StudyFinder
Search Results
69 Study Matches
Evaluating the Addition of the Immunotherapy Drug Atezolizumab to Standard Chemotherapy Treatment for Advanced or Metastatic Neuroendocrine Carcinomas That Originate Outside the Lung
This phase II/III trial compares the effect of immunotherapy with atezolizumab in combination with standard chemotherapy with a platinum drug (cisplatin or carboplatin) and etoposide versus standard therapy alone for the treatment of poorly differentiated extrapulmonary (originated outside the lung) neuroendocrine cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). The other aim of this trial is to compare using atezolizumab just at the beginning of treatment versus continuing it beyond the initial treatment. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cisplatin and carboplatin are in a class of medications known as platinum-containing compounds that work by killing, stopping or slowing the growth of cancer cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair, and it may kill cancer cells. Giving atezolizumab in combination with a platinum drug (cisplatin or carboplatin) and etoposide may work better in treating patients with poorly differentiated extrapulmonary neuroendocrine cancer compared to standard therapy with a platinum drug (cisplatin or carboplatin) and etoposide alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Namrata Peswani
ALL
18 Years and over
PHASE2
NCT05058651
STU-2023-0750
Inclusion Criteria:
* Participants must have histologically-confirmed (local site pathological confirmation sufficient) extrapulmonary poorly differentiated, neuroendocrine carcinoma (NEC)
* Participants must have disease that is unresectable or metastatic and not eligible for definitive therapy as deemed per the treating investigator
* Participants must have radiologically evaluable disease, measurable or non-measurable, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. All measurable and non-measurable lesions must be assessed by CT scan with IV contrast of the chest/abdomen/and pelvis (or CT chest without contrast and MRI abdomen/pelvis with gadolinium contrast, if contraindication to CT iodinated contrast) within 28 days prior to registration. While may be used for routine clinical evaluation, PET scans and bone scans alone are not acceptable for disease assessment while participating in this study. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form
* Participants must have brain MRI (or CT head with contrast if there is contraindication to MRI brain) if clinically indicated within 28 days prior to registration. Note: Brain imaging is not required in participants without known and/or clinical concern for brain metastases. Participants with asymptomatic central nervous system (CNS) metastases are eligible if one or more of the following apply:
* Participants who have received treatment for brain metastases must have:
* No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration
* Discontinued all corticosteroids at least 14 days prior to registration
* Participants with treatment-naive brain lesions must have:
* No lesion measuring \> 2.0 cm in size in any axis
* MRI brain or CT head with contrast (if there is contraindication to MRI brain) demonstrating no evidence for mass effect, edema, or other impending neurological compromise within 28 days prior to registration
* No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration
* No need for \> 2 mg of dexamethasone (or equivalent of \> 10 mg prednisone) per day at time of registration
* Participants must not have symptomatic central nervous system (CNS) metastases
* Participants must not have known or suspected leptomeningeal disease
* Participants with prior history of non-metastatic (localized/locally advanced disease) extrapulmonary poorly differentiated NEC may have had prior platinum-based therapy +/- radiation +/- surgery provided that all therapy was completed \>= 6 months prior to registration
* Participants must discontinue denosumab prior to study registration and plan to replace with a bisphosphonate while on the study
* Participants must not have had prior treatment for advanced or metastatic NEC EXCEPT one cycle of platinum (carboplatin/cisplatin) + etoposide is allowed prior to registration. Other chemotherapy regimens are not allowed. For participants with prostate or urothelial NEC, prior chemotherapy for the non-NEC component (e.g. adenocarcinoma or urothelial) is allowed as long as such therapy was completed \>= 24 weeks prior to registration and participants have recovered from all prior toxicities to =\< grade 1.
* Participants must not have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, CD137 agonists, anti-CTLA-4 agent, or any other immune checkpoint inhibitors for any neuroendocrine neoplasm. Immune checkpoint inhibitors given for other cancer indications are allowed provided last therapy was given at least 12 months prior to study registration
* Participants must not have received treatment with systemic immunostimulatory agents including, but not limited to, interferon and interleukin2 \[IL-2\] within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to registration
* Participants must not have had history of known severe allergy, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies, including to Chinese hamster ovary cell products or to any component of the atezolizumab formulation, cisplatin, carboplatin, or etoposide
* Participants must not be on active systemic therapy for another cancer with the exception of hormonal therapy including androgen deprivation therapy (e.g., gonadotropin-releasing hormone \[GnRH\] agonists or antagonists), which can be continued while participants are receiving protocol therapy. Use of enzalutamide or apalutamide is permitted after completion of chemotherapy and must be held during chemotherapy for participants receiving prior to enrollment. Use of darolutamide is permitted during chemotherapy. Glucocorticoid-containing regimens, including abiraterone, are not permitted.
* Participants must be \>= 18 years of age
* Participants must have a Zubrod performance status of =\< 2 within 28 days prior to registration
* Participants must have a complete medical history and physical exam within 28 days prior to registration
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9 /L (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Hemoglobin \>= 9.0 g/dl (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Platelet count \>= 100 x 10\^9/L (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x institutional upper limit of normal (ULN) (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Serum total bilirubin =\< 1.5 x ULN (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Adequate renal function as defined by any 1 of the following: 1) Measured creatinine clearance (CL) \> 50 mL/min OR 2) Calculated creatinine CL \> 50 mL/min by the Cockcroft-Gault formula OR by 24-hour urine collection for determination of creatinine clearance (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Participants must not have uncontrolled or symptomatic hypercalcemia (\> 1.5 mmol/L ionized calcium or calcium \> 12 mg/dL or corrected serum calcium \> ULN) within 14 days prior to registration. Participants who have asymptomatic hypercalcemia are eligible provided that medical therapy to treat the hypercalcemia is planned
* Participants must not have a diagnosis of immunodeficiency nor be receiving systemic steroid therapy (equivalent of \> 20 mg of hydrocortisone per day) or any other form of immunosuppressive therapy within 14 days prior to registration
* Participants must not have active or history of autoimmune disease or immune deficiency, including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis with the following exceptions:
* Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study
* Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
* Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
* Rash must cover \< 10% of body surface area
* Disease is well controlled at baseline and requires only low-potency topical corticosteroids
* No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
* Participants must not have history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. NOTE: History of radiation pneumonitis in the radiation field (fibrosis) is permitted
* Participants must not have significant cardiovascular disease, such as New York Heart Association class II or greater cardiac disease, myocardial infarction within 3 months prior to registration, unstable arrythmias, or unstable angina
* Participants must not have had a major surgical procedure other than for diagnosis within 28 days prior to registration. Participant must not plan to receive a major surgical procedure during the course of protocol treatment. NOTE: Patient port placement is not considered a major surgery
* Participants must not have severe infections (i.e., Common Terminology Criteria for Adverse Events \[CTCAE\] grade \>= 2) at time of registration, including but not limited to hospitalization for complications for infection, bacteremia, or severe pneumonia
* Participants must not have known active tuberculosis
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load, with testing performed as clinically indicated
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with active HCV infection who are currently on treatment must have an undetectable HCV viral load, with testing performed as clinically indicated
* Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at time of registration and have undetectable HIV viral load within 6 months of registration
* Participants must not have prior allogeneic bone marrow transplantation or solid organ transplant
* Participants must not have received administration of a live, attenuated vaccine (e.g., FluMist \[registered trademark\]) within 28 days prior to initiation of study treatment, during treatment with atezolizumab, and not plan to receive for 5 months after the last dose of atezolizumab
* Participants must not be pregnant due to the possibility of harm to the fetus. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method (with details provided as a part of the consent process) during the treatment period and for 5 months after the final dose of atezolizumab. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
* Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines BIOLOGICAL: Atezolizumab, PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Etoposide, PROCEDURE: Magnetic Resonance Imaging, OTHER: Patient Observation
Advanced Extrapulmonary Neuroendocrine Carcinoma, Metastatic Extrapulmonary Neuroendocrine Carcinoma, Recurrent Extrapulmonary Neuroendocrine Carcinoma, Unresectable Extrapulmonary Neuroendocrine Carcinoma
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.
Stage IV Non-Small Cell Lung Cancer, Cachexia
Lung cancer, Anorexia, Metabolism, Adipose, Muscle wasting
UT Southwestern; Parkland Health & Hospital System
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)
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
Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis (TETON)
Study RIN-PF-301 is designed to evaluate the superiority of inhaled treprostinil against placebo for the change in absolute forced vital capacity (FVC) from baseline to Week 52.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Maria.Goralski@UTSouthwestern.edu
Traci Adams
ALL
40 Years and over
PHASE3
NCT04708782
STU-2022-0821
Inclusion Criteria:
• Subject gives voluntary informed consent to participate in the study.
• Subject is ≥40 years of age, inclusive, at the time of signing informed consent.
• The subject has a diagnosis of IPF based on the 2018 ATS/ERS/JRS/ALAT Clinical Practice Guideline (Raghu 2018) and confirmed by central review of high-resolution computed tomography (HRCT) (performed within the previous 12 months), and if available, surgical lung biopsy.
• FVC ≥45% predicted at Screening.
• Subjects on pirfenidone or nintedanib must be on a stable and optimized dose for ≥30 days prior to Baseline. Concomitant use of both pirfenidone and nintedanib is not permitted.
• Women of childbearing potential must be non-pregnant (as confirmed by a urine pregnancy test at Screening and Baseline) and non-lactating, and will abstain from intercourse (when it is in line with their preferred and usual lifestyle) or use 2 medically acceptable, highly effective forms of contraception for the duration of the study, and at least 30 days after discontinuing study drug.
• Males with a partner of childbearing potential must use a condom for the duration of treatment and for at least 48 hours after discontinuing study drug.
• In the opinion of the Investigator, the subject is able to communicate effectively with study personnel, and is considered reliable, willing, and likely to be cooperative with protocol requirements, including attending all study visits.
Exclusion Criteria:
• Subject is pregnant or lactating.
• Subject has primary obstructive airway physiology: FEV1/FVC \<0.70 at Screening.
• The subject has shown intolerance or significant lack of efficacy to a prostacyclin or prostacyclin analogue that resulted in discontinuation or inability to effectively titrate that therapy.
• The subject has received any PAH-approved therapy, including prostacyclin therapy (epoprostenol, treprostinil, iloprost, or beraprost; except for acute vasoreactivity testing), IP receptor agonists (selexipag), endothelin receptor antagonists, phosphodiesterase type 5 inhibitors (PDE5-Is), or soluble guanylate cyclase stimulators within 60 days prior to Baseline. As needed use of a PDE5-I for erectile dysfunction is permitted, provided no doses are taken within 48 hours of any study-related efficacy assessments.
• Use of any of the following medications: azathioprine (AZA), cyclosporine, mycophenolate mofetil, tacrolimus, oral corticosteroids (OCS) \>20 mg/day or the combination of OCS+AZA+N-acetylcysteine within 30 days prior to Baseline; cyclophosphamide within 60 days prior to Baseline; or rituximab within 6 months prior to Baseline.
• The subject is receiving \>10 L/min of oxygen supplementation by any mode of delivery at rest at Baseline.
• Exacerbation of IPF or active pulmonary or upper respiratory infection within 30 days prior to Baseline. Subjects must have completed any antibiotic or steroid regimens for treatment of the infection or acute exacerbation more than 30 days prior to Baseline to be eligible. If hospitalized for an acute exacerbation of IPF or a pulmonary or upper respiratory infection, subjects must have been discharged more than 90 days prior to Baseline to be eligible.
• Uncontrolled cardiac disease, defined as myocardial infarction within 6 months prior to Baseline or unstable angina within 30 days prior to Baseline.
• In the opinion of the Investigator, the subject has any condition that would interfere with the interpretation of study assessments or would impair study participation or cooperation.
• Use of any other investigational drug/device or participation in any investigational study in which the subject received a medical intervention (ie, procedure, device, medication/supplement) within 30 days prior to Screening. Subjects participating in non-interventional, observational, or registry studies are eligible.
• Life expectancy \<6 months due to IPF or a concomitant illness.
• Acute pulmonary embolism within 90 days prior to Baseline.
DRUG: Placebo, DRUG: Inhaled Treprostinil, DEVICE: Treprostinil Ultrasonic Nebulizer
Idiopathic Pulmonary Fibrosis, Interstitial Lung Disease
Treprostinil, IPF, ILD
UT Southwestern
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, Wheezing, Lung/Thoracic
Wheezing Lower Respiratory Illness (WLRI)
Children’s Health
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
Advanced Squamous Non Small Cell Lung Cancer, Lung/Thoracic
UT Southwestern; Parkland Health & Hospital System
Study of CHS-388 (Formerly Known as SRF388) in Patients With Advanced Solid Tumors
This is a Phase 1/1b, open-label, first-in-human, dose-escalation and expansion study of CHS-388, a monoclonal antibody that targets IL-27, as a monotherapy and in combination in patients with solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Hans Hammers
ALL
18 Years and over
PHASE1
NCT04374877
STU-2020-0969
Part A and Part B Abbreviated
Inclusion Criteria:
* ≥ 18 years of age
* Locally advanced or metastatic (Stage IV) solid tumor that has progressed during or after standard therapy, and for whom no available therapies are appropriate (based on investigator judgment)
* Patients in Part B with advanced or metastatic ccRCC, HCC, or NSCLC must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* Patients with HCC in Part B must have at least 1 measurable target lesion according to modified RECIST (mRECIST)
* Patients with HCC must have unresectable disease, Barcelona Clinic Liver Cancer (BCLC1) Stage B (not eligible for transcatheter arterial chemoembolization \[TACE\]) or Stage C
* For patients in Part B with ccRCC, demonstrated progressive disease (PD) during or after the most recent treatment regimen. Prior treatment history must include progression during or after treatment with regimen(s) that have included a vascular endothelial growth factor (VEGF)-targeted agent and an immune checkpoint inhibitor. Patients who did not progress on but discontinued the VEGF-targeted agent for toxicity or intolerability are permitted.
* For patients in Part B with HCC, demonstrated PD during or after the most recent treatment regimen. Prior treatment history must include progression during or after treatment with a VEGF-targeted agent. Patients who did not progress on but discontinued the VEGF-targeted agent for toxicity or intolerability are permitted.
* For Part B patients in the tumor biopsy subsets only, must have tumor tissue that is accessible for pretreatment and on-treatment tumor biopsy in the opinion of the Investigator and be willing to undergo pretreatment and on-treatment biopsies per protocol
* Serum creatinine clearance ≥ 30 mL/min per Cockcroft-Gault formula or serum creatinine ≤ 2.0 x the upper limit of normal (ULN)
* Total bilirubin ≤ 1.5 x ULN (≤ 3 x ULN if elevated because of Gilbert's syndrome and ≤ 2 x ULN for patients with HCC or patients with known liver metastases)
* Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) \< 2.5 x ULN (\< 5 x ULN if liver metastasis or for patients with HCC)
* For patients with HCC, Child-Pugh class A or B7 with a serum albumin ≥ 2.8 g/dL (≥ 28 g/L)
* Adequate hematologic function, defined as absolute neutrophil count (ANC) ≥ 1.0 x 109/L, hemoglobin ≥ 9.0 g/dL, and platelet count ≥ 100 x 109/L. For patients with HCC, platelet count ≥ 75 x 109/L without transfusion
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Patients with NSCLC must have histologically confirmed locally advanced and/or metastatic Stage IV NSCLC
* Patients with NSCLC must have demonstrated progressive disease during or after the most recent treatment regimen
Part C Abbreviated Inclusion Criteria:
* ≥ 18 years of age
* Advanced RCC of any histology or advanced HCC previously treated with at least one systemic anticancer therapy OR histologically or cytologically confirmed metastatic or unresectable adenocarcinoma or squamous cell NSCLC
* Patients with HCC must have unresectable disease, Barcelona Clinic Liver Cancer (BCLC) Stage B (not eligible for transcatheter arterial chemoembolization) or Stage C
* At least 1 measurable lesion per RECIST 1.1
* Patients with HCC must have at least 1 measurable target lesion according to modified RECIST (mRECIST)
* ECOG performance status of 0-1
* ANC ≥1500/µL (1.5 x 109/L)
* Platelets ≥100 000/µL (≥ 100 x 109/L)
* Hemoglobin for participants with RCC: ≥9.0 g/dL; for participants with HCC: ≥8.5 g/dL
* Creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN
* Total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN
* AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
* International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
* For patients with HCC, Child-Pugh Class A or B7 with a serum albumin ≥ 2.8 g/dL (≥ 28 g/L)
* Willingness of male and female patients who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of the study drug period (or beginning 14 days before the initiation of pembrolizumab for oral contraception), including 75 days after the last dose of CHS-388 or 120 days after the last dose of pembrolizumab; male patients must refrain from donating sperm during this period. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception with spermicide. Azoospermic male patients and WCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, female patients must still undergo pregnancy testing as described in this section.
Part C Abbreviated Inclusion Criteria Specific to Patients with RCC or HCC from Part A or Part B:
* Progressed on CHS-388 by RECIST 1.1
* Did not experience prior Grade ≥ 3 toxicity related to CHS-388
* Willingness to undergo pretreatment core or excisional biopsy if deemed safe and tumor is accessible, in the opinion of the Investigator
* Has received no systemic anticancer therapies between CHS-388 doses
Part C Abbreviated Inclusion Criteria specific to NSCLC Patients:
* No more than 3 prior lines of systemic therapy for unresectable or metastatic disease with prior radiologic progression on or following platinum-based chemotherapy and prior anti-PD-(L)1 therapy whether given alone or in combination
Part A and Part B Abbreviated Exclusion Criteria:
* Previously received an anti-IL-27 antibody or anti-IL-27 targeted therapy
* For patients in Part B with renal cell carcinoma (RCC), non-clear cell RCC histology
* For patients with HCC, known fibrolamellar or mixed hepatocellular cholangiocarcinoma
* History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs
* Major surgery within 4 weeks prior to Screening
* Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition including pneumonitis and/or interstitial lung disease, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study
Part C Abbreviated Exclusion Criteria:
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug
* Previously received an anti-IL 27 antibody or anti-IL 27 targeted therapy (exception to patients who received CHS-388 in Part A or Part B)
* No prior systemic therapy for unresectable or metastatic disease
* Received \> 4 prior systemic regimens for unresectable or metastatic disease (prior PD-(L)1 inhibitors are allowed if the patient did not discontinue therapy due to ≥ Grade 3 drug-related toxicity)
* For patients with HCC, fibrolamellar histology or mixed hepatocellular cholangiocarcinoma
* For patients with HCC, moderate or severe ascites
* For patients with HCC, inability to undergo disease evaluation with triphasic computed tomography or magnetic resonance imaging because of contrast allergy or other contraindication
* For patients with HCC, imaging findings consistent with ≥ 50% liver occupation by HCC tumors
* History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs
* Surgeries that required general anesthesia must be completed at least 2 weeks before first study drug administration
* Prior autologous stem cell transplant ≤ 3 months before the first dose
* Prior allogeneic hematopoietic cell transplant within 6 months of the first dose or with a history of or current clinical Graft-Versus-Host Disease
* Has had an allogenic tissue/solid organ transplant
* Other unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study
Part D Abbreviated Inclusion Criteria
* ≥ 18 years of age
* Histologically or cytologically confirmed metastatic or unresectable adenocarcinoma or squamous cell NSCLC
* No more than 3 prior lines of systemic therapy for unresectable or metastatic disease with prior radiologic progression on or following platinum-based chemotherapy and prior anti-PD-(L)1 therapy whether given alone or in combination
* At least 1 measurable lesion per RECIST 1.1
* ECOG performance status of 0-1
* ANC ≥1500/µL (1.5 x 109/L)
* Platelets ≥100 000/µL (≥ 100 x 109/L)
* Hemoglobin for participants with RCC: ≥9.0 g/dL
* Creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN
* Total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN
* AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
* International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
* Willingness of male and female patients who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of the study drug period (or beginning 14 days before the initiation of pembrolizumab for oral contraception), including 75 days after the last dose of CHS-388 or 180 days after the last dose of toripalimab; male patients must refrain from donating sperm during this period. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception with spermicide. Azoospermic male patients and WCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, female patients must still undergo pregnancy testing as described in this section.
Part D Abbreviated Exclusion Criteria:
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug
* Previously received an anti-IL 27 antibody or anti-IL 27 targeted therapy (exception to patients who received CHS-388 in Part A or Part B)
* No prior systemic therapy for unresectable or metastatic disease
* Received \> 4 prior systemic regimens for unresectable or metastatic disease (prior PD-(L)1 inhibitors are allowed if the patient did not discontinue therapy due to ≥ Grade 3 drug-related toxicity)
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a ≥ Grade 3 irAE.
because of contrast allergy or other contraindication
* History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs
* Surgeries that required general anesthesia must be completed at least 2 weeks before first study drug administration
* Prior autologous stem cell transplant ≤ 3 months before the first dose
* Prior allogeneic hematopoietic cell transplant within 6 months of the first dose or with a history of or current clinical Graft-Versus-Host Disease
* Has had an allogenic tissue/solid organ transplant
* Other unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study DRUG: CHS-388, DRUG: Pembrolizumab, DRUG: Toripalimab
Advanced Solid Tumor, Clear Cell Renal Cell Carcinoma, Hepatocellular Carcinoma, Non-Small Cell Lung Cancer
metastatic solid tumors, advanced solid tumors, Phase 1, CHS-388, IL-27, safety, efficacy, immunotherapy, cancer, immuno-oncology, kidney cancer, renal cell carcinoma, liver cancer, hepatocellular carcinoma, non-small cell lung cancer, pembrolizumab, PD-1, toripalimab, SRF388
UT Southwestern
Study of Radiation Therapy Followed by Atezolizumab in Stage II or III Non-small Cell Lung Cancer Patients
This trial studies the side effects of radiation therapy followed by atezolizumab in treating patients with stage II or III non-small cell lung cancer. Hyperfractionated radiation therapy delivers smaller doses of radiation therapy over time and may kill more tumor cells and have fewer side effects. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The purpose of this study is to test the safety and effectiveness of radiation therapy followed by atezolizumab and find out what side effects, if any, it has on patient's non-small cell lung cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
ALL
18 Years and over
PHASE2
NCT04310020
STU-2021-0049
Inclusion Criteria:
* REGISTRATION STEP 1: Participants must have pathologic (cytological or histological) proof of non-small cell lung cancer (NSCLC)
* REGISTRATION STEP 1: Participants must have stage III NSCLC with Zubrod performance status of 2 or stage II NSCLC with Zubrod performance status of 0-2
* REGISTRATION STEP 1: Participants must not be candidates for surgical resection in the opinion of the treating investigator. Participants whose disease was previously resected must have experienced local or regional recurrence at least 12 months after resection
* REGISTRATION STEP 1: Participants must not be candidates for concurrent chemoradiation in the opinion of the treating investigator
* REGISTRATION STEP 1: Participants must have measurable or non-measurable disease documented by CT or MRI. Measurable disease must be assessed within 28 days prior to Registration Step 1. Non-measurable disease must be assessed within 42 days prior to Step 1 registration. The CT from a combined positron emission tomography (PET)/CT may be used only if it is of diagnostic quality. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1)
* REGISTRATION STEP 1: Participants must have an MRI or CT scan of the brain with contrast within 28 days prior to Registration Step 1
* REGISTRATION STEP 1: Participants' disease must fit within the radiation constraints in the opinion of a local radiation oncologist
* REGISTRATION STEP 1: Participants may have received prior treatment for their lung cancer, including surgery, chemotherapy, targeted agents, and/or radiation treatment. At least 12 months must have elapsed since last treatment
* REGISTRATION STEP 1: Participants may have had prior radiation therapy as long as the irradiated area does not overlap with the radiation field targeted for this study
* REGISTRATION STEP 1: Participants must have recovered from any adverse effects of prior major surgery to the satisfaction of the treating physician. Biopsies and central IV access placement are not considered major surgery
* REGISTRATION STEP 1: Absolute neutrophil count (ANC) \>= 1500/mcl (obtained within 28 days prior to Registration Step 1)
* REGISTRATION STEP 1: Platelet count \>= 100,000/mcl (obtained within 28 days prior to Registration Step 1)
* REGISTRATION STEP 1: Hemoglobin \>= 9 grams/dL (obtained within 28 days prior to Registration Step 1)
* REGISTRATION STEP 1: Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN) (obtained within 28 days prior to Registration Step 1)
* REGISTRATION STEP 1: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x IULN (obtained within 28 days prior to Registration Step 1)
* REGISTRATION STEP 1: Serum creatinine =\< 1.5 x IULN OR measured or calculated creatinine clearance \>= 40 mL/min (obtained within 28 days prior to Registration Step 1)
* REGISTRATION STEP 1: Participants must have percent predicted diffusing capacity of the lungs for carbon monoxide (DLCO) of at least 50% documented within 90 days prior to Registration Step 1
* REGISTRATION STEP 1: Patient must not have had a prior history of interstitial lung disease or \> grade 2 (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5) pneumonitis
* REGISTRATION STEP 1: Participants must not have active autoimmune disease requiring therapy within the past 6 months
* REGISTRATION STEP 1: Participants must not have an active infection requiring therapy
* REGISTRATION STEP 1: Participants must not be pregnant or nursing because atezolizumab has not been studied in pregnant or nursing women and the mechanism of action is expected to cause fetal harm. Women/men of reproductive potential must have agreed to use an effective contraceptive method while on protocol treatment and for five months after last dose of atezolizumab. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
* REGISTRATION STEP 1: Participants with known human immunodeficiency virus (HIV) infection must be on effective anti-retroviral therapy and must have undetectable viral load at their most recent viral load test and within 6 months prior to Registration Step 1
* REGISTRATION STEP 1: Patient must be tested for hepatitis B within 28 days prior to Registration Step 1. Patient must not have active (chronic or acute) hepatitis B virus (HBV) infection. Patients may have past or resolved HBV infection. Active HBV is defined as having a positive hepatitis B surface antigen (HBsAg) test. Past or resolved HBV is defined as having a negative HBsAG test and a positive total hepatitis B core antibody (HBcAb) test
* REGISTRATION STEP 1: Patients must not have active hepatitis C virus (HCV) infection. Active HCV is defined as having a positive HCV antibody test followed by a positive HCV ribonucleic acid (RNA) test. Patient must have an HCV antibody test within 28 days prior to Registration Step 1. If the HCV antibody test is positive, the patient must also have an HCV quantitative RNA test within 28 days prior to Registration Step 1
* REGISTRATION STEP 1: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years. Participants with localized prostate cancer who are being followed by an active surveillance program are also eligible
* REGISTRATION STEP 1: Participants must be offered optional participation in banking of specimens for future research
* REGISTRATION STEP 1: Participants 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
* REGISTRATION STEP 1: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
* REGISTRATION STEP 2: Participants must be registered to Step 2 within 42 days after completion of radiation treatment. Participants must have received at least 44 Gy of radiation treatment
* REGISTRATION STEP 2: Participants must have no evidence of progression per RECIST 1.1 on CT scan of the chest, abdomen, and pelvis performed between 2 and 5 weeks after completion of radiation therapy
* REGISTRATION STEP 2: Any toxicities from radiation therapy must have resolved to \< grade 2
* REGISTRATION STEP 2: Absolute neutrophil count (ANC) \>= 1.5 x 10\^3/uL (obtained within 28 days prior to Registration Step 2)
* REGISTRATION STEP 2: Platelet count \>= 100 x 10\^3/uL (obtained within 28 days prior to Registration Step 2)
* REGISTRATION STEP 2: Hemoglobin \>= 9 grams/dL (obtained within 28 days prior to Registration Step 2)
* REGISTRATION STEP 2: Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN) (obtained within 28 days prior to Registration Step 2)
* REGISTRATION STEP 2: AST and ALT =\< 2.5 x IULN (obtained within 28 days prior to Registration Step 2)
* REGISTRATION STEP 2: Serum creatinine =\< 1.5 x IULN OR measured or calculated creatinine clearance \>= 40 mL/min (obtained within 28 days prior to Registration Step 2)
* REGISTRATION STEP 2: Participants must not have received steroids in doses of more than prednisone 10 mg daily or equivalent within 14 days prior to Registration Step 2
* REGISTRATION STEP 2: Participants must not have received a live vaccine within 28 days prior to Registration Step 2 DRUG: Atezolizumab, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, RADIATION: Hypofractionated Radiation Therapy, PROCEDURE: Magnetic Resonance Imaging
Recurrent Lung Non-Small Cell Carcinoma, Stage II Lung Cancer AJCC v8, Stage III Lung Cancer AJCC v8, Unresectable Lung Non-Small Cell Carcinoma
UT Southwestern; Parkland Health & Hospital System
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-Small Cell Carcinoma, Lung Non-Small Cell Squamous Carcinoma, Lung Non-Squamous Non-Small Cell Carcinoma, Stage II Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIB 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. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. 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
Advanced Lung Non-Squamous Non-Small Cell Carcinoma, 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
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
UT Southwestern
Safety, Tolerability and Pharmacokinetics of a Monoclonal Antibody Specific to B-and T-Lymphocyte Attenuator (BTLA) as Monotherapy and in Combination With an Anti-PD1 Monoclonal Antibody for Injection in Subjects With Advanced Malignancies
The primary objective is to assess the safety and tolerability of TAB004 as monotherapy and in combination with toripalimab in subjects with selected advanced solid malignancies, including lymphoma, and to evaluate the recommended Phase 2 dose. The secondary objectives are to: 1) describe the pharmacokinetic (PK) profile of TAB004 monotherapy and in combination with toripalimab and to describe the PK profile of toripalimab when administered with TAB004, 2) evaluate antitumor activity of TAB004 monotherapy and in combination with toripalimab; and 3) determine the immunogenicity of TAB004 monotherapy and in combination with toripalimab and to determine the immunogenicity of toripalimab when administered with TAB004. The exploratory objectives are to: 1) evaluate pharmacodynamic effects of TAB004 on its target receptor BTLA, as well as effects on the immune system; 2) evaluate biomarkers that may correlate with activity of TAB004 as monotherapy and in combination with toripalimab; 3) evaluate the utility of BTLA ligand, herpesvirus-entry mediator (HVEM), and additional exploratory biomarkers that could aid in selection of appropriate subjects for TAB004 monotherapy and in combination with toripalimab.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Farrukh Awan
All
18 Years and over
Phase 1
NCT04137900
STU-2020-0419
Inclusion Criteria:
• 1. Able to understand and willing to sign the Informed Consent Form;
• 2. Male or female ≥ 18 years;
• 3. Subjects with histologically or cytologically confirmed advanced unresectable or metastatic solid tumor, including lymphoma that have progressed following prior treatment. In Part A, subjects must have received, or be ineligible for or intolerant of all available approved or standard therapies known to confer clinical benefit including immunotherapy, or for whom no standard therapy exists; in Part B, subjects with advanced or metastatic solid tumors, including but not limited to lymphoma, melanoma, NSCLC, or other tumors with agreement of the Sponsor, who must have received at least one line of therapy for advanced or metastatic disease, but are not required to have received all standard therapies known to confer clinical benefit; In Part C, subjects must have received at least one line of therapy for advanced or metastatic disease but are not required to have received all standard therapies known to confer clinical benefit; In Part D, subjects with advanced or metastatic solid tumors that may include but not limited to lymphoma, melanoma, NSCLC, RCC or UC who must have received at least one line of therapy for advanced or metastatic disease, but are not required to have received all standard therapies known to confer clinical benefit.
• 4. Measurable disease per RECISTv1.1 and iRECIST, or RECIL 2017 for lymphoma
• 5. ECOG performance status of 0 or 1 with life expectancy of 3 months in the opinion of the investigator.
• 6. Adequate organ and marrow function, as defined below:
• Hemoglobin 8.0 g/dL within first 2 weeks prior to first dose of TAB004 (are not requiring a transfusion within 14 days prior to dosing)
• Absolute neutrophil count (ANC) 1.0 x 109 /L (1,000 /mm3)
• Absolute lymphocyte count ≥ 0.6 x 109/L (600/mm3)
• Platelet count 75 x 109 /L (75,000 /mm3), and not requiring platelet transfusions within the 5 days prior to dosing
• Total bilirubin ≤ 1.5 x ULN except subjects with documented Gilbert's syndrome who must have a baseline total bilirubin ≤ 3.0 mg/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN; for subjects with hepatic metastases, ALT and AST ≤ 5 x ULN
• Serum creatinine ≤ 1.5 x ULN OR calculated creatinine clearance (CrCl) or 24 hour urine CrCl ≥ 40 mL/minute Cockcroft-Gault formula will be used to calculate CrCl. 24-hour urine CrCl will be derived using the measured creatinine clearance formula
• International normalized ratio (INR) ≤ 2.0 and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN; applies only to subjects who do not receive therapeutic anticoagulation; subjects receiving therapeutic anticoagulation (such as low-molecular weight heparin or warfarin) should be on a stable dose
• 7. Willingness to provide consent for biopsy samples (In Part A, fresh pre-treatment biopsies will be requested from subjects with safely accessible lesions. For subjects who cannot provide a fresh pre-treatment biopsy, request for the most recent accessible archival specimen will be required. In Part B, C and D, fresh pre-treatment biopsies will be required from subjects with safely accessible lesions. The most recent archival specimens will also be requested).
• 8. Females of childbearing potential who are sexually active with a nonsterilized male partner must use effective contraception from time of screening, and must agree to continue using such precautions for 90 days after the final dose of TAB004 or toripalimab; cessation of birth control after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control.
• 9. Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as at least 12 months with no menses confirmed by follicle-stimulating hormone [FSH] levels. FSH testing will be conducted at the Screening visit to confirm post-menopausal status).
• 10. Subjects must use effective contraception. Nonsterilized males who are sexually active with a female partner of childbearing potential must use effective contraception from Day 1 and for 90 days after receipt of the final dose of TAB004 or toripalimab.
Exclusion Criteria:
• 1. Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study.
• 2. Any concurrent anti-cancer therapy, such as but not limited to chemotherapy, targeted therapy, radiotherapy, immunotherapy, or biologic therapy. Radiation treatment for palliative intent is allowed provided that lesions other than those receiving radiation are available to measure response. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for type 2 diabetes and hormone replacement therapy) is acceptable. Note: Local treatment of isolated lesions for palliative intent is acceptable (e.g., by local surgery or radiotherapy).
• 3. Receipt of any investigational anticancer therapy within 28 days prior to the first dose of TAB004 or, provided documentable, 5 half lives whichever is shorter, except for lymphoma in which the exclusionary period is 2 weeks for immune checkpoint inhibitors only.
• 4. Current or prior use of immunosuppressive medication within 2 weeks prior to the first dose of TAB004, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids not to exceed 10 mg/day of prednisone or equivalent.
• 5. Prior exposure to anti-BTLA, or anti-HVEM antibodies for subjects enrolled into Part A and B only; prior treatment with anti-PD-1 or anti-PDL-1is allowed,including toripalimab for all subjects.
• 6. Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
• 7. Subjects with another malignancy, or history or other malignancy within 3 years that is not expected to relapse. Subjects with non-melanomatous skin cancer or cervical cancer that has been curatively surgically resected are eligible.
• 8. Major surgery (as defined by the investigator) within 28 days prior to first dose of TAB004 or has not recovered to at least Grade 1 from adverse effects from such procedure, or anticipation of the need for major surgery during study treatment.
• 9. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to baseline or to NCI-CTCAE v5.0 Grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria with the exception of neuropathies that are stable or improving and alopecia. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by TAB004 may be included (e.g., hearing loss) after consultation with the medical monitor.
• 10. Active or prior documented autoimmune disease, such as but not limited to systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, rheumatoid arthritis, autoimmune hepatitis, systemic sclerosis, autoimmune vasculitis, autoimmune neuropathies or type 1 insulin-dependent diabetes mellitus. Note: Subjects with the following are not excluded: vitiligo; alopecia; Grave's disease not requiring systemic treatment other than thyroid hormone replacement (within the past 2 years) psoriasis not requiring systemic treatment; controlled celiac disease; subjects with a history of autoimmune hypothyroidism requiring only thyroid hormone replacement therapy; And type 2 diabetes, provided that it is adequately controlled.
• 11. Clinically significant (intracranial, gastrointestinal) bleeding within 2 weeks prior to screening.
• 12. Known history of tuberculosis.
• 13. Subjects with history of or current drug-induced interstitial lung disease or pneumonitis ≥ Grade 2.
• 14. Subjects who have discontinued prior immune therapy due to immune mediated adverse reaction(s).
• 15. Subjects who are known to be human immunodeficiency virus positive.
• 16. Subjects with evidence of hepatitis B or C virus infection, unless their hepatitis is considered to have been cured. (Note that subjects with prior hepatitis B virus infection must have HBV viral load < 100 IU/mL before study enrollment, and must be treated according to local standards; hepatitis C virus infection must have, before study enrollment, no detectable viral load and must be treated according to local standards).
• 17. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis). Infection-related bowel inflammation, such as Clostridium difficile colitis, is not excluded provided that it has been fully resolved for ≥ 6 weeks.
• 18. History of anaphylaxis, or eczema that cannot be controlled with topical corticosteroids asthma.
• 19. Adult asthma that is moderate or severe, or asthma that has required: hospitalization in the last 2 years; invasive mechanical ventilation ever; systemic corticosteroids in the past year for exacerbations; or more than two short acting beta agonist (e.g., albuterol) administrations per month for breakthrough asthma symptoms. A history of childhood asthma or the presence of mild adult asthma that at baseline has symptoms that can be controlled well with inhaled corticosteroids or short acting beta agonists will not be excluded.
• 20. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure according to New York Heart Association Functional Classification ≥ 3, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring adverse events from TAB004, or compromise the ability of the subject to give written informed consent.
• 21. Untreated central nervous system and leptomeningeal metastases or requiring ongoing treatment for these metastases, including corticosteroids. Subjects with previously treated brain metastases may participate provided they are clinically stable for at least 28 days prior to study entry, have no evidence of new or enlarging metastases, and are off steroids.
• 22. Receipt of live attenuated vaccination within 28 days prior to study entry or within 30 days of receiving TAB004.
• 23. Any condition or treatment or diagnostic test that, in the opinion of the investigator or sponsor, would interfere with evaluation of TAB004 or interpretation of subject safety or study results.
• 24. Pregnancy or breast feeding women.
Drug: TAB004, Drug: Toripalimab
Advanced Unresectable Solid Tumor, Metastatic Solid Tumor, Hodgkins Lymphoma, Lung/Thoracic, Lymphoma, Melanoma, skin, Non-Hodgkins Lymphoma, Lymphoid Leukemia
immunotherapy, BTLA, HVEM, check point inhibitor, solid tumor, non-small cell lung cancer, NSCLC, melanoma, lymphoma, monoclonal antibody, phase 1 trial
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
Langerhan's Cell Histiocytosis, Juvenile Xanthogranuloma, Erdheim-Chester Disease, Rosai Dorfman Disease, Neuro-Degenerative Disease, Histiocytic Sarcoma, Histiocytic Disorders, Malignant, Bones and Joints, Brain and Nervous System, Liver, Lung/Thoracic, Other Hematopoietic
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
A Study of Oral LOXO-292 (Selpercatinib) in Pediatric Participants With Advanced Solid or Primary Central Nervous System (CNS) Tumors (LIBRETTO-121)
This is an open-label, multi-center Phase 1/2 study of oral LOXO-292 in pediatric participants with an activating rearranged during transfection (RET) alteration and an advanced solid or primary CNS tumor.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
All
6 Months to 21 Years old
Phase 1/Phase 2
NCT03899792
STU-2018-0444
Inclusion Criteria:
• Advanced or metastatic solid or primary CNS tumor which has failed standard of care therapies
• Evidence of an activating RET gene alteration in the tumor and/or blood
• Measurable or non-measurable disease
• Karnofsky (participants 16 years and older) or Lansky (participants younger than 16) performance score of at least 50
• Participant with primary CNS tumors or cerebral metastases must be neurologically stable for 7 days prior and must not have required increasing doses of steroids within the last 7 days
• Adequate hematologic, hepatic and renal function.
• Ability to receive study drug therapy orally or via gastric access
• Willingness of men and women of reproductive potential to observe conventional and effective birth control
Exclusion Criteria:
• Major surgery within two weeks prior to planned start of LOXO-292
• Clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292
• Active uncontrolled systemic bacterial, viral, fungal or parasitic infection
• Clinically significant active malabsorption syndrome
• Pregnancy or lactation
• Uncontrolled symptomatic hyperthyroidism or hypothyroidism (i.e. the participant required a modification to current thyroid medication in the 7 days before start of LOXO-292)
• Uncontrolled symptomatic hypercalcemia or hypocalcemia
• Known hypersensitivity to any of the components of the investigational agent, LOXO-292 or Ora-Sweet® SF and OraPlus®, for participants who will receive LOXO-292 suspension
• Prior treatment with a selective RET inhibitor(s) (including investigational selective RET inhibitor[s])
Drug: LOXO-292
Medullary Thyroid Cancer, Infantile Myofibromatosis, Infantile Fibrosarcoma, Papillary Thyroid Cancer, Soft Tissue Sarcoma, Brain and Nervous System, Anklylosing Spondylitis, Bones and Joints, Ovary, Prostate, Soft Tissue
Loxo, LOXO-292, KIF5B-RET, M918T, CCDC6-RET, RET-PTC1, NCOA4-RET, RET-PTC, RET-PTC3, RET-PTC4, PRKAR1A-RET, RET-PTC2, GOLGA5-RET, RET-PTC5, ERC1-RET, KTN1-RET, RET-PTC8, HOOK3-RET, PCM1-RET, TRIM24-RET, RET-PTC6, TRIM27-RET, TRIM33-RET, RET-PTC7, AKAP13-RET, FKBP15-RET, SPECC1L-RET, TBL1XR1-RET, BCR-RET, FGRF1OP-RET, RFG8-RET, RET-PTC9, ACBD5-RET, MYH13-RET, CUX1-RET, KIAA1468-RET, FRMD4A-RET, SQSTM1-RET, AFAP1L2-RET, PPFIBP2-RET, EML4-RET, PARD3-RET, G533C, C609F, C609G, C609R, C609S, C609Y, C611F, C611G, C611S, C611Y, C611W, C618F, C618R, C618S, C620F, C620R, C620S, C630R, C630Y, D631Y, C634F, C634G, C634R, C634S, C634W, C634Y, K666E, E768D, L790F, V804L, V804M, A883F, S891A, R912P, CLIP1-RET, Y806C, RET fusion, RET alteration, RET mutation, RET rearrangement, RET translocation, Neoplasms by Site, Neoplasms, Non-Small Cell Lung Cancer, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Cancer of Lung, Cancer of the Lung, Lung Cancer, Neoplasms, Lung, Neoplasms, Pulmonary, Pulmonary Cancer, Pulmonary Neoplasms, Respiratory Tract Neoplasms, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms, Medullary Thyroid Cancer, Papillary Thyroid Cancer, Thyroid Diseases, Thyroid Neoplasms, Cancer of the Thyroid, Cancer of Thyroid, Neoplasms, Thyroid, Thyroid Adenoma, Thyroid Cancer, Thyroid Carcinoma, Endocrine System Diseases, Endocrine Gland Neoplasms, Head and Neck Neoplasms, Thoracic Neoplasms, CNS tumor, Primary CNS tumor, Colonic Neoplasms, Cancer of Colon, Cancer of the Colon, Colon Cancer, Colon Neoplasms, Colonic Cancer, Neoplasms, Colonic, Malignant tumor of Breast, Mammary Cancer, Mammary Carcinoma, Human, Mammary Neoplasm, Human, Neoplasms, Breast, Tumors, Breast, Human Mammary Carcinoma, Malignant Neoplasm of Breast, Breast Carcinoma, Breast Tumors, Cancer of the Breast, Breast Neoplasms, Breast Cancer, RET Inhibitor, MTC, NSCLC, Soft tissue sarcoma, Infantile Myofibromatosis, Infantile Fibrosarcoma
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
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
PAH, Pulmonary Hypertension, Pulmonary Arterial Hypertension, Hypertension, Connective Tissue Diseases, Familial Primary Pulmonary Hypertension, Vascular Diseases, Cardiovascular Diseases, Hypertension, Pulmonary, Lung Diseases, Respiratory Tract Disease
Prostacyclin, Connective Tissue Disease-Associated, 6 Minute Walk Test, 6 Minute Walk Distance, Pulmonary Vascular Resistance, Right Ventricular Function
UT Southwestern
Mevrometostat Treatment of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma
A Phase 1 Dose Escalation and Expanded Cohort Study Of PF-06821497 (Mevrometostat) in Adult Patients With Relapsed/Refractory Small Cell Lung Cancer (SCLC), Castration Resistant Prostate Cancer (CRPC) And Follicular Lymphoma (FL).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE1
NCT03460977
STU-2022-0733
Key
• Prior Chemotherapy: Part 1C , Japan cohort and China cohort (CRPC): no more than 2 previous regimens of chemotherapy Part 2A: mCRPC: no more than 1 previous regimen of systemic chemotherapy Part 2B (mCRPC): no more than 1 previous regimen of chemotherapy * Prior irradiation to \>25% of the bone marrow. * QTcF interval \>480 msec at screening. * Hypertension that cannot be controlled by medications (\>150/90 mmHg despite optimal medical therapy). * Known or suspected hypersensitivity to PF 06821497 or any components or enzalutamide (CRPC) * Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery. Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed. * Current use or anticipated need for food or drugs that are known strong CYP3A4/5 inducers or inhibitors, including their administration within 10 days or 5 half lives of the CYP3A4/5 inhibitor, whichever is longer prior to first dose of investigational product.
Inclusion Criteria:
Histological or cytological diagnosis of advanced / metastatic solid tumor with the following tumor types in individual study parts:
Part 1A (closed to enrollment):
Part 1B (closed to enrollment):
Part 1C:
* Metastatic Castration resistant prostate cancer. Patients should have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression (per PCWG3) Japan cohort
* Castration resistant prostate cancer that is resistant to SOC or for which no local regulatory approved SOC is available that would confer significant clinical benefit in the medical judgement of the investigator. Patients should have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression (per PCWG3) China cohort
* Castration resistant prostate cancer that is intolerant/resistant to SOC or for which no local regulatory approved SOC is available that would confer significant clinical benefit in the medical judgement of the investigator. Patients who refused SOC may be eligible. Patients should have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression (per PCWG3)
Part 2A:
• Metastatic Castration resistant prostate cancer. Patients should have received either abiraterone and/or enzalutamide treatment, may have received up to 1 line of chemotherapy and have evidence of prostate cancer progression (per PCWG3)
Part 2B/2C:
* Metastatic Castration resistant prostate cancer. Patients should have received abiraterone treatment, may have received up to 1 prior line of chemotherapy, have not received prior enzalutamide, apalutamide or darolutamide and have evidence of prostate cancer progression (per PCWG3)
* Patients must have radiographic evidence of disease
Other inclusion criteria:
-Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
Key Exclusion Criteria:
• Prior Chemotherapy: Part 1C , Japan cohort and China cohort (CRPC): no more than 2 previous regimens of chemotherapy Part 2A: mCRPC: no more than 1 previous regimen of systemic chemotherapy Part 2B (mCRPC): no more than 1 previous regimen of chemotherapy * Prior irradiation to \>25% of the bone marrow. * QTcF interval \>480 msec at screening. * Hypertension that cannot be controlled by medications (\>150/90 mmHg despite optimal medical therapy). * Known or suspected hypersensitivity to PF 06821497 or any components or enzalutamide (CRPC) * Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery. Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed. * Current use or anticipated need for food or drugs that are known strong CYP3A4/5 inducers or inhibitors, including their administration within 10 days or 5 half lives of the CYP3A4/5 inhibitor, whichever is longer prior to first dose of investigational product.
DRUG: Mervometostat (PF-06821497), DRUG: Enzalutamide
Metastatic Castration Resistant Prostate Cancer (mCRPC), Small Cell Lung Cancer (SCLC), Follicular Lymphoma (FL)
EZH2, enhancer of zeste homolog 2, castrate resistant prostate cancer, prostatecancer-study.com, mCRPC, efficacy, safety, pharmacokinetics, pharmacodynamics, dose escalation, dose expansion, open-label, small cell lung cancer, SCLC, follicular lymphoma, FL, relapsed, refractory
UT Southwestern
Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants with Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy (ALLELE)
The purpose of this study is to determine the clinical benefit and characterize the safety profile of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ transplant (SOT) after failure of rituximab and rituximab plus chemotherapy or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
ALL
Not specified
PHASE3
NCT03394365
STU-2018-0349
Inclusion Criteria:
• Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these (C-SOT); or prior allogeneic HCT (C-HCT)
• A diagnosis of locally assessed, biopsy-proven EBV+ PTLD
• Availability of appropriate partially HLA-matched and restricted tabelecleucel has been confirmed by the sponsor
• Measurable, 18F-deoxyglucose (FDG)-avid (Deauville score ≥ 3) systemic disease using Lugano Classification response criteria by positron emission tomography (PET)-diagnostic computed tomography (CT), except when contraindicated or mandated by local practice, then magnetic resonance imaging (MRI) may be used. For subjects with treated central nervous system (CNS) disease, a head CT and/or brain/spinal MRI as clinically appropriate will be required to follow CNS disease response per Lugano Classification response criteria.
• Treatment failure of rituximab or interchangeable commercially available biosimilar monotherapy (C-SOT-R or C-HCT) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (C-SOT-R+C) for treatment of PTLD.
• Males and females of any age.
• Eastern Cooperative Oncology Group performance status ≤ 3 for subjects aged ≥ 16 years; Lansky score ≥ 20 for subjects \< 16 years
• For C-HCT only: If allogeneic HCT was performed as treatment for an acute lymphoid or myeloid malignancy, the underlying primary disease for which the subject underwent transplant must be in morphologic remission
• Adequate organ function
• Absolute neutrophil count ≥ 1000/μL, (C-SOT) or ≥ 500/μL (C-HCT), with or without cytokine support
• Platelet count ≥ 50,000/μL, with or without transfusion or cytokine support. For C-HCT, platelet count \< 50,000/μL but ≥ 20,000/μL, with or without transfusion support, is permissible if the subject has not had grade ≥ 2 bleeding in the prior 4 weeks (where grading of the bleeding is determined per the National Cancer Institute's Common Terminology Criteria for Adverse Events \[CTCAE\], version 5.0)
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin each \< 5 × the upper limit of normal; however, ALT, AST, and total bilirubin each ≤ 10 × upper limit of normal is acceptable if the elevation is considered by the investigator to be due to EBV and/or PTLD involvement of the liver as long as there is no known evidence of significant liver dysfunction
• Subject or subject's representative is willing and able to provide written informed consent
Exclusion Criteria:
• Burkitt lymphoma, classical Hodgkin lymphoma, or any T cell lymphoma
• Daily steroids of \> 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis
• Untreated CNS PTLD or CNS PTLD for which the subject is actively receiving CNS-directed chemotherapy (systemic or intrathecal) or radiotherapy at enrollment. NOTE:Subjects with previously treated CNS PTLD may enroll if CNS-directed therapy is complete.
• Suspected or confirmed grade ≥ 2 graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research consensus grading system at enrollment
• Ongoing or recent use of a checkpoint inhibitor agent (eg, ipilimumab, pembrolizumab, nivolumab) within 3 drug half-lives from the most recent dose to enrollment
• For C-HCT: active adenovirus viremia
• Need for vasopressor or ventilatory support
• Antithymocyte globulin or similar anti-T cell antibody therapy ≤ 4 weeks prior to enrollment
• Treatment with Epstein-Barr virus cytotoxic T lymphocytes or chimeric antigen receptor T cells directed against B cells within 8 weeks of enrollment (C-SOT or C-HCT), or unselected donor lymphocyte infusion within 8 weeks of enrollment (C-HCT only)
• Female who is breastfeeding or pregnant or female of childbearing potential or male with a female partner of childbearing potential unwilling to use a highly effective method of contraception
• Inability to comply with study-related procedures
• Any medical condition or organ system dysfunction that in the investigator\'s opinion, could compromise the participant\'s safety or ability to complete the study
BIOLOGICAL: tabelecleucel
Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Solid Organ Transplant Complications, Lymphoproliferative Disorders, Allogeneic Hematopoietic Cell Transplant, Stem Cell Transplant Complications
Epstein-Barr Virus (EBV)-associated Lymphoproliferative Disease (LPD), Epstein-Barr Virus (EBV), Cytotoxic T lymphocyte (CTL), Cancer After Transplant, Kidney transplant, Renal transplant, Liver transplant, Heart transplant, Lung transplant, Intestinal transplant, Pancreas transplant, Post-transplant Lymphoma, Solid Organ Transplant (SOT), Bone Marrow Transplant Complications, Epstein-Barr Virus-specific Cytotoxic T Lymphocytes (EBV-CTL), Hematopoietic Cell Transplant (HCT), Hematopoietic Stem Cell Transplantation (HSCT), Allogeneic Hematopoietic Cell Transplant, Allogeneic, Off-The-Shelf T-cell Immunotherapy
Children’s Health
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
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, Brain and Nervous System, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, Cardiovascular, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Eye and Orbit, Gall Bladder, Head and Neck, Hodgkins Lymphoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Lymphoid Leukemia, Lymphoma, Melanoma, skin, Multiple Myeloma, Nose, Other, 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, Sarcoma, Small Intestine, Soft Tissue, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva
UT Southwestern; Parkland Health & Hospital System
JoLT-Ca Sublobar Resection (SR) Versus Stereotactic Ablative Radiotherapy (SAbR) for Lung Cancer (STABLE-MATES)
To Determine if SAbR improves survival over SR in High Risk Operable Stage I NSCLC
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Robert Timmerman
ALL
18 Years and over
PHASE3
NCT02468024
STU 022015-069
Inclusion Criteria:
* Age \> 18 years.
* ECOG performance status (PS) 0, 1, or 2.
* Radiographic findings consistent with non-small cell lung cancer, including lesions with ground glass opacities with a solid component of 50% or greater. Those with ground glass opacities and \<50% solid component will be excluded.
* The primary tumor in the lung must be biopsy confirmed non-small cell lung cancer within 180 days prior to randomization.
* Tumor ≤ 4 cm maximum diameter, including clinical stage IA and selected IB by PET/CT scan of the chest and upper abdomen performed within 180 days prior to randomization. Repeat imaging within 90 days prior to randomization is recommended for re-staging but is not required based on institutional norms.
* All clinically suspicious mediastinal N1, N2, or N3 lymph nodes (\> 1 cm short-axis dimension on CT scan and/or positive on PET scan) confirmed negative for involvement with NSCLC by one of the following methods: mediastinoscopy, anterior mediastinotomy, EUS/EBUS guided needle aspiration, CT-guided, video-assisted thoracoscopic or open lymph node biopsy within 180 days of randomization.
* Tumor verified by a thoracic surgeon to be in a location that will permit sublobar resection.
* Tumor located peripherally within the lung. NOTE: Peripheral is defined as not touching any surface within 2 cm of the proximal bronchial tree in all directions. See below. Patients with non-peripheral (central) tumors are NOT eligible.
* No evidence of distant metastases.
* Availability of pulmonary function tests (PFTs - spirometry, DLCO, +/- arterial blood gases) within 180 days prior to registration. Patients with tracheotomy, etc, who are physically unable to perform PFTs (and therefore cannot be tested for the Major criteria in 3.1.11 below) are potentially still eligible if a study credentialed thoracic surgeon documents that the patient's health characteristics would otherwise have been acceptable for eligibility as a high risk but nonetheless operable patient (in particular be eligible for sublobar resection).
* Patient at high-risk for surgery by meeting a minimum of one major criteria or two minor criteria
* Major Criteria
* FEV1 ≤ 50% predicted (pre-bronchodilator value)
* DLCO ≤ 50% predicted (pre-bronchodilator value)
* Minor Criteria
* Age ≥75
* FEV1 51-60% predicted (pre-bronchodilator value)
* DLCO 51-60% predicted (pre-bronchodilator value)
* Pulmonary hypertension (defined as a pulmonary artery systolic pressure greater than 40mm Hg) as estimated by echocardiography or right heart catheterization
* Study credentialed thoracic surgeon believes the patient is potentially operable but that a lobectomy or pneumonectomy would be poorly tolerated by the patient for tangible or intangible reasons. The belief must be declared and documented in the medical record prior to randomization.
* Poor left ventricular function (defined as an ejection fraction of 40% or less)
* Resting or Exercise Arterial pO2 ≤ 55 mm Hg or SpO2 ≤ 88%
* pCO2 \> 45 mm Hg
* Modified Medical Research Council (MMRC) Dyspnea Scale ≥ 3.
* No prior intra-thoracic radiation therapy for previously identified intra-thoracic primary tumor (e.g. previous lung cancer) on the ipsilateral side. NOTE: Previous radiotherapy as part of treatment for head and neck, breast, or other non-thoracic cancer is permitted so long as possible radiation fields would not overlap. Previous chemotherapy or surgical resection specifically for the lung cancer being treated on this protocol is NOT permitted.
* No prior lung resection on the ipsilateral side.
* Non-pregnant and non-lactating. Women of child-bearing potential must have a negative urine or serum pregnancy test prior to registration. Peri-menopausal women must be amenorrheic \> 12 months prior to registration to be considered not of childbearing potential.
* No prior invasive malignancy, unless disease-free for ≥ 3 years prior to registration (exceptions: non-melanoma skin cancer, in-situ cancers).
* Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
* evidence of distant metastases
* prior intra-thoracic radiation therapy. NOTE: Previous radiotherapy as part of treatment for head and neck, breast, or other non-thoracic cancer is permitted so long as possible radiation fields would not overlap. Previous chemotherapy or surgical resection specifically for the lung cancer being treated on this protocol is NOT permitted. No prior lung resection on the ipsilateral side.
* pregnant and lactating women
* prior invasive malignancy, unless disease-free for ≥ 3 years prior to registration (exceptions: non-melanoma skin cancer, in-situ cancers). PROCEDURE: Lung Surgery, RADIATION: Radiation therapy
Non-Small Cell Lung Cancer
UT Southwestern; Parkland Health & Hospital System
Safety and Durability of Sirolimus for Treatment of LAM (MIDAS)
The MIDAS study aims to follow male and female LAM patients who are currently taking, have previously failed or been intolerant of, or may (at some time in the future) take mTOR inhibitors (sirolimus or everolimus) as part of their clinical care. Adult female TSC patients may also enroll, with or without lung cysts.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Reagan.Volzer@UTSouthwestern.edu
Carlos Girod
Female
18 Years and over
NCT02432560
STU 022017-055
Inclusion Criteria:
• Female or male, age 18 or over
• Diagnosis of LAM based on ATS/JRS criteria
• Signed and dated informed consent
• On chronic therapy, newly treated or may be considered for therapy with mTOR inhibitors or previously intolerant of or having failed mTOR inhibitor therapy
Exclusion Criteria:
• Inability to attend at least one RLD Clinic visit per year
• Inability to give informed consent
• Inability or unwillingness to perform pulmonary function testing
Drug: Sirolimus, Drug: Everolimus
Lymphangioleiomyomatosis, Lung/Thoracic
Lymphangioleiomyomatosis, LAM, rare lung, Rare Lung Disease
UT Southwestern
Genetic Testing in Screening Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been or Will Be Removed by Surgery (The ALCHEMIST Screening Trial)
This ALCHEMIST trial studies genetic testing in screening patients with stage IB-IIIA non-small cell lung cancer that has been or will be removed by surgery. Studying the genes in a patient's tumor cells may help doctors select the best treatment for patients that have certain genetic changes.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Gerber
ALL
18 Years and over
NA
NCT02194738
STU 092014-004
Inclusion Criteria:
* PATIENT PRE-REGISTRATION ELIGIBILITY CRITERIA:
* For pre-surgical patients
* Suspected diagnosis of resectable non-small cell lung cancer; cancers with a histology of "adenosquamous" are considered a type of adenocarcinoma and thus a "nonsquamous" histology; patients with squamous cell carcinoma are eligible
* Suspected clinical stage of IIIA, II (IIA or IIB) or large IB (defined as size \>= 4 cm); Note: IB tumors \< 4 cm are NOT eligible; stage IB cancer based on pleural invasion is not eligible unless the tumor size is \>= 4 cm; the 7th edition of American Joint Committee on Cancer (AJCC) staging will be utilized
* For post-surgical patients
* Completely resected non-small cell lung cancer with negative margins (R0); patients with squamous cell carcinoma are eligible only if they have not received adjuvant therapy
* Pathologic stage IIIA, II (IIA or IIB) or large IB (defined as size \>= 4 cm); Note: IB tumors \< 4 cm are NOT eligible; stage IB cancer based on pleural invasion is not eligible unless the tumor size is \>= 4 cm; the 7th edition of AJCC staging will be utilized
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Age ≥ 18 years
* No patients who have received neoadjuvant therapy (chemo- or radio-therapy) for this lung cancer
* No locally advanced or metastatic cancer requiring systemic therapy within 5 years prior to registration; no secondary primary lung cancer diagnosed concurrently or within 2 year prior to registration
* No prior treatment with agents targeting EGFR mutation, ALK rearrangement, and PD-1/PD-L1/CTLA-4
* No patients known to be pregnant or lactating
* Patients who have had local genotyping are eligible, regardless of the local result
* No patients with recurrence of lung cancer after prior resection
* Note: Post-surgical patients should proceed to registration immediately following preregistration
* PATIENT REGISTRATION ELIGIBILITY CRITERIA:
* Tissue available for the required analyses (either clinical tissue block or slides and scrolls)
* Completely resected NSCLC with negative margins (R0); cancers with a histology of "adenosquamous" are considered a type of adenocarcinoma and thus a "nonsquamous" histology
* Pathologic stage IIIA, IIA or IIB, or large IB (defined as size \>= 4 cm); Note: IB tumors \< 4 cm are NOT eligible; stage IB cancer based on pleural invasion is not eligible unless the tumor size is \>= 4 cm; the 7th edition of AJCC staging will be utilized
* Patients with squamous cell carcinoma are eligible only if they have not received adjuvant therapy
* In order to allow for time for central genotyping and eligibility for the ALCHEMIST treatment trial, patients must register within the following eligibility windows:
* Squamous patients:
* No adjuvant therapy permitted, register patient within 77 days following surgery
* Non-squamous patients:
* If no adjuvant therapy, register patient within 75 days following surgery
* If adjuvant chemotherapy or radiotherapy only, register patient within 225 days following surgery
* If adjuvant chemotherapy and radiation, register patient within 285 days following surgery PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Cisplatin, OTHER: Clinical Observation, PROCEDURE: Computed Tomography, DRUG: Crizotinib, OTHER: Cytology Specimen Collection Procedure, PROCEDURE: Echocardiography, DRUG: Erlotinib, DRUG: Gemcitabine Hydrochloride, BIOLOGICAL: Nivolumab, DRUG: Paclitaxel, BIOLOGICAL: Pembrolizumab, DRUG: Pemetrexed, DRUG: Pemetrexed Disodium, OTHER: Placebo Administration, PROCEDURE: Positron Emission Tomography
Stage IB Lung Non-Small Cell Carcinoma AJCC v7, Stage II Lung Non-Small Cell Cancer AJCC v7, Stage IIA Lung Cancer AJCC v8, Stage IIB Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIA Lung Non-Small Cell Cancer AJCC v7, Stage IIIB Lung Cancer AJCC v8
UT Southwestern; Parkland Health & Hospital System
Metabolic Biomarkers in Thoracic Cancers
The purpose of this research study is to develop a method of using magnetic resonance imaging (MRI) to evaluate lung tumors and other thoracic malignancies. An MRI is a scanning device that uses magnets to make images (pictures) of the body. This study is being done to determine what series of reactions (metabolic pathways) pulmonary nodules use as they burn sugar as fuel for growth. The manner in which the tumor burns (metabolizes) sugar for fuel is being investigated by using a natural, slightly modified, sugar solution (13C-glucose) and studying a small sample of the tumor once it is removed at the time of surgery.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kemp Kernstine
All
18 Years and over
N/A
NCT02095808
STU 052012-065
Inclusion Criteria:
• Patients must have known or probable malignant lesions requiring surgical biopsy or excision.
• Subjects of all races and ethnic origins over 18 years of age.
Exclusion Criteria:
• Not a surgical candidate.
• Poorly controlled diabetes.
Procedure: Imaging Biomarkers
Lung Cancer, Lung/Thoracic
UT Southwestern
Phase 1 Dose-escalating Study of MM-398 (Irinotecan Sucrosofate Liposome Injection) Plus Intravenous Cyclophosphamide in Recurrent or Refractory Pediatric Solid Tumors
This is a Phase 1 study of the combination of two drugs: MM-398 and Cyclophosphamide. The goal is to find the highest dose of MM-398 that can be given safely when it is used together with the chemotherapy drug Cyclophosphamide.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Patrick Leavey
All
12 Months to 20 Years old
Phase 1
NCT02013336
STU 092013-007
Inclusion Criteria:
• Histologically or cytologically-confirmed Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, or osteosarcoma
• Disease progression after prior therapy in locally advanced or metastatic setting
• Measurable or evaluable disease based on the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria
• Age 12 months to <21 years
• Adequate bone marrow reserves, hepatic function, and renal function
• Recovered from effects of any prior surgery or cancer therapy
• Patients 18 years or older will provide written consent. A parent or legal guardian of a patient <18 years of age will provide informed consent and patients 11 to 18 years of age will provide written assent or as per participating institutional policy.
Exclusion Criteria:
• Clinically significant gastrointestinal disorders
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
• Active infection or unexplained fever
• Known hypersensitivity to any of the components of MM-398 or other liposomal products
• Recent Investigational therapy
• Pregnant or breast feeding; females of child-bearing potential must test negative for pregnancy at the time of enrollment
Drug: MM-398 (Irinotecan Sucrosofate Liposome Injection) plus cyclophosphamide
Recurrent or Refractory Solid Tumors, Ewing Sarcoma, Rhabdomyosarcoma, Neuroblastoma, Osteosarcoma, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Eye and Orbit, Gall Bladder, Head and Neck, Hodgkins Lymphoma, Kaposis sarcoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Mycosis Fungoides, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Sarcoma, Small Intestine, Soft Tissue, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva
pediatric, MM-398, cyclophosphamide, irinotecan
Children’s Health
LCH-IV, International Collaborative Treatment Protocol for Children and Adolescents With Langerhans Cell Histiocytosis
The LCH-IV is an international, multicenter, prospective clinical study for pediatric Langerhans Cell Histiocytosis LCH (age < 18 years).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Erin Butler
All
up to 18 Years old
Phase 2/Phase 3
NCT02205762
STU-2018-0071
Inclusion Criteria:
• Stratum I
• Patients must be less than 18 years of age at the time of diagnosis.
• Patients must have histological verification of the diagnosis of Langerhans cell histiocytosis according to the criteria described in Section 6.1
• Signed informed consent form
• Stratum II
• Patients of Stratum I who have:
• Progressive disease (AD worse) in non-risk organs after 6 weeks (Initial Course
• AD intermediate or worse in non-risk organs or AD better in risk organs after 12 weeks (Initial Course 2)
• Disease progression (AD worse) in non-risk organs at any time during continuation treatment
• Active disease at the end of Stratum I treatment
• Disease reactivation in non-risk organs at any time after completion of Stratum I treatment
• Stratum III
• Patients from Stratum I who fulfill the following criteria:
• AD worse in risk organs after week 6 (after Initial Course 1), or AD worse or AD intermediate in risk organs after week 12 (after Initial Course 2).
• Presence of unequivocally severe organ dysfunction at the above mentioned evaluation points (hematological dysfunction, liver dysfunction, or both of them) as
• Hb <70 g/L (<7.0 g/dl) and/or transfusion dependency
• PLT <20 x109/L (20,000/μL) and/or transfusion dependency (both criteria have to be fulfilled) AND/OR
• Liver dysfunction (or digestive involvement with protein loss)
• Total protein <55 g/L or substitution dependency
• Albumin <25 g/L or substitution dependency (at least one of the two criteria to be fulfilled)
• Stratum IV
• Patients from Stratum I or Stratum III who fulfill the following criteria:
• AD worse in risk organs after week 6 (after Initial Course 1), or AD worse or AD intermediate in risk organs after week 12 (after Initial Course 2) of Stratum I OR
• AD worse after the 2nd and 3rd 2-CdA/Ara-C course, and those AD worse or AD intermediate after the 4th 2-CdA/Ara-C course of Stratum III AND
• Presence of unequivocally severe organ dysfunction at the above mentioned evaluation points (hematological dysfunction, liver dysfunction, or both of them) as defined in Table XI (see Section 10.3.1).
• Informed consent: All patients or their legal guardians (if the patient is <18 years of age) must sign an Ethics or institutional Review Board approved consent form indicating their awareness of the investigational nature and the risks of this study. When appropriate, younger patients will be included in all discussions in order to obtain assent.
• Adequate organ function: Patients should have adequate hepatic, renal, cardiac and pulmonary function to undergo reduced intensity HCT based upon local institutional guidelines, or at a minimum meet requirements noted in eligibility checklist Appendix A-VIII_1. However, significant hepatic and pulmonary dysfunction, if secondary to underlying LCH disease activity, will not exclude patients from protocol enrollment and should be discussed with the National PI Coordinator and the Coordinating Principal Investigator.
• Stratum V
• All patients with verified diagnosis of LCH and MRI findings consistent with ND-CNSLCH irrespective of previous treatments (also those not registered to other Strata ofLCH-IV).
• Patients with isolated tumorous CNS-LCH (including isolated DI with mass lesion in the hypothalamus-pituitary axis). In patients with already established diagnosis of LCH and radiologic finding of CNS lesions compatible with LCH, a biopsy of the lesion is not obligatory. In all other cases a biopsy of the lesion is needed for inclusion into the study
• Stratum VI -- Patients with newly diagnosed SS-LCH and localization other than "multifocal bone",isolated tumorous CNS lesion, or isolated "CNS-risk" lesion.
• Stratum VII -- All patients registered in LCH IV (regardless of treatment) as long as consent for longterm follow-up has not been withheld.
Exclusion Criteria:
• Stratum I
• Pregnancy (patients of child-bearing age must be appropriately tested before chemotherapy)
• LCH-related permanent consequences (e.g. vertebra plana, sclerosing cholangitis, lung fibrosis, etc.) in the absence of active disease
• Prior systemic therapy
• Stratum II
• Patients with progressive disease in risk organs
• Permanent consequences (e.g. sclerosing cholangitis, lung fibrosis, etc.) without evidence of active LCH in the same organ or in any other locations
• No written consent of the patient or his/her parents or legal guardian
• Stratum III
• The presence of any of the following criteria will exclude the patient from the study:
• Isolated sclerosing cholangitis without evidence of active hepatic LCH as the only evidence of risk organ involvement.
• Inadequate renal function as defined by serum creatinine > 3x normal for age
• Stratum IV
• Pulmonary failure (requiring mechanical ventilation) not due to active LCH.
• Isolated liver sclerosis or pulmonary fibrosis, without active LCH.
• Uncontrolled active life-threatening infection.
• Decreased renal function with a GFR of less than 50ml/1.73m2/min.
• Pregnancy or active breast feeding
• Failure to provide signed informed consent
• Stratum VI
• Patients with SS-LCH who have an isolated tumorous CNS lesion (they are eligible for Stratum V),
• Patients with isolated "CNS-risk" or multifocal bone lesions (they are eligible for Stratum I, Group 2)
Drug: Prednisone, Drug: Vinblastine, Drug: mercaptopurine, Drug: INDOMETHACIN, Drug: Methotrexate, Drug: Cytosine Arabinoside, Drug: 2-chlorodeoxyadenosine, Procedure: hematopoietic stem cell transplantation (RIC-HSCT), Biological: Intravenous immunoglobulin
Langerhans Cell Histiocytosis, Liver, Bones and Joints, Brain and Nervous System, Lung/Thoracic, Other Hematopoietic
Langerhans cell histiocytosis
Children’s Health
Durvalumab vs Placebo Following Stereotactic Body Radiation Therapy in Early Stage Non-small Cell Lung Cancer Patients (PACIFIC-4)
This is a Phase III, randomized, placebo-controlled, double-blind, multi-center study assessing the efficacy and safety of durvalumab versus placebo following SoC SBRT in patients with unresected clinical Stage I/II lymph node-negative (T1 to T3N0M0) NSCLC.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Shahed Badiyan
All
18 Years to 130 Years old
Phase 3
NCT03833154
STU-2019-0858
Key
• Age ≥18 years
• Histologically or cytologically documented Stage I to II NSCLC, with clinical Stage I/II lymph node-negative (T1 to T3N0M0) disease and planned to receive definitive treatment with SBRT. Patients may be medically inoperable or are medically operable and refusing surgery or choosing to have SBRT (Stereotactic Body Radiation Therapy) as definitive therapy
• Completion of SoC SBRT as definitive treatment prior to randomization
• World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) PS of 0, 1, or 2
• Life expectancy of at least 12 weeks
• Body weight >30 kg
• Tumor sample required
• Adequate organ and marrow function required
• Patients with central or peripheral lesions are eligible
• Staging studies must be done within 8 weeks before randomization Key
• Mixed small cell and non-small cell cancer histology
• History of allogeneic organ transplantation
• History of another primary malignancy with exceptions
• History of active primary immunodeficiency
• Any unresolved toxicity National Cancer Institute (NCI) CTCAE Grade ≥2 from SBRT (Stereotactic Body Radiation Therapy)
Inclusion Criteria:
• Age ≥18 years
• Histologically or cytologically documented Stage I to II NSCLC, with clinical Stage I/II lymph node-negative (T1 to T3N0M0) disease and planned to receive definitive treatment with SBRT. Patients may be medically inoperable or are medically operable and refusing surgery or choosing to have SBRT (Stereotactic Body Radiation Therapy) as definitive therapy
• Completion of SoC SBRT as definitive treatment prior to randomization
• World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) PS of 0, 1, or 2
• Life expectancy of at least 12 weeks
• Body weight >30 kg
• Tumor sample required
• Adequate organ and marrow function required
• Patients with central or peripheral lesions are eligible
• Staging studies must be done within 8 weeks before randomization Key
Exclusion Criteria:
• Mixed small cell and non-small cell cancer histology
• History of allogeneic organ transplantation
• History of another primary malignancy with exceptions
• History of active primary immunodeficiency
• Any unresolved toxicity National Cancer Institute (NCI) CTCAE Grade ≥2 from SBRT (Stereotactic Body Radiation Therapy)
Drug: Durvalumab, Other: Placebo
Carcinoma, Non-Small-Cell Lung, Lung/Thoracic
NSCLC, Double- Blind, PD-L1, MEDI4736, Durvalumab, PFS, OS
UT Southwestern; Parkland Health & Hospital System
PROSpect: Prone and Oscillation Pediatric Clinical Trial
Severe pediatric acute respiratory distress syndrome (PARDS) is a life-threatening and frequent problem experienced by thousands of children each year. Little evidence supports current supportive practices during their critical illness. The overall objective of this study is to identify the best positional and/or ventilation practice that leads to improved patient outcomes in these critically ill children. We hypothesize that children with severe PARDS treated with either prone positioning or high-frequency oscillatory ventilation (HFOV) will demonstrate more days off the ventilator when compared to children treated with supine positioning or conventional mechanical ventilation (CMV).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Eduardo.Rodriguez2@childrens.com
Peter Luckett
All
up to 18 Years old
N/A
NCT03896763
STU-2019-0488
Inclusion criteria:
Intubated and mechanically ventilated with moderate-severe PARDS for <48 hours per PALICC
guidelines (chest imaging consistent with acute pulmonary parenchymal disease and OI ≥12 or
OSI ≥10). We require two blood gases meeting moderate-severe PARDS criteria (separated by
at least 4 ± 2 hours during which time the clinical team is actively working to recruit
lung volume and optimize the patient's hemodynamic status per PALICC guidelines;
specifically, incremental and decremental PEEP changes to optimize lung volume). A second
blood gas is not required for OI ≥16.
Exclusion criteria:
• Perinatal related lung disease
• Congenital diaphragmatic hernia or congenital/acquired diaphragm paralysis
• Respiratory failure explained by cardiac failure or fluid overload
• Cyanotic heart disease
• Cardiomyopathy
• Unilateral lung disease
• Primary pulmonary hypertension
• Intubated for status asthmaticus
• Obstructive airway disease (e.g., Severe airways disease without parenchymal involvement or disease characterized by hypercapnia with FiO2 <0.30 and/or evidence of increased resistance visible on the flow - time scalar and/or presence of intrinsic PEEP)
• Active air leak
• Bronchiolitis obliterans
• Post hematopoietic stem cell transplant; specifically, patients receiving continuous supplemental oxygen for three or more days prior to intubation; receiving noninvasive ventilation for more than 24 hours prior to intubation; receiving more than one vasoactive medication at time of meeting inclusion criteria; spending more than four days in the PICU prior to intubation; supported on or with immediate plans for renal replacement therapies; with two or more allogeneic transplants; who relapsed after the transplant; or with diffuse alveolar hemorrhage
• Post lung transplant
• Home ventilator (including noninvasive) or home oxygen dependent (exception: night-time noninvasive ventilation (CPAP/BiPAP) or oxygen for obstructive sleep apnea is permitted)
• Neuromuscular respiratory failure
• Critical airway (e.g., post laryngotracheal surgery or new tracheostomy) or anatomical obstruction of the lower airway (e.g., mediastinal mass)
• Facial surgery or trauma in previous 2 weeks
• Head trauma (managed with hyperventilation)
• Intracranial bleeding
• Unstable spine, femur or pelvic fractures
• Acute abdominal process/open abdomen
• Morbid obesity (2w-24 months: WHO weight-for-length/height z-score ≥+3; ≥2 years: WHO body mass index (BMI)-for-age z-score ≥+3)
• Currently receiving either prone positioning or any high-frequency mode of MV with current illness (Up to 4 hours of prone positioning and/or any mode of high-frequency mode of MV is allowed as long as the therapies are off for least 4 hours prior to the subject meeting oxygenation criteria.)
• Supported on ECMO during the current admission
• Family/medical team not providing full support (patient treatment considered futile)
• Previously enrolled in current study
• Enrolled in any other interventional clinical trial not approved for co-enrollment
• Known pregnancy
• Perinatal related lung disease
• Congenital diaphragmatic hernia or congenital/acquired diaphragm paralysis
• Respiratory failure explained by cardiac failure or fluid overload
• Cyanotic heart disease
• Cardiomyopathy
• Unilateral lung disease
• Primary pulmonary hypertension
• Intubated for status asthmaticus
• Obstructive airway disease (e.g., Severe airways disease without parenchymal involvement or disease characterized by hypercapnia with FiO2 <0.30 and/or evidence of increased resistance visible on the flow - time scalar and/or presence of intrinsic PEEP)
• Active air leak
• Bronchiolitis obliterans
• Post hematopoietic stem cell transplant; specifically, patients receiving continuous supplemental oxygen for three or more days prior to intubation; receiving noninvasive ventilation for more than 24 hours prior to intubation; receiving more than one vasoactive medication at time of meeting inclusion criteria; spending more than four days in the PICU prior to intubation; supported on or with immediate plans for renal replacement therapies; with two or more allogeneic transplants; who relapsed after the transplant; or with diffuse alveolar hemorrhage
• Post lung transplant
• Home ventilator (including noninvasive) or home oxygen dependent (exception: night-time noninvasive ventilation (CPAP/BiPAP) or oxygen for obstructive sleep apnea is permitted)
• Neuromuscular respiratory failure
• Critical airway (e.g., post laryngotracheal surgery or new tracheostomy) or anatomical obstruction of the lower airway (e.g., mediastinal mass)
• Facial surgery or trauma in previous 2 weeks
• Head trauma (managed with hyperventilation)
• Intracranial bleeding
• Unstable spine, femur or pelvic fractures
• Acute abdominal process/open abdomen
• Morbid obesity (2w-24 months: WHO weight-for-length/height z-score ≥+3; ≥2 years: WHO body mass index (BMI)-for-age z-score ≥+3)
• Currently receiving either prone positioning or any high-frequency mode of MV with current illness (Up to 4 hours of prone positioning and/or any mode of high-frequency mode of MV is allowed as long as the therapies are off for least 4 hours prior to the subject meeting oxygenation criteria.)
• Supported on ECMO during the current admission
• Family/medical team not providing full support (patient treatment considered futile)
• Previously enrolled in current study
• Enrolled in any other interventional clinical trial not approved for co-enrollment
• Known pregnancy
Other: Either supine or prone positioning and either CMV or HFOV
Acute Respiratory Distress Syndrome in Children, Lung/Thoracic
Pediatric Acute Respiratory Distress Syndrome (PARDS), Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, child, pediatric intensive care unit
Children’s Health