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Suggestions within category "Lung & Respiratory"


88 Study Matches

Microglia Activation in Asthma (MAIA)

The primary purpose of this study is to provide preliminary data to determine if an acute increase in airway inflammation, provoked by an inhaled allergen challenge, is associated with an increase in microglial activation and may inform whether individuals with asthma, in the long-term, are at increased risk for neurodegeneration, cognitive decline, and forms of dementia. Though in the long-term airway inflammation may be associated with neurodegenerative processes, these changes reflect the accumulation over a lifetime of allergen exposures and disease-related changes. This relationship between peripheral inflammation and microglial activation is analogous to the impact of sleep loss. No single night of poor sleep will lead to long-term change in brain structure, function, or cognitive function, but the accumulation of frequent and repeated sleep loss over a lifetime has been shown to have a major impact. These data will be used for a larger scale study to determine if asthma is a risk factor for neurodegeneration, and will inform brain health issues in asthma more broadly.
Melissa Rosenkranz, PhD
All
18 Years to 50 Years old
This study is NOT accepting healthy volunteers
NCT04307667
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Inclusion Criteria:

• Male or female with no health concerns that might affect the outcome of the study
• Physician diagnosis of asthma for at least six months prior to screening (can be determined at the discretion of an asthma/allergy physician member of the study team)
• At least a 20% decrease in forced expiratory volume (FEV1) during the immediate response following inhaled allergen challenge
• FEV1 > 70% at baseline
• Positive immediate skin test for allergies to ragweed, cat dander, or house dust mite (historical data documented within the last 5 years is acceptable)
• Women of child-bearing potential (WCBP) must have a negative urine pregnancy test for human chorionic gonadotropin (hCG) at screening and within 48 hours of the inhaled allergen challenge(s) and the positron emission tomography (PET) scans. WCBP must agree to use a medically-acceptable form of birth control for the duration of the study (medically-acceptable birth control methods can include: abstinence, barrier methods, oral contraceptives, injection contraceptives or skin absorption contraceptives).
• Asthma medications consisting of only inhaled beta-agonists taken as needed or leukotriene inhibitors
• Ability to tolerate a simulated functional magnetic resonance imaging (fMRI) brain scanning session
• In the opinion of the investigator, capable and willing to grant written informed consent and cooperate with study procedures and requirements
• High-affinity TSPO-binding genotype. Mixed (high/low) binding-affinity genotype may be included at principal investigator's (PI) discretion.
Exclusion Criteria:

• Current smoker (defined as more than 0.5 pack per week for the past 6 months and any smoking within two weeks of study procedures) or has a smoking history exceeding 5 pack years within the last 10 years
• Currently receiving immunotherapy
• Not able to withhold medication(s) as outlined by the study
• Use of psychotropic medication that might affect function of neurocircuitry implicated in the investigator's hypotheses at the discretion of the PI or Co-Investigator (Co-I)
• Needle phobia or claustrophobia
• Major health problems such as autoimmune disease, heart disease, uncontrolled hypertension or lung diseases other than asthma. The listed health problems are definitively exclusionary, but decisions regarding major health problems not listed will be based upon the judgment of the investigator.
• Pre-existing chronic infectious disease
• Use of inhaled corticosteroids or oral corticosteroids within 1 month of screening
• Use of an investigational drug within 30 days of entering the study. This criteria will be reviewed on a case by case basis by the principal investigators or co-investigator to determine appropriate washout period. Appropriate wash out period may be greater than 30 days depending on the half-life of the investigational drug. Participants may be eligible for study participation after completing the washout period designated by the PI or Co-I (physician only).
• Any MRI incompatibility as determined by WIMRs most current MRI screening form
• Does not fit in the MRI scanner
• History of a diagnosed Bipolar Disorder, Schizophrenia, or Schizoaffective Disorder
• History of serious head trauma or seizure disorder (can be included at the discretion of the PI or Co-I)
• Unable, in the judgement of the investigator, to comply with directions and/or tolerate the procedures required for participation in this study
• Pregnant or breast-feeding or has a planned pregnancy during the course of the study
• History of positive COVID-19 test (nasal swab or antibody test)
• Have corrected vision and are not able to wear contacts or see sufficiently well to read without glasses or contacts, as glasses will not fit in the PET/MR head coil
• Any other medical condition or disease that would impact subject safety or data integrity in the opinion of the PIs
Asthma
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Use of High-resolution Manometry to Detect Upper Airway Obstruction During Sleep

Obstructive sleep apnea (OSA) is a major public health issue in both children and adults, present in 1-5% of children and 10-30% of adults. It is characterized by repeated episodes of airway obstruction during sleep, leading to brain arousal, sympathetic activation, oxygen desaturation, sleep fragmentation, and non-restorative sleep. Patients report daytime tiredness, insomnia, and morning headaches. Children with OSA experience daytime somnolence, difficulties at school, behavioral problems, enuresis, and reduced quality of life. If left untreated, OSA can lead to numerous complications including hypertension, cardiovascular disease, stroke, and insulin resistance. Sleep partners are also affected, with patients viewing their disorder as a burden and sleeping in separate rooms. Further, disease prevalence is increasing as obesity increases. Continuous positive airway pressure (CPAP) is the current gold standard treatment for OSA. If used effectively and consistently, it can improve patient symptoms. However, adherence is generally poor, with patients experiencing physical discomfort, chest discomfort, and dry mouth. For those patients that cannot tolerate CPAP, surgical intervention is an option. In children, this typically starts with adenotonsillectomy. However, 20-75% of children will have persistent symptoms after adenotonsillectomy. In adults, anatomic factors including tonsil hypertrophy and redundant pharyngeal tissue can contribute to upper airway obstruction and may also necessitate higher pressures for effective CPAP treatment. Even if surgical intervention does not cure the OSA, it may make CPAP more tolerable and improve CPAP adherence. Sleep-related airway obstruction is a complex phenomenon potentially involving multiple anatomic levels. For patients with persistent symptoms despite initial therapy or intolerance to CPAP, further evaluation of the upper airway is clinically valuable. Polysomnography (PSG) is the gold standard for diagnosing OSA, but it does not provide information on the location(s) of upper airway obstruction. Knowledge of the precise sites of obstruction is critical to planning effective sleep surgery. Currently, this is accomplished with drug-induced sleep endoscopy (DISE). DISE was originally proposed in 1991 and involves administering anesthetic to a patient to simulate a sleep state, and then visualizing the upper airway using transnasal flexible endoscopy. Sites of obstruction at key locations including the adenoids, soft palate, lateral oropharynx, tongue base, and epiglottis can be identified. Though DISE offers valuable clinical information, it has notable limitations. First, it cannot evaluate the entire upper airway simultaneously, as any obstruction occurring superiorly precludes visualization of any obstruction occurring more inferiorly. Second, interpretation of DISE is subjective and there is no universally accepted system for analysis. Rating systems are qualitative, using grades such as complete, partial, or no obstruction as opposed to quantitative measurements. The optimal sleep assessment would be quantitative, reliable, and provide information on the entire upper airway simultaneously. A potential alternative to DISE which could meet these criteria is sleep manometry. Measurement of upper airway pressures captures the effects of obstruction along the entire upper airway, from the nasopharynx to larynx. Prior studies have attempted to employ manometry, but have been limited primarily by inadequate equipment and suboptimal methods of data analysis. Woodson et al. used a solid-state manometer with diameter of 2.3 mm and 5 sensors to detect palatal obstruction and tongue base obstruction in patients with OSA. They also used the same approach to detect persistent tongue base obstruction following uvulopalatopharyngoplasty. While these studies help demonstrate that manometry can be a useful adjunct to OSA assessment, they are severely limited both by the type of manometer used as well as the lack of a clear, detailed description of the method of data analysis. High-resolution manometry (HRM) uses pressure censors spaced 1 cm apart to allow for pressure measurement along the entire upper airway. The investigators have previously applied HRM to assessment of swallow physiology. Sophisticated methods of automated data analysis have been developed that have been shown to be reliable for both expert and novice users . Further, pattern recognition techniques have been applied to identify dysphagia and specific swallowing abnormalities. Application of this technology and modification of existing data analysis platforms will allow for a quantitative, reliable, and comprehensive assessment of upper airway obstruction during sleep in both children and adults, with potential for development of algorithms to predict effects of targeted surgical therapy at all levels of the upper airway.
Timothy Mcculloch
All
5 Years to 90 Years old
NA
This study is also accepting healthy volunteers
NCT04139499
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Inclusion Criteria:
ADULTS
• Age 18-90
• Any participant undergoing sleep endoscopy as part of standard clinical care would be eligible. This entails physician concern for sleep-disordered breathing and corresponding questionnaire and/or polysomnogram results supporting a diagnosis of obstructive sleep apnea.
• Participants without apnea are eligible, provided they are undergoing tonsillectomy or bronchoscopy for either chronic tonsillitis or airway assessment without concern for history of sleep apnea.
• Women with childbearing potential will not be excluded, as the proposed experiment would have no potential ramifications on childbearing potential. CHILDREN
• Age 5-17
• Any patients undergoing sleep endoscopy as part of standard clinical care would be eligible.
• Participants undergoing either tonsillectomy for chronic tonsillitis or bronchoscopy for airway assessment.
• Women with childbearing potential will not be excluded, as the proposed experiment would have no potential ramifications on childbearing potential.
Exclusion Criteria:

• Participant desire to avoid added anesthesia time.
• Inability to safely tolerate the added anesthesia time (about 5-10 minutes) for the experiment (as judged by either otolaryngologist or anesthesiologist).
• Pregnant women
• Vulnerable groups (i.e., prisoners, individuals lacking consent capacity, individuals unable to read the consent form).
Obstructive Sleep Apnea, Acute obstructive laryngitis [croup] and epiglottitis
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OAR-Based, Dose Escalated SBRT With Real Time Adaptive MRI Guidance for Liver Metastases

Stereotactic Body Radiation Therapy (SBRT) is a noninvasive local therapy with proven efficacy in a number of solid tumor types. However, colorectal cancer (CRC) liver metastases have been shown to be particularly resistant to SBRT, and often are found to have significantly worse rates of control compared with other histologies. Higher SBRT dose was recently shown to improve local control in CRC pulmonary metastases, however, increasing dose delivery with SBRT has been limited based on the risk of toxicity to adjacent structures, and the ability to visualize them during treatment. This is particularly relevant in treating liver tumors, as tumor and small bowel movement can often make tumor targeting and organs-at-risk (OAR) avoidance especially difficult. MRI-guided SBRT for liver tumors is both safe and feasible and offers an as yet unprecedented opportunity to achieve the highest possible safe dose to liver tumors. The purpose of this trial is to identify a safe maximum tolerated dose level for MRI-guided SBRT treatment of bowel and liver metastases, respectively. Eligible participants will be on study for up to 12 months.
Michael Bassetti, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT04020276
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Inclusion Criteria:

• For Phase I trial, have a diagnosis of histologically confirmed or clinically suspected metastatic cancer to the liver; for Phase IB trial have have a diagnosis of histologically confirmed or clinically suspected metastatic CRC to the liver.
• Participant must be a candidate for SBRT to at least one intrahepatic lesion but no more than 6 intrahepatic lesions.
• Participant must be a candidate for treatment on the ViewRay treatment unit. Must be screened to rule out implants and devices that are not MRI compatible.
• Be willing and able to provide written informed consent.
• Participants may be chemotherapy-naïve or have had prior chemotherapy up to two weeks prior to study entry.
• No active central nervous system (CNS) metastatic disease. NOTE: Subjects with CNS involvement must meet all of the following to be eligible:
• At least 28 days from prior definitive treatment of their CNS disease by surgical resection, SBRT or Whole Brain Radiation Therapy (WBRT) at the time of registration
• AND asymptomatic and off systemic corticosteroids and/or enzyme-inducing antiepileptic medications for brain metastases for >14 days prior to registration.
• Demonstrate adequate organ function as defined in the following table; all screening labs should be performed within 28 days of SBRT treatment initiation.
• Platelet count greater than or equal to 50000 /µL
• Absolute Neutrophil Count (ANC) greater than or equal to 1000 /µL
• Hemoglobin (Hgb) greater than or equal to 8 g/dL or greater than or equal to 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
• Serum creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) Creatinine/Calculated creatinine clearance (CrCl) greater than or equal to 30 mL/min for subject with creatinine levels greater than 1.5 X institutional upper limit of normal (ULN)
• Bilirubin greater than or equal to 1. 5 × ULN OR direct bilirubin greater than or equal to ULN for participants with total bilirubin levels greater than 1.5 ULN
• Aspartate aminotransferase (AST) and ALT (SGPT) greater than or equal to 5 × ULN for subjects with liver metastases
• Alanine aminotransferase (ALT) greater than or equal to 2.5 × ULN, greater than or equal to 5 × ULN in setting of metastatic disease
• International Normalized Ratio (INR) or Prothrombin Time (PT) greater than or equal to 1.5 X ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Activated Partial Thromboplastin Time (aPTT) greater than or equal to 1.5 X ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• For participants enrolled on the liver dose escalation arm, screening labs must be consistent with Child Pugh class A unless therapeutic anticoagulation places them in Child Pugh B. In that case, trial entry or exclusion will be at the discretion of the treating physician.
• Have a performance status of 2 or less on the Eastern Cooperative Oncology Group (ECOG) performance scale.
• Life expectancy of > 12 weeks.
• Women of childbearing potential (WOCP) should have a negative urine or serum pregnancy test prior to initiation of radiation therapy. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• WOCP must not be pregnant or breast-feeding.
• WOCP must be willing to use an effective method of birth control such as an oral, implantable, injectable, or transdermal hormonal contraceptive, an intrauterine device (IUD), use of a double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), or total abstinence for the duration of the radiotherapy and 60 days thereafter. NOTE: A person of childbearing potential is anyone (regardless of sexual orientation, gender identity, having undergone a tubal ligation, or remaining celibate by choice) who was born with a uterus and at least one ovary and meets both of the following criteria:
• Is post-menarcheal (i.e., has had at least one prior menses)
• 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).
• Participant is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
Exclusion Criteria:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the initiation of SBRT.
• History of a second invasive cancer in the last 3 years (except for appropriately treated low-risk prostate cancer, treated non-melanoma skin cancer, appropriately treated ductal carcinoma in situ or early stage invasive carcinoma of breast appropriately treated in situ/early stage cervical/endometrial cancer.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with follow up scans or visits.
• Has a primary tumor histology of germ cell tumor, leukemia, or lymphoma.
• Has a primary liver cancer such as cholangiocarcinoma or hepatocellular carcinoma.
• Has had prior radiation therapy that significantly overlaps with the liver.
• Has a diagnosis of Crohn's disease, ulcerative colitis, or scleroderma.
• Participants with Gilbert's disease or other primary disorders of bilirubin metabolism will not be allowed on the trial.
• Has pre-existing liver disease such that patients are classified as Child Pugh B or worse. If the participant is anti-coagulated such that their INR places them in the CP-B classification, exclusion or inclusion will be at the discretion of the treating physician.
• Pregnancy or women of childbearing potential and men who are sexually active and refuse to use medically acceptable forms of contraception.
• Participants with implanted hardware that would preclude MRIs.
Breast, Colon, Lung, Colon and Rectum, Liver Metastases, Stereotactic Body Radiation Therapy, MRI-guided Treatment
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E-Cigarette Effects on Markers of Cardiovascular and Pulmonary Disease

This study is designed to enhance the understanding of the possible health effects of e-cigarette use by relating the acute and long-term use of e-cigarettes and conventional cigarettes ("products") to well-validated cardiovascular and pulmonary disease biomarkers. Participants will be enrolled in 3 groups: exclusive e-cigarette users, exclusive cigarette smokers, and a control group of never-users. Participants can expect up to 4 weeks of study participation.
James Stein
All
18 Years and over
NA
This study is also accepting healthy volunteers
NCT03863509
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Inclusion Criteria:

• able to read and write English
• no plans to quit smoking and/or e-cig use in the next month
• not using cigars/smokeless/snus tobacco >/= 1 time per week
• having a stable pattern of current product use
• able to walk at least 2 blocks without assistance or stopping
• Specific to Exclusive Smokers:
• smokes daily
• >/= 5 cigs/day for last 6 months
• < 3 uses E-cigs in lifetime
• >/= 5 ppm carbon monoxide (CO)
• Cotinine > 100 ng/ml
• Specific to Exclusive E-cig users:
• >/= 5 days per week E-cig use for last 3 months
• Cotinine > 100 ng/ml
• Specific to Never-users
• < 100 cigarettes in a lifetime, none for > 5 years
• < 3 E-cig uses in a lifetime
• Continine < 100 ng/ml
Exclusion Criteria:

• current use of a smoking cessation medication
• women who are pregnant or plan to get pregnant in the coming month
• women who might be pregnant
• incarcerated individuals
• history of sarcoidosis in past 5 years, or active interstitial lung/pulmonary fibrosis
• history of positive COVID-19 test
Tobacco Use, E-Cigarette Use, Cardiovascular Diseases, Pulmonary Disease, Nicotine dependence, Secondary hypertension, Atherosclerosis, Tobacco use, Prevention & Screening, Heart & Vascular, Lung & Respiratory
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University of Wisconsin Severe Asthma Research Program III

The overall goal of this proposal is to better understand the basis of structural airway changes in severe asthma and how asthma exacerbations may contribute to their progression over time. The investigators propose to study a well-characterized cohort of adult and pediatric subjects with asthma using a multidisciplinary state-of-the-art approach. We hypothesize that severe asthma exacerbations, in some patients, are associated with incomplete recovery and activation of airway inflammatory cells in a regional distribution. The end result is a more permanent and less reversible airway obstruction that is a prominent feature of severe asthma.
Loren Denlinger, MD, PhD
All
6 Years and over
This study is also accepting healthy volunteers
NCT01760915
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Inclusion Criteria:
1. Physician diagnosis of asthma 2. Age 6 years and older 3. Evidence of historical reversibility, including either: 1. FEV1 bronchodilator reversibility ≥ 12%, or 2. Airway hyperresponsiveness reflected by a methacholine PC20 ≤16 mg/mL.
Exclusion Criteria:
1. No primary medical caregiver, 2. Pregnancy (if undergoing methacholine challenge or bronchoscopy), 3. Current smoking 4. Smoking history > 10 pack years if ≥ 30 years of age or smoking history > 5 pack years if < 30 years of age (Note: If a subject has a smoking history, no smoking within the past year) 5. Other chronic pulmonary disorders associated with asthma-like symptoms,including (but not limited to) cystic fibrosis, chronic obstructive pulmonary disease, chronic bronchitis, vocal cord dysfunction that is the sole cause of asthma symptoms, severe scoliosis or chest wall deformities that affect lung function, or congenital disorders of the lungs or airways, 6. History of premature birth before 35 weeks gestation, 7. Evidence that the participant or family may be unreliable or poorly adherent to their asthma treatment or study procedures, 8. Planning to relocate from the clinical center area before study completion, or 9. Any other criteria that place the subject at unnecessary risk according to the judgment of the Principal Investigator and/or attending physician(s) of record.
Asthma
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Treatment of Cytomegalovirus (CMV) Infections With Viral-Specific T Cells

The present trial will consist of the treatment of 20 pediatric and adult Hematopoietic Stem Cell Transplantation (HSCT) recipients or immunocompromised participants diagnosed with opportunistic Cytomegalovirus (CMV) infections with virus-specific, antigen-selected T-cells. CMV-specific T-cells will be isolated from donor leukapheresis products using the CliniMACS® Prodigy. Prior studies on transfer of CMV specific T-cells have been shown to be safe and efficacious in the treatment of CMV infections. The main trial objective is to evaluate the feasibility and safety of CMV-specific T-cell transfer in adult and pediatric participants suffering from CMV infections or reactivation following HSCT or due to other immunocompromised states (e.g.; primary immunodeficiency, cytotoxic therapy). Participants will be followed for one year.
Inga Hofmann, M.D.
All
1 Month and over
Phase 1
This study is NOT accepting healthy volunteers
NCT03798301
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Inclusion Criteria:
1. Adult or pediatric patient suffering from CMV reactivation/infections following HSCT or due to other immunocompromised states (e.g.; primary immunodeficiency, cytotoxic therapy).
• CMV reactivation/viremia defined as positive (>500 copies/ml) CMV qPCR and/or
• Presence of symptoms secondary to CMV infection or evidence of invasive CMV infection (e.g. pneumonitis, colitis) AND
• Patients must have ONE OF THE FOLLOWING CRITERIA:
• Absence of an improvement of viral load after ≥ 14 days of antiviral therapy with ganciclovir, valganciclovir or foscarnet (decrease by at least 1 log, i.e. 10-fold), or
• New, persistent and/or worsening CMV-related symptoms, signs and/or markers of end organ compromise while on antiviral therapy with ganciclovir, valganciclovir or foscarnet, or
• Have contraindications or experience adverse effects of antiviral therapy with ganciclovir, valganciclovir or foscarnet, or
• Known resistance to ganciclovir and/or foscarnet based on molecular testing. 2. Recipients of an allogeneic HSCT must be 28 days after stem cell infusion at the time of T-cell transfer. 3. Written informed consent given by patient or legal representative. 4. Minimum patient age 1 month. 5. Minimum weight 7 lbs. 6. Female patients of childbearing age with negative pregnancy tests. 7. Patient Karnofsky/Lansky Performance Status >30%. 8. Donor eligible based on FACT infectious screening requirements.
Exclusion Criteria:
1. Patient with acute GVHD > grade 2 or active moderate or severe chronic GVHD at time of T-cell transfer 2. Patient receiving steroids (>1.0 mg/kg body weight (BW) prednisone equivalent) at the time of T-cell transfer 3. Patient received allogeneic HSCT less than 28 days prior to T-cell transfer 4. Patient treated with donor lymphocyte infusion (DLI) within 28 days prior to T-cell transfer 5. Patient treated with Thymoglobulin (ATG), Alemtuzumab or T-cell immunosuppressive monoclonal antibodies within 28 days. 6. Patient with organ dysfunction or failure as determined by Karnofsky (patients >16 years) or Lansky (patients ≤16 years) score ≤30% (Appendix 5) 7. Patients with CMV retinitis 8. Concomitant enrollment in another clinical trial with endpoints interfering with this study 9. Any medical condition which could compromise participation in the study according to the investigator's assessment 10. Known HIV infection 11. Female patient who is pregnant or breast-feeding, or adult of reproductive potential not willing to use an effective method of birth control during study treatment. Note: Women of childbearing potential must have a negative serum pregnancy test at study entry. 12. Patients unwilling or unable to comply with the protocol or unable to give informed consent. Donor Eligibility: The original donor will be the first choice as source of T cells. If the original donor is not available for donation (such as NMDP donor, cord blood unit, or related donor not available) of peripheral mononuclear cells or does not meet all donor eligibility criteria (including donor selection criteria based on University of Wisconsin
•Madison Standard Operating Procedures for the selection of allogeneic donors), alternative related donors will be selected, with preference for those who have full HLA matching in 6/6 loci over those with partial HLA matching (≥ 3/6 HLA loci). 1. All donors must be ≥ 18 years old, available, CMV IgG positive, eligible and capable of undergoing a single standard 2 blood volume leukapheresis. If original HSCT donor is not available, CMV IgG negative or ineligible, a CMV IgG positive fully matched or haploidentical family donor will be used. 2. Related donors must be at least partially HLA compatible, matching with recipient in at least 3/6 HLA loci (HLA-A, HLA-B and HLA-DRB1 will be considered for this). 3. Donors must be CMV IgG seropositive. 4. Donors must show CMV T-cell activation after incubation with MACS GMP PepTivator Peptide Pools of CMV pp65 before undergoing leukapheresis. 5. Donor must meet the criteria for donor selection defined in the Standard Operating Procedures of the University of Wisconsin Hospitals and Clinics Stem Cell Transplant Program and in FACT standards.
Anus, Any Site, Bones and Joints, Brain and Nervous System, Breast, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Hodgkin's Lymphoma, Ill-Defined Sites, Kaposi's Sarcoma, Kidney, Larynx, Leukemia, other, Lip, Oral Cavity and Pharynx, Liver, Lung, Lymphoid Leukemia, Melanoma, Skin, Multiple Myeloma, Mycosis Fungoides, Myeloid and Monocytic Leukemia, Non-Hodgkin's Lymphoma, 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, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder, Head and Neck, Gastrointestinal cancers, other, Colon and Rectum, Anal, Sarcoma, Melanoma/Skin cancer, Hematologic cancers, other, Uterus, Genitourinary cancers, other, Bladder, Brain/Central Nervous System, Endocrine cancers, Lymphoma, Leukemia, CMV Infection, Cytomegalovirus Infections, CMV Viremia, Opportunistic Infections
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Safety of TAS-102 in Combination With Temozolomide for Metastatic Pancreatic NETs

The goal of this study is to establish maximum tolerated doses/recommended phase 2 dose (RP2D) of temozolomide (TMZ) and TAS-102 when these agents are used in combination and to evaluate the safety profile of this drug combination.
Nataliya Uboha, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT02943733
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Inclusion Criteria:

• Part 1: Patients with histologically or cytologically confirmed metastatic or locally advanced NETs of any origin and grade
• Part 1: Presence of evaluable OR measurable disease
• Part 2: Patients with histologically confirmed unresectable or metastatic pNETs of grade 1 or 2.
• Part 2: Presence of measurable disease by RECIST 1.1 criteria
• Concurrent somatostatin analogues are allowed provided that the dose has been stable (+/- 10mg) for at least 8 weeks
• Prior chemoembolization or radiation therapy (including Y90) must be performed at least 2 weeks before study enrollment
• ECOG performance status 0-2
• Life expectancy more than 3 months
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
• Hemoglobin ≥ 9 g/dL
• Platelets ≥ 100 x 10^9/L
• AST/ALT ≤ 3 x ULN (≤5 x ULN in case of liver metastases)
• Total serum bilirubin of ≤ x institutional ULN (except for Grade 1 hyperbilirubinemia solely due to a medical diagnosis of Gilbert's syndrome)
• Serum creatinine ≤ 1.5 x institutional ULN (Cockcroft and Gault formula)
• Ability to take oral medication (i.e. no feeding tube)
• Female patients of childbearing potential must have a negative pregnancy test (urine or serum) within 14 days prior to the start of the study drug treatment and must agree to use adequate birth control if conception is possible during the study and up to 6 months after discontinuation of study drug treatment
• Male patients must agree to use adequate birth control during the study and up to 6 months after discontinuation of study drug treatment
• Women who are nursing must discontinue breast feeding prior to the enrollment in the trial
• Patient must be able and willing to comply with study procedures as per protocol
• Patient able to understand and willing to sign and date the written voluntary informed consent form (ICF) at screening visit prior to any protocol-specific procedures
Exclusion Criteria:

• Part 2: Grade 3 tumors or tumors with small cell histology will be excluded
• Previous treatment with TAS-102 or TMZ
• History of partial or total gastrectomy
• Symptomatic CNS metastases requiring treatment
• Prior radiation therapy irradiating more than 10% of total bone marrow
• Other active malignancy requiring treatment within the last 2 years (except for non-melanoma skin cancer, a non-invasive/in situ cancer, or indolent nonmetastatic Gleason 6 prostate cancer)
• Pregnancy or breast feeding
• Active infection requiring treatment
• Known chronic infection with human immunodeficiency virus, hepatitis B, or hepatitis C
• Major surgery within prior 4 weeks (the surgical incision should be fully healed prior to drug administration)
• Any anticancer therapy treatments, including other investigational agents within prior 2 weeks
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAS-102 or TMZ
• Extended field radiation within prior 4 weeks or limited field radiation within prior 2 weeks
• Psychological, familial, or sociological condition potentially hampering compliance with the study protocol and follow-up schedule
• Ascites, pleural effusion or pericardial fluid requiring drainage in the last 4 weeks
• Uncontrolled diabetes mellitus
• Intestinal obstruction
• Pulmonary fibrosis
• Myocardial infarction within the last 12 months, severe/unstable angina, symptomatic congestive heart failure NYHA class III or IV
• Gastrointestinal hemorrhage
Lung, Other Digestive Organ, Pancreas, Unknown Sites, Gastrointestinal cancers, other, Neuroendocrine Tumors, Neoplasms, Cancer, Tumors
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Alpha/Beta CD19+ Depleted Haploidentical Transplantation + Zometa for Pediatric Hematologic Malignancies and Solid Tumors

This phase I trial studies the safety of transplantation with a haploidentical donor peripheral blood stem cell graft depleted of TCRαβ+ cells and CD19+ cells in conjunction with the immunomodulating drug, Zoledronate, given in the post-transplant period to treat pediatric patients with relapsed or refractory hematologic malignancies or high risk solid tumors.
Christian Capitini, MD
All
7 Months to 21 Years old
Phase 1
This study is NOT accepting healthy volunteers
NCT02508038
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Inclusion Criteria:

• Availability of an eligible haploidentical donor
• Hematologic malignancy or solid tumor
• Patients with more than one malignancy (hematologic or solid tumor) are eligible
• Patients with hematologic malignancy must have no HLA identical sibling or suitable unrelated donor OR time needed to find an acceptable unrelated donor match would likely result in disease progression such that the patient may become ineligible for any type of potentially curative transplant
• Relapsed or primary therapy-refractory AML with bone marrow blast < 20%
• High-risk refractory or relapsed ALL in patients for whom transplantation is deemed indicated (relapse occurring < 30 months from diagnosis, patients relapsing after previous allogeneic transplant, relapse after 2nd remission, primary induction failure or hypodiploidy)
• Relapsed Hodgkin lymphoma unable to achieve 2nd remission or Very Good Partial Response (VGPR) and therefore ineligible to receive autologous hematopoietic stem cell transplant (auto-HSCT)
• Hodgkin lymphoma relapsing after auto-HSCT
• Primary refractory or relapsed non-Hodgkin lymphoma unable to achieve 2nd remission or VGPR and therefore ineligible to receive auto-HSCT
• Non-Hodgkin lymphoma relapsing after auto-HSCT
• Myelodysplastic Syndrome/Myeloproliferative Syndrome Solid Tumor
• Patients with solid tumor must have failed or have been ineligible to receive auto-HSCT or if auto-HSCT would not offer > 20% chance of cure
• Neuroblastoma
• high risk with relapsed or refractory disease
• Soft tissue sarcomas (Rhabdomyosarcoma, Ewing sarcoma, Primitive Neuroectodermal Tumor or other high-risk extracranial solid tumors)
• Relapsed or primary refractory metastatic
• 1st complete remission, but very high-risk features (i.e., < 20% survival with conventional therapy)
• Osteosarcoma
• Failure to achieve Complete Response (CR) following initial therapy
• Relapsed with pulmonary or bone metastases and did not achieve a CR with surgery and/or chemotherapy
• Karnofsky (patients > 16 years) or Lansky (patients 16 years or older) performance score of ≥ 60
• Life expectancy of ≥ 3 months
• Patient must have fully recovered from acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Study enrollment no earlier than 3 months after preceding HSCT
• Glomerular Filtration Rate (GFR) ≥ 60 ml/min/1.73m2
• Total bilirubin < 3 mg/dL
• ALT (alanine aminotransferase, SCPT) ≤ 5 x Upper LImit of Normal (ULN) for age
• Ejection fraction of > 40% by Multigated Acquisition Scan (MUGA) or echocardiogram
• No evidence of dyspnea at rest
• No supplemental oxygen requirement
• If measured, carbon monoxide diffusion capacity (DLCO) >50%
• No severe peripheral neuropathy, signs of leukoencephalopathy or active Central Nervous System (CNS) infection
• Patients with seizure disorders may be enrolled if seizures are well controlled on anticonvulsant therapy
• If of reproductive potential, negative pregnancy test and willing to use effective birth control method
• Informed consent from patient or legal guardian (if patient is minor) Inclusion Criteria for Donors:
• Donor must be 18 years of age minimum, 65 years of age maximum
• Donor must be in good general health as determined by evaluating medical provider
• Must meet donor criteria for human cells, tissues, and cellular and tissue-based products per Code of Federal Regulations 21 CFR 1271, subpart C. Specifically:
• Donor screening in accordance with 1271.75 indicates that the donor:
• Is free from risk factors for, and clinical evidence of, infection due to relevant communicable disease agents and diseases; and
• Is free from communicable disease risks associated with xenotransplantation; and
• The results of donor testing for relevant communicable disease agents in accordance with 1271.80 and 1271.85 are negative or nonreactive, except as provided in 1271.80(d)(1).
• Haploidentical by HLA-typing
• Preference will be given to donors who demonstrate KIR incompatibility with recipient HLA class I ligands defined as the donor expressing a KIR gene for which the corresponding HLA class I ligand is not expressed by the recipient.
• Negative testing for relevant communicable diseases:
• Hepatitis B surface antigen (HBsAg)
• Hepatitis B core antibody (Anti-HBc)
• Hepatitis C antibody (Anti-HCV)
• HIV 1 & 2 antibody (Anti-HIV-1, 2 plus O)
• HTLV I/II antibody (Anti-HTLV I/II)
• RPR (Syphilis TP)
• CMV (Capture CMV)
• MPX for: HepB (HBV-PCR), HepC (HCV-PCR), HIV (HIV-PCR)
• NAT for West Nile Virus (WNV-PCR)
• T. Cruzi
•EIA (Chagas)
Exclusion Criteria:

• Pregnant or breast-feeding
• HIV infection
• Heart failure or uncontrolled cardiac rhythm disturbance
• Uncontrolled, Serious Active Infection
• Prior organ allograft
• Significant serious intercurrent illness unrelated to cancer or its treatment not covered by other exclusion criteria expected to significantly increase the risk of HSCT
• Any mental or physical condition, in the opinion of the PI (or PI designee), which could interfere with the ability of the subject (or the only parent or legal guardian available to care for the subject) to understand or adhere to the requirements of the study
• Enrollment in any other clinical study from screening up to Day 100 (unless PI judges such enrollment would not interfere with endpoints of this study) Exclusion Criteria for Donors:
• Lactating females
• Pregnant females
Bones and Joints, Brain and Nervous System, Colon, Esophagus, Eye and Orbit, Hodgkin's Lymphoma, Ill-Defined Sites, Kidney, Leukemia, other, Liver, Lung, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Non-Hodgkin's Lymphoma, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Urinary Bladder, Brain/Central Nervous System, Hematologic cancers, other, Leukemia, Lymphoma, Sarcoma, Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Myelodysplastic Syndrome, Myeloproliferative Syndrome, Rhabdomyosarcoma, Ewing Sarcoma, Primitive Neuroectodermal Tumor, Osteosarcoma, Neuroblastoma
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Improving Pulmonary Function Following Radiation Therapy

The purpose of this study is to develop radiation plans that will help preserve lung function in healthy tissue surrounding the tumor. We believe that 4DCT scans can be useful in designing radiation treatment plans that help us avoid healthy normal functioning lung tissue close to lung tumors. Currently 4DCT scans are used to help us determine exactly where the tumor is and how it moves when you breathe. In this study we will also use the 4DCT scans to try to identify high functioning normal lung tissue.
John Bayouth
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT02843568
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Inclusion Criteria:

• Histologic diagnosis of non-small cell lung cancer or lung metastasis from a solid tumor. One biopsy site is adequate for multiple sites of thoracic disease.
• Treatment includes localized radiation therapy with or without chemotherapy
• Karnofsky ≥ 60%
• Not pregnant per radiation oncology standard procedures
• Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:

• Prior (within last 6 months) or future planned therapeutic surgery for the treatment of the existing lung cancer
• Prior thoracic radiotherapy
• Severe COPD defined as disease requiring an inpatient stay for respiratory deterioration within the past 3 months
• Oxygen dependence of > 2 L/min continuously throughout the day at baseline
• Known underlying collagen vascular disease or intrinsic lung disease that could complicate expected sequelae of radiation (idiopathic pulmonary fibrosis, Wegener's granulomatosis)
• 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 would limit compliance with study requirements.
Lung, Non-Small Cell Lung Cancer
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Hyperpolarized Imaging for New Treatments (HyPOINT)

The introduction of triple combination CFTR modulator therapy for patients with Cystic Fibrosis (CF) with at least one copy of the deltaF508 mutation is expected to provide major health benefits, but will also require novel outcome measures that can detect CF lung disease at an early stage, capture the efficacy of new therapies when disease manifestations are limited, as well as determine whether stopping existing chronic maintenance therapies does not have negative effects. In the past decade, research has focused on the multiple breath washout (MBW) test, as a sensitive outcome measure, especially if highly-effective modulator therapies are initiated in early childhood. Even LCI, however, may not adequately capture early lung function changes, thus warranting investigation of even more sensitive outcome measures. Magnetic resonance imaging (MRI) has the advantage of being a radiation-free modality, making it more suitable for assessing response to therapy in a shorter time frame with repeated imaging. Inhalation of a hyperpolarized gas enables the visualization and quantification of regional ventilation in the lung and can be combined with structural MRI to assess both structure and function in parallel. The main Investigator and others have recently formed an international consortium (the 129Xe MRI Clinical Trial Consortium), comprised of both imaging experts and pulmonary clinicians to standardize imaging procedures, thus facilitating multi-site implementations. Data from this proposed study (HyPOINT; Hyperpolarized Imaging for New Treatments) will inform the future utility of MRI for both longitudinal studies to track disease progression over time as well as for future interventional trials. Further, the current study could inform the design of future trials of interventions of patients for whom currently no effective CFTR modulator therapy is available and for patients with rare genotypes thus laying the groundwork for a more personalized medicine approach in the near-term future.
Michael Rock, MD
All
6 Years to 18 Years old
Phase 4
This study is NOT accepting healthy volunteers
NCT04259970
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Inclusion Criteria:
1. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative. 2. Willingness and ability to adhere to the study visit schedule and other protocol requirements. 3. Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria: 1. Sweat chloride equal to or greater than 60 mEq/liter by quantitative pilocarpine iontophoresis test 2. Two well-characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene 4. Phase 1 only: Age 6 to 18 years, inclusive, at the time of consent. 5. Phase 2 only: Ages 9 to 18 years, inclusive, at the time of consent. 6. Clinically stable with no acute antibiotic usage in the 14 days prior to the first visit. 7. Genotype with F508del on at least one allele. 8. No change in chronic pulmonary medications or therapies in the 28 days prior to the first visit. 9. Stable CFTR modulator therapy (TEZ/IVA or LUM/IVA) for at least 28 days prior to the first visit or currently not receiving CFTR modulator therapy. 10. Ability to cooperate with MRI procedures. 11. Phase 1 only: FEV1 greater than or equal to 80% predicted based on GLI reference equations.
Exclusion Criteria:
1. Standard MRI exclusions (Metal implants, claustrophobia). 2. For females of childbearing potential: Positive urine pregnancy test at Screening or Visit 1 or Lactating. 3. Any other condition that, in the opinion of the Site Investigator/designee, would preclude informed consent or assent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
Cystic Fibrosis, Cystic fibrosis
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Childhood Allergy and the Neonatal Environment (CANOE)

The purpose of this research study is to study the relationship between childhood asthma, allergies, and early-life environmental factors that may cause childhood asthma and allergies. Previous birth cohort studies have found early-life environmental factors such as allergies, pollutants, viruses and bacteria have all contributed to the development of asthma and allergies. Investigators are doing this research because there continues to be a strong need to understand the root causes of asthma and allergies. The CANOE study is an observational cohort study, which means investigators are not asking participants or participant's child to change their medications and investigators will not be giving participants or participant's child a study drug.
Anne Singh
All
Not specified
NA
This study is NOT accepting healthy volunteers
NCT04215783
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Inclusion Criteria:
1. History of or concurrent asthma or allergic rhinitis (hay fever) in either biologic parent or sibling (at least one shared biological parent) by parental report. The presence of paternal or sibling allergy or asthma will be ascertained by maternal report. 2. Maternal age greater than or equal to 18 years at the time of study enrollment.
Exclusion Criteria:
1. Maternal HIV infection at time of delivery. 2. Plans for the family to move out of the geographic area during the period of the study. 3. Does not speak English. 4. Current maternal use of progesterone during pregnancy to prevent preterm birth.
• Progesterone use is only an exclusion if currently being taken at time of enrollment for preterm birth. Previous use to prevent preterm birth or use at any time for other indications is allowed. 5. Pregnancy is a result of an embryo donor (egg and sperm donor pregnancies are permitted). 6. Past or current medical problems or findings from physical examination or laboratory testing which, in the opinion of the investigator or designee, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
Asthma in Children, Allergy, Allergic rhinitis due to pollen, Allergic rhinitis due to food, Allergic rhinitis due to animal (cat) (dog) hair and dander, Asthma, Infections, Immune System & Allergies
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Dose Escalation Study of CLR 131 in Children, Adolescents, and Young Adults With Relapsed or Refractory Malignant Tumors Including But Not Limited to Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma (CLOVER-2)

The study evaluates CLR 131 in children, adolescents, and young adults with relapsed or refractory malignant solid tumors and lymphoma and recurrent or refractory malignant brain tumors for which there are no standard treatment options with curative potential.
Diane Puccetti, M.D.
All
2 Years to 25 Years old
Phase 1
This study is NOT accepting healthy volunteers
NCT03478462
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Inclusion Criteria:
All Patients
• Previously confirmed (histologically or cytologically) pediatric solid tumor (e.g., neuroblastoma, sarcoma), lymphoma (including Hodgkin's lymphoma), or malignant brain tumors that are clinically or radiographically suspected to be relapsed, refractory, or recurrent for which there are no standard treatment options with curative potential. Note: patients with diffuse intrinsic pontine glioma (DIPG) may enroll without histological or cytological confirmation.
• ≥ 2 years of age and ≤ 25 years of age at time of consent/assent
• If ≥ age 16 years, Karnofsky performance status of ≥ 60. If < age 16 years, Lansky performance status ≥ 60
• Platelets ≥ 75,000/µL (last transfusion, if any, must be at least 1 week prior to study registration, and, unless deemed medically necessary, no transfusions are allowed between registration and dosing)
• Absolute neutrophil count ≥ 750/µL
• Hemoglobin ≥ 8 g/dL (last transfusion must be at least 1 week prior to study registration, and, unless deemed medically necessary, no transfusions are allowed between registration and dosing)
• Using the bedside Schwartz formula, estimated GFR (creatinine clearance) > 60 ml/min/1.73m2
• Alanine aminotransferase < 3 × ULN
• Bilirubin < 2 × ULN
• Patients who have undergone autologous or allogeneic bone marrow transplant must be at least 3 months from transplant.
• Patients enrolling at total dose levels > 30 millicurie (mCi)/m2 must have availability or ability to collect an autologous hematopoietic stem cell back-up product prior to CLR 131 administration. At minimum, 2 x 10^6/kg cryopreserved CD34+ cells must be available.
• Patient or his or her legal representative is judged by the Investigator to have the initiative and means to be compliant with the protocol. Patients with Pediatric Solid Tumor or Lymphoma
• At least 1 measurable lesion with longest diameter of at least 10 mm. Patients with a lesion(s) that are determined to be Metaiodobenzylguanidine (MIBG) or positron emission tomography (PET) positive may be enrolled at the investigator's discretion, even if not associated with a measurable lesion of at least 10 mm. Patients with neuroblastoma who have detectable disease may enroll provided they meet the requirements of the International Neuroblastoma Response Criteria.
• Patients with known brain metastases must have completed any radiotherapy or systemic treatments for brain metastases prior to enrollment; by investigator assessment be considered stable with no new signs or symptoms for at least 1 month, and on a stable dose of steroids (unchanged for three weeks prior to registration or on a steroid tapering regimen). Patients with Recurrent or Refractory Brain Tumors
• At least 1 measurable lesion with longest diameter of at least 10 mm on any imaging sequence.
• Patients with previously known neurological deficits must be clinically stable at time of enrollment and able to complete all study related procedures. Patients with documented or newly diagnosed neurological deficits will be enrolled at the investigator's discretion.
• If patient receives steroids for neurological symptom control, the dose must be stable (unchanged for three weeks prior to registration) or on a steroid tapering regimen. Initiation of steroids per routine care immediately prior to CLR 131 dosing is acceptable.
Exclusion Criteria:

• Patients receiving active treatment for central nervous system metastases or those that are likely to require active treatment during anticipated participation in this trial. Patients with stable brain metastases treated with steroids may enroll at the investigator's discretion
• For solid tumor and lymphoma patients only, central nervous system involvement unless previously treated with surgery, systemic therapy, or radiotherapy with the patient neurologically stable. Patients with metastatic brain tumors that have been previously treated are allowed, provided the patient is neurologically stable (determined at the investigator's discretion).
• Antitumor therapy or investigational therapy, within 2 weeks of dosing. For certain types of radiation (craniospinal, total abdominal, whole lung [spot irradiation to skull-based metastases is not considered craniospinal radiation for the purposes of this study]), at least 3 months must have elapsed. No washout is required for palliative focal radiation. NOTE: Patients participating in non-interventional clinical trials (i.e., non-drug) are allowed to participate in this trial
• Patients previously treated with iodine-131 (131I)-MIBG who have already received a cumulative I-131 dose > 54 mCi/kg or who would exceed 54 mCi/kg by participating in this trial, are not eligible.
Anus, Bones and Joints, Brain and Nervous System, Breast, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Hodgkin's Lymphoma, Ill-Defined Sites, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung, Non-Hodgkin's Lymphoma, 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, Small Intestine, Soft Tissue, Stomach, Thyroid, Urinary Bladder, Head and Neck, Gastrointestinal cancers, other, Colon and Rectum, Anal, Sarcoma, Melanoma/Skin cancer, Uterus, Genitourinary cancers, other, Bladder, Brain/Central Nervous System, Endocrine cancers, Lymphoma, Pediatric Solid Tumor, Pediatric Lymphoma, Pediatric Brain Tumor, DIPG, Neuroblastoma, Ewing Sarcoma, Rhabdomyosarcoma, Osteosarcoma
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PrecISE (Precision Interventions for Severe and/or Exacerbation-Prone Asthma) Network Study

The primary objective of this study is to evaluate several interventions given to participants with severe asthma. Interventions are administered in a crossover manner with 16-week treatment periods followed by 8 to 16 week washout.
Loren Denlinger, MD, PhD
All
12 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04129931
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Inclusion Criteria:
1. Provision of signed and dated informed consent form 2. Started willingness to comply with all study procedures and availability for the duration of the study 3. Male or female, age ≥ 12 years 4. No change in asthma medications for the past 2 months and use of medium or high dose inhaled corticosteroids (ICS) (defined by Table 1A) + an additional asthma controller/biologic (defined in Tables 1B and 1C). Participants entered into the run-in on medium dose ICS will be switched to high dose ICS. They must meet all entry criteria at the time of randomization including the criteria for uncontrolled asthma as assessed by symptoms during the two weeks prior to the randomization. 5. Baseline poor or uncontrolled asthma, defined as meeting at least one of the following: 1. FEV1 <80% predicted (for adults ≥18) or FEV1<90% (pediatric participants <18) AND with 12% bronchodilator reversibility 2. Poor symptom control
•Asthma Control Questionnaire ( ACQ-6) Score ≥1.5 3. ≥1 exacerbation defined as a documented burst of systemic corticosteroids (>3 days for adults and adolescents or >1 day for adolescents treated with dexamethasone) in prior year for those not receiving chronic OCS or an increase in >50% of baseline corticosteroid dose for ≥3 days in those receiving chronic OCS.
• For patients on a biologic agent, at least one asthma exacerbation must have occurred at least 2 months after the initiation of the biologic agent. The definition of acceptable documentation for asthma exacerbations can be found in Section 6.5.3. 6. Evidence of asthma demonstrated by either bronchodilator reversibility or methacholine responsiveness either during the run-in or by historical evidence of either criterion if testing was performed under the same standards of the PrecISE Network at a PrecISE recruitment center. These criteria are defined as: 1. An increase in FEV1 ≥12% (and 200 ml) after up to 8 puffs of albuterol OR 2. Positive methacholine defined as PC20 ≤16 mg/ml, or PD20 ≤400 mcg/ml 7. Agreement to adhere to Lifestyle Considerations (see Section 5.4) throughout study duration 8. Owns a device compatible with the eDiary system used for CompEx, that is, an iOS 11+ device such as iPhone, iPad or iPod, or a smartphone or tablet running on Android 5.0+
Exclusion Criteria:
1. Current participation in an interventional trial (e.g. drugs, diets, etc.) 2. Enrollment in a clinical trial where the study medication was administered within the past 60 days or within 5 half-lives (whichever is greater) 3. Physician diagnosis of other chronic pulmonary disorders associated with asthma-like symptoms, including, but not limited to, cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema, severe scoliosis or chest wall deformities that affect lung function, or congenital disorders of the lungs or airways 4. Receiving one or more immune-modulating therapies for diseases other than asthma 5. Receiving methotrexate, mycophenolate (CellCept®), or azathioprine (Imuran®) 6. Receiving aero allergen immunotherapy and not on at least 3 months of maintenance allergen immunotherapy 7. Underwent a bronchial thermoplasty within the last two years 8. Born before 35 weeks of gestation 9. Uncontrolled hypertension, defined as systolic blood pressure >160 mm/Hg, or diastolic blood pressure >100 mm/Hg 10. History of malignancy except non-melanoma skin cancer within the last five years 11. History of smoking 1. If <30 years old: Smoked for ≥5 pack-years*
• Can still be enrolled if <30, smoked <5 5 pack years and none in past year, and normal (negative) urine cotinine 2. If 30-39 years old: Smoked for ≥10 pack years
• Can still be enrolled if ≥30, smoked <10 pack years and none in past year, provided participant demonstrates a normal (negative) urine cotinine 3. If ≥40 years old: Smoked ≥15 pack years
• Can still be enrolled if ≥40 years old, smoked <15 pack years and none in the last year, provided participant demonstrates normal (negative) urine cotinine. Patients with a smoking history of ≥10 to <15 pack years will also need to demonstrate a normal Diffusing Capacity for Carbon Monoxide (DLCO) (>70% predicted) * Smoking equivalent pack years. One pack of cigarettes a day for 1 year is equivalent to: 1. 1 cigar or pipe per day for 1 year 2. Smoked hookah or shisha =1 session per day for 1 year 3. Vaped e-cigarettes =0.5 mLs e-liquid per day for 1 year, or =1 cartridge/tank/pod per day for 1 year 4. 1 use of marijuana per day for 1 year 12. Active use of any inhalant >1 time per month in the past year 1. Active smoking of conventional tobacco, inhaling of marijuana or other drugs, or vaping of e-cigarettes or vape pods >1 time per month in the past year 2. Any form of tobacco qualifies, such as: 1 cigarette, 1 hookah or shisha sessions, 1 cigar, 1 pipe, etc. 3. Any electronic (e)-device included: e-cigarette e-cig, mod, vape pen, JUUL vaping device, e-cigar, e-hookah, e-pipe, vape pods, etc. 4. Any form of inhaled marijuana, including smoking marijuana leaves or inhaling THC (tetrahydrocannabinol) via e-cigarette or device 13. Substance abuse within the last year 14. Unwillingness to practice medically acceptable birth control or complete abstinence during the study, current pregnancy, or lactation. Medically acceptable birth control/abstinence is defined as: 1. Career, lifestyle, or sexual orientation precludes intercourse with a male partner 2. For those in a monogamous relationship that precludes sexual activity with other partners, one of the sexual partners has been sterilized by vasectomy (in males) or hysterectomy and/or bilateral salpingo-oophorectomy (in females) 3. Use of highly effective methods of birth control defined as those, alone or in combination, that result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. Contraception should be used for at least 1 month prior to screening, throughout study participation and for an additional 16 weeks after the end of the final test treatment.
• Pregnancy tests will be given to each female participant prior to study enrollment and at each clinic visit
• Each male participant will agree to inform his sexual partner(s) of the potential for harm to an unborn child. If a sexual partner becomes pregnant while he is participating in the study, he will notify study staff within 24 hours of receiving medical confirmation. His partner will be advised to promptly notify her doctor
• Any pregnancy (of a participant or a partner) will be monitored for adverse events with respect to pregnancy outcome until one month after birth. 15. Requirement for daily systemic corticosteroids above 10 mg of prednisone (or equivalent) per day for the past 2 months 16. Respiratory infection within 1 month of screening 17. Intubation for asthma in the last 12 months 18. Use of warfarin, current or last 30 days 19. Any clinically significant abnormal findings in the history, physical examination, vital signs, electrocardiogram, hematology or clinical chemistry during run-in period, which in the opinion of the site investigator, may put the participant at risk because of his/her participation in the study, or may influence the results of the study, or the participant's ability to complete the entire duration of the study 20. Additional exclusions for specific interventions (and not for others) are listed in the Appendices I-VI, Section 5.2 Safety
Exclusion Criteria:
Participants who meet the following criteria will be excluded from the study: 1. Hemoglobin <10 g/dL 2. Absolute Neutrophil Count (ANC) <1000/µl for black participants, <1500/µl for other participants 3. Lymphocytes <500/µl 4. Platelet count <100,000/µl 5. Alanine Transaminase (ALT)/Aspartate Aminotransferase (AST) >2x upper limits of normal (ULN) 6. Bilirubin ≥2x ULN 7. Estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 sq m 8. Positive Human Immunodeficiency Virus, Types 1 & 2 (HIV 1&2) Ab/Ag immunoassay followed by a confirmatory positive test (Geenius™ HIV-1/HIV-2 antibody differentiation immunoassay) 9. Positive Hepatitis B surface Ag (active infection) or Hepatitis B core total antibody (marker of past infection that could reactivate) 10. Positive Hepatitis C RNA test following positive Hepatitis C Antibody 11. EKG with significant clinical findings A positive QuantiFERON-TB (tuberculosis) Gold test requires further screening. A participant may be included in PrecISE if at least one of the following criteria are met: 1. A chest radiograph (CXR) done within the last six months of the test that shows no evidence of active TB 2. A chest CT scan done within the last six months of the test that shows no evidence of active TB 3. Documentation of adequate treatment for latent TB In cases of an indeterminate QuantiFERON-TB test result, a second blood specimen must be drawn. A chest x-ray is not required if the participant has a negative QuantiFERON-TB Gold test. Comorbid Conditions: Comorbidities are commonly present in severe asthma. Specific questionnaires will be used to identify common comorbidities as follows: 1. Sleep apnea: STOP-BANG 2. GERD (GERD- Questionnaire) 3. VCD (Pittsburgh vocal cord dysfunction index) 4. Chronic Rhinitis Sinusitis (Sinonasal questionnaire-SNQ5) 5. Depression-Anxiety (Hospital anxiety and depression Scale: HADS) These questionnaires are best used as screening tools. As such they typically have high sensitivity but relatively low specificity. Many of their symptoms overlap with the symptoms reported by participants with asthma who do not suffer from these conditions. Therefore, participants who meet the established cut offs for these questionnaires will need to be evaluated by the investigator to consider the clinical significance of the positive questionnaire based on history and physical and available testing. The investigator will need to judge the presence, severity and control of a specific condition and determine if it is sufficiently controlled to keep the participant in the PrecISE protocol. If the comorbid condition(s) is/are not adequately controlled, the investigator may refer the participant for further evaluation/treatment, prior to enrollment in PrecISE. Rescreening is permitted (after at least four weeks) to determine if the participant is able to move forward in PrecISE once the comorbid condition(s) is/are under adequate control. It is expected that some of the participants may also have other conditions such as cardiovascular disease, diabetes and obesity. These should be evaluated clinically as part of the complete history and physical done at initial evaluation. Their inclusions should be based on the investigator clinical judgement in line with good clinical practice principles.
Asthma
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Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH) (A DUE)

Combination therapy in pulmonary arterial hypertension (PAH) has been the subject of active investigation for more than a decade, with the benefit of targeting different pathways known to be involved in the pathogenesis of the disease. Adherence to prescribed therapy has an impact on clinical outcomes. Reducing the pill/tablet count and frequency has a major impact on patients' adherence to therapies and therefore the observed clinical outcomes. One way to simplify treatment is to use fixed-dose combination (FDC) products that combine multiple treatments targeting different pathways into a single tablet. This study aims to demonstrate that the FDC of macitentan and tadalafil is more effective than therapy with 10 mg of macitentan alone or 40 mg of tadalafil alone. This phase 3 study will evaluate the efficacy and safety at 16 weeks of an FDC (macitentan 10 mg and tadalafil 40 mg) against these two PAH-approved therapies given as monotherapy to further confirm the added value of the FDC.
James Runo, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03904693
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Inclusion Criteria:

• Signed and dated informed consent form (ICF)
• Confirmed diagnosis of symptomatic PAH in WHO FC II or III
• Symptomatic PAH belonging to one of the following subgroups of WHO Group 1 pulmonary hypertension:
• Idiopathic
• Heritable
• Drug- or toxin-induced
• Associated with connective tissue disease, HIV infection, portal hypertension or congenital heart disease with simple systemic-to-pulmonary shunt with persistent pulmonary hypertension documented by a right heart catheterization (RHC) ≥ 1 year after surgical repair
• PAH diagnosis confirmed by hemodynamic evaluation at rest (through central reading), evaluated within 5 weeks prior to randomization:
• Mean pulmonary artery pressure (mPAP) ≥ 25 mmHg, AND
• Pulmonary artery wedge pressure (PAWP) or left ventricular end diastolic pressure (LVEDP) ≤ 15 mmHg, AND
• Pulmonary vascular resistance (PVR) ≥ 3 WU (i.e., ≥ 240 dyn∙sec∙cm-5)
• Negative vasoreactivity test in idiopathic, heritable, and drug/toxin-induced PAH. (Participants for whom no vasoreactivity test was performed at diagnosis can be eligible if currently treated with PAH therapy for more than 3 months and PAH diagnosis confirmed by hemodynamic evaluation at least 3 months after introduction of their PAH therapy).
• Currently receiving a stable dose of ERA or PDE-5i monotherapy for at least 3 months prior to baseline RHC, within the prespecified doses in the study protocol or no history of PAH-specific treatment
• Participant able to perform the 6MWT with a minimum distance of 100 m and maximum distance of 450 m at Screening
• A woman of childbearing potential must:
• have negative serum pregnancy test at Screening and a negative urine pregnancy test at Randomization
• agree to undertake monthly urine pregnancy tests during the study and up to at least 30 days after study treatment discontinuation
• agree to follow the contraception scheme from Screening up to at least 30 days after study treatment discontinuation
Exclusion Criteria:

• Treatment with a soluble guanylate cyclase stimulator, L-arginine, any form of prostanoids or prostacyclin-receptor agonists (including oral, inhaled, or infused routes) in the 3-month period prior to start of treatment
• Treatment with combination therapy of ERA and PDE-5i in the 3-month period prior to start of treatment or history of intolerance to ERA and PDE-5i combination therapy
• Hypersensitivity to any of the study treatments or any excipient of their formulations
• Treatment with a strong cytochrome P450 3A4 (CYP3A4) inducer in the 1-month period prior to start of treatment
• Treatment with a strong CYP3A4 inhibitor or a moderate dual CYP3A4/CYP2C9 inhibitor or co-administration of a combination of moderate CYP3A4 and moderate CYP2C9 inhibitors in the 1-month period prior to start of treatment
• Treatment with doxazosin
• Treatment with any form of organic nitrate, either regularly or intermittently
• Diuretic treatment initiated or dose changed within 1 week prior to the RHC or start of treatment
• Treatment with another investigational drug in the 3-month period prior to start of treatment
• Body mass index (BMI) > 40 kg/m2 at Screening
• Known presence of three or more of the following risk factors for heart failure with preserved ejection fraction at Screening:
• BMI > 30 kg/m2
• Diabetes mellitus of any type
• Essential hypertension (even if well controlled)
• Coronary artery disease, i.e. history of stable angina or known more than 50% stenosis in a coronary artery or history of myocardial infarction or history of or planned coronary artery bypass grafting and/or coronary artery stenting
• Known presence of moderate or severe obstructive lung disease any time prior to Screening as specified in study protocol
• Known presence of moderate or severe restrictive lung disease any time prior to Screening as specified in study protocol
• Clinically significant aortic or mitral valve disease; pericardial constriction; restrictive or congestive left-sided cardiomyopathy; life-threatening cardiac arrhythmias; significant left ventricular dysfunction; or left ventricular outflow obstruction, in the opinion of the investigator
• Known permanent atrial fibrillation, in the opinion of the investigator
• Known or suspected uncontrolled thyroid disease (hypo- or hyperthyroidism)
• Documented pulmonary veno-occlusive disease
• Hemoglobin < 100 g/L (<10 g/dL) at Screening
• Known severe hepatic impairment as specified in study protocol
• Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 × upper limit of normal (ULN) at Screening
• Severe renal impairment at Screening as specified in study protocol
• Systemic hypotension at Screening or Randomization and systemic hypertension at Screening as specified in study protocol
• Acute myocardial infarction or cerebrovascular event (e.g., stroke) within the last 26 weeks prior to Screening
• Known bleeding disorder, in the opinion of the investigator
• Loss of vision in one or both eyes because of non-arteritic anterior ischemic optic neuropathy
• Hereditary degenerative retinal disorders, including retinitis pigmentosa
• History of priapism, conditions that predispose to priapism (example, sickle cell anemia, multiple myeloma, or leukemia) or anatomical deformation of the penis (example, angulation, cavernosal fibrosis, or Peyronie's disease)
• Difficulty swallowing large pills/tablets that would interfere with the ability to comply with study treatment regimen
• Any planned surgical intervention (including organ transplant) during the double-blind treatment period, except minor interventions
• Exercise training program for cardiopulmonary rehabilitation in the 12-week period prior to start of treatment, or planned to be started during the double-blind period of the study
• Pregnant, planning to become pregnant or lactating
• Any known factor or disease that might interfere with treatment adherence, full participation in the study or interpretation of the results as judged by the investigator (e.g., drug or alcohol dependence etc.)
• Known concomitant life-threatening disease with a life expectancy less than (<) 12 months
• Calcium channel blocker treatment initiated, or dose changed within 3 months prior to right heart catheterization (RHC) at screening
Pulmonary Hypertension, Heart & Vascular, Pulmonary Arterial Hypertension (PAH) (WHO Group 1 PH)
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A Study of Biomarker-Directed, Pembrolizumab (MK-3475) Based Combination Therapy for Advanced Non-Small Cell Lung Cancer (MK-3475-495/KEYNOTE-495)

This study will investigate the utility of biomarker-based triage for study participants with advanced non-small cell lung cancer (NSCLC) without prior systemic therapy. Study participants within groups defined by a biomarker-based classifier (gene expression profile [GEP] and tumor mutational burden [TMB]) will be randomized to receive pembrolizumab in combination with quavonlimab (MK-1308), favezelimab (MK-4280), or lenvatinib. The primary hypotheses are as follows: In participants receiving pembrolizumab in combination with either quavonlimab, favezelimab, or lenvatinib, the Objective Response Rate (ORR) will be 1) greater than 5% among participants with low GEP and low TMB, 2) greater than 20% among participants with low GEP and high TMB, 3) greater than 20% among participants with high GEP and low TMB, and 4) greater than 45% among participants with high GEP and high TMB.
Toby Campbell, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03516981
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Inclusion Criteria:

• Has a histologically- or cytologically-confirmed diagnosis of Stage IV (American Joint Committee on Cancer [AJCC] v 8) NSCLC and has not had prior systemic therapy for advanced disease
• Has confirmation that epidermal growth factor receptor- (EGFR-), anaplastic lymphoma kinase- (ALK-), c-ros oncogene 1- (ROS1-), or B isoform of rapidly accelerated fibrosarcoma- (B-Raf-) directed therapy is not indicated as primary therapy (documentation of absence of tumor activating EGFR mutations, B-Raf mutations, ALK gene rearrangements, and ROS1 gene rearrangements)
• Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology
• Male participants must agree to use contraception during the treatment period and for ≥120 days, after the last dose of study treatment and refrain from donating sperm during this period. Male participants with pregnant partners must agree to use a condom
• Female participants eligible to participate if not pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP) or is a WOCBP who agrees to follow contraceptive guidance during the treatment period and for ≥120 days after the last dose of study treatment
• Provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Has adequate organ function
Exclusion Criteria:

• Has significant cardiovascular impairment within 12 months of the first dose of study drug: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident (CVA) stroke, or cardiac arrhythmia associated with hemodynamic instability, significant cardiovascular impairment, or a left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram
• Prolongation of QTc interval to >480 milliseconds (ms)
• Has symptomatic ascites or pleural effusion
• Has had an allogenic tissue/solid organ transplant
• WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study treatment
• Has not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy, or has had major surgery within 3 weeks prior to first dose of study intervention
• Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula, gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
• Radiographic evidence of major blood vessel invasion/infiltration
• Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
• Has received prior systemic chemotherapy treatment for metastatic/recurrent NSCLC
• Has current NSCLC disease that can be treated with curative intent with surgical resection, localized radiotherapy, or chemoradiation
• Is expected to require any other form of systemic or localized antineoplastic therapy while on study (including maintenance therapy with another agent for NSCLC, radiation therapy, and/or surgical resection)
• 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
• Has received previous treatment with another agent targeting the Lymphocyte-activation gene 3 (LAG-3) receptor
• Has received previous treatment with another agent targeting vascular endothelial growth factor (VEGF) or the VEGF receptor
• Has received prior anticancer therapy including investigational agents within 4 weeks prior to randomization
• Has received prior radiotherapy within 2 weeks of start of study treatment or received lung radiation therapy of >30 Gy within 6 months prior to the first dose of study intervention
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study treatment
• 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 treatment.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab, favezelimab, or lenvatinib and/or any of its excipients
• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs)
• Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
• Has an active infection requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
• Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days (females and males) after the last dose of study treatment.
Advanced Non-Small Cell Lung Cancer, Lung
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Testing the Timing of Pembrolizumab Alone or With Chemotherapy as First Line Treatment and Maintenance in Non-small Cell Lung Cancer

This phase III trial studies whether pembrolizumab alone as a first-line treatment, followed by pemetrexed and carboplatin with or without pembrolizumab after disease progression is superior to induction with pembrolizumab, pemetrexed and carboplatin followed by pembrolizumab and pemetrexed maintenance in treating patients with stage IV non-squamous non-small cell lung cancer. 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. Drugs used in chemotherapy, such as pemetrexed and carboplatin, 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. It is not yet known whether giving first-line pembrolizumab followed by pemetrexed and carboplatin with or without pembrolizumab works better in treating patients with non-squamous non-small cell cancer.
Anne Traynor, M.D.
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03793179
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Inclusion Criteria:

• Patients must have histologically or cytologically confirmed stage IV non-squamous non-small cell lung cancer (NSCLC) (includes M1a, M1b, and M1c stage disease, American Joint Committee on Cancer [AJCC] 8th edition). Patients with Stage IIIB and IIIC disease are eligible if they are not candidates for combined chemotherapy and radiation
• Patients must have PD-L1 expression Tumor Proportion Score (TPS) >= 1% in tumor cells. If PD-L1 expression TPS is unevaluable or the testing could not be completed, the patients are not eligible. The assay must have been performed by a Clinical Laboratory Improvement Act (CLIA) (or equivalent) certified laboratory
• Patients must have measurable or non-measurable disease. The presence of malignant pleural fluid alone is sufficient to satisfy this eligibility criterion. Baseline imaging assessments and measurements used to evaluate all measurable or non-measurable sites of disease must be done within 4 weeks prior to study registration
• NOTE: If patient receives pemetrexed, follow institutional guidelines to drain fluids
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Patients must NOT have received the following:
• Prior systemic chemotherapy or immunotherapy for advanced metastatic NSCLC. Patients treated with any prior checkpoint inhibitors for metastatic lung cancer are ineligible. Chemotherapy for non-metastatic disease (e.g. adjuvant therapy) or immunotherapy for locally advanced Stage III disease is allowed if at least 6 months have elapsed between the last dose of the prior therapy and study registration. Local therapy, e.g. palliative radiation, is allowed as long as a period of 14 days has passed between completion of local therapy and study registration. Registration prior to treatment during the 14 days is allowed. Palliative radiation must be to non-target lesions
• Methotrexate (MTX) given in low doses for non-malignant conditions with last dose at least 14 days prior to date of registration will be allowed. Other low dose chemotherapeutics for non-malignant conditions will be considered, but review by the study chair is required
• Patients with known EGFR mutations (except exon 20 insertion), BRAF mutations (V600) or ALK or ROS1 translocations that can be treated with oral tyrosine kinase inhibitors are excluded
• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. CNS progression counts as progression and patients must move on to the next phase after CNS treatment. Patients with asymptomatic new (at screening) or progressive brain metastases (active brain metastases at screening) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
• Patients are eligible if off steroids for at least 14 days prior to protocol treatment
• Palliative radiation to non-target lesions (bone metastasis) is allowed if patient develops symptoms
• Anticonvulsants are allowed
• Patients with asymptomatic, sub-centimeter brain metastasis who at the discretion of investigators do not need immediate CNS directed therapies are eligible
• Patients with 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 must not have known pre-existing and clinically active interstitial lung disease, or a known history of (non infectious) pneumonitis that required steroids, or current pneumonitis
• Patients must not have significant gastrointestinal disorders with diarrhea as a major symptom (e.g. Crohn's disease, malabsorption, etc.)
• Patients must not have history of auto-immune condition requiring ongoing or intermittent systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
• Patients must not have any other concomitant serious illness or organ system dysfunction that in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the study drug
• Patients must not receive any other investigational agents during the course of therapy
• Women must not be pregnant or breast-feeding due to potential harm to the fetus or infant from cytotoxic chemotherapy and the unknown risk of MK-3475 (pembrolizumab). Patients must also not expect to conceive or father children from the time of registration, while on study treatment, and until at least 120 days after the last dose of study treatment
• All females of childbearing potential must have a blood test or urine study within 72 hours prior to registration to rule out pregnancy
• A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: has achieved menarche at some point; has not undergone a hysterectomy or bilateral oophorectomy; or 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)
• Women of childbearing potential and sexually active males must use an accepted and effective method of contraception or abstain from sexual intercourse from time of registration, while on study treatment, and continue for 120 days after the last dose of study treatment
• Absolute neutrophil count (ANC) >= 1500/mm^3 (within 14 days of randomization)
• Platelets >= 100,000/mm^3 (within 14 days of randomization)
• Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 Or if patient on therapeutic anticoagulation, PT/INR =< 3.0 (within 14 days of randomization)
• Partial thromboplastin time (PTT) =< institutional upper limit of normal (ULN) OR, if patient is on therapeutic anticoagulation, PTT must be =< 1.5 x ULN (within 14 days of randomization)
• Total bilirubin =< 1.5 mg/dL (obtained within 14 days of randomization)
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) < 5 x upper limit of normal (ULN) (obtained within 14 days of randomization)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 5 x upper limit of normal (ULN) (obtained within 14 days of randomization)
• Calculated creatinine clearance >= 45 ml/min to be eligible to receive pemetrexed (obtained within 14 days prior to randomization)
• Serum creatinine =< 1.5 x institutional upper limit of normal (ULN) (obtained within 14 days prior to randomization)
• Patients must not have a known history of active tuberculosis (TB)
• Patients must not have a diagnosis of immunodeficiency or receive systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of protocol treatment
• Patients must not have received a live vaccine within 30 days prior to randomization. Seasonal flu vaccines that do not contain live virus are permitted
• 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 or 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
Lung Non-Squamous Non-Small Cell Carcinoma, Stage IIIB Lung Cancer AJCC v8, Stage IIIC Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8, Lung
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Crizotinib in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Removed by Surgery and ALK Fusion Mutations (An ALCHEMIST Treatment Trial)

This randomized phase III trial studies how well crizotinib works in treating patients with stage IB-IIIA non-small cell lung cancer that has been removed by surgery and has a mutation in a protein called anaplastic lymphoma kinase (ALK). Mutations, or changes, in ALK can make it very active and important for tumor cell growth and progression. Crizotinib may stop the growth of tumor cells by blocking the ALK protein from working. Crizotinib may be an effective treatment for patients with non-small cell lung cancer and an ALK fusion mutation.
Anne Traynor, M.D.
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT02201992
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Inclusion Criteria:

• Patients must have undergone complete surgical resection of their stage IB (>= 4 cm), II, or non-squamous IIIA NSCLC per American Joint Committee on Cancer (AJCC) 7th edition and have had negative margins; N3 disease is not allowed
• Baseline chest computed tomography (CT) with or without contrast must be performed within 6 months (180 days) prior to randomization to ensure no evidence of disease; if clinically indicated additional imaging studies must be performed to rule out metastatic disease
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Patients must be registered to the ALCHEMIST-SCREEN (ALLIANCE A151216) trial prior to randomization
• Positive for translocation or inversion events involving the ALK gene locus (e.g. resulting in echinoderm microtubule associated protein like 4 [EML4]-ALK fusion) as determined by the Vysis Break Point fluorescence in situ hybridization (FISH) assay and defined by an increase in the distance between 5? and 3? ALK probes or the loss of the 5? probe; this must have been performed:
• By a local Clinical Laboratory Improvement Amendments (CLIA) certified laboratory: report must indicate the results as well as the CLIA number of the laboratory which performed the assay; tissue must be available for submission for central, retrospective confirmation of the ALK fusion status via ALCHEMIST-SCREEN (ALLIANCE A151216) OR
• Patient registered to and the ALK fusion status performed centrally on the ALCHEMIST-SCREEN (ALLIANCE A151216)
• Women must not be pregnant or breast-feeding
• All females of childbearing potential must have a blood or urine pregnancy test within 72 hours prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• Women of childbearing potential and sexually active males must be strongly advised to practice abstinence or use an accepted and effective method of contraception
• Patients must NOT have uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• No known interstitial fibrosis or interstitial lung disease
• No prior treatment with crizotinib or another ALK inhibitor
• No ongoing cardiac dysrhythmias of grade >= 2 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, uncontrolled atrial fibrillation (any grade), or corrected QT (QTc) interval > 470 msec
• No use of medications, herbals, or foods that are known potent cytochrome P450, subfamily 3A, polypeptide 4 (CYP3A4) inhibitors or inducers, included but not limited to those outlined
• Patients must be adequately recovered from surgery at the time of randomization
• The minimum time requirement between date of surgery and randomization must be at least 4 weeks (28 days)
• The maximum time requirement between surgery and randomization must be:
• 3 months (90 days) if no adjuvant chemotherapy was administered
• 8 months (240 days) if adjuvant chemotherapy was administered
• 10 months (300 days) if adjuvant chemotherapy and radiation therapy were administered
• Patients must have completed any prior adjuvant chemotherapy or radiation therapy 2 or more weeks (6 or more weeks for mitomycin and nitrosoureas) prior to randomization and be adequately recovered at the time of randomization
• NOTE: Patients taking low dose methotrexate for non-malignant conditions and other cytotoxic agents for non-malignant conditions are allowed to continue treatment while on study
• NOTE: Neo-adjuvant chemotherapy or radiation therapy for the resected lung cancer is not permitted
• Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
• Total serum bilirubin =< 1.5 x ULN
• Absolute neutrophil count (ANC) >= 1500/mm^3
• Platelets >= 30,000/mm^3
• Hemoglobin >= 8.0 g/dL
• Serum creatinine =< 2 x ULN
• Prior to randomization patients with any non-hematologic toxicity from surgery, chemotherapy, or radiation must have recovered to grade =< 1 with the exception of alopecia and the criteria outlined
• Patients must not have any history of locally advanced or metastatic cancer requiring systemic therapy within 5 years from randomization, with the exception of in-situ carcinomas and non-melanoma skin cancer; patients must have no previous primary lung cancer diagnosed concurrently or within the past 2 years
• Patients may not be receiving any other investigational agents while on study
ALK Gene Rearrangement, ALK Gene Translocation, ALK Positive, Stage IB Non-Small Cell Lung Carcinoma AJCC v7, Stage II Non-Small Cell Lung Cancer AJCC v7, Stage IIA Non-Small Cell Lung Carcinoma AJCC v7, Stage IIB Non-Small Cell Lung Carcinoma AJCC v7, Stage IIIA Non-Small Cell Lung Cancer AJCC v7, Lung
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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.
Anne Traynor, M.D.
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT02194738
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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
• 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
Lung Adenocarcinoma, Lung Large Cell Carcinoma, Resectable Lung Non-Small Cell Carcinoma, Stage IB Lung Non-Small Cell Carcinoma AJCC v7, Stage IB Lung Squamous Cell Carcinoma AJCC v7, Stage II Lung Non-Small Cell Cancer AJCC v7, Stage II Lung Squamous Cell Carcinoma AJCC v7, Stage IIA Lung Non-Small Cell Carcinoma AJCC v7, Stage IIA Lung Squamous Cell Carcinoma AJCC v7, Stage IIB Lung Non-Small Cell Carcinoma AJCC v7, Stage IIB Lung Squamous Cell Carcinoma AJCC v7, Stage IIIA Lung Non-Small Cell Cancer AJCC v7, Stage IIIA Lung Squamous Cell Carcinoma AJCC v7, Lung
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Early Integrated Telehealth Versus In-Person Palliative Care for Patients With Lung Cancer (REACH PC)

This research study is evaluating ways to provide palliative care to patients who have recently been diagnosed with lung cancer and their families.
Toby Campbell, MD
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT03375489
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Inclusion Criteria:

• Patient Eligibility Criteria
• Diagnosed with advanced non-small cell lung cancer being treated with non-curative intent, and informed of advanced disease within the prior twelve weeks
• Eastern Cooperative Oncology Group (ECOG) Performance Status from 0 (asymptomatic) to 3 (symptomatic and in bed >50% of the day)
• The ability to read and respond to questions in English or Spanish
• Receiving primary cancer care at one of the participating sites
• Age > or = 18 years
• Lives in a state where their institutions' palliative care clinicians are licensed to practice
• Caregiver Eligibility Criteria
• Relative or friend who is identified by the patient participant and lives with the patient or has contact with them at least twice per week.
• The ability to read and respond to questions in English or Spanish
• Age > or = 18 years
Exclusion Criteria:

• Patient Exclusion Criteria
• Already receiving outpatient PC or hospice services
• Cognitive or psychiatric conditions as determined by the treating oncologist to prohibit study consent or participation
• Caregiver Exclusion Criteria --Cognitive or psychiatric conditions as determined by the treating oncologist to prohibit study consent or participation
Lung Cancer, Lung
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CHaractErizing CFTR Modulated Changes in Sweat Chloride and Their Association With Clinical Outcomes (CHEC-SC)

This is a multicenter, cross-sectional, cohort study which will collect contemporary sweat chloride (SC) values from approximately 5000 Cystic Fibrosis (CF) patients prescribed and currently receiving commercially approved Cystic Fibrosis transmembrane conductance regulator (CFTR) modulator therapies.
Michael Rock, MD
All
4 Months and over
NA
This study is NOT accepting healthy volunteers
NCT03350828
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Inclusion Criteria:

• Written informed consent (and assent when applicable) obtained from subject or subject's legal representative
• Enrolled in the Cystic Fibrosis Foundation Patient Registry (CFFPR)
• Male or female ≥ 4 months of age on day of study visit
• Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:
• Sweat chloride equal to or greater than 60 milliequivalent (mEq)/liter by quantitative pilocarpine iontophoresis test (QPIT)
• Two well-characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
• Current treatment with a prescribed commercially approved CFTR modulator for at least 3 months prior to enrollment
• Able to perform the testing and procedures required for this study, as judged by the investigator
Exclusion Criteria:

• Presence of a condition or abnormality that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data
• Currently enrolled in an investigational trial (including open-label follow-on studies and Expedited Access Pathway (EAP)) of an agent expected to have an impact on sweat chloride (refer to current list provided on study website)
Respiration Disorders [C08], Cystic Fibrosis
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A Study to Evaluate the Safety of Long-term Ivacaftor Treatment in Subjects With Cystic Fibrosis Who Are Less Than 24 Months of Age at Treatment Initiation and Have an Approved Ivacaftor-Responsive Mutation

This is a Phase 3, 2-arm, multicenter study with an open-label ivacaftor arm and an observational arm to evaluate the safety and efficacy of long-term ivacaftor treatment in subjects with cystic fibrosis (CF) who are <24 months of age at treatment initiation and have an approved Ivacaftor-Responsive mutation
Michael Rock, MD
All
up to 24 Months old
Phase 3
This study is NOT accepting healthy volunteers
NCT03277196
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Inclusion Criteria:
Ivacaftor Arm: Subjects From Study 124 (NCT02725567 ) Part B:
• Subjects transitioning from Study 124 Part B must have completed the last study visit of Study 124 Part B.
• As judged by the investigator, parent or legal guardian must be able to understand protocol requirements, restrictions, and instructions; and must sign the informed consent form (ICF). Ivacaftor Arm: Subjects Not From Study 124 Part B:
• Confirmed diagnosis of CF, or 2 CF-causing mutations.
• An ivacaftor- responsive CFTR mutation on at least 1 allele. Subjects will be eligible in countries/regions where ivacaftor is approved for use in subjects 2 years of age and older.
• As judged by the investigator, parent or legal guardian must be able to understand protocol requirements, restrictions, and instructions; and must sign the ICF. Observational Arm:
• Received ivacaftor treatment in Study 124 Part B and elected not to enroll or ineligible to enroll in the ivacaftor arm of Study 126.
Exclusion Criteria:
Ivacaftor Arm: Subjects From Study 124 Part B:
• History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering ivacaftor to the subject.
• Subjects receiving commercially available ivacaftor treatment Ivacaftor Arm: Subjects Not From Study 124 Part B:
• History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering ivacaftor to the subject
• An acute upper or lower respiratory infection, or pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks of Day 1
• Abnormal liver function at screening
• Hemoglobin <9.5 g/dL at screening
• History of solid organ or hematological transplantation
• Use of any moderate or strong inducers or inhibitors of CYP3A within 2 weeks of Day 1 Observational Arm:
• Receiving ivacaftor treatment Other protocol defined Inclusion/Exclusion criteria may apply.
Cystic Fibrosis, Cystic fibrosis
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APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors (SPARTA)

The primary Phase 1 purpose of this study was to assess overall safety, tolerability and recommended Phase 2 dose (RP2D) of APL-101. The Phase 2 portion will assess efficacy of the dose determined in Phase 1 in individuals with Non-Small Cell Lung Cancer with c-Met EXON 14 Skip Mutations; individuals with cancers associated with c-Met amplifications; individuals with cancers associated with c-Met fusion
Mark Burkard, MD, PhD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT03175224
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Major
Inclusion Criteria:

• Able to understand and comply with study procedures, understand the risks involved, and provide written informed consent.
• For Phase 1, histologically and / or cytological confirmed unresectable or metastatic solid malignancy, refractory to standard therapies with no more than three prior lines of therapy.
• For Phase 2, five cohorts will be enrolled: Cohort A-1: NSCLC EXON 14 skip mutation (c-Met naïve) for first line treatment, Cohort A-2: NSCLC EXON 14 skip mutation (c-Met naïve) pretreated subjects with no more than 3 lines of prior therapy, Cohort B: NSCLC EXON 14 skip mutation (c-Met experienced; radiographic progression on prior c-Met inhibitor), Cohort C: basket of tumor types with c-Met high level amplification (NSCLC EXON 14 skip mutation excluded), Cohort D: basket of tumor type with c-Met fusions.
• Local/archival result (tissue and/or plasma) of a positive c-Met dysregulation is required (except in Cohort A-1 in the US).
• Measurable disease according to RECIST v1.1. (or relevant criteria per tumor type).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• For all prior anticancer treatment, including radiotherapy, chemotherapy or targeted agents or hormonal therapy, a duration of more than 30 days or 5 half-lives of the agents used, whichever is shorter, must have elapsed, and any encountered toxicity must have resolved to levels meeting all the other eligibility criteria prior to the first dose of study treatment.
• No planned major surgery within 4 weeks of first dose of APL-101 Major
Exclusion Criteria:

• Hypersensitivity to APL-101, excipients of the drug product, or other components of the study treatment regimen.
• Known actionable mutation/gene rearrangement of EGFR (except for Cohort C), ALK, ROS1, RET, NTRK, KRAS, and BRAF.
• Unstable angina or myocardial infarction within 1 year prior to first dose of APL-101, symptomatic or unstable arrhythmia requiring medical therapy, history of congenital prolonged QT syndrome, prolonged QT interval corrected by Fridericia formula (QTcF) at screening (> 450 msec based on the average of 3 measurements), or concurrent treatment with a medication that is a known risk for prolonging the QT interval.
• Unable to swallow orally administered medication whole.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g., Crohn's, ulcerative colitis, active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
• Women who are breastfeeding.
Anus, Bones and Joints, Brain and Nervous System, Breast, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Ill-Defined Sites, Kaposi's Sarcoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung, Melanoma, Skin, Mycosis Fungoides, 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, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder, Head and Neck, Gastrointestinal cancers, other, Colon and Rectum, Anal, Sarcoma, Melanoma/Skin cancer, Hematologic cancers, other, Uterus, Genitourinary cancers, other, Bladder, Brain/Central Nervous System, Endocrine cancers, Solid Tumor, Advanced Cancer, Renal Cancer, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, NSCLC, Lung Cancer, Brain Tumor, Glioblastoma Multiforme
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Assessing the Clinical Benefit of Molecular Profiling in Patients With Solid Tumors

Many patients are treated for advanced cancer without knowledge of underlying molecular features that might indicate FDA approved therapies or potential eligibility for biomarker-selected clinical trials. The Strata Trial (STR-001-001) has been initiated by Strata Oncology to evaluate the clinical benefit of systematic comprehensive genomic profiling for participants with advanced cancer using real-world data and endpoints, while assessing the proportion of participants available for clinical trials and approved targeted therapies in advanced and/or aggressive cancers. The Strata Trial uses surplus, or leftover, tumor specimens for molecular profiling and does not require additional study-specific procedures.
Mark Burkard, MD, PhD
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT03061305
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Inclusion Criteria:

• Subjects must be ≥ 18 years of age.
• Subjects must have histologically documented solid tumors (including lymphoma and multiple myeloma).
• Specific criteria for individual tumor types are as follows: 1. Participants with gliomas are eligible at any stage of disease 2. Participants with pancreatic carcinoma are eligible at any stage of disease 3. Participants with rare tumors (i.e. cancer started in an unusual place in the body, it is unusual type and requires special treatment) are eligible at stages II-IV. 4. Participants with other tumor types must have recurrent, relapsed, refractory, metastatic, or advanced stages III or IV cancer.
• Must have an adequate formalin-fixed paraffin-embedded tumor specimen for genomic sequencing.
Anus, Any Site, Bones and Joints, Brain and Nervous System, Breast, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Hodgkin's Lymphoma, Ill-Defined Sites, Kaposi's Sarcoma, Kidney, Larynx, Leukemia, other, Lip, Oral Cavity and Pharynx, Liver, Lung, Lymphoid Leukemia, Melanoma, Skin, Mycosis Fungoides, Myeloid and Monocytic Leukemia, Non-Hodgkin's Lymphoma, 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, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder, Head and Neck, Gastrointestinal cancers, other, Colon and Rectum, Anal, Sarcoma, Melanoma/Skin cancer, Hematologic cancers, other, Uterus, Genitourinary cancers, other, Bladder, Brain/Central Nervous System, Endocrine cancers, Leukemia, Cancer, Adult Solid Tumor, Lymphoma, Multiple Myeloma
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Study to Evaluate the Efficacy and Safety of Ibrexafungerp in Patients With Fungal Diseases That Are Refractory to or Intolerant of Standard Antifungal Treatment (FURI)

This is a multicenter, open label, non-comparator, single arm study to evaluate the efficacy and safety of ibrexafungerp (SCY-078) in patients ≥ 18 years of age with a documented fungal disease that has been intolerant or refractory (rIFI) to Standard of Care (SoC) antifungal treatment.
David Andes, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03059992
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Key
Inclusion Criteria:
1. Must have a documented eligible invasive and/or severe fungal disease that is refractory or intolerant to Standard-of-Care treatment 2. Be able to tolerate medication orally or through a nasogastric (NG) tube or percutaneous endoscopic gastrostomy (PEG) tube 3. Be able to understand and sign a written informed consent form (ICF), which must be obtained prior to treatment and any study-related procedures. 4. Be able to understand and sign a consent or authorization form which shall permit the use, disclosure and transfer of the subject's personal health information. (e.g., in the U.S. HIPAA Authorization form). 5. Be able to understand and follow all study-related procedures including study drug administration. 6. Agree to use a medically acceptable method of contraception while receiving protocol-assigned product. Key
Exclusion Criteria:
1. An invasive fungal disease with CNS involvement. 2. Subject has an inappropriately controlled fungal disease source (e.g., persistent catheters that cannot be removed and are likely the source of infection). 3. Subject is hemodynamically unstable, requiring vasopressor medication for blood pressure support. 4. A life expectancy < 30 days. 5. Subject with abnormal liver test parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT) >10 x the upper limit of normal (ULN), and/or total bilirubin > 5 x ULN. 6. Subject is pregnant or lactating. 7. Subject has used an investigational drug within 30 days prior to the baseline visit.
Fungi [B01], Invasive Candidiasis, Mucocutaneous Candidiasis, Coccidioidomycosis, Histoplasmosis, Blastomycosis, Chronic Pulmonary Aspergillosis, Allergic Bronchopulmonary Aspergillosis, Invasive Pulmonary Aspergillosis, Recurrent Vulvovaginal Candidiasis, Other Emerging Fungi
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Preventing Asthma in High Risk Kids (PARK)

This trial is a randomized, double-blind, placebo controlled trial designed to test whether two years treatment of preschool children aged 2-3 years of age at high risk for asthma with omalizumab (anti-IgE) for two years will prevent the progression to childhood asthma, as reflected by a reduction in the prevalence of active asthma in the Final 12 months during 2 year observation period off study drug.
Daniel Jackson
All
24 Months to 47 Months old
Phase 2
This study is NOT accepting healthy volunteers
NCT02570984
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Inclusion Criteria:
1. Parent/guardian must be able to understand and provide signed and dated written informed consent; he/she must also be able to communicate with study staff. 2. 24-47 months of age at randomization 3. 2-4 wheezing episodes in the past year 4. positive allergy to aeroallergen 5. first degree relative with history or current diagnosis of asthma or allergy 6. Parent-reported history of clinical varicella or administration of varicella vaccine 7. If is participating in a food immunotherapy treatment that is not part of a clinical trial, has been on an established maintenance regimen implemented continuously for a minimum of 2 months.
Exclusion Criteria:
1. >4 episodes of wheezing in the past year 2. Use of Step 5 or Step 6 therapy (ICS plus LABA ) at the time of enrollment (Visit 0). 3. Need for systemic corticosteroids or a hospitalization for respiratory symptoms within four weeks prior to screening. 4. Three or more courses of systemic corticosteroids for wheezing illnesses in the last year 5. More than four days of symptoms of wheezing, or tightness in the chest or cough in the past two weeks causing at least minimal limitation of activity 6. More than four days of albuterol treatment (for symptoms) in the past two weeks 7. More than one night of symptoms of wheezing, or tightness in the chest or cough causing sleep disruption in the past two weeks 8. More than one night of albuterol treatment (for symptoms) in the past two weeks 9. Prematurity (<34 weeks gestation) 10. Need for oxygen for more than 5 days in the neonatal period 11. History of intubation or mechanical ventilation for respiratory illness 12. Other significant medical conditions, including: major congenital anomalies, cystic fibrosis, chronic pulmonary diseases, bronchopulmonary dysplasia, thoracic surgery, history of tuberculosis, immunodeficiency (primary or secondary), seizure disorders 13. Expecting to relocate within 4 years of study initiation to a place which would make in-person clinical visits impossible 14. Deemed unable to adhere to study activities 15. Prior aeroallergen immunotherapy or use of biologics including anti-IgE 16. Prior IVIG or systemic immunosuppressant other than corticosteroids 17. History of hypoxic seizures during a wheezing episode 18. Total IgE outside of the omalizumab dosing range. 19. Enrolled in any clinical medication trial within the past 30 days. 20. With platelet counts < 150 x 109/L at the Screening Visit (V0) 21. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or may impact the quality or interpretation of the data obtained from the study. 22. History of severe anaphylactic/anaphylactoid reactions from any cause
Healthy Volunteers, Asthma
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Oral Bacterial Extract for the Prevention of Wheezing Lower Respiratory Tract Illness (ORBEX)

The primary objective of this study is to evaluate if Broncho-Vaxom® given to high risk infants for 10 days, monthly, for two consecutive years can increase time to occurrence of the first episode of wheezing lower respiratory tract illness (WLRI) during a three year observation period off therapy.
Daniel Jackson
All
6 Months to 18 Months old
Phase 2
This study is also accepting healthy volunteers
NCT02148796
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Inclusion Criteria:

• Adequate completion of informed consent process with written documentation. The participant's legally acceptable representative must have provided the appropriate written informed consent. Assent forms will not be used due to the age of the participant population; however, for procedures later in the study when participants are older, age appropriate assent will be obtained, if required by local Institutional Review Board (IRB).
• Age: 6-18 months of age inclusive at randomization which means 5 to 17 months of age inclusive on entry into the one month run-in period. At least half of all enrolled children will be between 6 and 12 months of age at randomization.
• Participants will meet at least one of the following criteria, which have been associated with an increased risk of wheezing respiratory illnesses and asthma: a) Parental history of asthma -or- b) Physician-diagnosed atopic dermatitis in the participant
•or- c) Physician-diagnosed asthma in a blood sibling aged 4 years or more.
• Participants may be either male or female.
• Participants will have at least one parent/guardian who can communicate with the study staff to allow assessment of study outcomes. All study materials used by parent/guardian will be made available in English and in Spanish. The child's parent/guardian must have a working direct contact telephone.
Exclusion Criteria:

• Participants may not have had more than two prior WLRI episodes.
• Participants may not have had any SWLRI episodes.
• Participants may not have a physician's diagnosis of asthma.
• Participants may not have a systemic illness (other than allergy) including (but not limited to) recurrent seizures, chronic gastroesophageal reflux (GER) requiring medical treatment, major congenital anomalies, physical and intellectual delay, cerebral palsy, chest surgery, tuberculosis or other chronic infections, primary or secondary immunodeficiency, gastrointestinal malformation or disease or cardiac disorder (except a hemodynamically insignificant atrial septal defect (ASD), ventricular septal defect (VSD) or benign heart murmur).
• Participants may not have been born earlier than 36 weeks of gestation.
• Participants may not have received oxygen for more than 5 days in the neonatal period, or received mechanical ventilation with the exclusion of ventilation during anesthesia for a minor surgical procedure.
• Participants may not have significant neurodevelopmental delay.
• Participants may not be below the 3rd percentile for weight.
• Participants may not have any other chronic lung disease; e.g. chronic lung disease of prematurity (CLDP) or cystic fibrosis.
• Participants may not have a history of any life-threatening respiratory illness that required intubation and mechanical ventilation.
• The participant's family may not be expected to relocate out of study area within 3 years of the initiation of the study.
• Participants may not have received inhaled or systemic corticosteroids for respiratory related illness ever, or for other conditions in the month prior to randomization.
• Participants may not have ever received immunotherapy.
• Participants may not have ever received i.v. gammaglobulins or systemic immunosuppressants.
• Participants may not have received probiotics (Lactobacilli and Bifidobacteria) in medicinal form; (i.e. not including food), regularly for more than 4 months in the 6 to <12 mo age group or 6 months in the 12 to 18 month group prior to enrollment.
• Participant has known sensitivity to any of the study products and any of the ingredients to be administered.
• Participant has previously been randomized in this study. Participants who failed run-in and were not randomized may have study participation terminated and then be re-enrolled for a second run-in period.
• Participant is currently enrolled in or has completed any other investigational device or drug study <30 days prior to screening, or is receiving other investigational agent(s).
• Participant has a significant medical condition(s), anticipated need for major surgery during the study, or any other kind of disorder that may be associated with increased risk to the participant, or may interfere with study assessments, outcomes, or the ability to provide written informed consent or comply with study procedures, in the Investigator's opinion.
• The one month run-in period will be used to evaluate adherence to study drug administration and electronic communication. At randomization the participant must continue to meet enrolment criteria and also have demonstrated 80% adherence to the placebo during treatment period; i.e. 8 out of 10 days and a75% response rate to weekly mobile phone text queries; i.e. 3 out of 4 weekly text queries.
• Ongoing infection (of any organ system) at the time of randomization. This includes infections that are being adequately treated.
• Unable or unlikely to complete study assessments or the study intervention poses undue risk to patient in the opinion of the Investigator.
• Families will speak English and/or Spanish.
Asthma, Wheezing, Healthy Volunteers
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Phase 3 Study of Sitravatinib Plus Nivolumab vs Docetaxel in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer (SAPPHIRE)

This study will compare the efficacy of the investigational agent sitravatinib in combination with nivolumab versus docetaxel in patients with advanced non-squamous NSCLC who have previously experienced disease progression on or after platinum-based chemotherapy and checkpoint inhibitor therapy.
Toby Campbell, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03906071
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Inclusion Criteria:

• Diagnosis of Non-Squamous Non-Small Cell Lung Cancer
• Receipt of at least one but not more than two prior treatment regimens in the advanced setting
• Prior treatment with PD-1/PD-L1 checkpoint inhibitor therapy and platinum-based chemotherapy in combination or in sequence (i.e., platinum-based chemotheraphy followed by checkpoint inhibitor therapy)
• Most recent treatment regimen must have included a checkpoint inhibitor therapy with radiographic disease progression on or after treatment
• Candidate to receive docetaxel as second or third line therapy
Exclusion Criteria:

• Uncontrolled brain metastases
• Tumors that have tested positive for EGFR, ROS1, ALK mutations, or ALK fusions
• Unacceptable toxicity with prior checkpoint inhibitor therapy
• Receipt of systemic anti-cancer therapy post checkpoint inhibitor therapy, other than maintenance chemotherapy
• Impaired heart function
Metastatic Non-Squamous Non-Small Cell Lung Cancer, Lung
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Sleep for Stroke Management and Recovery Trial (Sleep SMART)

The purpose of this study is to determine whether treatment of obstructive sleep apnea (OSA) with positive airway pressure starting shortly after acute ischemic stroke or high risk TIA (1) reduces recurrent stroke, acute coronary syndrome, and all-cause mortality 6 months after the event, and (2) improves stroke outcomes at 3 months in patients who experienced an ischemic stroke.
Robert Dempsey, MD
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT03812653
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Inclusion Criteria:
1. TIA with ABCD2 ≥4 or ischemic stroke, within the prior 14 days.
Exclusion Criteria:
1. pre-event inability to perform all of own basic ADLs 2. unable to obtain informed consent from subject or legally authorized representative 3. incarcerated 4. known pregnancy 5. current mechanical ventilation (can enroll later if this resolves) or tracheostomy 6. current use of positive airway pressure, or use within one month prior to stroke 7. anatomical or dermatologic anomaly that makes use of CPAP interface unfeasible 8. severe bullous lung disease 9. history of prior spontaneous pneumothorax or current pneumothorax 10. hypotension requiring current treatment with pressors (can enroll later if this resolves) 11. other specific medical circumstances that conceivably, in the opinion of the site PI, could render the patient at risk of harm from use of CPAP 12. massive epistaxis or previous history of massive epistaxis 13. cranial surgery or head trauma within the past 6 months, with known or possible CSF leak or pneumocephalus 14. recent hemicraniectomy or suboccipital craniectomy (i.e. those whose bone has not yet been replaced), or any other recent bone removal procedure for relief of intracranial pressure 15. current receipt of oxygen supplementation >4 liters per minute 16. current contact, droplet, respiratory/airborne precautions
Cerebral infarction, Brain & Neurological, Ischemic Stroke, Sleep Apnea, Sleep Apnea, Obstructive, TIA, Stroke, CPAP, Telemedicine, Home Sleep Apnea Test, Randomized Clinical Trial, Multicenter Trial
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Expanded Access to Ensartinib for Participants With ALK+ NSCLC

This is an open-label, multicenter, intermediate-sized expanded access treatment protocol to the existing IND 111,695 for ensartinib (X-396). The treatment plan is designed to provide ensartinib to participants with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC).
Anne Traynor, M.D.
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT04146571
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Inclusion Criteria:
1. Adult patients (>18 years-of-age) with advanced ALK-positive NSCLC as determined by an FDA approved test. 2. Eastern Cooperative Group (ECOG) Performance Status score of 0 or 1. 3. Informed consent must be provided by each patient. 4. Patient is not eligible or does not have access for participation in any of the other ongoing clinical trials for ensartinib. 5. Ability to swallow and retain oral medication. 6. Male and female patients must agree to abstain or to use two highly effective forms of contraception during the treatment period and for 90 days after the last dose of study medication. 7. Adequate organ system function. 8. Patients with treated CNS metastases are eligible if they are asymptomatic with respect to the CNS metastases and do not require escalating doses of systemic corticosteroids. ALK-positive patients with untreated CNS lesions may be allowed to enroll as long as the patients are asymptomatic with respect to the CNS metastases and do not require systemic corticosteroids or anticonvulsants.
Exclusion Criteria:
1. Patients currently receiving cancer therapy. 2. Use of an investigational or targeted drug within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of ensartinib. A minimum of 10 days between termination of the treatment and administration of ensartinib is required. However, in the case of ALK TKIs, a 2-day window between termination of the TKI and the start of ensartinib is allowed. In addition, any drug-related toxicity should have recovered to Grade 1 or less, with the exception of alopecia. 3. Any major surgery or immunotherapy within the last 21 days (focal radiation does not require a washout period; ≥4 weeks for whole brain radiotherapy). Chemotherapy regimens with delayed toxicity within the last 4 weeks (or within the last 6 weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the last 2 weeks. 4. Patients with a known allergy or delayed hypersensitivity reaction to drugs chemically related to ensartinib (e.g., crizotinib) or to the active ingredient of ensartinib or to tartrazine, a dye used in the ensartinib 100 mg capsules. 5. Patients receiving CYP3A substrates with narrow therapeutic indices, strong CYP3A inhibitors, and strong CYP3A inducers. 6. Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of ensartinib. 7. Clinically significant cardiovascular disease. 8. Patients who are immunosuppressed (including known HIV infection), have a serious active infection at the time of treatment, have known hepatitis C, or have any serious underlying medical condition that would impair the ability of the patient to receive protocol treatment. 9. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol. 10. Have a history or the presence at baseline of pulmonary interstitial lung disease, drug-related pneumonitis, or radiation pneumonitis. 11. Females who are pregnant or breastfeeding. 12. Patient with any concurrent condition or receiving any concurrent medication that, in the investigator's opinion, would impart excessive risk associated with study participation or otherwise make it inappropriate for the patient to participate.
Non-Small Cell Lung Cancer, ALK Gene Rearrangement Positive, Lung
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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.
Anne Traynor, M.D.
All
18 Years and over
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT03851445
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5.1 Registration Step 0: 1. 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: 2. 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. 3. 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: 1. 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). 2. 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. 4. 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. 5. 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. 6. Patients must have Zubrod performance status 0-1 (see Section 10.2) documented within 28 days prior to Step 1 registration. 7. Patients must be ≥ 18 years of age. 8. Patients must also be offered participation in banking for future use of specimens as described in Section 15.0. 9. Patients must be willing to provide prior smoking history as required on the LUNGMAP Onstudy Form. 10. 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. 11. 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. 12. 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.
Previously Treated Non-Small Cell Lung Cancer, Lung
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