StudyFinder
Search Results Within Category "Lung Disease & Asthma"
81 Study Matches
4D-710 in Adult Patients with Cystic Fibrosis (CF)
This is a Phase 1/2 multicenter, open-label, single dose trial of 4D-710 investigational gene therapy in adults with cystic fibrosis.
Call 214-648-5005
studyfinder@utsouthwestern.edu, LYNN.FERNANDEZ@UTSouthwestern.edu
Raksha Jain
ALL
18 Years and over
PHASE1
NCT05248230
STU-2022-0409
Key Inclusion Criteria (Primary Study):
• 18 years and older
• Confirmed diagnosis of cystic fibrosis (CF) and CF lung disease including:
• Sweat chloride ≥ 60 mmol/L
• Mutation Status * Bi-allelic mutations in the CFTR gene, or * Single mutation in the CFTR gene and clinical manifestations of CF lung disease
• Ineligible for CFTR modulator therapy, or previously received modulator therapy but discontinued due to adverse effects.
• Forced expiratory volume in 1 second (FEV1) ≥ 50% and ≤ 90% of predicted (per Global Lung Function Initiative) at Screening
• Resting oxygen saturation ≥ 92% on room air at Screening Key Inclusion Criteria (Sub-Study):
• 18 years and older
• Confirmed diagnosis of cystic fibrosis (CF) and CF lung disease including:
• Sweat chloride ≥ 60 mmol/L
• Mutation Status * Bi-allelic mutations in the CFTR gene, or * Single mutation in the CFTR gene and clinical manifestations of CF lung disease
• Currently on a stable dose of CFTR modulator therapy (elexacaftor/tezacaftor/ivacaftor) for a minimum of 60 days prior to Screening and agree to maintain current regimen through the 12-month Observation Period
• FEV1 ≥ 40% and \< 70% predicted (per Global Lung Function Initiative) at Screening, AND/OR experienced at least 2 pulmonary exacerbations in the last year requiring intravenous antibiotics Key Exclusion Criteria (Primary and Sub Study):
• Any prior gene therapy for any indication (Exception: mRNA-based therapies are not exclusionary)
• Active Mycobacterium abscessus infection requiring ongoing treatment at Screening
• Active allergic bronchopulmonary aspergillosis requiring management with systemic corticosteroids or antifungal therapy
• Contraindication to systemic corticosteroid therapy
• Requires chronic use of systemic corticosteroids or immunosuppressants to treat another condition
• If no known diagnosis of cystic fibrosis related diabetes (CFRD), Type I, or Type II diabetes: Hemoglobin A1C ≥ 6.5% at Screening
• If known diagnosis of CFRD, Type I or Type II diabetes: Hemoglobin A1C \> 7.5% at Screening
• Recent history of symptomatic hyperglycemia or unstable blood glucose levels as per Investigator's assessment
• Other conditions that, in the Investigator's opinion, may interfere with management of corticosteroid-related hyperglycemia
• Body Mass Index (BMI) \< 16
• Laboratory abnormalities at screening: * ALT, AST or GGT ≥ 3 × the upper limit of normal (ULN) * Total bilirubin ≥ 2 × ULN * Hemoglobin \< 10 g/dL
• Requirement for continuous or night-time oxygen supplementation
• Known CF liver disease with evidence of multilobular cirrhosis
• History of thrombosis (excluding catheter-related thrombosis) or conditions associated with increased risk of thrombosis
• 18 years and older
• Confirmed diagnosis of cystic fibrosis (CF) and CF lung disease including:
• Sweat chloride ≥ 60 mmol/L
• Mutation Status * Bi-allelic mutations in the CFTR gene, or * Single mutation in the CFTR gene and clinical manifestations of CF lung disease
• Ineligible for CFTR modulator therapy, or previously received modulator therapy but discontinued due to adverse effects.
• Forced expiratory volume in 1 second (FEV1) ≥ 50% and ≤ 90% of predicted (per Global Lung Function Initiative) at Screening
• Resting oxygen saturation ≥ 92% on room air at Screening Key Inclusion Criteria (Sub-Study):
• 18 years and older
• Confirmed diagnosis of cystic fibrosis (CF) and CF lung disease including:
• Sweat chloride ≥ 60 mmol/L
• Mutation Status * Bi-allelic mutations in the CFTR gene, or * Single mutation in the CFTR gene and clinical manifestations of CF lung disease
• Currently on a stable dose of CFTR modulator therapy (elexacaftor/tezacaftor/ivacaftor) for a minimum of 60 days prior to Screening and agree to maintain current regimen through the 12-month Observation Period
• FEV1 ≥ 40% and \< 70% predicted (per Global Lung Function Initiative) at Screening, AND/OR experienced at least 2 pulmonary exacerbations in the last year requiring intravenous antibiotics Key Exclusion Criteria (Primary and Sub Study):
• Any prior gene therapy for any indication (Exception: mRNA-based therapies are not exclusionary)
• Active Mycobacterium abscessus infection requiring ongoing treatment at Screening
• Active allergic bronchopulmonary aspergillosis requiring management with systemic corticosteroids or antifungal therapy
• Contraindication to systemic corticosteroid therapy
• Requires chronic use of systemic corticosteroids or immunosuppressants to treat another condition
• If no known diagnosis of cystic fibrosis related diabetes (CFRD), Type I, or Type II diabetes: Hemoglobin A1C ≥ 6.5% at Screening
• If known diagnosis of CFRD, Type I or Type II diabetes: Hemoglobin A1C \> 7.5% at Screening
• Recent history of symptomatic hyperglycemia or unstable blood glucose levels as per Investigator's assessment
• Other conditions that, in the Investigator's opinion, may interfere with management of corticosteroid-related hyperglycemia
• Body Mass Index (BMI) \< 16
• Laboratory abnormalities at screening: * ALT, AST or GGT ≥ 3 × the upper limit of normal (ULN) * Total bilirubin ≥ 2 × ULN * Hemoglobin \< 10 g/dL
• Requirement for continuous or night-time oxygen supplementation
• Known CF liver disease with evidence of multilobular cirrhosis
• History of thrombosis (excluding catheter-related thrombosis) or conditions associated with increased risk of thrombosis
BIOLOGICAL: 4D-710
Lung/Thoracic, Cystic Fibrosis Lung
CF, Cystic Fibrosis, Gene Therapy
UT Southwestern
Thoracotomy Versus Thoracoscopic Management of Pulmonary Metastases in Patients With Osteosarcoma
This phase III trial compares the effect of open thoracic surgery (thoracotomy) to thoracoscopic surgery (video-assisted thoracoscopic surgery or VATS) in treating patients with osteosarcoma that has spread to the lung (pulmonary metastases). Open thoracic surgery is a type of surgery done through a single larger incision (like a large cut) that goes between the ribs, opens up the chest, and removes the cancer. Thoracoscopy is a type of chest surgery where the doctor makes several small incisions and uses a small camera to help with removing the cancer. This trial is being done evaluate the two different surgery methods for patients with osteosarcoma that has spread to the lung to find out which is better.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Matthew Campbell
ALL
up to 50 Years old
PHASE3
NCT05235165
STU-2022-0187
Inclusion Criteria:
* Patients must be \< 50 years at the time of enrollment.
* Patients must have =\< 4 nodules per lung consistent with or suspicious for metastases, with at least one of which being \>= 3 mm and all of which must be =\< 3 cm size.
* Note: Patient must have eligibility confirmed by rapid central imaging review.
* Lung nodules must be considered resectable by either open thoracotomy or thoracoscopic surgery. Determination of resectability is made by the institutional surgeon.
* Patients must have a histological diagnosis of osteosarcoma.
* Patients must have evidence of metastatic lung disease at the time of initial diagnosis, or at time of 1st recurrence following completion of therapy for initially localized disease.
* Patients with newly diagnosed disease must have completed successful gross tumor resection for their primary tumor or surgical local control of primary tumor must be planned to be performed simultaneously with thoracic surgery.
* Newly diagnosed patients must be receiving or recently completed (within 60 days) systemic therapy considered by the treating physician to be standard treatment for newly diagnosed osteosarcoma (eg, cisplatin-doxorubicin or ifosfamide-based drug regimens) at the time of enrollment on this study. Dose and drug modifications for toxicity do not exclude patients from participation.
* Patients at time of 1st recurrence must have completed systemic therapy for their initial primary tumor, considered by the treating physician to be standard treatment for newly diagnosed osteosarcoma (eg, cisplatin-doxorubicin or ifosfamide-based drug regimens) at the time of enrollment on this study. Dose and drug modifications for toxicity do not exclude patients from participation.
Exclusion Criteria:
* Patients with unresectable primary tumor.
* Patients with pulmonary metastatic lesions that would require anatomic resection (lobectomy or pneumonectomy) or lesions that are defined as "central" (i.e., central lesion involves or is proximal to segmental bronchi and peripheral is lesion distal to segmental bronchi).
* Patients with chest wall or mediastinal based metastatic lesions, or with significant pleural effusion.
* Patients with disease progression at either the primary or pulmonary metastatic site while on initial therapy. Note: Once the patient has been enrolled on the study, additional computed tomography (CT) scans are not anticipated prior to thoracic surgery. Note: Some variation in nodule size measurements over the course of pre-operative therapy is anticipated and does not qualify for exclusion unless deemed true disease progression by the primary treatment team.
* Patients with evidence of extrapulmonary metastatic disease.
* Patients who received therapeutic pulmonary surgery for lung metastasis prior to enrollment.
* All patients and/or their parents or legal guardians must sign a written informed consent.
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met. PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, OTHER: Questionnaire Administration, PROCEDURE: Thoracoscopy, PROCEDURE: Thoracotomy
Osteosarcoma, Metastatic Osteosarcoma, Metastatic Malignant Neoplasm in the Lung, Bones and Joints, Lung/Thoracic
Children’s Health
A Study of a Mean Pulmonary Artery Pressure-Targeted Approach With Early and Rapid Treprostinil Therapy to Reverse Right Ventricular Remodeling in Participants With Pulmonary Arterial Hypertension (ARTISAN)
The primary objective of this study is to assess the effect of early and rapid treprostinil therapy for mean pulmonary artery pressure (mPAP) reduction to improve right ventricular (RV) function and reverse RV remodeling in participants with pulmonary arterial hypertension (PAH).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Khyati.Vadera@UTSouthwestern.edu
Kelly Chin
ALL
18 Years and over
PHASE4
NCT05203510
STU-2023-0020
Inclusion Criteria:
* Confirmed PAH (WHO Group 1) classified by one of the following subgroups:
* Idiopathic, heritable or drug/toxin induced (with the exception of amphetamine-induced PAH)
* Associated with repaired congenital systemic-to-pulmonary shunts (repaired ≥1 year)
* Associated with connective tissue disease
* Associated with human immunodeficiency virus infection
* Baseline visit right heart catheterization (RHC) must also meet the following criteria:
* mPAP \>35 mmHg
* Pulmonary vascular resistance (PVR) \>2 Wood units
* Pulmonary artery wedge pressure (PAWP) ≤15 mmHg
* On a stable dose of an endothelin receptor antagonist (ERA) and/or phosphodiesterase type 5 inhibitor (PDE-5i) or soluble guanylate cyclase stimulator (sGC) therapy or if treatment naïve, willing to take one of these medications in addition to study drug
* REVEAL Lite 2 risk score ≤9
* WHO FC II or III
* 6MWD \>165 meters
Exclusion Criteria:
PAH-related Exclusion Criteria:
* Prior or current use of epoprostenol, treprostinil, iloprost, beraprost, or selexipag
* Positive vasoreactivity test in idiopathic, heritable, or drug/toxin induced PAH
* Amphetamine use within the past 12 months
* WHO Groups 2, 3, 4, and 5
* Use of any other investigational drug, device, or therapy within 30 days of the Baseline visit
* Moderate or severe hepatic impairment (Child-Pugh Class B and C)
* Any other clinically significant illness or abnormal laboratory value(s) measured during screening that, in the opinion of the Investigator, might adversely affect interpretation of the study data or participant safety (for example, active infection, chronic thromboembolic pulmonary hypertension, or acute/recent deep vein thrombosis or pulmonary embolism)
* Chronic atrial fibrillation, multiple premature ventricular or atrial contractions of clinical significance, or any other condition that would interfere with proper cardiac gating during cMRI
* Permanent cardiac pacemaker or automatic internal cardioverter that would interfere with conduct of cMRI
* Metallic implant (for example, defibrillator, neurostimulator, hearing aid, permanent infusion device, implantable pump, or body plates/screws/bolts) that would interfere with conduct of cMRI
CardioMEMS-related Exclusion Criteria, if applicable:
* Previously implanted with CardioMEMS pulmonary artery Sensor or unwilling/unable to permit collection and perform upload (transmission) of pulmonary artery pressure (PAP) readings
* Unable to take dual antiplatelet or anticoagulation therapy for 30 days after CardioMEMS PA Sensor implantation unless the participant has an indication for warfarin or direct oral anticoagulant
NOTE: Other inclusion and exclusion criteria may apply. DRUG: Parenteral Treprostinil, DRUG: Oral Treprostinil
Pulmonary Arterial Hypertension, Cardiovascular
UT Southwestern
Study of XL092 in Combination With Immuno-Oncology Agents in Subjects With Solid Tumors (STELLAR-002)
This is a multicenter Phase 1b, open label, dose-escalation and cohort-expansion study, evaluating the safety, tolerability, PK, preliminary antitumor activity, and effect of biomarkers of XL092 administered alone, and in combination with nivolumab (doublet), nivolumab + ipilimumab (triplet) and nivolumab + relatlimab (triplet) in subjects with advanced solid tumors. In the Expansion Stage, the safety and efficacy of XL092 as monotherapy and in combination therapy will be further evaluated in tumor-specific Expansion Cohorts.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Hans Hammers
All
18 Years and over
Phase 1
NCT05176483
STU-2022-0177
Inclusion Criteria:
• Cytologically or histologically confirmed solid tumor that is unresectable, locally advanced or metastatic.
• Dose-Escalation Cohorts: Subjects with a solid tumor that is unresectable or metastatic and for which life-prolonging therapies do not exist or available therapies are intolerable or no longer effective.
• Expansion Cohort 1 (ccRCC): Subjects with unresectable advanced or metastatic RCC with a clear cell component who have not received prior systemic therapy.
• Note: Prior non-VEGF targeted adjuvant or neoadjuvant is allowed if disease recurrence occurred 6 months after the last dose.
• Expansion Cohort 2 (ccRCC): Subjects with unresectable advanced or metastatic RCC with a clear cell component.
• Must have radiographically progressed after a combination therapy consisting of a PD-1/PD-L1 targeting mAb with a VEGFR-TKI or a PD-1 targeting mAb with a CTLA-4 mAb as the preceding line of therapy.
• Must have received no more than one prior systemic anticancer therapy for unresectable advanced or metastatic renal cell carcinoma.
• Expansion Cohort 3 (mCRPC): Men with metastatic adenocarcinoma of the prostate.
• Must have progressed during or after one NHT given for castration-sensitive locally advanced (T3 or T4) or metastatic castration-sensitive prostate cancer (CSPC), M0 CRPC, or mCRPC.
• Expansion Cohort 4 (UC, ICI-naive): Subjects with histologically confirmed unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra).
• Must have progressed during or after prior first-line platinum-based combination therapy, including subjects who received prior neoadjuvant or adjuvant platinum-containing therapy with disease recurrence < 12 months from the end of last therapy.
• Must have received no more than 1 prior line of systemic anticancer therapy for unresectable, locally advanced or metastatic disease.
• Expansion Cohort 5 (UC, ICI-experienced): Subjects with histologically confirmed unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra).
• Must have progressed during or after prior PD-1/PD-L1 targeting ICI therapy given as monotherapy, combination therapy, maintenance therapy or adjuvant therapy.
• Must have received no more than 2 prior lines of systemic anticancer therapy for unresectable advanced or metastatic disease.
• Expansion Cohort 6 (nccRCC): Subjects with unresectable advanced or metastatic nccRCC of the following subtypes: Papillary RCC (any type), unclassified RCC, and translocation-associated. Among the eligible histologic subtypes, sarcomatoid features are allowed.
• No prior systemic anticancer therapy is allowed except adjuvant or neoadjuvant therapy if disease recurrence occurred at least 6 months after the last dose.
• Expansion Cohort 7 (HCC): Subjects with inoperable locally advanced, recurrent, or metastatic HCC that is not amenable to curative treatment or locoregional therapy.
• Expansion Cohort 8 (NSCLC): Subjects with Stage IV non-squamous NSCLC with positive PD-L1 expression (tumor proportion score [TPS] 1-49%) and without prior systemic anticancer therapy for metastatic disease.
• Expansion Cohort 9 (NSCLC): Subjects with Stage IV non-squamous NSCLC who have radiologically progressed following treatment with one prior immune checkpoint inhibitor (anti-PD-1 or anti-PD-L1) for metastatic disease.
• Expansion Cohort 10 (CRC): Subjects with histologically confirmed unresectable, locally advanced, or metastatic adenocarcinoma of the colon or rectum.
• Expansion Cohort 11 (HNSCC): Subject with inoperable, refractory, recurrent or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx. PD-L1 combined positive score (CPS) ≥1.
• For all Expansion Cohorts except Cohort 3: Measurable disease per RECIST 1.1 as determined by the Investigator.
• For expansion cohorts only: Archival tumor tissue material, if available, or fresh tumor tissue if it can be safely obtained.
• Recovery to baseline or ≤ Grade 1 CTCAE v5 from AE(s) related to any prior treatments unless AE(s) are deemed clinically nonsignificant by the Investigator and/or stable on supportive therapy.
• Karnofsky Performance Status (KPS) ≥ 70%.
• Adequate organ and marrow function.
• Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception.
• Female subjects of childbearing potential must not be pregnant at screening.
Exclusion Criteria:
• For all Dose-Escalation cohorts: Prior treatment with XL092. For all Expansion Cohorts: Prior treatment with XL092, nivolumab, ipilimumab or relatlimab with the following exceptions: Prior PD-1/PD-L1, LAG-3 and CTLA-4 targeting therapy for locally advanced or metastatic disease is allowed for Cohort 2 (ccRCC), Cohort 5 (UC), Cohort 9 (NSCLC).
• For all Dose-Escalation Cohorts and Expansion Cohort 2 (ccRCC), 3 (mCRPC), Cohort 5 (UC), Cohort 9 (NSCLC) and Cohort 10 (CRC): Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
• For Cohort 3 (mCRPC): Receipt of abiraterone within 1 week; cyproterone within 10 days; or receipt of flutamide, nilutamide, bicalutamide, enzalutamide, or other androgen receptor inhibitors within 2 weeks before first dose of study treatment.
• For all Dose-Escalation Cohorts and Expansion Cohort 2 (ccRCC), Cohort 3 (mCRPC), Cohort 5 (UC), Cohort 9 (NSCLC) and Cohort 10 (CRC): Receipt of any type of anticancer antibody or systemic chemotherapy within 4 weeks before first dose of study treatment.
• Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study treatment.
• Prior external radiation therapy for bone metastasis within 2 weeks, for other tumor sites within 4 weeks, and prior radium-223 therapy within 6 weeks before first dose of study treatment, unless otherwise specified.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy (including radiosurgery) or surgically removed and stable for at least 4 weeks before first dose of study treatment.
• Concomitant anticoagulation with oral anticoagulants and platelet inhibitors.
• Administration of a live, attenuated vaccine within 30 days prior to enrollment.
• Uncontrolled, significant intercurrent or recent illness.
• Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per electrocardiogram (ECG) within 14 days before first dose of study treatment.
• Subjects with inadequately treated adrenal insufficiency.
• Pregnant or lactating females.
• Any other active malignancy within two years before first dose of study treatment, except for locally curable cancers that have been apparently cured such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
• For Cohort 2 (ccRCC, 2L): Receipt of a prior triplet therapy including a VEGFR-TKI, a PD1 targeting mAb, and a CTLA-4 mAb.
• For Cohort 3 (mCRPC): Receipt of a taxane-based chemotherapy for mCRPC.
• For Cohort 4 (UC, ICI-naïve): Subjects who have had recurrence within the 6 months of completing adjuvant anti-PD-(L)1 treatment.
• For Cohort 6 (nccRCC, 1L): Subjects with chromophobe, renal medullary carcinoma, or pure collecting duct nccRCC.
• For Cohort 7 (HCC):
• Documented hepatic encephalopathy (HE) within 6 months before randomization (see Section 6.5.2 for a case definition of HE).
• Clinically meaningful ascites (ie, ascites requiring paracentesis or escalation in diuretics) within 6 months before randomization.
• Subjects who have received any local anticancer therapy including surgery, PEI, RFA, MWA, transarterial chemoembolization (TACE), or transarterial radioembolization (TARE) within 28 days prior to randomization.
• Subjects with known fibrolamellar carcinoma, sarcomatoid HCC, or mixed hepatocellular cholangiocarcinoma
• For Cohort 10 (CRC, 2L+): Receipt of prior therapy with regorafenib and/or TAS-102.
• For Cohort 11 (HNSCC): Primary tumor site of the nasopharyngeal area.
• For Cohorts 1 (ccRCC, 1L), 2 (ccRCC, 2L), 4, 5 (UC), 7 (HCC), 8 (NSCLC 1L PD-L1 low), 9 (NSCLC, 2L+), 10 (CRC, MSS, 2L+), and 11 (HNSCC):
• Troponin T (TnT) or I (TnI) > 2 × institutional ULN. Note: Additional Inclusion and Exclusion criteria may apply.
Drug: XL092, Drug: Nivolumab, Drug: Ipilimumab, Drug: Nivolumab, Drug: Nivolumab, Drug: Nivolumab + Relatlimab
Non-Small Cell Lung Cancer, Hepatocellular Carcinoma, Colorectal Cancer, Renal Cell Carcinoma, Head and Neck Squamous Cell Carcinoma, Urothelial Carcinoma, Solid Tumor, Kidney, Prostate, Urinary Bladder, Metastatic Castration-resistant Prostate Cancer
UT Southwestern
Premedication for Less Invasive Surfactant Administration Study (PRELISA) (PRELISA)
The purpose of this study is to conduct a double blinded randomized control trial to determine the safety and efficacy of using IV fentanyl and atropine prior to Less Invasive Surfactant Administration (LISA) procedure in preterm infants with Respiratory Distress Syndrome compared to the local standard of care to perform this procedure without any premedication. Hypothesis: In infants greater than or equal to 29 weeks gestational age requiring the Less Invasive Surfactant Administration procedure, premedication with a combination of IV atropine and IV fentanyl will be associated with fewer combined bradycardia events, defined as heartrate less than 100 beats per minute for longer than 10 seconds, and hypoxemia events, defined as saturations less than or equal to 80% for longer than 30 seconds, during the procedure compared with placebo. Specific Aims: - To determine if infants receiving IV fentanyl and atropine prior to LISA will have a decrease in hypoxemia and bradycardia events during the procedure compared to infants receiving placebo - To determine if infants receiving premedication prior to Less Invasive Surfactant Administration will have higher procedure first attempt success rate compared with infants receiving placebo - To determine the effect of premedication on cerebral oxygenation compared to placebo during and for 12 hours after Less Invasive Surfactant Administration using cerebral Near Infrared Spectroscopy - To determine the effect of premedication prior to Less Invasive Surfactant Administration on the need for mechanical ventilation for 24 hours after the procedure
Call 214-648-5005
studyfinder@utsouthwestern.edu, Kathryn.Mazioniene@UTSouthwestern.edu
Venkatakrishna Kakkilaya
All
0 Hours to 72 Hours old
Phase 4
NCT05065424
STU-2021-0380
Inclusion Criteria:
• Infants ≥29 weeks gestational age between 0-72 hours of life on CPAP for respiratory support who qualify for the LISA procedure as determined by the primary team using Parkland OPTISURF guidelines
Exclusion Criteria:
• Infants requiring intubation prior to surfactant therapy
• Infants with known severe congenital anomalies (including complex congenital heart disease, airway, and central nervous system anomalies)
• Infants born to mothers with known opioid addiction or in a methadone treatment program
Drug: IV Atropine and Fentanyl Premedication Arm, Drug: IV Normal Saline Placebo Arm
Respiratory Distress Syndrome, Newborn, Lung/Thoracic
Premedication for Less Invasive Surfactant Administration, Fentanyl and Atropine for Less Invasive Surfactant Administration, Cerebral Near Infrared Spectroscopy monitoring in neonates, Premedication for LISA, Fentanyl and Atropine for LISA, Cerebral NIRS monitoring in neonates
Parkland Health & Hospital System
Phase 1/2 Study of Avutometinib (VS-6766) + Sotorasib With or Without Defactinib in KRAS G12C NSCLC Patients (RAMP203)
This study will assess the safety and efficacy of avutometinib (VS-6766) in combination with sotorasib with or without defactinib in patients with KRAS G12C Non-Small Cell Lung Cancer (NSCLC) in patients who have been exposed to prior G12C inhibitor and those who have not been exposed to prior G12C inhibitor.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Jonathan Dowell
ALL
18 Years to old
PHASE1
NCT05074810
STU-2023-0799
Inclusion Criteria:
* Male or female patients ≥ 18 years of age
* Histologic or cytologic evidence of NSCLC
* Known KRAS G12C mutation
* Have not received a KRAS inhibitor to be included in Part A (avutometinib + sotorasib) and Part B (avutometinib + sotorasib + defactinib), Cohort 1
* Received at least 1 dose of a G12C inhibitor to be included in Part A (avutometinib + sotorasib + defactinib) and Part B, Cohort 2
* Must have received appropriate treatment with at least one prior systemic regimen, but no more than 2 prior regimens, for Stage 3B-C or 4 NSCLC
* Measurable disease according to RECIST 1.1
* An Eastern Cooperative Group (ECOG) performance status ≤ 1
* Adequate organ function
* Adequate recovery from toxicities related to prior treatments
* Agreement to use highly effective method of contraceptive
Exclusion Criteria:
* Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy
* History of prior malignancy, with the exception of curatively treated malignancies
* Major surgery within 4 weeks, minor surgery within 2 weeks (excluding placement of vascular access)
* History of treatment with a direct and specific inhibitor of MEK
* Exposure to strong CYP3A4 inhibitors or inducers within 14 days prior to the first dose and during the course of therapy
* Symptomatic brain metastases requiring steroids or other local interventions.
* Known SARS-Cov2 infection ≤28 days prior to first dose of study therapy
* Known hepatitis B, hepatitis C, or human immunodeficiency virus infection that is active
* Active skin disorder that has required systemic therapy within the past year
* History of rhabdomyolysis
* Concurrent ocular disorders
* Concurrent heart disease or severe obstructive pulmonary disease
* Inability to swallow oral medications
* Female patients that are pregnant or breastfeeding
* Previously treated with sotorasib and were dose reduced due to toxicity DRUG: avutometinib and sotorasib, DRUG: avutometinib and sotorasib and defactinib
Non Small Cell Lung Cancer, Lung/Thoracic, KRAS Activating Mutation
NSCLC, KRAS G12C
UT Southwestern
Metabolic Remodeling in Pulmonary Arterial Hypertension (PAH)
Pulmonary arterial hypertension (PAH) is a progressive disease in which clinically relevant symptoms present a few years after the onset in rise of pulmonary arterial pressure. Increased PA pressure presents an overload on the right ventricle (RV), with RV failure being a common cause of mortality in PAH. Current therapeutic targets help reduce vascular resistance and RV afterload, however, RV dysfunction may continue to progress. Therefore, the reason for RV failure in PAH cannot be contributed to altered vascular hemodynamics alone but may be related to metabolic alterations and failure of adaptive mechanisms in the RV. Providing a better understanding of metabolic remodeling in RV failure may permit the development of RV-targeted pharmacological agents to maintain RV function despite increased pulmonary vascular pressures. This study will evaluate how cardiac metabolism changes in response to pulmonary vasodilator therapy in patients with pulmonary arterial hypertension.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Clarissa.Osagie@UTSouthwestern.edu
Kara Goss
All
18 Years to 75 Years old
NCT04968210
STU-2020-1351
Inclusion Criteria:
• WHO group 1 PAH, characterized by mean pulmonary artery pressure ≥25 mmHg, PVR >3 Woods units, and pulmonary capillary wedge pressure or left ventricular end diastolic pressure ≤15 mmHg. Participants must be further classified as idiopathic PAH (IPAH) or connective tissue disease associated PAH (CTD-PAH).
• New York Heart Association (NYHA) classification I - III criteria of heart failure.
• Vasodilator therapy naïve, with the intent to initiate pulmonary vasodilator therapy.
• Age 18 - 75.
• English speaking and able to provide informed consent.
Exclusion Criteria:
• Recent syncope.
• Baseline 6MWD < 400 feet or NYHA class IV heart failure.
• Metabolic disorders such as uncontrolled diabetes (A1c > 8%) that may alter cardiac metabolism.
• Baseline use of oral steroids.
• FEV1/FVC <60%
• Contraindications to MRI, including those noted on the UTSW MRI Screening Form such as implants contraindicated at 3T, pacemakers, Implantable Cardioverter Defibrillators (ICD), or significant claustrophobia.
• Weight >210 lbs (exceeds current IND weight-based dosing guidelines) 8 . Women who are pregnant, lactating or planning on becoming pregnant during the study.
• Not suitable for study participation due to other reasons at the discretion of the investigators
Pulmonary Arterial Hypertension
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
Lymphoma, Sarcoma, Anorexia, Multiple Myeloma, Mycosis Fungoides, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, Carcinoid Tumor, Cardiovascular, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Leukemia, Other, Hodgkins Lymphoma, Heart, Kaposis sarcoma, Leukemia, Not Otherwise Specified, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Other Hematopoietic, Psychiatric Disorders, Small Intestine, Soft Tissue, Unknown Sites, Ill - Defined Sites
UT Southwestern
Ruxolitinib for Cancer Cachexia
To assess toxicity with use of Ruxolitinib in NSCLC cachexia patients; to associate levels of JAK/STAT signaling in blood, adipose, and muscle pre- and post-ruxolitinib treatment with changes in cachexia and anorexia.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tu Dan
ALL
18 Years and over
EARLY_PHASE1
NCT04906746
STU-2021-0475
Inclusion Criteria:
• Male or female subjects at least 18 years of age;
• Ability to understand and the willingness to sign a written informed consent;
• Histological or biopsy proven Non-Small Cell Lung Cancer (squamous or non-squamous);
• ECOG performance status of 0-2;
• Patients with evidence of: * cancer cachexia, defined by the International Cancer Cachexia Consensus Definition (\>5% weight loss over the preceding 6 months prior to diagnosis); OR * Patients with evidence of cancer pre-cachexia, defined by the International Cancer Cachexia Consensus Definition (0 to \<=5% weight loss over the preceding 6 months prior to diagnosis);
• Any de novo stage IV NSCLC disease diagnosis as defined by AJCC 8th edition staging. Staged with PET/CT, MRI brain, or other acceptable staging tool; measurable disease as defined by RECIST 1.1;
• Adequate end-organ function, based on routine clinical and laboratory workup and institutional guidelines, as determined by oncology team offering patient standard of care therapy, including:
• ANC \>1,000 cells/µl, Platelets \> 100,000 cells/µl, Hemoglobin \> 10.0 g/dl;
• Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 45 ml/min;
• Total bilirubin ≤ 1.5 x ULN (or direct bilirubin below the ULN), AST and ALT ≤ 2.5 x ULN;
• International normalized ratio (INR) (or prothrombin time (PT)) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy, if values are within the intended therapeutic range;
• Women of child-bearing potential (WOCBP) and men 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 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: a. Has not undergone a hysterectomy or bilateral oophorectomy; or b. 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);
• Male subjects who are surgically sterile or are using a medically acceptable form of contraception for 90 days following the completion of therapy;
• Life expectancy anticipated to be 6 months or greater;
• No prior therapy for advanced lung cancer.
Exclusion Criteria:
• Subjects with confirmed stage I-III NSCLC;
• Patients whose tumors have actionable mutations treatable with targeted therapies;
• Patients with no evidence of cancer cachexia, defined by the International Cancer Cachexia Consensus Definition (\>5% weight loss over the preceding 6 months prior to diagnosis); OR Patients with no evidence of cancer pre-cachexia, defined by the International Cancer Cachexia Consensus Definition (0 to \<=5% weight loss over the preceding 6 months prior to diagnosis);
• Active malignancy other than lung cancer that requires concurrent treatment other than hormonal therapy and is deemed by the treating physicians to be likely to affect the subject's survival duration;
• Subjects who have not recovered or have disease control from prior treatment-related to toxicities judged by treating physician;
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib or other agents used in study;
• Uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements;
• Inadequate liver or renal function, if out of the acceptable ranges of the inclusion criteria;
• Significant bacterial, fungal, parasitic, or viral infection requiring treatment;
• Previous treatment with a JAK inhibitor;
• Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of ruxolitinib;
• Females who are pregnant, breast-feeding or plan to become pregnant;
• Participation in other clinical trials either to treat diagnosed lung or other cancers (patients on registry trials are eligible);
• Requirement for treatment with drugs that may, in the judgment of the treating investigator, create a risk for a precipitous change in patient's health;
• Any other conditions that, in the Investigator's opinion, might indicate the subject to be unsuitable for the study;
• Life expectancy of less than 6 months;
• Prior therapy for the newly diagnosed advanced lung cancer.
• Patients taking therapies that are strong CYP3A4 inhibitors and fluconazole.
DRUG: Identify any dose-limiting toxicity (DLT) when ruxolitinib is administered to NSCLC cachexia patients.
Cachexia, Stage IV Non-Small Cell Lung Cancer, Lung/Thoracic
Lung cancer, Anorexia, Metabolism, Adipose, Muscle wasting
UT Southwestern; Parkland Health & Hospital System
PLAN Intervention to Enhance Engagement of Latino Cancer Patients in Advanced Care Planning
This trial tests whether Planning for Your Advance Care Needs (PLAN) intervention works to enhance Latino patients' understanding of and engagement in advanced care planning. The PLAN intervention may be an effective method to help people with cancer plan for and talk about advance care planning (the care they would want if they were unable to communicate) with their loved ones and doctors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Mary Paulk
ALL
18 Years and over
NA
NCT04889144
STU-2021-0192
Inclusion Criteria:
* Identifying ethnically as Latino.
* Locally advanced or metastatic cancer and/or have experienced disease progression on at least first-line chemotherapy.
* Ability to provide informed consent.
Exclusion Criteria:
* Not fluent in English or Spanish.
* Severely cognitively impaired (as measured by Short Portable Mental Status Questionnaire scores of \>= 6 to be delivered by trained study research staff during screening).
* Too ill or weak to complete the interviews (as judged by interviewer).
* Currently receiving palliative care/hospice at the time of enrollment (to allow prediction of \[advanced care planning\] ACP).
* Children and young adults under age 18.
* Patients deemed inappropriate for the study by their treating oncologist. OTHER: Communication Intervention, OTHER: Best Practice, OTHER: Questionnaire Administration
Lymphoma, Sarcoma, Metastatic Malignant Solid Neoplasm, Cervix, Colon, Esophagus, Gall Bladder, Head and Neck, Liver, Lung/Thoracic, Other Female Genital, Other Urinary, Ovary, Pancreas, Stomach, Locally Advanced Malignant Solid Neoplasm
advance care planning, Latinos, communication
UT Southwestern; Parkland Health & Hospital System
Study of Sotatercept in Newly Diagnosed Intermediate- and High-Risk PAH Participants (MK-7962-005/A011-13) (HYPERION)
The objective of this study is to evaluate the effects of sotatercept (MK-7962, formerly called ACE-011) treatment (plus background pulmonary arterial hypertension (PAH) therapy) versus placebo (plus background PAH therapy) on time to clinical worsening (TTCW) in participants who are newly diagnosed with PAH and are at intermediate or high risk of disease progression.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Ramatoulaye.Diallo@UTSouthwestern.edu
Kelly Chin
ALL
18 Years and over
PHASE3
NCT04811092
STU-2022-0704
Inclusion Criteria:
Eligible participants must meet all of the following criteria to be enrolled in the study:
• Age ≥ 18 years
• Documented diagnostic right heart catheterization (RHC) within 12 months of screening documenting a minimum PVR of ≥ 4 Wood units and pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) of ≤ 15 mmHg, with the diagnosis of WHO PAH Group 1 in any of the following subtypes: * Idiopathic PAH * Heritable PAH * Drug/toxin-induced PAH * PAH associated with connective tissue disease * PAH associated with simple, congenital systemic to pulmonary shunts at least 1 year following repair
• Symptomatic PAH classified as WHO FC II or III
• Either Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) Lite 2 Risk Score ≥ 6 or Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) 2.0 risk score ≥2 (intermediate to-low-risk or above)
• Diagnosis of PAH within 12 months of screening and on stable doses of a double or triple combination of background PAH therapies and diuretics (if any) for at least 90 days prior to screening
• Six-minute walk distance ≥ 150 m repeated twice at screening at least 4 hours apart, but no longer than 1 week apart, and both values are within 15% of each other (calculated from the highest value)
• Females of childbearing potential must meet the following criteria: * Have 2 negative urine or serum pregnancy tests as verified by the investigator prior to starting study drug administration; she must agree to ongoing urine or serum pregnancy testing during the course of the study and until 8 weeks after the last dose of the study drug * If sexually active with a male partner, have used highly effective contraception without interruption, for at least 28 days prior to starting the investigational product AND agreed to use the same highly effective contraception in combination with a barrier method during the study (including dose interruptions) and for 16 weeks (112 days) after discontinuation of study treatment * Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration of the study and for at least 16 weeks (112 days) after the last dose of study treatment
• Male participants must meet the following criteria: * Agree to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (e.g., polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for at least 16 weeks (112 days) following investigational product discontinuation, even if he has undergone a successful vasectomy * Refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study treatment
• Ability to adhere to study visit schedule and understand and comply with all protocol requirements
• Ability to understand and provide written informed consent
Exclusion Criteria:
Participants will be excluded from the study if any of the following criteria are met:
• Diagnosis of pulmonary hypertension (PH) WHO Groups 2, 3, 4, or 5
• Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus (HIV)-associated PAH and PAH associated with portal hypertension, schistosomiasis-associated PAH, pulmonary veno occlusive disease, and pulmonary capillary hemangiomatosis
• Hemoglobin at screening above gender-specific upper limit of normal (ULN), per local laboratory test
• Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) \> 180 mmHg or sitting diastolic BP \> 110 mmHg during the Screening Visit after a period of rest
• Baseline systolic BP \< 90 mmHg at screening
• Pregnant or breastfeeding women
• Any of the following clinical laboratory values at the Screening Visit: * Estimated glomerular filtration rate \< 30 mL/min/1.73 m2 (as defined by MDRD equation) * Serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels \> 3 × ULN * Platelet count \< 50,000/mm3 (\< 50.0 × 109 /L)
• Currently enrolled in or have completed any other investigational product study within 30 days for small molecule drugs or within 5 half-lives for investigational biologics prior to the date of documented informed consent
• Known allergic reaction to sotatercept (ACE-011), its excipients, or luspatercept
• History of pneumonectomy
• Pulmonary function test values of forced vital capacity \< 60% predicted within 1 year prior to the Screening Visit
• Stopped receiving any PH chronic general supportive therapy (e.g., diuretics, oxygen, anticoagulants, and digoxin) within 60 days prior to the Screening Visit
• Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to the Screening Visit or planned initiation during the study (participants who are stable in the maintenance phase of a program and who will continue for the duration of the study are eligible)
• Untreated more than mild obstructive sleep apnea
• History of known pericardial constriction
• History of restrictive or congestive cardiomyopathy
• History of atrial septostomy within 180 days prior to the Screening Visit
• Electrocardiogram with Fridericia's corrected QT interval \> 500 ms during the Screening Period
• Personal or family history of long QT syndrome or sudden cardiac death
• Left ventricular ejection fraction \< 50% on historical echocardiogram (ECHO) within 1 year prior to the Screening Visit
• Any current or prior history of symptomatic coronary disease (prior myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain) in the past 6 months prior to the Screening Visit
• Cerebrovascular accident within 3 months prior to the Screening Visit
• Acutely decompensated heart failure within 30 days prior to the Screening Visit, as per investigator assessment
• Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease
• Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, and vasopressin) within 30 days prior to the Screening Visit
• Has an active malignancy with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or prostate cancer that is not currently or expected, during the study, to be treated with radiation therapy, chemotherapy, and/or surgical intervention, or hormonal treatment
DRUG: Sotatercept, OTHER: Placebo
Pulmonary Arterial Hypertension, Cardiovascular, Lung/Thoracic
Pulmonary, Hypertension, Sotatercept
UT Southwestern
A Phase 1 Study With ABBV-CLS-484 in Subjects With Locally Advanced or Metastatic Tumors
The study will assess the safety, PK, PD, and preliminary efficacy of ABBV-CLS-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 ABBV-CLS-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:
• Subjects with histologically or cytologically proven metastatic or locally advanced tumors, for which no effective standard therapy exists, or where standard therapy has failed. Subjects must have received at least 1 prior systemic anticancer therapy for the indication being considered.
For Monotherapy Dose Expansion only:
* Subjects 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
* Subjects no recent history of hemorrhage, including hemoptysis, hematemesis, or melena
* Subjects 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: Programmed Cell Death-1 (PD-1) Inhibitor, DRUG: Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)
Cervix, Colon, Kidney, Lung/Thoracic, Ovary, Advanced Solid Tumor Cancer
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
A Long-term Follow-up Study of Sotatercept for PAH Treatment (MK-7962-004/A011-12) (SOTERIA)
This study is being conducted to assess the long-term safety, tolerability, and efficacy of sotatercept (MK-7962, formerly called ACE-011) in participants with Pulmonary Arterial Hypertension (PAH). This open-label, long-term follow-up (LTFU) study is supported by data from the PULSAR study (Phase 2, NCT03496207) in which treatment with sotatercept resulted in hemodynamic and functional improvements in the study participants, including those receiving maximal PAH therapy with double/triple drug combinations and intravenous prostacyclin. The primary objective of this open-label, LTFU study is to evaluate the long-term safety and tolerability of sotatercept when added to background PAH therapy in adult participants with PAH who have completed prior sotatercept studies. The secondary objective is to evaluate continued efficacy in adult participants with PAH who have completed prior sotatercept studies.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Ramatoulaye.Diallo@UTSouthwestern.edu
Kelly Chin
ALL
18 Years and over
PHASE3
NCT04796337
STU-2022-0826
Inclusion Criteria:
* Have completed their current respective PAH sotatercept clinical study and its requirements, and must not have discontinued early
* Must be willing to adhere to the study visit schedule and understand and comply with all protocol requirements
* Must have the ability to understand and provide documented informed consent
* Females of childbearing potential must:
* Have a negative pregnancy test as verified by the investigator prior to starting study drug administration; she must agree to ongoing pregnancy testing during the course of the study and until 8 weeks after the last dose of the study drug
* If sexually active, have used, and agree to continue to use highly effective contraception in combination with a barrier method without interruption, for at least 28 days prior to starting the investigational product, during the study (including dose interruptions), and for 16 weeks (112 days) after discontinuation of study drug
* Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration of the study and for at least 16 weeks (112 days) after the last dose of study drug
* Male participants must:
* Agree to use a condom, defined as a male latex condom or non latex condom NOT made out of natural (animal) membrane (e.g., polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for at least 16 weeks (112 days) following investigational product discontinuation, even if he has undergone a successful vasectomy
* Refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study drug
* Must agree not to participate in any other trials of investigational drugs/devices while they are enrolled in the MK-7962-004 study
Exclusion Criteria:
* Did not participate in a sotatercept PAH parent trial
* Missed more than the equivalent of 4 consecutive doses between the end of parent study and the start of this study.
* Presence of an ongoing serious adverse event (SAE) that occurred during a PAH sotatercept clinical study that is assessed to be possibly or probably related to sotatercept
* Pregnant or breastfeeding females BIOLOGICAL: Sotatercept
Pulmonary Arterial Hypertension, PAH
UT Southwestern
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
Interstitial Lung Disease, Idiopathic Pulmonary Fibrosis
Treprostinil, IPF, ILD
UT Southwestern
AZithromycin Therapy in Preschoolers With a Severe Wheezing Episode Diagnosed at the Emergency Department (AZ-SWED)
AZ-SWED is a parallel group, double blind, placebo control efficacy clinical trial with two separate hypotheses. The trial will compare the 5-day outcome of preschool children presenting to an Emergency Department (ED) with an acute, severe wheezing episode and treated with either once daily oral Azithromycin (12 mg/kg/day for 5 days) or placebo. The AZ-SWED researchers will make separate comparisons in children in whom specific pathogenic bacteria are isolated from nasopharyngeal swabs, and in those in whom they are not isolated. The primary outcome will be the Asthma Flare-up Diary for Young Children (ADYC), a validated instrument that caregivers will transmit electronically daily after discharge from the ED. Families will be contacted daily during the five-day treatment to collect the ADYC, and to assess compliance and complications. A randomly chosen subset of enrolled children will participate in two follow-up visits 5-8 days and 14-21 days after visit 1 to assess development of resistance to study drug and treatment response related changes in the airway microbiome.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Maraki.Shebeshi@UTSouthwestern.edu
Mohamed Badawy
All
18 Months to 60 Months old
Phase 3
NCT04669288
STU-2023-0897
Inclusion Criteria:
• Age 18 months to <60 months.
• The presence of expiratory wheezing as ascertained by a physician or nurse practitioner at admission to the ED.
• A Pediatric Respiratory Assessment Measurement (PRAM) score of greater than or equal to 4 at any time during the ED admission.
Exclusion Criteria:
• Presence of acute infection that requires systemic antibiotics, as determined by the physician.
• Current or previous use of systemic antibiotics within the last 2 weeks.
• Current or previous use of a steroid for wheezing within the last 2 weeks.
• Suspected foreign body induced aspiration during the last 2 weeks.
• A known systemic illness (other than allergy) including but not limited to:
• Recurrent seizures
• Gastroesophageal reflux (GER) requiring medical treatment
• Major congenital anomalies
• Physical and intellectual delay
• Cerebral palsy
• A history of chest surgery
• Tuberculosis or other chronic infections
• Primary or secondary immunodeficiency
• Gastrointestinal malformation or disease
• Cardiac disorder (except for a hemodynamically insignificant atrial septal defect (ASD), ventricular septal defect (VSD) or benign heart murmur)
• Born at less than 36 weeks estimated gestational age.
• Received oxygen for more than 5 days in the neonatal period, or received invasive mechanical ventilation.
• Significant developmental delay / failure to thrive, defined as a child plotting less than 3rd percentile.
• Any chronic lung disease.
• The study intervention poses undue risk to patient in the opinion of the treating physician
• Known sensitivity or allergy to AZ.
• Participation in the evaluation of a drug or medical device currently or within the last 30 days.
• Previous enrollment into this trial.
• Inability of the parent or guardian to speak English or Spanish.
• Positive PCR or antigen test for COVID-19 from hospital/doctor's office/testing center within the past 30 days.
Drug: Azithromycin, Drug: Placebo
Asthma, Lung/Thoracic, Wheezing
Wheezing Lower Respiratory Illness (WLRI)
Children’s Health
FUVID Study: Functional Characterization of Children with Chronic Venous Thromboembolic Disease
This is a multi-center prospective cohort study of patients with first-episode deep venous thrombosis and pulmonary embolism.
Call 214-648-5005
studyfinder@utsouthwestern.edu, kendra.malone@childrens.com, FUVID@utsouthwestern.edu
Ayesha Zia
ALL
8 Years to 21 Years old
NCT04583878
STU-2020-0868
Inclusion Criteria:
* Ages 8 to ≤ 21 years
* Participant must be able to speak and understand English
* Be willing to participate and able to comply with the study protocol
* For participants with PE: Children with acute, radiologically confirmed pulmonary embolism (PE) with our without DVT
* For control group: Cohort 1: Children who are prescribed physical activity restrictions for 2 up to 12 weeks following any minor outpatient surgery or, minor injury (surgery or injury is referred to as "diagnosis" hereafter) Cohort 2: Children who are not prescribed physical activity restrictions and are otherwise considered to be healthy.
Exclusion Criteria:
* Congenital heart disease with abnormal pulmonary circulation or with in-situ pulmonary artery thrombosis
* Chronic kidney disease
* Chronic inflammatory or an autoimmune disorder (such as systemic lupus erythematosus, juvenile rheumatoid disorder, inflammatory bowel disease, and sickle cell disease)
* A metabolic or endocrinological disorder such as diabetes mellitus or thyroid disorder
* History of or active cancer
* Pregnant
* Musculoskeletal limitations to exercise expected to be present uptil 4 months post-diagnosis
* Weight ≥ 300 lbs
* Contraindications to magnetic resonance imaging
* Frequent severe exacerbations of asthma defined by two or more bursts of systemic glucocorticoids (more than three days each) in the previous year or at least one hospitalization, intensive care unit stay or mechanical ventilation in the previous year. Patients should also be excluded if there are daily symptoms of asthma requiring daily use of short-acting bronchodilators such as albuterol or levalbuterol administration. The use of controller medications such as daily inhaled corticosteroids for mild persistent asthma is not exclusionary.
* Has any other medical condition, which in the opinion of the investigator may potentially compromise the safety or compliance of the patient or may preclude the patient's successful completion of the clinical study
Additional exclusion criteria for participants with PE:
* Prior history of DVT or PE (upper extremity, cerebral sinus venous thrombosis and abdominal thromboses encountered as a neonate are not exclusion criteria)
* Lack of anticoagulant treatment for the acute VTE due to contraindications DIAGNOSTIC_TEST: Blood draw (Visit 1), DIAGNOSTIC_TEST: Blood draw (Visits 2 and 3)
Pulmonary Embolism, Deep Venous Thrombosis, Cardiovascular, Lung/Thoracic
UT Southwestern; Children’s Health; Parkland Health & Hospital System
Phase 2 Trial of Afatinib Plus Prednisone for Advanced Squamous NSCLC
To determine the efficacy of combined afatinib and prednisone in previously treated advanced squamous NSCLC
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Sheena Bhalla
ALL
18 Years and over
PHASE2
NCT04497584
STU-2020-1363
Inclusion Criteria:
* Written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure.
* Previously treated (up to three prior lines of therapy), histologically proven advanced squamous NSCLC.
* No prior treatment with EGFR inhibitors, IMIDs (eg, thalidomide, lenalidomide), or anti-TNF antibodies.
* No treatment with systemic glucocorticoids within 3 weeks of initiation of study therapy (topical and inhaled glucocorticoids are permitted).
* Age ≥ 18 years.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Adequate organ and marrow function as defined below:
* absolute neutrophil count ≥ 1,000/μL
* platelets ≥ 50,000/μl
* total bilirubin within normal institutional limits
* AST(SGOT)/ALT(SPGT) ≤ 2.5 X institutional upper limit of normal
* CrCl ≥ 45 ml/min
* For both male and female patients, effective methods of contraception must be used throughout the study and for 3 months following the last dose of study treatment.
* Adequate archival tissue (5-10 slides) for correlative studies.
* Subject must have measurable disease per RECIST 1.1
Exclusion Criteria:
* Chemotherapy, radiotherapy, or other cancer therapy within two weeks prior to starting study treatment. Subjects must have recovered from prior treatment-related to toxicities to grade 1 or baseline (excluding alopecia and clinically stable toxicities requiring ongoing medical management, such as hypothyroidism from prior immune checkpoint inhibitor treatment).
* Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
* Symptomatic brain metastases or brain metastases requiring escalating doses of corticosteroids
* History of hypersensitivity or allergic reactions attributed to afatinib or prednisone.
* Uncontrolled intercurrent illness including but not limited to poorly controlled diabetes (which may worsen in setting of chronic prednisone therapy), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
* Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants. DRUG: Afatinib + Prednisone
Lung/Thoracic, Advanced Squamous Non Small Cell Lung Cancer
UT Southwestern; Parkland Health & Hospital System
Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS) (POPS or POP02)
The study investigators are interested in learning more about how drugs, that are given to children by their health care provider, act in the bodies of children and young adults in hopes to find the most safe and effective dose for children. The primary objective of this study is to evaluate the PK of understudied drugs currently being administered to children per SOC as prescribed by their treating provider.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Aruna.Ayalasomayajula@UTSouthwestern.edu
Mia Maamari
ALL
0 Years to 20 Years old
NCT04278404
STU-2021-0176
Inclusion Criteria:
• Participant is \< 21 years of age
• Parent/ Legal Guardian/ Adult Participant can understand the consent process and is willing to provide informed consent/HIPAA:
• (a) Participant is receiving one or more of the study drugs of interest at the time of enrollment or (b) Participant is NOT receiving one or more of the study drugs of interest but is SARS-COV-2 positive within 60 days prior to enrollment
Exclusion Criteria:
• Participant has a known pregnancy Below exclusion criteria apply only to: Participants receiving one or more of the study drugs of interest at the time of enrollment, DOI administration or PK sampling: (Refer to DOI specific appendices for details on enrollment cohort specifications and additional eligibility criteria)
• Has had intermittent dialysis within previous 24 hours
• Has had a kidney transplant within previous 30 days
• Has had a liver transplant within previous 1 year
• Has had a stem cell transplant within previous 1 year
• Has had therapeutic hypothermia within previous 24 hours
• Has had plasmapheresis within the previous 24 hours
• Has a Ventricular Assist Device
• Has any condition which would make the participant, in the opinion of the investigator, unsuitable for the study
DRUG: The POP02 study is collecting bodily fluid samples (i.e., whole blood, effluent samples) of children prescribed the following drugs of interest per standard of care:
Bronchopulmonary Dysplasia, Heart Failure, Pulmonary Arterial Hypertension, Hypertension, Hyperphosphatemia, Pain, Pneumonia, Insomnia, Menorrhagia, Down Syndrome, Hemophilia, Fibrinolysis, Hemorrhage, Coronavirus Infection (COVID-19), Urinary Tract Infections in Children, Primary Hyperaldosteronism, Edema, Hypokalemia, Skin Infection, Arrythmia, Asthma in Children, Adrenal Insufficiency, Attention Deficit Hyperactivity Disorder, Multisystem Inflammatory Syndrome in Children (MIS-C), Kawasaki Disease, Coagulation Disorder
Children’s Health
Testing the Addition of a Type of Drug Called Immunotherapy to the Usual Chemotherapy Treatment for Non-Small Cell Lung Cancer, ALCHEMIST Trial
This phase III ALCHEMIST trial tests the addition of pembrolizumab to usual chemotherapy for the treatment of stage IIA, IIB, IIIA or IIIB non-small cell lung cancer that has been removed by surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as cisplatin, pemetrexed, carboplatin, gemcitabine hydrochloride, and paclitaxel, 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. Giving pembrolizumab with usual chemotherapy may help increase survival times in patients with stage IIA, IIB, IIIA or IIIB non-small cell lung cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Gerber
ALL
18 Years and over
PHASE3
NCT04267848
STU-2020-0684
Inclusion Criteria:
* A female of childbearing potential is a sexually mature female who:
* 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)
* Previously registered to A151216
* Central and/or local testing of EGFR with no EGFR exon 19 deletion or EGFR L858 R mutation (applicable to non-squamous patients only)
* Central and/or local testing of ALK with no ALK rearrangement (failed testing is considered negative) (applicable to non-squamous patients only)
* Central and/or local testing of PD-L1 immunohistochemistry (IHC) using one of the following assays: DAKO 22C3, DAKO 28-8, EIL3N or SP263
* Note: Central testing of EGFR was discontinued as of A081801 Update 10; central testing of ALK and PD-L1 will continue. Local testing results by a local CLIA certified laboratory is required for EGFR and acceptable for ALK. The report must indicate the result as well as the CLIA number of the laboratory that performed the assay. Local result of PD-L1 by DAKO 22C3, Dako 28-8, EIL3N or SP263 are acceptable for enrollment on A081801. Patients with local results for EGFR, ALK and PD-L1 still need to be registered to A151216 and follow all the submissions requirements but do NOT need to wait for the results to proceed to A081801 registration.
* Completely resected stage IIA, IIB IIIA or IIIB (T3-4N2) non-small cell lung cancer (NSCLC) (squamous or non-squamous) with negative margins (complete R0 resection). Patients will be staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual, 2017
* Note: Patients with pathologic N2 disease, completely resected, are eligible. However, patients known to have N2 disease prior to surgery are not eligible; guidelines do not recommend up-front surgery for this population
* Complete recovery from surgery. Registration to A081801 must be 30-77 days following surgery
* No prior neoadjuvant or adjuvant therapy for current lung cancer diagnosis
* No prior allogeneic tissue/solid organ transplant
* Patients must NOT have uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, uncontrolled cardiac arrhythmia, unstable angina pectoris, that would limit compliance with study requirements
* No current pneumonitis or history of (non-infectious) pneumonitis that required steroids
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0-1
* No active auto-immune disease that has required systemic treatment within the last 2 years (e.g., disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid release therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
* Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
* Therefore, for women of childbearing potential only, a negative pregnancy test done =\< 7 days prior to registration is required
* No patients with a "currently active" second malignancy that is progressing or has required active treatment within the last 3 years. Participants with non-melanoma skin cancers or carcinoma in situ (e.g., breast carcinoma or cervical cancer in situ) that have undergone potentially curative therapy are eligible
* No hypersensitivity (\>= grade 3) to pembrolizumab and/or any of its excipients
* No live vaccine within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
* No known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known hepatitis C virus (defined as HCV ribonucleic acid \[RNA\] \[qualitative\] is detected) infection
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Hemoglobin \>= 8 gm/dl
* Calculated (Calc.) creatinine clearance \>= 45 mL/min
* Total bilirubin =\< 1.5 x upper limit of normal (ULN)
* Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN) PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography, DRUG: Gemcitabine Hydrochloride, PROCEDURE: Magnetic Resonance Imaging, OTHER: Observation, DRUG: Paclitaxel, BIOLOGICAL: Pembrolizumab, DRUG: Pemetrexed Disodium, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration
Lung Non-Squamous Non-Small Cell Carcinoma, Stage IIIB Lung Cancer AJCC v8, Lung Non-Small Cell Carcinoma, Lung Non-Small Cell Squamous Carcinoma, Stage II Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8
UT Southwestern; Parkland Health & Hospital System
Osimertinib With or Without Bevacizumab as Initial Treatment for Patients With EGFR-Mutant Lung Cancer
This phase III trial compares the effect of bevacizumab and osimertinib combination vs. osimertinib alone for the treatment of non-small cell lung cancer that has spread outside of the lungs (stage IIIB-IV) and has a change (mutation) in a gene called EGFR. The EGFR protein is involved in cell signaling pathways that control cell division and survival. Sometimes, mutations in the EGFR gene cause EGFR proteins to be made in higher than normal amounts on some types of cancer cells. This causes cancer cells to divide more rapidly. Osimertinib may stop the growth of tumor cells by blocking EGFR that is needed for cell growth in this type of cancer. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving osimertinib with bevacizumab may control cancer for longer and help patients live longer as compared to osimertinib alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Sheena Bhalla
ALL
18 Years and over
PHASE3
NCT04181060
STU-2022-0495
Inclusion Criteria:
* Patient must have a pathologically-confirmed diagnosis of non-squamous, non-small cell lung cancer (NSCLC)
* Patient must have advanced disease, defined as - either stage IV disease, stage IIIB disease not amenable to definitive multi-modality therapy, or recurrent disease after a prior diagnosis of stage I-III disease. All staging is via the American Joint Committee on Cancer (AJCC)/International Association for the Study of Lung Cancer (IASLC) 8th edition staging criteria
* Patient must have somatic activating sensitizing mutation in EGFR (e.g. but not limited to Exon 19 deletion, L858R, E709X, G719X, exon 19 insertions, L861Q, S768I). Patients with non-sensitizing mutations in EGFR (EGFR exon 20 insertions) are not eligible. Test results originating from a Clinical Laboratory Improvement Act (CLIA)-certified or similarly accredited laboratory are acceptable; no specific assay is mandated. Plasma, cytology, or tumor tissue can be utilized for mutation testing
* Patient must not have received any prior treatment with an anti-VEGF agent
* NOTE: Prior treatment with an EGFR TKI is not allowed, however if a candidate for this study has already started osimertinib within 21 days prior to randomization, the exact osimertinib start date is known, and the patient had the required study baseline imaging completed prior to the osimertinib start date, the patient will be eligible
* Patients that have received prior radiation therapy are eligible. Radiation (limited field stereotactic radiation or conventional radiation) must have been completed at least one week prior to study drug initiation and more extensive field radiation (i.e., whole-brain radiotherapy \[WBRT\]) must have been completed at least two weeks prior to drug initiation
* Patient must not have any risk factors for anti-VEGF administration, specifically, hemoptysis, active cardiovascular disease, uncontrolled hypertension, significant proteinuria (screening urinalysis \> 300 mg/dl) and tumor invading major blood vessels
* Patient must have measurable disease. Baseline measurements of sites of disease must be obtained within 4 weeks prior to study randomization. If a potential target lesion is previously irradiated without subsequent growth and/or is radiated after the imaging from which baseline measurements are obtained, they cannot be included as target lesions, and additional target lesions are required to meet criteria for measurable disease
* Patient must not have had any prior systemic treatment for metastatic disease
* Patient must be ≥ 18 years of age
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used
* All females of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy
* A female of childbearing potential is defined as any woman, 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)
* Patient of childbearing potential and sexually active males must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for 2 weeks prior to the start of treatment, while on study treatment, and for
* 6 weeks after the last dose of protocol treatment for female patients on the osimertinib (AZD9291) alone arm
* 4 months after the last dose of protocol treatment for male patients on osimertinib (AZD9291) alone arm
* 6 months after the last dose of protocol treatment for all patients on osimertinib (AZD9291) plus bevacizumab combination arm
* NOTE: Female patients should also not breastfeed while on treatment and for 6 months after the last dose bevacizumab
* Leukocytes \>= 3,000/mcL (obtained =\< 14 days prior to randomization)
* Absolute neutrophil count \>= 1,500/mcL (obtained =\< 14 days prior to randomization)
* Platelets \>= 100,000/mcL (obtained =\< 14 days prior to randomization)
* Hemoglobin \>= 9 g/dL (obtained =\< 14 days prior to randomization)
* Total bilirubin and creatinine =\< 1.5 x institutional upper limit of normal (ULN) (obtained =\< 14 days prior to randomization)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (obtained =\< 14 days prior to 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
* Patients with treated brain metastases are eligible if neurologically stable without glucocorticoid therapy after the stated washout period from radiation therapy (RT) or surgery provided the metastatic lesions are non-hemorrhagic
* Patients with untreated brain metastases or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required provided the metastatic lesions are non-hemorrhagic and are neurologically stable without glucocorticoid therapy
* 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
* Patients with known history or current symptoms of cardiac disease, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* Patient must have the ability to understand and the willingness to sign a written informed consent document and comply with study requirements
* Patient must not have had treatment with any investigational drug within five half-lives or 3 months (whichever is greater), prior to study initiation
* Patient must not be currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4. For any patient currently receiving such inducers of CYP3A4, they must discontinue use prior to first dose of study treatment. All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4
* Patient must not have any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of randomization, with the exception of alopecia and grade 2 prior platinum-therapy-related neuropathy
* Patient must not have any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it challenging for the patient to participate in the study. Screening for chronic conditions is not required
* Patient must not have refractory nausea and vomiting, chronic gastrointestinal diseases, the inability to swallow the osimertinib tablets or previous significant bowel resection that would preclude adequate absorption of osimertinib
* Patient must not have a medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
* Patient must not have a history of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib
* Patient must not have mean resting corrected QT interval (QTc) \> 470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value (using Bazett's correction)
* Patient must not have any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second-degree heart block
* Patient must not have any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities (including: potassium \< lower limit of normal \[LLN\]; magnesium \< LLN; calcium \< LLN), congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval and cause torsades de pointes BIOLOGICAL: Bevacizumab, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan, DRUG: Osimertinib
Metastatic Lung Non-Squamous Non-Small Cell Carcinoma, Recurrent Lung Non-Squamous Non-Small Cell Carcinoma, Stage IIIB Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, Advanced Lung Non-Squamous Non-Small Cell Carcinoma
UT Southwestern; Parkland Health & Hospital System
Hyperinflation Respiratory Therapies in Cardiac Surgery Patients
The purpose of this prospective randomized clinical trial is to evaluate three different types of hyperinflation respiratory therapies, Intermittent Positive Pressure Breathing (IPPB), Intermittent positive end expiratory pressure (EzPAP), Metaneb. Investigators will examine which hyperinflation therapy provides better lung expansion and may improve lung recovery after surgery.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Emily.Melikman@UTSouthwestern.edu
Jaffer Odeh
ALL
18 Years to 80 Years old
NA
NCT04164173
STU-2019-1242
Inclusion Criteria:
• Age 18 years and older
• Admitted to Cardiovascular ICU (CVICU) after coronary artery bypass grafting (CABG), isolated valve repair/replacement, or CABG + valve repair/replacement
• Cardiac surgery performed via median sternotomy
Exclusion Criteria:
• BMI\>40
• Refusal to be consented
• Prior or current lung transplant patients
DEVICE: EzPAP, DEVICE: Metaneb, DEVICE: Intermittent Positive Pressure Breathing (IPPB)
Pulmonary Disease, Postoperative Complications, Cardiovascular
UT Southwestern
Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders (NACHO-COBI)
This is a research study of a drug called cobimetinib in children and adults diagnosed with Langerhans cell histiocytosis (LCH), and other histiocytic disorders that has returned or does not respond to treatment. Cobimetinib blocks activation of a protein called Mitogen-activated protein kinase (MEK) that is part of incorrect growth signals in histiocytosis cells. Four different groups of patients will be enrolled.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Erin Butler
All
Not specified
Phase 2
NCT04079179
STU-2021-0830
INCLUSION CRITERIA:
Age at study entry
• For Group 1: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 2: Participant may be at least 6 months of age at the time of enrollment
• For Group 3: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 4: Participant must be 21 years of age or older at the time of enrollment
• Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet which may be taken by mouth or other enteral route such as nasogastric or gastric tube.
• Biopsy proven LCH -AND
• Failure of at least front-line therapy for LCH with evaluable disease. -OR
• Diagnosis of LCH-associated neurodegenerative disease with radiologic or clinical progression within the past 3 months. -OR
• Biopsy proven JXG, ECD, RDD, histiocytic sarcoma, or other histiocytic lesion (newly diagnosed or relapsed/refractory disease) with evaluable active disease. Performance Level: -Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age. Adequate Hematologic Function Defined as:
• ANC ≥ 0.75 x 10^9/L (unsupported/without growth factor stimulant)
• Platelet count ≥ 75 x 10^9/L (unsupported/without transfusion within the past 7 days).
• Patients with marrow disease must have platelet count of >/= 75 x 10^9/L (transfusion support allowed) and must not be refractory to platelet transfusions.
• Hemoglobin ≥ 8 g/dL (unsupported/without transfusion within the past 7 days)
• Patients with marrow disease must have hemoglobin ≥ 8 g/dL (transfusion support allowed). Adequate Renal Function Defined as:
• Calculated creatinine clearance (or radioisotope GFR) ≥ 70 mL/min/1.73m^2 or serum creatinine based on age/gender as follows: Maximum Serum Creatinine (mg/dL) Age 2 to < 6 years: Male 0.8 mg/d, Female 0.8; 6 to < 10 years: Male 1 mg/dL,Female 1; 10 to < 13 years: Male 1.2 mg/dL; Female 1.2; 13 to < 16 years: Male 1.5 mg/dL ; Female 1.4; ≥ 16 years: Male 1.7 mg/dL; Female 1.4; Adequate Liver Function Defined as:
• Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
• AST and ALT ≤ 3x ULN (≤ 5 x ULN for participants with liver involvement)
• Serum albumin ≥ 2 g/dL. For patients with liver disease caused by histiocytic disorder: • Patients may be enrolled with abnormal bilirubin, AST, ALT and albumin with documentation of histiocytic liver disease. Adequate Cardiac Function Defined as:
• Fractional shortening (FS) of ≥ 30% or ejection fraction of ≥ 50% by echocardiogram at baseline, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to enrollment. Depending on institutional standard, either FS or LVEF is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above Pregnancy/Birth Control
• Female patients of childbearing potential require a negative urine or serum pregnancy test for eligibility and again at database registration, if more than 2 weeks has elapsed.
• Female patients of childbearing potential must agree to follow the contraceptive requirements using two forms of effective contraceptive methods for the duration of the study treatment. Male patients with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) must agree to use two forms of effective methods of contraception (one of which must be a barrier method) during the treatment period and for at least 3 months after the last dose of the study drug to avoid pregnancy and/or potential adverse effects on a developing embryo. Agreement to true abstinence (not periodic abstinence or withdrawal method) is an acceptable method of birth control. EXCLUSION CRITERIA:
• Prior and Concomitant Use of Drugs with CYP3A4 inducing/inhibiting activity: Patient taking strong inducers or inhibitors of CYP3A4 within 14 days prior to study enrollment, including but not limited to the following: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort.
• Prior Therapy Restrictions Completion of previous chemotherapy, immunotherapy, radiotherapy, or targeted therapy for LCH (or other histiocytic disorder) at least 28 days (except where specified below) prior to study enrollment, with resolution of all associated toxicity to ≤ Grade 1 prior to study enrollment (exception for alopecia and ototoxicity which do not need to be resolved ≤ Grade 1). 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 laboratory eligibility criteria are met, the patient is considered to have recovered adequately.
• Radiation therapy within the 28 days prior to enrollment.
• Any prior treatment with Cobimetinib.
• Treatment with a long-acting hematopoietic growth factor within 14 days prior to initiation of study drug or a short-acting hematopoietic growth factor within 7 days prior to enrollment.
• Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives), immunotherapy, biologic therapy, investigational therapy, or herbal cancer therapy within 28 days or < 5 half-lives, whichever is longer, prior to study enrollment.
• Treatment with high-dose chemotherapy and stem-cell rescue (autologous stem cell transplant) or allogeneic stem cell transplant within 90 days prior to enrollment. Anti-GVHD agents post-transplant: 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.
• For patients with brain tumors (intracranial masses), use of anticoagulants within 7 days prior to enrollment.
• Corticosteroid therapy <0.5 mg/kg/day averaged during the month prior to study enrollment is permissible but must be discontinued fourteen (14) days prior to enrollment. Patients with documented brain lesions receiving corticosteroids for management of cerebral edema must be on a stable dose for fourteen (14) days prior to enrollment.
• Patient has received treatment with investigational therapy within 4 weeks prior to initiation of study drug.
• Patients taking anticoagulants or have a pre-existing bleeding disorder unrelated to histiocytic disease.
• Exclusions for other illness
• Other active malignancy or history of secondary malignancy.
• Refractory nausea and vomiting, malabsorption, external biliary shunt
• Infection: Patients who have a known active infection (excluding documented fungal infection of the nail beds) within 28 days prior to enrollment that has not completely resolved.
• Major surgical procedure or significant traumatic injury within 28 days prior to enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days prior to study enrollment (provided that the wound has healed).
• History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease.
• History of pneumonitis.
• Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion are not eligible. Specifically, patients with a history of retinal vein occlusion (RVO), retinal detachment, retinal pathology on ophthalmologic exam, retinopathy of prematurity, central serous chorioretinopathy (CSSCR), neovascular retinopathy, intraocular pressure > 21 mmHg, and predisposing factors to RVO (e.g., uncontrolled hypertension, diabetes, or hyperlipidemia, coagulopathy) will be excluded. Patients with longstanding and stable ophthalmologic findings secondary to existing conditions are eligible with appropriate written documentation and approval from Study Chair.
• History of solid organ transplantation: Patients who have received a prior solid organ transplantation are not eligible.
• Any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that in the opinion of the investigator contraindicates use of an investigational drug or places the patient at unacceptable risk from treatment complications.
• History of clinically significant cardiac dysfunction, including the following:
• Clinically significant cardiac arrhythmias including brady-arrhythmias and/or patients who require anti-arrhythmic therapy (with the exception of beta blockers or digoxin). Patients with controlled atrial fibrillation are not excluded.
• Unstable arrhythmia
• Unstable angina, or new-onset angina within 3 months prior to initiation of study treatment
• Symptomatic congestive heart failure, defined as New York Heart Association Class II or higher
• Myocardial infarction within 3 months prior to initiation of study treatment
• Known chronic human immunodeficiency virus (HIV).
• History of Grade ≥ 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of enrollment.
• Female patients who are pregnant or lactating. Pregnant or lactating women will not be entered on this study because there is no available information regarding human fetal or teratogenic toxicities.
• For Group 1: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 2: Participant may be at least 6 months of age at the time of enrollment
• For Group 3: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 4: Participant must be 21 years of age or older at the time of enrollment
• Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet which may be taken by mouth or other enteral route such as nasogastric or gastric tube.
• Biopsy proven LCH -AND
• Failure of at least front-line therapy for LCH with evaluable disease. -OR
• Diagnosis of LCH-associated neurodegenerative disease with radiologic or clinical progression within the past 3 months. -OR
• Biopsy proven JXG, ECD, RDD, histiocytic sarcoma, or other histiocytic lesion (newly diagnosed or relapsed/refractory disease) with evaluable active disease. Performance Level: -Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age. Adequate Hematologic Function Defined as:
• ANC ≥ 0.75 x 10^9/L (unsupported/without growth factor stimulant)
• Platelet count ≥ 75 x 10^9/L (unsupported/without transfusion within the past 7 days).
• Patients with marrow disease must have platelet count of >/= 75 x 10^9/L (transfusion support allowed) and must not be refractory to platelet transfusions.
• Hemoglobin ≥ 8 g/dL (unsupported/without transfusion within the past 7 days)
• Patients with marrow disease must have hemoglobin ≥ 8 g/dL (transfusion support allowed). Adequate Renal Function Defined as:
• Calculated creatinine clearance (or radioisotope GFR) ≥ 70 mL/min/1.73m^2 or serum creatinine based on age/gender as follows: Maximum Serum Creatinine (mg/dL) Age 2 to < 6 years: Male 0.8 mg/d, Female 0.8; 6 to < 10 years: Male 1 mg/dL,Female 1; 10 to < 13 years: Male 1.2 mg/dL; Female 1.2; 13 to < 16 years: Male 1.5 mg/dL ; Female 1.4; ≥ 16 years: Male 1.7 mg/dL; Female 1.4; Adequate Liver Function Defined as:
• Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
• AST and ALT ≤ 3x ULN (≤ 5 x ULN for participants with liver involvement)
• Serum albumin ≥ 2 g/dL. For patients with liver disease caused by histiocytic disorder: • Patients may be enrolled with abnormal bilirubin, AST, ALT and albumin with documentation of histiocytic liver disease. Adequate Cardiac Function Defined as:
• Fractional shortening (FS) of ≥ 30% or ejection fraction of ≥ 50% by echocardiogram at baseline, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to enrollment. Depending on institutional standard, either FS or LVEF is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above Pregnancy/Birth Control
• Female patients of childbearing potential require a negative urine or serum pregnancy test for eligibility and again at database registration, if more than 2 weeks has elapsed.
• Female patients of childbearing potential must agree to follow the contraceptive requirements using two forms of effective contraceptive methods for the duration of the study treatment. Male patients with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) must agree to use two forms of effective methods of contraception (one of which must be a barrier method) during the treatment period and for at least 3 months after the last dose of the study drug to avoid pregnancy and/or potential adverse effects on a developing embryo. Agreement to true abstinence (not periodic abstinence or withdrawal method) is an acceptable method of birth control. EXCLUSION CRITERIA:
• Prior and Concomitant Use of Drugs with CYP3A4 inducing/inhibiting activity: Patient taking strong inducers or inhibitors of CYP3A4 within 14 days prior to study enrollment, including but not limited to the following: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort.
• Prior Therapy Restrictions Completion of previous chemotherapy, immunotherapy, radiotherapy, or targeted therapy for LCH (or other histiocytic disorder) at least 28 days (except where specified below) prior to study enrollment, with resolution of all associated toxicity to ≤ Grade 1 prior to study enrollment (exception for alopecia and ototoxicity which do not need to be resolved ≤ Grade 1). 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 laboratory eligibility criteria are met, the patient is considered to have recovered adequately.
• Radiation therapy within the 28 days prior to enrollment.
• Any prior treatment with Cobimetinib.
• Treatment with a long-acting hematopoietic growth factor within 14 days prior to initiation of study drug or a short-acting hematopoietic growth factor within 7 days prior to enrollment.
• Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives), immunotherapy, biologic therapy, investigational therapy, or herbal cancer therapy within 28 days or < 5 half-lives, whichever is longer, prior to study enrollment.
• Treatment with high-dose chemotherapy and stem-cell rescue (autologous stem cell transplant) or allogeneic stem cell transplant within 90 days prior to enrollment. Anti-GVHD agents post-transplant: 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.
• For patients with brain tumors (intracranial masses), use of anticoagulants within 7 days prior to enrollment.
• Corticosteroid therapy <0.5 mg/kg/day averaged during the month prior to study enrollment is permissible but must be discontinued fourteen (14) days prior to enrollment. Patients with documented brain lesions receiving corticosteroids for management of cerebral edema must be on a stable dose for fourteen (14) days prior to enrollment.
• Patient has received treatment with investigational therapy within 4 weeks prior to initiation of study drug.
• Patients taking anticoagulants or have a pre-existing bleeding disorder unrelated to histiocytic disease.
• Exclusions for other illness
• Other active malignancy or history of secondary malignancy.
• Refractory nausea and vomiting, malabsorption, external biliary shunt
• Infection: Patients who have a known active infection (excluding documented fungal infection of the nail beds) within 28 days prior to enrollment that has not completely resolved.
• Major surgical procedure or significant traumatic injury within 28 days prior to enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days prior to study enrollment (provided that the wound has healed).
• History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease.
• History of pneumonitis.
• Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion are not eligible. Specifically, patients with a history of retinal vein occlusion (RVO), retinal detachment, retinal pathology on ophthalmologic exam, retinopathy of prematurity, central serous chorioretinopathy (CSSCR), neovascular retinopathy, intraocular pressure > 21 mmHg, and predisposing factors to RVO (e.g., uncontrolled hypertension, diabetes, or hyperlipidemia, coagulopathy) will be excluded. Patients with longstanding and stable ophthalmologic findings secondary to existing conditions are eligible with appropriate written documentation and approval from Study Chair.
• History of solid organ transplantation: Patients who have received a prior solid organ transplantation are not eligible.
• Any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that in the opinion of the investigator contraindicates use of an investigational drug or places the patient at unacceptable risk from treatment complications.
• History of clinically significant cardiac dysfunction, including the following:
• Clinically significant cardiac arrhythmias including brady-arrhythmias and/or patients who require anti-arrhythmic therapy (with the exception of beta blockers or digoxin). Patients with controlled atrial fibrillation are not excluded.
• Unstable arrhythmia
• Unstable angina, or new-onset angina within 3 months prior to initiation of study treatment
• Symptomatic congestive heart failure, defined as New York Heart Association Class II or higher
• Myocardial infarction within 3 months prior to initiation of study treatment
• Known chronic human immunodeficiency virus (HIV).
• History of Grade ≥ 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of enrollment.
• Female patients who are pregnant or lactating. Pregnant or lactating women will not be entered on this study because there is no available information regarding human fetal or teratogenic toxicities.
Drug: Cobimetinib
Histiocytic Sarcoma, Juvenile Xanthogranuloma, Brain and Nervous System, Bones and Joints, Liver, Lung/Thoracic, Other Hematopoietic, Langerhan's Cell Histiocytosis, Erdheim-Chester Disease, Rosai Dorfman Disease, Neuro-Degenerative Disease, Histiocytic Disorders, Malignant
Cobimetinib, Langerhans Cell Histiocytosis (LCH)
Children’s Health
Efficacy and Safety of Benralizumab in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With a History of Frequent Exacerbations (RESOLUTE)
Phase 3 study to evaluate the efficacy and safety of a benralizumab in patients with moderate to very severe COPD with a history of frequent COPD exacerbations and elevated peripheral blood eosinophils (≥300/μL). Eligible patients must have a history of ≥2 moderate and/or severe COPD exacerbations in the previous year despite receiving triple (ICS/LABA/LAMA) background therapy for at least 3 months and ICS-based dual inhaled treatment for the remainder of the year. Eligible patients must also have an elevated blood eosinophil count. The treatment period will be of variable duration and will continue until the last patient has the opportunity to complete a minimum of 56 weeks, at which point all patients will complete the study. The primary endpoint will be analyzed at Week 56.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Khyati.Vadera@UTSouthwestern.edu
Muhanned Abu-Hijleh
All
40 Years to 85 Years old
Phase 3
NCT04053634
STU-2022-0825
Inclusion Criteria:
• Provision of informed consent
• Age 40 to 85 years
• Male and/or female.
• Current or former smoker with a tobacco history of ≥10 pack-years.
• History of moderate to very severe COPD with a post-bronchodilator FEV1/FVC<0.70 and FEV1 ≤65% of predicted normal value.
• Documented history of 2 or more COPD exacerbations that required treatment with systemic corticosteroids and/or hospitalization within 52 weeks prior to enrollment.
• Exacerbations treated with antibiotics alone are excluded unless accompanied by treatment with systemic corticosteroids and/or hospitalization.
• Hospitalization is defined as an inpatient admission ≥24 hours
• Previous exacerbations should be confirmed to have occurred while on stable triple therapy for COPD.
• At least one qualifying COPD exacerbation should occur while on stable uninterrupted triple therapy prior to enrolment.
• Documented use of triple (ICS/LABA/LAMA) background therapy for COPD for ≥3 months immediately prior to enrollment.
• Treatment with at least double inhaled therapy containing ICS (e.g. ICS/LABA or ICS/LAMA) for the remaining of 52 weeks prior to enrolment. Use of LABA/LAMA is allowed if ICS cannot be tolerated.
• ICS in a dose approved for COPD or equivalent to ≥250 mcg of fluticasone propionate daily.
• Total cumulative duration of not being on double or triple background therapy must not exceed 2 months.
• Stable therapy/doses for the last 3 months prior to randomization.
• Blood eosinophil count ≥300/μL at screening and documented historical eosinophil count of ≥150/μL within 52 weeks of enrollment (or repeated testing during run-in).
• CAT total score ≥15 at Visit 1.
• Negative pregnancy test for females of childbearing potential (WOCBP) at Visit 1.
• Women of childbearing potential (WOCBP) must agree to use a highly effective method of birth control from enrollment throughout the study and within 12 weeks after last dose of IP. Women not of childbearing potential are defined as women who are either permanently sterilized or postmenopausal (confirmed by FSH test for women <50 years).
Exclusion Criteria:
• Clinically important pulmonary disease other than COPD
• Current diagnosis of asthma, prior history of asthma or asthma-COPD overlap according to GINA/GOLD. Childhood history of asthma is allowed and defined as asthma diagnosed and resolved before the age of 18.
• Radiological findings of a respiratory disease other than COPD contributing to respiratory symptoms. Solitary pulmonary nodules without appropriate follow up or findings of acute infection.
• Another pulmonary or systemic disease associated with elevated peripheral eosinophil counts.
• Any unstable disorder that could affect patient safety, study findings or the patient's ability to complete the study.
• Any clinically significant abnormal findings in physical examination, vital signs, ECG, laboratory tests could affect patient safety, study findings or the patient's ability to complete the study.
• Cor pulmonale and/or right ventricular failure.
• Long-term treatment with oxygen >4.0 L/min and/or oxyhemoglobin saturation <89% while breathing supplemental oxygen.
• Use of any non-invasive positive pressure ventilation device (NIPPV). Note: use of CPAP for Sleep Apnea Syndrome is allowed.
• Known immunodeficiency disorder, including positive HIV-1/2 testing.
• Active liver disease. Chronic stable hepatitis B and C (including positive HBsAg or hepatitis C antibody testing), or other stable chronic liver disease are acceptable.
• ALT or AST ≥3 times the upper limit of normal, confirmed by repeated testing during the run-in period.
• Helminth parasitic infection within 24 weeks prior to enrollment, not treated or failed to respond to standard of care therapy.
• Alcohol or drug abuse within the past year, which may compromise the study data.
• Malignancy, current or within the past 5 years, except for adequately treated non invasive basal cell and squamous cell carcinoma of the skin and cervical carcinoma-in-situ treated with apparent success more than 1 year prior to Visit 1. Suspected malignancy or undefined neoplasms.
• Evidence of active tuberculosis, as judged by investigator. Patients with a recent (within 2 years) first-time or newly positive PPD or Quantiferon test need to complete an appropriate course of treatment before enrollment. Evaluation will be according to the local standard of care.
• Participation, or planned participation, in intensive COPD rehabilitation program (maintenance phase of a rehabilitation is allowed).
• History of surgical or endoscopic lung volume reduction within the 6 months prior to enrollment. History of partial or total lung resection (single lobe or segmentectomy is acceptable).
• Scheduled major surgical procedure during the study. Minor elective procedures are allowed.
• History of anaphylaxis to any biologic therapy or vaccine.
• Receipt of blood products or immunoglobulins within 30 days prior to randomization.
• Receipt of marketed or investigational biologic product within 4 months or 5 half-lives prior to randomization, whichever is longer. Exception: Patients on stable therapy for 3 months before randomization who intend to stay on treatment throughout the study with marketed biologic products that are not likely to interfere with the safety assessment and/or efficacy of benralizumab, for example, for the treatment of osteoporosis, migraine, pain, diabetes, obesity, ocular, cardiovascular, or metabolic diseases, can participate in the study.
• Receipt of live attenuated vaccines 30 days prior to randomization.
• Chronic use of immunosuppressive medication or expected need for chronic use during the study.
• Chronic use of antibiotics if duration of treatment is <9 months prior to randomization. Chronic macrolide or other antibiotic therapy is allowed provided the patient has been on stable dose/regimen for ≥9 months prior to randomization and has had ≥2 COPD exacerbations while on stable therapy.
• Receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to enrollment.
• Receipt of benralizumab within 12 months prior to enrollment.
• Known history of allergy or reaction to any component of the IP formulation.
Biological: Benralizumab, Biological: Placebo
Chronic Obstructive Pulmonary Disease, Lung/Thoracic
Chronic Obstructive Pulmonary Disease, COPD, benralizumab, Fasenra, ICS, inhaled corticosteroids, exacerbations, Lung Disease, LABA/LAMA
UT Southwestern
Markers of Osteoporosis in Cystic Fibrosis
Main Study Up to 100 subjects, both non-CF volunteers and Cystic Fibrosis (CF) patients, will participate in a single study visit that will include a DEXA scan, micro CT, and blood collection. Denosumab (Prolia) Sub study Approximately 10 adult subjects with CF who participated in the main study and have results indicating bone disease will receive treatment with Denosumab for up to 5 years. They will be asked to return annually for repeat DEXA scans, micro CT, and blood collection.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Maria.Mcleod@UTSouthwestern.edu
Raksha Jain
All
18 Years to 64 Years old
Phase 4
NCT03921060
STU 052018-007
Cystic Fibrosis Main Study
• Must have CF diagnosis confirmed by sweat test or genotype analysis
• Subjects (and parents/legal guardians as applicable) must have the ability to read and write in English Sub-study
• No CF diagnosis
• Men or women without osteoporosis
• Less than 18 years of age
• Unwilling to return annually for study visits for up to 5 years
• Unwilling and/or medically unable to take denosumab
Inclusion Criteria:
• Must have CF diagnosis confirmed by sweat test or genotype analysis
• Subjects (and parents/legal guardians as applicable) must have the ability to read and write in English Sub-study
Exclusion Criteria:
• No CF diagnosis
• Men or women without osteoporosis
• Less than 18 years of age
• Unwilling to return annually for study visits for up to 5 years
• Unwilling and/or medically unable to take denosumab
Drug: Denosumab
Cystic Fibrosis, Bones and Joints, Lung/Thoracic
UT Southwestern; Children’s Health
Lung-MAP: A Master Screening Protocol for Previously-Treated Non-Small Cell Lung Cancer
This screening and multi-sub-study randomized phase II/III trial will establish a method for genomic screening of similar large cancer populations followed by assigning and accruing simultaneously to a multi-sub-study hybrid Master Protocol (Lung-MAP). The type of cancer trait (biomarker) will determine to which sub-study, within this protocol, a participant will be assigned to compare new targeted cancer therapy, designed to block the growth and spread of cancer, or combinations to standard of care therapy with the ultimate goal of being able to approve new targeted therapies in this setting. In addition, the protocol includes non-match sub-studies which will include all screened patients not eligible for any of the biomarker-driven sub-studies.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Sawsan Rashdan
ALL
18 Years and over
PHASE2
NCT03851445
STU-2019-0578
• 1 Registration Step 0:
• Patients who need the fresh biopsy must also submit whole blood for ctDNA testing (see Section 15.3). These patients must be registered to Step 0 to obtain a patient ID number for the submission. Patients registered to Step 0 are not registered to the LUNGMAP protocol. To participate in LUNGMAP, patients must be registered to Step 1 after evaluation of patient eligibility, including tumor tissue adequacy, per protocol Section 5.1, Step 1. Patients registered at Step 0 must use the same SWOG patient ID for registration at Step 1. Step 1:
• Patients must have pathologically proven non-small cell lung cancer (all histologic types) confirmed by tumor biopsy and/or fine-needle aspiration. Disease must be Stage IV as defined in Section 4.0, or recurrent. The primary diagnosis of non-small cell lung cancer should be established using the current WHO/IASLC-classification of Thoracic Malignancies. All histologies, including mixed, are allowed.
• Patients must either be eligible to be screened at progression on prior treatment or to be pre-screened prior to progression on current treatment. These criteria are:
• Screening at progression on prior treatment: To be eligible for screening at progression, patients must have received at least one line of systemic therapy for any stage of disease (Stages I-IV) and must have progressed during or following their most recent line of therapy. * For patients whose prior systemic therapy was for Stage I-III disease only (i.e. patient has not received any treatment for Stage IV or recurrent disease), disease progression on platinum-based chemotherapy must have occurred within one year from the last date that patient received that therapy. For patients treated with consolidation anti-PD-1 or anti-PD-L1 therapy for Stage III disease, disease progression on consolidation anti-PD-1 or anti-PD-L1 therapy must have occurred within one year from the date or initiation of such therapy. * For patients whose prior therapy was for Stage IV or recurrent disease, the patient must have received at least one line of a platinum-based chemotherapy regimen or anti-PD-1/PD-L1 therapy, alone or in combination (e.g. Nivolumab or Pembrolizumab).
• Pre-Screening prior to progression on current treatment: To be eligible for pre-screening, current treatment must be for Stage IV or recurrent disease and patient must have received at least one dose of the current regimen. Patients must have previously received or currently be receiving a platinum-based chemotherapy regimen or anti-PD-1/PD-L1 therapy, alone or in combination (e.g. Nivolumab or Pembrolizumab). Patients on first-line treatment are eligible upon receiving Cycle 1, Day 1 infusion. Note: Patients will not receive their sub-study assignment until they progress and the LUNGMAP Notice of Progression is submitted.
• Patients must have adequate tumor tissue available, defined as ≥ 20% tumor cells and ≥ 0.2 mm3 tumor volume. * The local interpreting pathologist must review the specimen. * The pathologist must sign the LUNGMAP Local Pathology Review Form confirming tissue adequacy prior to Step 1 registration. Patients must agree to have this tissue submitted to Foundation Medicine for common broad platform CLIA biomarker profiling, PD-L1, and c-MET IHC (see Section 15.2). If archival tumor material is exhausted, then a new fresh tumor biopsy that is formalin-fixed and paraffin-embedded (FFPE) must be obtained. Patients who need the fresh biopsy must also submit whole peripheral blood for ctDNA testing. A tumor block or FFPE slides 4-5 microns thick must be submitted. Bone biopsies are not allowed. If FFPE slides are to be submitted, at least 12 unstained slides plus an H\&E stained slide, or 13 unstained slides must be submitted. However, it is strongly recommended that 20 FFPE slides be submitted. Note: Previous next-generation DNA sequencing (NGS) will be repeated if done outside this study for sub-study assignment. Patients must agree to have any tissue that remains after testing retained for the use of sub-study Translational Medicine (TM) studies at the time of consent the patient is enrolled in.
• Patients with known EGFR sensitizing mutations, EGFR T790M mutation, ALK gene fusion, ROS 1 gene rearrangement, or BRAF V600E mutation are not eligible unless they have progressed following all standard of care targeted therapy. EGFR/ALK/ROS/BRAF testing is not required prior to Step 1 registration, as it is included in the Foundation One testing for screening/pre-screening.
• Patients must have Zubrod performance status 0-1 (see Section 10.2) documented within 28 days prior to Step 1 registration.
• Patients must be ≥ 18 years of age.
• Patients must also be offered participation in banking for future use of specimens as described in Section 15.0.
• Patients must be willing to provide prior smoking history as required on the LUNGMAP Onstudy Form.
• As a part of the OPEN registration process (see Section 13.4 for OPEN access instructions) the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.
• Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
• U.S. patients who can complete the survey and the interview by telephone or email in English must be offered participation in the S1400GEN Survey Ancillary Study if local institution's policies allow participants to receive the Amazon gift card (see Sections 15.7 and 18.5). Patients at institutions that cannot offer the survey must still participate in the main study.
DRUG: Screening Platform
Previously Treated Non-Small Cell Lung Cancer, Lung/Thoracic
UT Southwestern; Parkland Health & Hospital System
The Dallas Asthma Brain and Cognition (ABC) Study
Asthma is a chronic inflammatory airway disease that leads to episodic symptom exacerbations, which exerts a substantial burden on quality of life and can influence other health domains if not adequately controlled. Asthma prevalence rates have increased in the past decade, affecting 8.4% (25.7 million people) of the United States population. The economic costs of asthma have been estimated annually with $56 billion in the US alone. Despite progress in pharmacological treatment, overall asthma control remains unsatisfactory and treatment non-adherence is extremely high. Asthma is particularly under diagnosed and understudied in aging adults. This problem will increase in coming decades given demographic trends and will disproportionally contribute to the societal and personal economic costs associated with asthma treatment and management. In the proposed 4-year project we will evaluate, in a two-session assessment recruiting a total of 126 asthma patients and 66 healthy controls aged 40-69 years, the extent to which asthma and aging are associated with changes in cognition and brain chemistry, structure, and function.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Genesis.GonzalezAlvarez@UTSouthwestern.edu
Edson Brown
All
40 Years to 69 Years old
N/A
NCT03794856
STU-2018-0034
Inclusion Criteria:
• For asthma patients: diagnosis of asthma (verified by a medical documentation) for at least 2 years; for healthy volunteers: no significant medical or psychiatric history.
• Ages 40 to 69 years old.
• Proficient in English.
• Education level of at least 10th grade level.
Exclusion Criteria:
• Treatment with oral corticosteroids in the previous 6 weeks, because of the potent effects of this drug on airway reactivity.
• Spirometry: Peak expiratory flow (PEF) below 60% of predicted.
• Diagnosis of vocal cord dysfunction (identified by abnormalities in spirometric flow-volume curves), clinically significant chronic obstructive pulmonary disease, or emphysema.
• Presence or history of medical or neurological disorder that may affect brain function and the physiological systems of interest (e.g. angina, myocardial infarction, congestive heart failure, transient ischemic attacks, cerebrovascular accidents, emphysema, or chronic obstructive pulmonary disease, history of seizures or head trauma, endocrine disorders or renal disease, chemotherapy or radiation presently or in the past 5 years, uncontrolled diabetes, blood pressure above 160/90 (self-reported or measured at session 1).
• Corrected vision poorer than 20/30 on Snellen Eye Chart.
• Presence or history of Schizophrenia, Psychosis, Dementia, Bipolar I, Bipolar II, PTSD or Acute Stress Disorder
• Current or recent history (within 1 year) of Substance Related Disorders, current recreational drug use (defined as past 30 days) or consuming more than 20 alcoholic drinks per week.
• Current treatment with anti-psychotics, sedatives, benzodiazepines with a half-life longer than 6 hours.
• Previous electroconvulsive therapy.
• Presence of history of orthopaedic circumstances and metallic inserts interfering with MR scanning (prior surgeries and/or implant pacemakers, pacemaker wires, artificial heart value, brain aneurysm surgery, middle ear implant, non-removable hearing aid or jewelry, braces or extensive dental work, cataract surgery or lens implant, implanted mechanical or electrical device, artificial limb or joint, foreign metallic objects in the body such as bullets, BB's, shrapnel, or metalwork fragments, pregnancy, claustrophobia, uncontrollable shaking, or inability to lie still for one hour.
• Not proficient in English.
• In the opinion of the principal investigator, participant is otherwise unsuitable for this study.
Other: Functional and Structural Magnetic Resonance Imaging (research grade), Other: Cognitive Function Testing (non-diagnostic), Other: Asthma and Psychological Questionnaires (non-diagnostic)
Asthma
Healthy participants, Asthma, Cognitive functioning, MRI
UT Southwestern; Parkland Health & Hospital System
A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
Study ROR-PH-301, ADVANCE OUTCOMES, is designed to assess the efficacy and safety of ralinepag when added to pulmonary arterial hypertension (PAH) standard of care or PAH-specific background therapy in subjects with World Health Organization (WHO) Group 1 PAH.
Call 214-648-5005
studyfinder@utsouthwestern.edu, tatyana.ganz@utsouthwestern.edu
Sonja Bartolome
ALL
18 Years and over
PHASE3
NCT03626688
STU 062018-068
Inclusion Criteria:
• At least 18 years of age.
• Evidence of a personally signed and dated informed consent form indicating that the subject has been informed of all pertinent aspects of the study prior to initiation of any study-related procedures.
• Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
• Primary diagnosis of symptomatic PAH.
• Has had a right heart catheterization (RHC) performed at or within 3 years prior to Screening (RHC will be performed during Screening if not available) that is consistent with the diagnosis of PAH.
• Has WHO/ NYHA functional class II to IV symptoms.
• If on PAH-specific background oral therapy, subject is on stable therapy with either an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 inhibitor (PDE5-I) or a soluble guanylate cyclase (sGC) stimulator.
• Has a 6MWD of ≥150 meters.
• If taking concomitant medications that may affect the clinical manifestations of PAH (eg, calcium channel blockers, diuretics, digoxin, or L arginine supplementation, beta blockers, angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers), must be on a stable dose for at least 30 days prior to the Baseline Visit and the dosage maintained throughout the study. The exception is that the dose of diuretics must be stable for at least the 10 days prior to Baseline.
• Both male and female subjects agree to use a highly effective method of birth control throughout the entire study period from informed consent through to the 30-Day Follow-up Visit, if the possibility of conception exists. Eligible male and female subjects must also agree not to participate in a conception process during the study and for 30 days after the last dose of IMP. Eligible male subjects must agree not to participate in sperm donation for 90 days after the last dose of IMP.
Exclusion Criteria:
• For subjects with known HIV-associated PAH, a cluster designation 4 (CD4+) T-cell count \<200/mm3 within 90 days of Baseline.
• Must not have 3 or more left ventricular dysfunction risk factors as defined in the study protocol.
• Has evidence of more than mild lung disease on pulmonary function tests performed within 180 days prior to, or during Screening.
• Has evidence of thromboembolic disease as determined by a V/Q lung scan or local standard of care diagnostic evaluation at or after diagnosis of PAH.
• Current diagnosis of ongoing and clinically significant sleep apnea as defined by the Investigator.
• Male subjects with a corrected QT interval using Fridericia's formula (QTcF) \>450 msec and female subjects with a QTcF \>470 msec on ECG recorded at Screening and analyzed by the central ECG laboratory. Subjects with evidence of intraventricular conduction delay, defined as a QRS interval greater than 110 msec, will be excluded if the QTcF is \>500 msec for both males and females.
• Severe chronic liver disease (ie, Child-Pugh Class C), portal hypertension, cirrhosis or complications of cirrhosis/portal hypertension (eg, history of variceal hemorrhage, encephalopathy).
• Confirmed active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
• Subjects with alanine aminotransferase or aspartate aminotransferase ≥3 times the upper limit of normal (ULN) or total bilirubin ≥2 × ULN at Screening.
• Chronic renal insufficiency as defined by serum creatinine \>2.5 mg/dL or requiring dialysis at Screening.
• Hemoglobin concentration \<9 g/dL at Screening.
• Subjects treated with an IV or SC prostacyclin pathway agent (eg, epoprostenol, treprostinil, or iloprost) for PAH at any time prior to Baseline (use in vasoreactive testing is permitted).
• Subjects currently on or who were treated with an inhaled or oral prostacyclin pathway agent (iloprost, treprostinil, beraprost, or selexipag) for \>6 months or within 90 days prior to Baseline.
• Subject has pulmonary veno-occlusive disease.
• Malignancy diagnosed and/or treated within 5 years prior to Screening, with the exception of localized non-metastatic basal cell or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix excised with curative intent.
• Subject tests positive for amphetamine, cocaine, methamphetamine, methylenedioxymethamphetamine or phencyclidine in urine drug screen performed at Screening, or has a recent history (6 months) of alcohol or drug abuse. A subject will not be excluded due to a positive drug screen caused by prescribed medications.
• Initiation or discontinuation of a cardio-pulmonary rehabilitation program based upon exercise within 90 days prior to Screening and/or planned during study participation.
• Prior participation in any study of ralinepag or participation in another interventional clinical study with medicinal products within 30 days prior to Screening. Concurrent participation in registry or observational studies is allowed, as long as the subject can fulfill all other entry criteria and comply with all study procedures.
• Any reason that, in the opinion of the Investigator or Medical Monitor, precludes the subject from participating in the study (eg, any previous or intercurrent medical condition) that may increase the risk associated with study participation or that would confound study analysis or impair study participation or cooperation.
• Known hypersensitivity to ralinepag or any of the excipients.
• Life expectancy \<12 months based on the Investigator's opinion.
• Women who are pregnant, lactating or breast-feeding.
DRUG: Ralinepag, DRUG: Placebo
Pulmonary Hypertension, Pulmonary Arterial Hypertension, Hypertension, Cardiovascular Diseases, Hypertension, Pulmonary, PAH, Connective Tissue Diseases, Familial Primary Pulmonary Hypertension, Vascular Diseases, Lung Diseases, Respiratory Tract Disease, Lung/Thoracic
Prostacyclin, Connective Tissue Disease-Associated, 6 Minute Walk Test, 6 Minute Walk Distance, Pulmonary Vascular Resistance, Right Ventricular Function
UT Southwestern
A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements (TRIDENT-1)
Phase 1 dose escalation will determine the first cycle dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD), the biologically effective dose and recommended Phase 2 dose (RP2D) of repotrectinib given to adult subjects with advanced solid malignancies harboring an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. Midazolam DDI substudy will examine effect of of repotrectinib on CYP3A induction. Phase 2 will determine the confirmed Overall Response Rate (ORR) as assessed by Blinded Independent Central Review (BICR) of repotrectinib in each subject population expansion cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. The secondary objective will include the duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and clinical benefit rate (CBR) of repotrectinib in each expansion cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
All
12 Years and over
Phase 1/Phase 2
NCT03093116
STU-2019-1323
PHASE 1
Key
• Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) (Stage IV, American Joint Committee on Cancer v.7) that harbors an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement by protocol specified tests.
• ECOG PS 0-1.
• Age ≥18 (or age ≥ 20 of age as required by local regulation).
• Capability to swallow capsules intact (without chewing, crushing, or opening).
• At least 1 measurable target lesion according to RECIST version 1.1. CNS-only measurable disease as defined by RECIST version 1.1 is allowed.
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• Patients with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
• Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance Within normal limits or > 40 mL/min; Total serum bilirubin < 1.5 × ULN; Liver transaminases (ASTs/ALTs) < 2.5 × ULN; < 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); < 2.5 × ULN; < 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation
• Life expectancy ≥ 3 months. PHASE 2 Key Inclusion Criteria
• Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) that harbors a ROS1, or NTRK1-3 gene fusion.
• Subject must have a documented ROS1 or NTRK1-3 gene fusion determined by tissue-based local testing using either:
• a next-generation sequencing (NGS) or quantitative polymerase chain reaction (qPCR) test will be accepted to determine molecular eligibility. • Adequate tumor tissue needs to be sent to the Sponsor designated central diagnostic laboratory for retrospective confirmation by a central diagnostic laboratory test selected by the Sponsor. OR
• a fluorescence in situ hybridization (FISH) test AND prospective confirmation of fusion status by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment will be accepted to determine molecular eligibility.
• Adequate tumor tissue must be sent to the Sponsor designated central diagnostic laboratory for prospective confirmation by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
• Age ≥12 (or age ≥ 20 as required by local regulation).
• Willing and able to provide written institutional review board (IRB)/institutional ethics committee-approved Informed Consent or an Assent signed by a parent or legal guardian for subjects age 12 to 17.
• At least 1 measurable target lesion according to RECIST (v1.1) prospectively confirmed by Blinded Independent Central Radiology Review (BICR), selected by Sponsor, PRIOR to enrollment. Subjects with CNS-only measurable disease ≥10 mm as defined by RECIST (v1.1) are eligible.
• Subjects with advanced solid tumors harboring ROS1, NTRK1, NTRK2, or NTRK3 rearrangement will be assigned into 6 distinct expansion (EXP) cohorts provided all inclusion and exclusion criteria are met. i. EXP-1: ROS1 TKI-naïve ROS1+ NSCLC ii. EXP-2: 1 Prior ROS1 TKI and 1 Platinum based chemo ROS1+ NSCLC iii. EXP-3: 2 Prior ROS1 TKIs ROS1+ NSCLC (No Chemo or IO) iv. EXP-4: 1 Prior ROS1 TKI ROS1+ NSCLC (No Chemo or IO) v. EXP-5: TRK TKI-naïve NTRK+ solid tumors vi. EXP-6: TRK TKI-pretreated NTRK+ solid tumors
• Subjects with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
• Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance > 40 mL/min; Total serum bilirubin < 1.5 × ULN; Liver transaminases (ASTs/ALTs) < 2.5 × ULN; < 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); < 2.5 × ULN; < 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation
• Life expectancy ≥ 3 months. Key Exclusion Criteria PHASE 1 and PHASE 2
• Concurrent participation in another therapeutic clinical trial.
• Symptomatic brain metastases or leptomeningeal involvement.
• History of previous cancer, except for squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected, requiring therapy within the previous 2 years.
• Major surgery within 4 weeks of start of repotrectinib treatment. Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. Palliative radiation (≤10 fractions) must have been completed at least 48 hours prior to study entry
• Clinically significant cardiovascular disease (either active or within 6 months prior to enrollment): myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Classification Class ≥ II), cerebrovascular accident or transient ischemic attack, symptomatic bradycardia, requirement for anti-arrhythmic medication. Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2
• Any of the following cardiac criteria: Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTcF) > 470 msec obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250 msec) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval.
• Known active infections (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Peripheral neuropathy of CTCAE ≥grade 2.
• History of extensive, disseminated, bilateral, or presence of CTCAE grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis. Subjects with history of prior radiation pneumonitis are not excluded.
Inclusion Criteria:
• Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) (Stage IV, American Joint Committee on Cancer v.7) that harbors an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement by protocol specified tests.
• ECOG PS 0-1.
• Age ≥18 (or age ≥ 20 of age as required by local regulation).
• Capability to swallow capsules intact (without chewing, crushing, or opening).
• At least 1 measurable target lesion according to RECIST version 1.1. CNS-only measurable disease as defined by RECIST version 1.1 is allowed.
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• Patients with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
• Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance Within normal limits or > 40 mL/min; Total serum bilirubin < 1.5 × ULN; Liver transaminases (ASTs/ALTs) < 2.5 × ULN; < 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); < 2.5 × ULN; < 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation
• Life expectancy ≥ 3 months. PHASE 2 Key Inclusion Criteria
• Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) that harbors a ROS1, or NTRK1-3 gene fusion.
• Subject must have a documented ROS1 or NTRK1-3 gene fusion determined by tissue-based local testing using either:
• a next-generation sequencing (NGS) or quantitative polymerase chain reaction (qPCR) test will be accepted to determine molecular eligibility. • Adequate tumor tissue needs to be sent to the Sponsor designated central diagnostic laboratory for retrospective confirmation by a central diagnostic laboratory test selected by the Sponsor. OR
• a fluorescence in situ hybridization (FISH) test AND prospective confirmation of fusion status by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment will be accepted to determine molecular eligibility.
• Adequate tumor tissue must be sent to the Sponsor designated central diagnostic laboratory for prospective confirmation by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
• Age ≥12 (or age ≥ 20 as required by local regulation).
• Willing and able to provide written institutional review board (IRB)/institutional ethics committee-approved Informed Consent or an Assent signed by a parent or legal guardian for subjects age 12 to 17.
• At least 1 measurable target lesion according to RECIST (v1.1) prospectively confirmed by Blinded Independent Central Radiology Review (BICR), selected by Sponsor, PRIOR to enrollment. Subjects with CNS-only measurable disease ≥10 mm as defined by RECIST (v1.1) are eligible.
• Subjects with advanced solid tumors harboring ROS1, NTRK1, NTRK2, or NTRK3 rearrangement will be assigned into 6 distinct expansion (EXP) cohorts provided all inclusion and exclusion criteria are met. i. EXP-1: ROS1 TKI-naïve ROS1+ NSCLC ii. EXP-2: 1 Prior ROS1 TKI and 1 Platinum based chemo ROS1+ NSCLC iii. EXP-3: 2 Prior ROS1 TKIs ROS1+ NSCLC (No Chemo or IO) iv. EXP-4: 1 Prior ROS1 TKI ROS1+ NSCLC (No Chemo or IO) v. EXP-5: TRK TKI-naïve NTRK+ solid tumors vi. EXP-6: TRK TKI-pretreated NTRK+ solid tumors
• Subjects with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
• Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance > 40 mL/min; Total serum bilirubin < 1.5 × ULN; Liver transaminases (ASTs/ALTs) < 2.5 × ULN; < 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); < 2.5 × ULN; < 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation
• Life expectancy ≥ 3 months. Key Exclusion Criteria PHASE 1 and PHASE 2
• Concurrent participation in another therapeutic clinical trial.
• Symptomatic brain metastases or leptomeningeal involvement.
• History of previous cancer, except for squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected, requiring therapy within the previous 2 years.
• Major surgery within 4 weeks of start of repotrectinib treatment. Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. Palliative radiation (≤10 fractions) must have been completed at least 48 hours prior to study entry
• Clinically significant cardiovascular disease (either active or within 6 months prior to enrollment): myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Classification Class ≥ II), cerebrovascular accident or transient ischemic attack, symptomatic bradycardia, requirement for anti-arrhythmic medication. Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2
• Any of the following cardiac criteria: Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTcF) > 470 msec obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250 msec) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval.
• Known active infections (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Peripheral neuropathy of CTCAE ≥grade 2.
• History of extensive, disseminated, bilateral, or presence of CTCAE grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis. Subjects with history of prior radiation pneumonitis are not excluded.
Drug: Oral repotrectinib (TPX-0005)
Locally Advanced Solid Tumors, Metastatic Solid Tumors, Colon, Liver, Lung/Thoracic, Pancreas, Rectum, Stomach
ALK, ROS1, NTRK, Sarcoma, Lung Neoplasms, Carcinoma, NSCL, NSCLC, Non Small Cell Lung, Thyroid Disease, Colonic Neoplasms, Thyroid Neoplasms, Carcinoma, Neuroendocrine, Respiratory Tract Neoplasms, Thoracic Neoplasms, Neoplasms by Site, Neoplasms, Lung Disease, Respiratory Tract Disease, Carcinoma, Bronchogenic, Bronchial Neoplasms, Endocrine System Disease, Colorectol Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Gastrointestinal Disease, Colonic Disease, Intestinal Disease, Endocrine Gland Neoplasms, Head and Neck Neoplasms, Neuroendocrine Tumors, Neuroectodermal Tumors, Neoplasms, Germ Cell and Embryonal, Neoplasms by Histologic Type, Adenocarcinoma, Non Small Cell Lung Cancer, Solid Tumors, Rearrangements, TRIDENT-1, TKI, TKI naive, TKI pretreated, Anti-tumor activity, Repotrectinib, Advanced Solid Malignancies
UT Southwestern; Parkland Health & Hospital System
COMPASSION S3 - Evaluation of the SAPIEN 3 Transcatheter Heart Valve in Patients With Pulmonary Valve Dysfunction
This study will demonstrate the safety and effectiveness of the Edwards Lifesciences SAPIEN 3/SAPIEN 3 Ultra RESILIA Transcatheter Heart Valve (THV) Systems in subjects with a dysfunctional right ventricular outflow tract (RVOT) conduit or previously implanted valve in the pulmonic position with a clinical indication for intervention.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Kirstie.LeDoux@UTSouthwestern.edu
Surendranath Veeram Reddy
ALL
Not specified
NA
NCT02744677
STU-2023-0688
Inclusion Criteria:
• Weight ≥ 20 kg (44 lbs.)
• Dysfunctional RVOT conduit or previously implanted valve in the pulmonic position with a clinical indication for intervention and with a landing zone diameter ≥ 16.5 mm and ≤ 29 mm immediately prior to study device insertion as per the Instructions for Use
• Subject presents with at least moderate PR and/or mean RVOT gradient ≥ 35 mmHg.
• The subject/subject's legally authorized representative has been informed of the nature of the study, agrees to its provisions and has provided written informed consent.
Exclusion Criteria:
• Active infection requiring current antibiotic therapy (if temporary illness, subject may be a candidate 2 weeks after discontinuation of antibiotics)
• History of or active endocarditis (active treatment with antibiotics) within the past 180 days
• Leukopenia, anemia, thrombocytopenia or any known blood clotting disorder
• Inappropriate anatomy for femoral introduction and delivery of the study valve
• Need for concomitant atrial septal defect or ventricular septal defect closure or other concomitant interventional procedures other than pulmonary artery or branch pulmonary artery stenting or angioplasty
• Angiographic evidence of coronary artery compression that would result from transcatheter pulmonic valve implantation (TPVI)
• Interventional/surgical procedures within 30 days prior to the TPVI procedure.
• Any planned surgical, percutaneous coronary or peripheral procedure to be performed within the 30 day follow-up from the TPVI procedure.
• History of or current intravenous drug use
• Major or progressive non-cardiac disease resulting in a life expectancy of less than one year
• Known hypersensitivity to aspirin or heparin and cannot be treated with other antiplatelet and/or antithrombotic medications
• Known hypersensitivity to cobalt-chromium, nickel or contrast media that cannot be adequately premedicated
• Participating in another investigational drug or device study that has not reached its primary endpoint.
• Female who is lactating or pregnant
DEVICE: SAPIEN 3/SAPIEN 3 Ultra RESILIA THV, DEVICE: SAPIEN 3 THV, DEVICE: SAPIEN 3 Ultra RESILIA THV
Pulmonary Valve Insufficiency, Complex Congenital Heart Defect, Dysfunctional RVOT Conduit, Pulmonary Valve Degeneration
Tetralogy of Fallot, Aortic Valve Defect/Disease Resulting in Ross Procedure, Pulmonary Atresia, Pulmonary Stenosis, Truncus Arteriosus, Transposition of the Great Arteries, Transcatheter pulmonary valve implantation, Transcatheter pulmonary valve replacement, TPV, TPVR, TPVI
UT Southwestern; Children’s Health
Stereotactic Radiosurgery (SRS) Dose-Escalation Study for Brain Metastasis (SRS)
SRS dose escalation for brain metastases in radiation-naïve patients will establish true tolerable doses, which may exceed the current standard doses. This may lead to an improvement in local control, patient survival, and/or quality-of life.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Robert Timmerman
All
18 Years and over
N/A
NCT02645487
STU 022015-106
Inclusion Criteria
• Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ cell cancer, or unknown primary tumor.
• Radiographic evidence by MRI (or by CT scan with CT contrast if ineligible or intolerant of MRI) of brain metastasis. (If patient is unable to tolerate MRI contrast, an MRI without contrast is acceptable if lesions are visible)
• All brain metastases must be outside the brain stem (midbrain, pons and medulla).
• Patient must have 10 or less brain metastases.
• The maximum diameter of any lesion must be less than or equal to 3.0 cm.
• Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any targeted agents are allowed provided that:
• Radiation was not to the brain.
• Surgery to the brain was > 7 days prior to SRS and there remains at least one additional brain metastasis that can be targeted with SRS
• Age ≥ 18 years.
• ECOG Performance Score of 2 or better/Karnofsky Performance Status score of 50-60 or better.
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. 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).
• Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria
• Patients had craniotomy and surgery to the brain within 7 days from the date of SRS.
• Patients with leptomeningeal metastasis. NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.
• Patients with a contraindication to both MRI (with or without contrast) and CT scan (with contrast)
• Patients with life expectancy < 3 months.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing at the time of SRS treatment due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ cell cancer, or unknown primary tumor.
• Radiographic evidence by MRI (or by CT scan with CT contrast if ineligible or intolerant of MRI) of brain metastasis. (If patient is unable to tolerate MRI contrast, an MRI without contrast is acceptable if lesions are visible)
• All brain metastases must be outside the brain stem (midbrain, pons and medulla).
• Patient must have 10 or less brain metastases.
• The maximum diameter of any lesion must be less than or equal to 3.0 cm.
• Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any targeted agents are allowed provided that:
• Radiation was not to the brain.
• Surgery to the brain was > 7 days prior to SRS and there remains at least one additional brain metastasis that can be targeted with SRS
• Age ≥ 18 years.
• ECOG Performance Score of 2 or better/Karnofsky Performance Status score of 50-60 or better.
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. 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).
• Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria
• Patients had craniotomy and surgery to the brain within 7 days from the date of SRS.
• Patients with leptomeningeal metastasis. NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.
• Patients with a contraindication to both MRI (with or without contrast) and CT scan (with contrast)
• Patients with life expectancy < 3 months.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing at the time of SRS treatment due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
Radiation: Stereotactic Radiosurgery
Brain Neoplasms, Adult, Malignant, Lymphoma, Sarcoma, Multiple Myeloma, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, Cardiovascular, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Hodgkins Lymphoma, Lymphoid Leukemia, Small Intestine, Soft Tissue
UT Southwestern; Parkland Health & Hospital System