposide, BIOLOGICAL: Filgrastim, DRUG: Ifosfamide, PROCEDURE: Magnetic Resonance Imaging, DRUG: Mesna, BIOLOGICAL: Pegfilgrastim, PROCEDURE: Peripheral Blood Stem Cell Transplantation, OTHER: Questionnaire Administration, RADIATION: Radiation Therapy, RADIATION: Radiation Therapy, PROCEDURE: Second-Look Surgery, DRUG: Thiotepa
Central Nervous System Nongerminomatous Germ Cell Tumor, Choriocarcinoma, Embryonal Carcinoma, Immature Teratoma, Malignant Teratoma, Mixed Germ Cell Tumor, Pineal Region Germ Cell Tumor, Pineal Region Immature Teratoma, Pineal Region Yolk Sac Tumor, Suprasellar Germ Cell Tumor, Brain and Nervous System
UT Southwestern; Children’s Health
Randomized Study in Children and Adolescents With Migraine: Acute Treatment
The purpose of this study is to test the safety and efficacy of BHV-3000 versus placebo in the acute treatment of moderate or severe migraine in children and adolescents.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Kiley.Poppino@UTSouthwestern.edu
Deryk Walsh
ALL
6 Years to 17 Years old
PHASE3
NCT04649242
STU-2021-0107
Inclusion Criteria:
• History of migraine (with or without aura) for \> 6 months before Screening according to the IHS Classification ICHD-319 specifications for pediatric migraine. History may be verified using both medical records and recall by the participant and/or participant's parent(s)/legal representative(s).
• History of 1 to 8 moderate or severe attacks per month during the 2 months prior to enrollment, with attacks lasting \> 3 hours without treatment, and attacks occurring at intervals \> 24 hours.
• Prophylactic migraine medication are permitted if the dose has been stable for at least 12 weeks prior to the Baseline Visit, and the dose is not expected to change during the course of the study.
• Participants may remain on one (1) medication with possible migraine prophylactic effects, excluding CGRP antagonists \[biologic or small molecule\], during the treatment phases.
• Concomitant use of a CGRP antagonist, such as erenumab or fremanezumab, is prohibited.
• Previously discontinued prophylactic migraine medication must have done so at least 90 days prior to the Screening Visit.
• Verbally distinguish between migraine and other types of headaches.
• Participants must have a weight \> 40 kg at the Screening Visit.
• Adequate venous access for blood sampling.
• Male and female participants ≥ 6 to \< 18 years of age (participants must not reach their 18th birthday during the study).
Exclusion Criteria:
• History of cluster headache or hemiplegic migraine headache.
• Confounding and clinically significant pain syndrome that may interfere with the participant's ability to participate in this study.
• Current psychiatric condition that is uncontrolled and/or untreated for a minimum of 6 months prior to the Screening Visit. Participants with a lifetime history of psychosis and/or mania.
• History of suicidal behavior or major psychiatric disorder.
• Current diagnosis or history of substance abuse; positive drug test at Screening.
• History of moderate or severe head trauma or other neurological disorder (including seizure disorder) or systemic medical disease that is likely to affect central nervous system functioning.
• Recent or planned surgery, requiring general anesthesia, \<8 weeks prior to the Screening Visit.
• Participant has had gastrointestinal surgery that interferes with physiological absorption and motility (i.e., gastric bypass, duodenectomy, or gastric banding).
• Current diagnosis of viral hepatitis or a history of liver disease.
• Conditions considered clinically relevant in the context of the study such as uncontrolled hypertension (high blood pressure), diabetes, a life-threatening allergy
DRUG: Rimegepant/BHV3000, DRUG: Matching placebo
Pediatric Migraine, Brain and Nervous System
Migraine, Acute treatment, Phonophobia, Photophobia, Nausea, Pediatric, Children, Adolescent, Pediatric Migraine
Children’s Health