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604 Study Matches
Impact of Intensive Treatment of SBP on Brain Perfusion, Amyloid, and Tau (IPAT Study) (IPAT)
The purpose of this study is to determine if intensive lowering of systolic blood pressure
(SBP), using FDA approved medications (antihypertensive), reduces Alzheimer's Disease
pathology (i.e., excessive brain amyloid and tau protein deposition) in older adults at high
risk for memory decline or dementia.
* Age 60-85, all races/ethnicities, and both sexes are eligible;
* Mini-Mental State Exam (MMSE) ≥ 26 to exclude gross dementia; based on clinical judgment, may be rescreened in ≥ 7 days;
* Individuals with SBP ≥ 130 and SBP ≤ 180 if on 0 or 1 antihypertensive medications; ≥130 and ≤170 on up to 2 medications; ≥130 and ≤160 on up to 3 medications; ≥130 and ≤150 on up to 4 medications. Those on antihypertensives are eligible. If an individual, not treated for hypertension (HTN), has a SBP ≥ 125 mmHg, consider rescreening after 24 hours;
* Willingness to be randomized into the treatment groups and ability to return to clinic for follow-up visits over 24 months;
* Fluency in English or Spanish or both, adequate visual and auditory acuity to allow neuropsychological testing;
* Participants must have a regular healthcare provider.
Exclusion Criteria:
* Clinically documented history of stroke, focal neurological signs or other major cerebrovascular diseases based on clinical judgment or MRI/CT scans such as evidence of infection, infarction, or other brain lesions;
* Diagnosis of AD or other type of dementia, or significant neurologic diseases such as Parkinson's disease, seizure disorder, multiple sclerosis, history of severe head trauma or normal pressure hydrocephalus;
* Evidence of severe major depression (GDS ≥ 12, may be rescreened after 12 weeks or longer if evidence of reactive depression or temporary mood disturbances) or clinically significant psychopathology, (e.g., psychosis and schizophrenia); if hospitalized in past year, can be rescreened in 6 months; or presence of a major psychiatric disorder that in the investigator's opinion, could interfere with adherence to research assessments or procedures.
* Unstable heart disease based on clinical judgment (e.g., heart attack/cardiac arrest, cardiac bypass procedures within previous 6 months and congestive heart failure), or other severe medical conditions;
* History of atrial fibrillation and evidence on ECG with any of the following: active symptoms of persistent palpitation, dizziness, history of syncope, chest pain, dyspnea, orthopnea, shortness of breath at rest, or paroxysmal nocturnal dyspnea within the past 6 months; resting heart rate of \< 30 or \> 110 bpm; taking class I or III antiarrhythmic drugs including flecainide, propafenone, dronedarone, sotalol, dofetilide, and amiodarone; or clinical concerns for safely participating in lowering blood pressure.
* Systolic BP equal or greater than 180 mmHg and/or diastolic BP equal or greater than 110 mmHg, may be rescreened in 1 week.
* Orthostatic hypotension, defined as the third standing SBP \< 100mmHg, may be rescreened after 2 weeks;
* History of significant autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis or polymyalgia rheumatica;
* Significant history of alcoholism or drug abuse within the last five years;
* Uncontrolled diabetes mellitus, defined as hemoglobin A1C \> 7.5%, or requiring insulin treatment;
* Regularly smoking cigarettes within the past year;
* Pacemaker or other medical device of metal that precludes performing MRI;
* Women with a potential for pregnancy, lactation/childbearing (2 year post-menopausal or surgically sterile to be considered not childbearing potential);
* Participant enrolled in another investigational drug or device study, either currently or within the past 2 months;
* Severe obesity with BMI \> 40 ; clinical judgment should be applied in all cases to assess patient safety and anticipated compliance;
* Allergy to angiotensin receptor blockers (ARBs), i.e., drugs that have a suffix "-sartan"; allergy to amlodipine;
* Abnormal screening laboratory tests (e.g., liver ALT and AST \> 3 x ULN, GFR \< 30 or Hct \< 28%); may be rescreened after 2 weeks or longer;
* A medical condition likely to limit survival to less than 3 years;
* Participant has any condition(s) judged by the study investigator to be medically inappropriate, risky or likely to cause poor study compliance. For example:
• Plans to move outside the clinic catchment area in the next 2 years;
• Significant concerns about participation in the study from spouse, significant other, or family members;
• Lack of support from primary health care provider;
• Residence too far from the study clinic site such that transportation is a barrier including persons who require transportation assistance provided by the study clinic funds for screening or randomization visits;
• Residence in a nursing home; persons residing in an assisted living or retirement community are eligible if they meet the other criteria;
• Other medical, psychiatric, or behavioral factors that, in the judgment of the site PI or clinician, may interfere with study participation or the ability to follow the study Protocol.
• Couples or significant partners who live together cannot be enrolled or participate simultaneously in the study.
DRUG: Angiotensin II Receptor Blockers (ARBs, losartan) and Calcium Channel Blockers (CCB, amlodipine), OTHER: PCP
Hypertension, Cognitively Normal Older Adults, Subjective Cognitive Decline, Family History of Dementia
Dementia, Alzheimer's Disease, Cognitive Function, Blood Pressure, Amyloid, Tau
Neoadjuvant Lenvatinib and Pembrolizumab for IVC Tumor Thrombus
This study will be evaluating safety and efficacy of the combination of lenvatinib and
pembolizumab neoaadjuvant therapy prior to surgical resection of locally advanced renal cell
carcinoma with IVC tumor thrombus.
• Male/female participants who are at least 18 years of age
• Have histologically confirmed cT3-4,N0-1,M0-1 (clinical stage III-IV) diagnosis of
renal cell carcinoma (any subtype) with level II-IV inferior vena cava tumor thrombus
• The primary tumor and thrombus may be assessed to be resectable or unresectable at the
time of enrollment
• Male participants: A male participant must agree to use a protocol-approved
contraception during the 120 day neoadjuvant treatment period and for at least 90 days
after the last dose of study treatment and refrain from donating sperm during this
period.
• Female participants: A female participant is eligible to participate if she is not
pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the protocol-approved contraceptive guidance during
the treatment period and for at least 30 days after the last dose of study
treatment.
• The participant (or legally acceptable representative if applicable) provides written
informed consent for the trial.
• Have measurable disease based on RECIST 1.1. Lesions situated in a previously
irradiated area are considered measurable if progression has been demonstrated in such
lesions.
• Have provided archival tumor tissue sample or newly obtained core or excisional biopsy
of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE)
tissue blocks are preferred to slides. Newly obtained biopsies are preferred to
archived tissue.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Evaluation of ECOG is to be performed within 7 days prior to the first dose of study
intervention.
• Have adequate organ function as defined in the following table. Specimens must be
collected within 10 days prior to the start of study intervention.
• Absolute neutrophil count (ANC): ≥1500/µL
• Platelets: ≥100 000/µL
• Hemoglobin: ≥9.0 g/dL or ≥ 5.6 mmol/La
• Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in
place of creatinine or CrCl): ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine
levels >1.5 × institutional ULN
• Total bilirubin: ≤1.5 ×ULN OR direct bilirubin ≤ ULN for participants with total
bilirubin levels >1.5 × ULN
• AST (SGOT) and ALT (SGPT): ≤2.5 × ULN (≤5 × ULN for participants with liver
metastases)
• International normalized ratio (INR) OR prothrombin time (PT) OR Activated partial
thromboplastin time (aPTT): ≤1.5 × ULN unless participant is receiving anticoagulant
therapy as long as PT or aPTT is within therapeutic range of intended use of
anticoagulants
• ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST
(SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase);
GFR=glomerular filtration rate; ULN=upper limit of normal.
• Criteria must be met without erythropoietin dependency and without packed red blood
cell (pRBC) transfusion within last 2 weeks.
• Creatinine clearance (CrCl) should be calculated per institutional standard.
• Note: This includes eligibility-defining laboratory value requirements for treatment;
laboratory value requirements should be adapted according to local regulations and
guidelines for the administration of specific chemotherapies.
Exclusion Criteria:
• A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation.
If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
test will be required.
• 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 (eg, CTLA-4,
OX 40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents prior
to allocation.
• Has received prior radiotherapy within 2 weeks of start of study intervention.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Has received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
are generally killed virus vaccines and are allowed; however, intranasal influenza
vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. COVID-19
vaccines are permitted provided they are not live attenuated vaccines.
• Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose of
study intervention.
• Has 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 to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment
within the past year. Participants with basal cell carcinoma of the skin, squamous
cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical
cancer, bladder in situ) that have undergone potentially curative therapy are not
excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with
previously treated brain metastases may participate provided they are radiologically
stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging
(note that the repeat imaging should be performed during study screening), clinically
stable and without requirement of steroid treatment for at least 14 days prior to
first dose of study intervention.
• Has more than three different sites of metastatic renal cell carcinoma.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and lenvatinib and/or any of
its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
• 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 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
cooperation with the requirements of the trial.
• 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
after the last dose of trial treatment.
• Has had an allogenic tissue/solid organ transplant.
• Has prolongation of QTcF interval to >480 ms.
• Has a left ventricular ejection fraction (LVEF) below the institutional (or local
laboratory) normal range, as determined by multigated acquisition (MUGA) or
echocardiogram (ECHO)
• Has clinically significant cardiovascular disease within 12 months from first dose of
study intervention, including New York Heart Association Class III or IV congestive
heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or
cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled
arrhythmia would be permitted
• Has urine protein ≥1 g/24 hours. Note: Participants with proteinuria ≥2+>1+ (≥100
mg/dL) on urine dipstick testing (urinalysis) will undergo 24-hour urine collection
for quantitative assessment of proteinuria.
• Uncontrolled blood pressure (Systolic BP>140 mmHg or diastolic BP >90 mmHg) in spite
of an optimized regimen of antihypertensive medication.
A Study of CNTY-101 in Participants With CD19-Positive B-Cell Malignancies (ELiPSE-1)
ELiPSE-1 is a Phase 1, multi-center, dose-finding study to evaluate the safety,
pharmacokinetics, and preliminary efficacy of CNTY-101 in participants with relapsed or
refractory cluster of differentiation (CD)19-positive B-cell malignancies.
• Diagnosis of CD19-positive relapsed or refractory (R/R) B-cell Non-Hodgkin's Lymphoma (NHL).
• Must have met the following criteria for prior treatment:
• Participants with aggressive NHL must have received at least 2 lines of systemic therapy (if not intended for transplant, have already undergone or be unwilling or unable to undergo chimeric antigen receptor \[CAR\] T-cell therapy to be eligible), or at least 3 lines of systemic therapy. Previous therapy must have included a CD20-targeted agent and an anthracycline or alkylator.
• Participants with follicular lymphoma (FL) must have received at least 2 lines of systemic therapy and have high-risk disease. Previous therapy must have included a CD20-targeted agent and an alkylator.
• Participants with marginal zone lymphoma (MZL) must have received at least 2 prior systemic therapies.
• Measurable disease on screening evaluations.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function.
• Life expectancy of ≥12 weeks.
Exclusion Criteria:
• Any condition that confounds the ability to interpret data from the study.
• Central nervous system (CNS)-only involvement by malignancy. (Note: participants with secondary CNS involvement are allowed.)
• Prior allogeneic stem cell transplant.
• Presence of clinically significant CNS pathology.
• Other comorbid conditions defined in the protocol.
• Use of prohibited medications within the washout period defined in the protocol.
Mechanistic Study of the Effect of Itepekimab on Airway Inflammation in Patients With COPD (AERIFY-3)
This study is an exploratory, two-part, 12-week, Phase 2a study to evaluate the mechanism of
action of Itepekimab (anti-IL-33-mAb) and its impact on airway inflammation in former and
current smokers with COPD, aged 40 to 70 years.
This study consists of participants who have been on a standard-of-care (SoC) mono
(long-acting β2-agonist [LABA]) or long-acting muscarinic antagonist [LAMA]), double (inhaled
corticosteroid [ICS] + LABA, LABA + LAMA or ICS + LAMA), or triple (ICS + LABA + LAMA)
controller therapy for COPD for at least 3 months prior to Screening (Visit 1) with stable
dose and regimen for controller therapy for ≥1 month prior to Screening (Visit 1) and during
the screening period. Participants will stay on their established controller medications for
COPD throughout the duration of the study, with the exception of systemic corticosteroids
and/or antibiotics used for acute exacerbation of COPD (AECOPD).
The total study duration for each part (Part A and Part B) is approximately 36 weeks:
- 4-week screening period
- 12-week treatment period
- 20-week followup period
studyfinder@utsouthwestern.edu
ALL
40 Years to 70 Years old
PHASE2
This study is NOT accepting healthy volunteers
NCT05326412
Show full eligibility criteria
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Inclusion Criteria:
* Participant must be 40 to 70 years of age inclusive
* Physician diagnosis of COPD for at least 1 year (based on the Global Initiative for Chronic Obstructive Lung Disease \[GOLD\] definition).
* Smoking history of ≥10 pack-years
* For former smokers: Participants who report that they are not currently smoking, and smoking cessation must have occurred ≥6 months prior to Screening (Visit 1) with an intention to quit permanently.
* For current smokers (not eligible for Part A): Participants who report that they are currently smoking tobacco (participant smoked at least 5 cigarettes per day on average during the past 7 days) at Screening (Visit 1) and at Baseline, and who are not currently participating in, or planning to initiate, a smoking cessation intervention at Screening (Visit 1) or during the screening period.
* Participant-reported history of signs and symptoms of chronic bronchitis (chronic productive cough for at least 3 months in the year before screening in a participant in whom other causes of chronic cough \[eg, inadequately treated gastroesophageal reflux or chronic rhinosinusitis; or clinical diagnosis of bronchiectasis\] have been excluded).
* Documented or self-reported history of exacerbation having had ≥1 moderate or severe exacerbation within the 5 years prior to Screening (Visit 1), with at least 1 exacerbation treated with systemic corticosteroids:
* Moderate exacerbations are defined as an acute worsening of respiratory symptoms that requires either systemic corticosteroids (intramuscular \[IM\], intravenous \[IV\], or oral) and/or antibiotics.
* Severe exacerbations are defined as AECOPD that require hospitalization or observation for \>24 hours in emergency department/urgent care facility.
* Participants treated with SoC controller therapy for ≥3 months before Screening (Visit 1) and at a stable dose and regimen of controller therapy for at least 1 month before the screening visit AND during the screening period, including either: triple therapy with LAMA + LABA + ICS or double therapy with ICS + LABA or LABA + LAMA or ICS + LAMA, or monotherapy with LABA or LAMA.
* Participants who have received appropriate vaccination according to local recommendations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), administered a minimum of 1 week prior to Screening (Visit 1).
* Body mass index (BMI) ≥18 kg/m2
* A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
* Not a women of child-bearing potential (WOCBP) or
* A WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 20 weeks after the last dose of study intervention.
Exclusion Criteria:
* Current diagnosis or previously confirmed diagnosis of asthma according to the Global Initiative for Asthma (GINA) guidelines unless asthma resolved before 18 years of age and has not recurred.
* For former smokers (Parts A and B): Active smoking or vaping of any products (eg, nicotine, tetrahydrocannabinol \[THC\]) within 6 months prior to Screening (Visit 1) or during the screening period. For current smokers (Part B): vaping of any products (eg, nicotine, THC) within 6 months prior to Screening (Visit 1) or during the screening period.
* Participants who are expected to be regularly exposed to environmental (ie, 'second hand') tobacco smoke in an indoor setting during the screening or treatment periods (former smokers only).
* Clinically significant new abnormal electrocardiogram (ECG) within 6 months before or at Screening (Visit 1) that may affect the participant's participation in the study.
* Clinically significant and current pulmonary disease other than COPD, eg, sarcoidosis, interstitial lung disease, bronchiectasis (clinical diagnosis), diagnosis of α1 anti-trypsin deficiency, or another diagnosed pulmonary disease.
* Diagnosis of cor pulmonale, evidence of right cardiac failure, or moderate-to-severe pulmonary hypertension.
* Participants who require more than 2 L/min of long-term treatment with oxygen at rest. Participants who use up to 4L/min of supplemental oxygen during exercise may enroll. Oxygen during sleep is allowed.
* Hypercapnia that requires bi-level positive airway pressure (BiPAP).
* Moderate or severe exacerbation of COPD (AECOPD) within 8 weeks prior to Screening (Visit 1) or during the screening period.
* Prior history of pneumonectomy, lobectomy, segmentectomy, or therapeutic bronchoscopy procedure (including bronchoscopic volume reduction). Note: Prior history of surgical lung biopsy or wedge resection are not exclusion criteria.
* Any surgery or major procedures (including those requiring conscious sedation) planned to occur during the study. Minor skin procedures are allowed.
* Unstable ischemic heart disease, including acute myocardial infarction within 1 year before Screening (Visit 1), or unstable angina within 6 months before Screening (Visit 1) or during the screening period.
* Cardiac arrhythmias, including paroxysmal (eg, intermittent) atrial fibrillation. Participants with isolated premature ventricular contractions (PVCs) or premature atrial contractions (PACs) may be considered for inclusion.
* Cardiomyopathy, as defined by Stage III-IV (New York Heart Association) cardiac failure, or other relevant cardiovascular disorder that that may affect the participant's participation in the study.
* Any underlying disease requiring the use of prophylaxis for endocarditis.
* Uncontrolled hypertension (ie, systolic blood pressure \[BP\] \>180 mm Hg or diastolic BP \>110 mm Hg with or without use of antihypertensive therapy).
* Participants with active tuberculosis (TB), latent TB, a history of incompletely treated TB, suspected extrapulmonary TB infection (TBI), or who are at high risk of contracting TB (such as close contact with individuals with active or latent TB) or received Bacillus Calmette Guérin (BCG)-vaccination within 12 weeks before Screening (Visit 1).
* History of human immunodeficiency virus (HIV) infection or positive HIV 1/2 serology at Screening (Visit 1).
* Suspicion of, or confirmed, coronavirus disease 2019 (COVID-19) infection or contact with known exposure to COVID19 at Screening (Visit 1) or during the screening period; known history of COVID19 infection within 6 weeks before Screening (Visit 1); history of requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO) secondary to COVID-19 within 12 months before Screening (Visit 1); participants who have had a COVID-19 infection before Screening (Visit 1) who have not yet sufficiently recovered to participate in the procedures of a clinical trial.
* Evidence of acute or chronic infection requiring systemic treatment with antibacterial, antiviral, antifungal, antiparasitic, or antiprotozoal medications within 6 weeks before Screening (Visit 1) or during the screening period, significant viral infections within 6 weeks before Screening (Visit 1) or during the screening period that may not have been treated with antiviral treatment (eg, influenza receiving only symptomatic treatment).
* Participants with active autoimmune disease or participants taking immunosuppressive therapy for autoimmune disease (eg, rheumato arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis).
* History of malignancy within 5 years before Screening (Visit 1), or during the screening period, except completely treated in situ carcinoma of the cervix, completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin.
* Symptomatic herpes zoster within 3 months prior to screening.
* Previous use of Itepekimab.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
• Histologically confirmed GBM (MGMT unmethylated, IDH wild type) at first, second, third, or fourth recurrence after concurrent chemoradiotherapy. Patients with an initial diagnosis of a lower-grade glioma are eligible if a subsequent biopsy determined the progressive tumor to be GBM.
• Imaging confirmation of first tumor progression or regrowth as defined by the Response Assessment in Neuro-Oncology (RANO) criteria. A minimum of 12 weeks must have elapsed from the completion of radiotherapy to study entry to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, unless there is a new lesion outside the radiation field or unequivocal evidence of viable tumor on histopathological sampling.
• Karnofsky Performance Status (KPS) ≥ 60%.
• Patients must be willing and able to provide written informed consent and to comply with the study protocol as judged by the investigator.
• Age ≥ 18 years.
• Patients must be able to swallow oral medications.
• For women who are of child-bearing potential and who are sexually active and who are not surgically sterile (absence of ovaries and/or uterus): to use an adequate method of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly) during the treatment period and for at least 6 months after last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. For male patients who are partners of premenopausal women: agreement to use a barrier method of contraception during the treatment period and for at least 6 months after the last dose of study drug.
• 1 A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Patients who have undergone recent surgery for recurrent or progressive tumor are eligible provided that:
• 1 Surgery must have confirmed the recurrence.
• 2 A minimum of 28 days must have elapsed from the day of surgery to study entry. For core or needle biopsy, a minimum of 7 days must have elapsed prior to study entry.
• 3 Craniotomy or intracranial biopsy site must be adequately healed and free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of randomization.
• Patients must have recovered (Common Terminology Criteria for Adverse Events CTCAE version 6\] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to randomization. Minimum times from prior therapies include:
• 1 Greater than or equal to 28 days elapsed from the administration of any investigational agent.
• 2 Greater than or equal to 28 days elapsed from the administration of any prior cytotoxic agents, except ≥ 42 days from nitrosoureas. NOTE: Prior treatment with Novo-TTF therapy is allowed at initial diagnosis but must be discontinued prior to study entry.
• GBMs of the study patients must have EGFR gene amplification, which will be detected by next generation sequencing of tumor tissue from resected sample.
• Prior use of bevacizumab is allowed, however patient must be off of this medication for 180 days.
• Patients must have adequate organ and marrow function as defined by the following criteria:
* ANC ≥1.5 × 10(9)/L
* Platelets ≥100 × 10(9)/L
* Hemoglobin ≥8 g/dL
* Total bilirubin ≤1.5 × ULN Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted.
ALT and AST ≤3 × ULN
Exclusion Criteria:
• Prior treatment with an EGFR or JAK inhibitor.
• Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
• Patients unable to undergo brain MRI scans with IV gadolinium contrast.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Tofacitinib
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Prior history of hypertensive crisis, hypertensive encephalopathy, or inadequately controlled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg while on antihypertensive medication).
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant gastrointestinal resection that would preclude adequate absorption of the trial medications.
• History of another malignancy in the previous 3 years, with a disease-free interval of \< 3 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.
• Concurrent use of Bevacizumab.
UroLift System With SAbR for Prostate Cancer and BPH
Confirming safety of combining UroLift System prior to SAbR for patients with newly diagnosed
prostate cancer and a history of BPH, by measuring the acute complication rate of UroLift
System implant in patients with BPH undergoing SAbR (within 90 days of treatment completion)
• AJCC 8th edition clinical stage T1 (a, b, or c) or T2 (a, b, or c) adenocarcinoma of
the prostate gland, Gleason 3+3 = 6 or 3+4 = 7, with no direct evidence of regional or
distant metastases following appropriate staging studies. See Appendix I for details
on AJCC 8th Edition staging criteria. T-staging may be assessed by multi-parametric
imaging alone if digital rectal examination was deferred
• Histologic confirmation of prostate cancer is required by biopsy performed within 18
months of registration.
• Age > 45 years.
• Eastern Cooperative Oncology Group (ECOG) Performance status 0-1.
• American Society of Anesthesia (ASA) physical status score of 1-3
• Baseline AUA symptom score ≥ 17 regardless of medical therapy
• The serum PSA should be < 20 ng/ml within 120 days of registration
• Study entry PSA must not be obtained during the following time frames: (1) 10-day
period following prostate biopsy; (2) following initiation of ADT or anti-androgen
therapy; (3) within 30 days after discontinuation of finasteride; (4) within 90 days
after discontinuation of dutasteride; (5) within 5 days of a digital rectal
examination
• Ultrasound or MRI based volume estimation of prostate gland < 100 grams, regardless of
cytoreduction with pharmacotherapy
• Ability to undergo general anesthesia for <60 minutes
• Ability to understand and the willingness to sign a written informed consent.
• All men must agree to use adequate contraception (barrier method of birth control;
abstinence) prior to study entry, for the duration of study participation, and for 90
days following completion of therapy.
Exclusion Criteria:
• Contraindications to UroLift System placement including:
• Prostate volume >100 cc based on imaging-based estimation
• Urethral conditions (e.g. urethral strictures and neoplams) that may prevent insertion
of UroLift System delivery system into the bladder
• Urinary incontinence due to incompetent sphincter
• An active urinary tract infection
• Current gross hematuria
• In addition to the contraindications if there is a known allergy to nickel, titanium,
or stainless steel these patients should be excluded
• Prior transurethral resection of the prostate (TURP), median lobe manipulation, simple
prostatectomy, or other ablative procedures for benign prostatic hyperplasia.
• Foley / self-catheterization in the last 12 months.
• Patients with all three intermediate risk factors (PSA >10 and ≤ 20, Gleason 7,
clinical stage T2b-T2c) who ALSO have ≥50% of the number of their template biopsy
cores positive for cancer are ineligible.
• Prior pelvic radiotherapy, chemotherapy, or surgery for prostate cancer.
• Current active androgen deprivation therapy
Testing the Addition of Nivolumab to Standard Treatment for Patients With Metastatic or Unresectable Colorectal Cancer That Have a BRAF Mutation
This phase II trial tests whether adding nivolumab to the usual treatment (encorafenib and
cetuximab) works better than the usual treatment alone to shrink tumors in patients with
colorectal cancer that has spread to other places in the body (metastatic) or that cannot be
removed by surgery (unresectable) and whose tumor has a mutation in a gene called BRAF.
Encorafenib is in a class of medications called kinase inhibitors. It is used in patients
whose cancer has a certain mutation (change) in the BRAF gene. It works by blocking the
action of mutated BRAF that signals cancer cells to multiply. This helps to stop or slow the
spread of cancer cells. Cetuximab is in a class of medications called monoclonal antibodies.
It binds to a protein called EGFR, which is found on some types of cancer cells. This may
help keep cancer cells from growing. Immunotherapy with monoclonal antibodies, such as
nivolumab, may help the body's immune system attack the cancer, and may interfere with the
ability of tumor cells to grow and spread. Giving nivolumab in combination with encorafenib
and cetuximab may be more effective than encorafenib and cetuximab alone at stopping tumor
growth and spreading in patients with metastatic or unresectable BRAF-mutant colorectal
cancer.
* Participants must have a histologically or cytologically confirmed diagnosis of adenocarcinoma of the colon or rectum. The date of diagnosis will be determined according to the pathologic date of diagnosis
* Participants must have measurable disease according to RECIST1.1 criteria. Computed tomography (CT) scans or magnetic resonance imaging (MRIs) used to assess measurable disease must have been completed within 28 days prior to registration. CT scans or MRIs used to assess non-measurable disease must have been completed within 42 days prior to registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form
* Participants must have documented unresectable and/or metastatic disease on CT or MRI imaging. All disease must be assessed and documented on the Baseline Tumor Assessment Form
* Participants must have BRAF\^V600E mutated colorectal cancer as tested in a Clinical Laboratory Improvement Act (CLIA)-certified laboratory
* Participants must have proficient mismatch repair (pMMR) or microsatellite stable (MSS) status as tested in a CLIA-certified laboratory and documented by the treating clinician. Proficient mismatch repair status can be determined by intact expression by immunohistochemistry of all 4 mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2). Microsatellite instability can be determined by polymerase chain reaction (PCR)
* Participants with brain metastases must have completed surgery or radiation therapy \>= 28 days prior to registration. These participants must have a CT or MRI of the brain showing no new or enlarging lesions within 42 days prior to registration. These participants must also be neurologically asymptomatic and without corticosteroid treatment for at least 7 days prior to registration. Metastatic brain parenchymal disease must have been treated and participant must be off steroids for 7 days prior to registration. The presence of leptomeningeal disease (LMD) is not considered stable disease, and participants with LMD are not eligible for this study
* Participants with known evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within 28 days prior to registration
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment must have an undetectable HCV viral load within 28 days prior to registration
* Participants must have had one or two prior regimens of systemic chemotherapy for metastatic or locally advanced, unresectable disease. (A maintenance regimen of 5-fluorouracil or capecitabine, with or without bevacizumab, should not be counted as a separate line of treatment. The re-introduction of an initially successful induction regimen will not be counted as one additional line of treatment). Prior treatment for metastatic disease is not required for patients who experienced disease recurrence during or within 6 months of completion of adjuvant chemotherapy
* Participants must be of age \>= 18 years at the time of informed consent
* Participants must have a Zubrod performance status of 0 or 1
* Participants must have a complete medical history and physical exam within 28 days prior to registration
* Absolute neutrophil count \>= 1.0 x 10\^3/uL (within 28 days prior to registration)
* Hemoglobin \>= 9 g/dL (within 28 days prior to registration)
* Platelets \>= 75 x 10\^3/uL (within 28 days prior to registration)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to registration)
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3 x institutional ULN (within 28 days prior to registration)
* If liver metastases are present, then it is acceptable for AST level =\< 5.0 x ULN, and/or an ALT level =\< 5.0 x ULN (within 28 days prior to registration)
* Participants must have serum creatinine =\< the IULN OR measured OR calculated creatinine clearance \>= 50 mL/min using the Cockroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration
* Participants must be able to swallow and retain pills
* Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2 or better
* Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines.
* Note: As a part of the OPEN registration process, the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Exclusion Criteria:
* Participants must not have a known positive serology for human immunodeficiency virus (HIV). Encorafenib is contraindicated with concomitant use of non-nucleoside analog reverse transcriptase inhibitors like efavirenz and etravirine. In addition, it is recommended in the investigator brochure of encorafenib to avoid using encorafenib with protease inhibitors. Therefore, because all participants on this study would receive encorafenib for either randomized arm of treatment, participants with HIV who receive these components of highly active antiretroviral therapy (HAART) would be at high risk for complications of drug-drug interaction
* Participants must not have had prior treatment with a BRAF inhibitor (including, but not limited to, encorafenib, dabrafenib, or vemurafenib), MEK inhibitor (including, but not limited to, trametinib, selumetinib, or binimetinib), or ERK inhibitor (of note, regorafenib is not considered a BRAF inhibitor for the context of eligibility criteria)
* Participants must not have had prior treatment with anti-EGFR therapies
* Participants must not have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
* Participants must not have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of registration. Inhaled or topical steroids and adrenal replacement doses \< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \< 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted, as long as there has been a washout period for corticosteroids of \>= 7 days prior to registration
* Participants must not have received a live vaccine within 30 days prior to study registration. Seasonal flu and COVID vaccines that do not contain a live virus are permitted
* Participants must not be receiving any other investigational agents
* Participants must not have impaired gastrointestinal function or disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption)
* Participants must not have a history of inflammatory bowel disease, (including ulcerative colitis and Crohn's disease), symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[e.g., Wegener's Granulomatosis\]); central nervous system (CNS) or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome and myasthenia gravis, multiple sclerosis).
* Note: Participants with Graves' disease will be allowed
* Participants must not have a history of pneumonitis that has required oral or intravenous (IV) steroids within the last 12 months
* Participants must not have a history of a grade 3 or 4 allergic reaction attributed to humanized or human monoclonal antibody therapy
* Participants must not have a history of a prior allogeneic tissue or solid organ transplant
* Participants must not have a history of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) within 6 months prior to study registration
* Participants must not have uncontrolled blood pressure and hypertension within 28 days prior to registration.
* Uncontrolled blood pressure and hypertension is defined as systolic blood pressure (SBP) \> 170 mmHg or diastolic blood pressure (DBP) \> 100 mmHg within 28 days prior to registration. Participants are permitted to be receiving multiple anti-hypertensive medications (unless otherwise indicated in the study). All blood pressure measurements within the 28 days prior to registration must be SBP =\< 170 and DBP =\< 100. An exception can be made by a healthcare provider for a participant with a single blood pressure elevation who upon rechecking has a normal blood pressure
* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen or requires concurrent therapy
* Participants must not be pregnant or nursing. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion and vasectomy with testing showing no sperm in the semen
* Participants must not be planning treatment with other systemic anti-cancer agents (e.g., chemotherapy, hormonal therapy, immunotherapy) or other treatments not part of protocol-specified anti-cancer therapy including concurrent investigational agents of any type
Stage III Colon Cancer AJCC v8, Stage III Rectal Cancer AJCC v8, Stage IV Colon Cancer AJCC v8, Stage IV Rectal Cancer AJCC v8, Metastatic Colon Adenocarcinoma, Metastatic Rectal Adenocarcinoma, Unresectable Colon Adenocarcinoma, Unresectable Rectal Adenocarcinoma
UT Southwestern; Parkland Health & Hospital System
Chemotherapy for the Treatment of Patients With Newly Diagnosed Very Low-Risk and Low Risk Fusion Negative Rhabdomyosarcoma
Rhabdomyosarcoma is a type of cancer that occurs in the soft tissues in the body. This phase
III trial aims to maintain excellent outcomes in patients with very low risk rhabdomyosarcoma
(VLR-RMS) while decreasing the burden of therapy using treatment with 24 weeks of vincristine
and dactinomycin (VA) and examines the use of centralized molecular risk stratification in
the treatment of rhabdomyosarcoma. Another aim of the study it to find out how well patients
with low risk rhabdomyosarcoma (LR-RMS) respond to standard chemotherapy when patients with
VLR-RMS and patients who have rhabdomyosarcoma with DNA mutations get separate treatment.
Finally, this study examines the effect of therapy intensification in patients who have RMS
cancer with DNA mutations to see if their outcomes can be improved.
• All patients must be enrolled on APEC14B1 (NCT02402244) and consented to the Molecular
Characterization Initiative (Part A) prior to enrollment and treatment on ARST2032
(this trial).
• Patients must be =< 21 years at the time of enrollment.
• Patients must have newly diagnosed embryonal rhabdomyosarcoma (ERMS), spindle
cell/sclerosing RMS, or FOXO1 fusion negative alveolar rhabdomyosarcoma (ARMS)
(institutional FOXO1 fusion results are acceptable). RMS types included under ERMS
include those classified in the 1995 International Classification of Rhabdomyosarcoma
(ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified
in the 2020 World Health Organization (WHO) classification as ERMS (classic, dense and
botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical
spindle cell ERMS variant and the newly recognized sclerosing RMS variant). Enrollment
in APEC14B1 is required for all patients.
• All patients will be evaluated for stage and clinical group. Note that clinical
group designation assigned at the time of enrollment on study remains unchanged
regardless of any second-look operation that may be performed.
• Patients will be eligible for the very low-risk stratum (Regimen VA) if they
have Stage 1, CG I disease.
• Patients will be eligible for the low-risk stratum (Regimen VAC/VA) if they
have Stage 1, CG II disease, Stage 2, CG I or II disease, or Stage 1, CG III
(orbit only) disease.
• Paratesticular Tumors: Staging ipsilateral retroperitoneal lymph node sampling
(SIRLNS) is required for all patients >= 10 years of age with paratesticular
tumors who do not have gross nodal involvement on imaging.
• Extremity Tumors: Regional lymph node sampling is required for histologic
evaluation in patients with extremity tumors.
• Clinically or radiographically enlarged nodes must be sampled for histologic
evaluation.
• Patients must have a Lansky (for patients =< 16 years of age) or Karnofsky (for
patients > 16 years of age) performance status score of >= 50. Patients who are unable
to walk because of paralysis, but who are up in a wheelchair, will be considered
ambulatory for the purpose of assessing performance score.
• Peripheral absolute neutrophil count (ANC) >= 750/uL (within 7 days prior to
enrollment).
• Platelet count >= 75,000/uL (transfusion independent) (within 7 days prior to
enrollment).
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine (within 7 days prior to enrollment) based on
age/gender as follows:
• Age: 1 month to < 6 months; Maximum serum creatinine (mg/dL): 0.4 (male) : 0.4
(female)
• Age: 6 months to < 1 year; Maximum serum creatinine (mg/dL): 0.5 (male) : 0.5
(female)
• Age: 1 to < 2 years; Maximum serum creatinine (mg/dL): 0.6 (male) : 0.6 (female)
• Age: 2 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 (male) : 0.8 (female)
• Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 (male) : 1 (female)
• Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 (male) : 1.2
(female)
• Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 (male) : 1.4
(female)
• Age >= 16 years; Maximum serum creatinine (mg/dL): 1.7 (male) : 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment), and
• If there is evidence of biliary obstruction by the tumor, then the total
bilirubin must be < 3 x ULN for age.
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L.
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
U/L (within 7 days prior to enrollment).
• All patients and/or their parents or legal guardians must sign a written informed
consent.
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met.
Exclusion Criteria:
• Patients who have received prior chemotherapy and/or radiation therapy for cancer
prior to enrollment. Surgical resection alone of previous cancer(s) is permitted.
• Patients who have received chemotherapy or radiation for non-malignant conditions
(e.g., autoimmune diseases) are eligible. Patients must discontinue chemotherapy for
non-malignant conditions prior to starting protocol therapy.
• Vincristine is sensitive substrate of the CYP450 3A4 isozyme. Patients must not have
received drugs that are moderate to strong CYP3A4 inhibitors and inducers within 7
days prior to study enrollment.
• Patients unable to undergo radiation therapy, if necessary, as specified in the
protocol.
• Evidence of uncontrolled infection.
• Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs. A pregnancy test is required for female
patients of childbearing potential.
• Lactating females who plan to breastfeed their infants.
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation.
Evaluate Durvalumab and Tremelimumab +/- Lenvatinib in Combination With TACE in Patients With Locoregional HCC (EMERALD-3)
A global study to evaluate transarterial chemoembolization (TACE) in combination with
durvalumab, tremelimumab and lenvatinib therapy in patients with locoregional hepatocellular
carcinoma
• No evidence of extrahepatic disease
• Disease not amenable to curative surgery or transplantation or curative ablation but
disease amenable to TACE
• Child Pugh score class A
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment
• Measurable disease by Modified Response Criteria in Solid Tumors (mRECIST) criteria
• Adequate organ and marrow function
Exclusion Criteria:
• History of symptomatic congestive heart failure, unstable angina pectoris,
uncontrolled cardia arrhythmia
• History of hepatic encephalopathy
• Major portal vein thrombosis visible on baseline imaging
• Uncontrolled arterial hypertension
• Co-infection with HBV and HDV
A Study to Evaluate Safety, Efficacy of FF-10832 in Combo With Pembrolizumab in Urothelial & Non-small Cell Lung Cancer
To confirm a recommended Phase 2 dose (RP2D) of FF-10832 (Gemcitabine Liposome Injection)
given intravenously Day 1 of a 21-day cycle, in combination with 200 mg pembrolizumab given
intravenously Day 1 of the same 21-day cycle, for treatment of advanced solid tumors.
• Written informed consent is provided by patient or legally acceptable representative;
• Age ≥ 18 years;
• Patient populations:
• In the Safety Run-in, patients with histologically or cytologically confirmed advanced or metastatic solid tumors who have disease progression after treatment with standard therapies for metastatic disease that are known to confer clinical benefit, or are intolerant to treatment or refuse standard treatment will be enrolled in therapy
• In Expansion Phase, patient must have urothelial or NSCLC, and have failed prior anti-PD-1 or anti-PD-L1
• Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology
• Eastern Cooperative Oncology Group performance status of 0 to 1
• Life expectancy of ≥ 3 months
Exclusion Criteria:
• Positive urine pregnancy test within 72 hours prior to treatment
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (or 5 half-lives, whichever is shorter) prior to treatment;
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), AND was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event;
• Has received prior radiotherapy within 2 weeks of start of study treatment.
• For patients with NSCLC:
• Patients who have received radiation therapy to the lung that is \>30 Gy within 6 months of the first dose of trial treatment are excluded;
• Patients with mutations (e.g., EGFR mutations or ALK gene rearrangements) will be excluded unless they have been previously treated with all specific targeted therapies.
• Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
• Has had an allogeneic tissue /solid organ transplant.
DRUG: Pembrolizumab, DRUG: FF-10832
Advanced Urothelial Carcinoma, Advanced Non Small Cell Lung Cancer
Phase 2/3 Adaptive Study of VX-147 in Adult and Pediatric Participants With APOL1- Mediated Proteinuric Kidney Disease (AMPLITUDE)
The purpose of this study is to evaluate the efficacy, safety, tolerability, and
pharmacokinetics (PK) of VX-147 in adult and pediatric participants with apolipoprotein L1
(APOL1)-mediated proteinuric kidney disease.
* APOL1 genotype of G1/G1, G2/G2, or G1/G2
* Proteinuric kidney disease
Key
Exclusion Criteria:
* Solid organ or bone marrow transplant
* Uncontrolled hypertension
* History of diabetes mellitus
* Known underlying cause of kidney disease including but not limited to sickle cell disease
Other protocol defined Inclusion/Exclusion criteria apply.
A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors (PIKASSO-01)
The main purpose of this study is to learn more about the safety, side effects, and
effectiveness of LOXO-783. LOXO-783 may be used to treat breast cancer and other solid tumors
that have a change in a particular gene (known as the PIK3CA gene). Participation could last
up to 36 months (3 years) and possibly longer if the disease does not get worse.
* Have advanced breast cancer or another solid tumor with the presence of a phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) H1047R mutation (or other Sponsor and safety review committee (SRC)-approved, activating PIK3CA mutations other than H1047R mutation)
* Have adequate archival tumor tissue sample available or be approved by the Sponsor for enrollment if no tumor sample is available.
* Have stopped all cancer treatment and have recovered from the major side effects
* Have adequate organ function, as measured by blood tests
* Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
* Patients must have
* Measurable disease
--- Patients with non-breast tumor types must have at least 1 measurable lesion
* Non-measurable bone disease (at least 1 bone lesion in breast cancer patients only)
* For patients with an estrogen receptor (ER)+ breast cancer diagnosis:
* If female, must be postmenopausal
* If male, must agree to use hormone suppression
* Phase 1a:
-- Dose escalation and backfill patients:
* Advanced solid tumor
* Patients may have had up to 5 prior regimens for advanced disease
* Phase 1b:
* Part A:
* ER+/human epidermal growth factor receptor 2 (HER2)- advanced breast cancer
* Patients may have had up to 5 prior regimens for advanced disease ---- Prior cyclin dependent kinase (CDK)4/6 inhibitor therapy required
* Part B:
* ER+/HER2- advanced breast cancer
* Patients may have had up to 2 prior regimens for advanced disease.
* Part C:
* ER+/HER2- advanced breast cancer
* Patients may have had up to 5 prior regimens for advanced disease.
---- Prior CDK4/6 inhibitor therapy required.
* Have a diagnosis of diabetes mellitus Type 2
* Part D:
* Advanced breast cancer
* Patients may have had up to 5 prior regimens for advanced disease.
* Part E:
* Advanced solid tumor
* Patients may have had up to 3 prior regimens for advanced disease advanced disease
* Part F:
* ER+/HER2- advanced breast cancer
* Patients may have had up to 5 prior regimens for advanced disease
* Prior cyclin dependent kinase (CDK)4/6 inhibitor therapy required
Exclusion Criteria:
* Medical Conditions
* Colorectal cancer
* Endometrial cancers with specific concurrent oncogenic alterations
* A history of known active or suspected
* Diabetes mellitus Type 1 or
* Diabetes mellitus Type 2 requiring antidiabetic medication (Phase 1a and all parts of Phase 1b except Part C).
* Serious concomitant systemic disorder
* Known or suspected history of untreated or uncontrolled central nervous system (CNS) involvement.
* Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection, or other clinically significant active disease process
* Prior exposure to phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) inhibitor(s), except in certain circumstances
Ocrelizumab Discontinuation in Relapsing Multiple Sclerosis (AMS05)
This study is a prospective, multi-center, randomized, double blinded, placebo-controlled
study of OCR treatment-discontinuation in patients with early RMS. All eligible participants
will be initiated on OCR using the standard approved administration schedule of two 300 mg
infusions separated by 14 days (i.e., Days 0 and 14) for a total of 600 mg, followed by 600
mg infusions at Month 6 and Month 12. At Month 12, participants will be randomized (1:1:1) to
one of three Arms with randomized treatment beginning at Month 18: Arm 1: placebo infusions
every 6 months; Arm 2: OCR infusions at Months 18 and 24 and then after Month 24 switch to
placebo infusions every 6 months; Arm 3: OCR infusions every 6 months. The treatment period
will be for a total of 48 months.
• Have at least one clinical episode that satisfies McDonald 2017 criteria for early
Multiple sclerosis (MS) for up to 2 years post-event with a dissemination in time that
can be met clinically, by Magnetic Resonance Imaging (MRI), or based on oligoclonal
band (OCB) positivity
• Have a length of disease duration, from first symptom, of ≤ 2 years
• For women of childbearing potential: Agreement to remain abstinent (refrain from
heterosexual intercourse) or use effective methods of contraception during the
treatment period and for at least 6 months after the last dose of study drug:
• A woman is considered to be of childbearing potential if she is postmenarcheal,
has not reached a postmenopausal state (≥12 continuous months of amenorrhea with
no identified cause other than menopause), and has not undergone surgical
sterilization (removal of ovaries and/or uterus)
• Examples of contraceptive methods include bilateral tubal ligation, male
sterilization, established hormonal contraceptives that inhibit ovulation,
hormone- releasing intrauterine devices, and copper intrauterine devices
• The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the
participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
post ovulation methods) and withdrawal are not acceptable methods of
contraception
• Barrier methods must always be supplemented with the use of a spermicide
Exclusion Criteria:
• Inability or unwillingness of a participant to give written informed consent or comply
with study protocol
• History of Primary Progressive Multiple Sclerosis (PPMS), Progressive Relapsing
Multiple Sclerosis (PRMS), or Secondary Progressive Multiple Sclerosis (SPMS)
• Any metallic material or electronic device in the body, or condition that precludes
the participant from undergoing Magnetic resonance imaging (MRI)
• Known presence or history of other neurological disorders, including but not limited
to the following:
• Ischemic cerebrovascular disorders, including but not limited to transient
ischemic attack, subarachnoid hemorrhage, cerebral thrombosis, cerebral embolism,
or cerebral hemorrhage
• Central Nervous System (CNS) or spinal cord tumor, metabolic or infectious cause
of myelopathy, genetically inherited progressive CNS disorder, CNS sarcoidosis,
or systemic autoimmune disorders potentially causing progressive neurologic
disease or affecting ability to perform the study assessments
• Pregnancy or lactation
a. Female participants of childbearing potential must have a negative urine pregnancy
test at screening
• Any concomitant disease that may require chronic systemic treatment with
corticosteroids or immunosuppressants during the course of the study
• Lack of peripheral venous access
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
antibodies
• Significant, inadequately controlled (e.g. diagnostic evaluations indicated or change
in medications warranted) disease, such as cardiovascular (including cardiac
arrhythmia), pulmonary (including obstructive pulmonary disease), renal, hepatic,
endocrine, and gastrointestinal or any other significant disease that in the opinion
of the investigator may preclude participant from participating in the study
• Functional status of NY Heart Association (NYHA) Class III or higher for heart failure
at the screening visit
• Known active bacterial, viral, fungal, mycobacterial infection or other infection
(including tuberculosis [TB] or atypical mycobacterial disease but excluding limited
superficial fungal or viral infections of the skin or nails) or any severe episode of
infection requiring hospitalization or treatment with Intravenous (IV) antibiotics
within 4 weeks prior to baseline visit or oral antibiotics within 2 weeks prior to
baseline visit
• Active or chronic infection with Human Immunodeficiency Virus (HIV), syphilis or TB
(see laboratory tests below)
• Evidence of past or current hepatitis B or hepatitis C infection, including treated
hepatitis B or hepatitis C. Hepatitis B surface antibody following hepatitis B
immunization is not considered to be evidence of past infection
• Known active malignancy or active monitoring for recurrence of malignancy, including
solid tumors and hematological malignancies, except basal cell, in situ squamous cell
carcinoma of the skin, and in situ carcinoma of the cervix for the uterus that have
been excised with clear margins
• Substance use disorder, including the recurrent use of alcohol and /or drugs within
the past year associated with clinically significant impairment associated with
failure to meet major responsibilities at work, school, or home
• Receipt of a live vaccine within 6 weeks prior to baseline; in rare cases when
participant requires vaccination with a live vaccine, the screening period may need to
be extended but cannot exceed 8 weeks
• Contraindications to or severe intolerance of oral or IV corticosteroids, including
Intravenous (IV) methylprednisolone administered according to the country label,
including:
• Psychosis not controlled by a treatment
• Hypersensitivity to any of the constituents or excipients of the preceding
steroids
• Treatment with any Multiple sclerosis (MS) disease-modifying treatments (DMTs)
including but not limited to: glatiramer acetate preparations, beta-interferon
preparations, fingolimod and related agents, fumarates, cladribine, natalizumab,
anti-CD20 molecules, alemtuzumab, and chemotherapeutic agents
• Current or prior treatment with any investigational agent or treatment with any
experimental procedure for MS (e.g. treatment for chronic cerebrospinal venous
insufficiency)
• Systemic corticosteroid therapy within 4 weeks prior to screening
• Laboratory test results as follows:
a. Positive infection screening tests for:
i. Hepatitis C (HCV) antibody, if positive screen for HCV RNA Polymerase Chain
Reaction (PCR)
ii. Rapid plasma reagin (RPR)
iii. HIV
iv. At or within twelve months of screening:
• Positive QuantiFERON(R)-TB Gold test or positive purified protein derivative
tuberculin skin test (PPD) (>5mm induration, regardless of Bacille Calmette
Guerin [BCG] vaccine administration) unless completion of treatment has been
documented for active TB
• An indeterminate QuantiFERON(R)-TB Gold test unless followed by a subsequent
negative PPD or negative QuantiFERON(R)-TB Gold test as well as a consultation
with and clearance by local infectious disease (ID) department
b. Levels of serum IgG<565 mg/dL
c. Levels of serum IgM<40 mg/dL
d. End stage renal disease estimated glomerular filtration rate (eGFR) < 60
mL/min/1.73 m^2 using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
equation
e. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)>= 2.0 x the
upper limit of normal (ULN)
f. Platelet count < 100,000 plt/mcL (< 100 x 10^9/L)
g. Hemoglobin < 10 g/dL
h. Total neutrophil count < 1.5 x 10^3/mL
• 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 that may impact the quality or
interpretation of the data obtained from the study
Study With Elranatamab Versus Lenalidomide in Patients With Newly Diagnosed Multiple Myeloma After Transplant (MagnetisMM-7)
studyfinder@utsouthwestern.edu
ALL
18 Years to old
PHASE3
This study is NOT accepting healthy volunteers
NCT05317416
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
* Diagnosis of MM as defined according to IMWG criteria (Rajkumar, 2014) with measurable disease at diagnosis
* Part 1 patients must be MRD positive, Part 2 patients can be MRD negative or MRD positive
* History of induction therapy for newly diagnosed MM, followed by high dose therapy and autologous stem cell transplant. Randomization must occur within 120 days from the stem cell transplant. For participants who receive consolidation therapy after ASCT, randomization must occur within 60 days of consolidation and within 7 months from ASCT.
* Partial Response or better according to IMWG criteria at the time of randomization
* Must have an archival bone marrow aspirate sample(s) to identify the dominant malignant (index) clone by central laboratory NGS test (ClonoSEQ assay) that is used to track MRD status. This sample should preferably be collected before induction treatment (eg, at diagnosis) or before transplant.
* ECOG performance status ≤1
* Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤ 1
* Not pregnant and willing to use contraception
Exclusion Criteria:
* Plasma cell leukemia
* Amyloidosis, Waldenström's macroglobulinemia
* POEMS syndrome
* Known active CNS involvement or clinical signs of myelomatous meningeal involvement
* Previous MM maintenance treatment
* Prior treatment with BCMA targeted therapy
* Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ
* Active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) HBV, HCV, and known HIV or AIDS-related illness
* Previous administration with an investigational drug or vaccine within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer)
Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory SMARCB1 or SMARCA4 Deficient Tumors
This phase I/II trial studies how well tiragolumab and atezolizumab works when given to
children and adults with SMARCB1 or SMARCA4 deficient tumors that have either come back
(relapsed) or do not respond to therapy (refractory). SMARCB1 or SMARCA4 deficiency means
that tumor cells are missing the SMARCB1 and SMARCA4 genes, seen with some aggressive cancers
that are typically hard to treat. Immunotherapy with monoclonal antibodies, such as
tiragolumab and atezolizumab, may help the body's immune system attack the cancer, and may
interfere with the ability of tumor cells to grow and spread.
* Patients must be \>= 12 months of age at the time of study enrollment. For part A, patients must be \< 18 years old at enrollment. For part B, there is no upper age limit
* The Part B (phase 2) cohorts will initially open concurrently with the part A but will only enroll patients at least 18 years of age. Patients \< 18 years of age will be included in the part B cohorts only after the tiragolumab monotherapy dose has been assessed to be safe in the part A portion
* Patients must have SMARCB1 (INI1) or SMARCA4 deficient tumors verified through institutional immunohistochemistry (IHC) or molecular confirmation of a pathologic SMARCB1 (INI1) or SMARCA4 loss or mutation from a Clinical Laboratory Improvement Act (CLIA) certified lab with the following disease histologies:
* Renal medullary carcinoma
* Malignant rhabdoid tumor (extra-CNS)
* Atypical teratoid rhabdoid tumor (CNS)
* Poorly differentiated chordoma
* Epithelioid sarcoma
* Other SMARCB1 or SMARCA4 deficient tumors
* Note: Molecular studies will only be used if IHC is equivocal or cannot be performed. Documentation of the institutional IHC or molecular testing must be uploaded via the RAVE system
* Part A: Patients must have either measurable or evaluable disease Part B: Patients must have either measurable disease per RECIST v1.1 for non-CNS tumors or CNS response criteria for CNS tumors
* Note: See protocol for specific exclusion for patients with CNS primary or metastatic disease
* Patients must have relapsed, refractory disease or newly diagnosed disease for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (Karnofsky/Lansky score of \>= 50). Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: See Developmental Therapeutics (DVL) homepage on the Children's Oncology Group (COG) Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment
* \>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea). Please refer to the table of myelosuppressive/Anticancer Agents on the COG website: https://www.cogmembers.org/uploadedFiles/Site/Disc/DVL/Documents/TableOfMyelosuppressiveAnti-CancerAgents.pdf
* Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent. See the DVL homepage on the COG Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell infusions (with or without total-body irradiation \[TBI\]):
* Autologous stem cell infusion including boost infusion: \>= 30 days
* Cellular therapy: \>= 30 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.)
* External radiation therapy (XRT)/external beam irradiation including protons: \>= 14 days after local XRT; \>= 90 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, iodine I 131 metaiodobenzylguanidine \[131I MIBG\]): \>= 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have had prior TIGIT targeting therapy
* Patients must not have received prior therapy with an anti- PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA4 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (i.e. OX-40, CD137)
* Patients must not have received live/attenuated vaccine within 30 days of first dose of treatment
* Patients must not be receiving concomitant systemic steroid medications and \>= 14 days must have elapsed since last dose of systemic corticosteroid with the following exceptions:
* The use of physiologic doses of corticosteroids (5 mg/m\^2/day up to 10 mg/day of prednisone equivalent) is acceptable
* The use of topical, inhaled, or ophthalmic corticosteroids are acceptable
* The use of acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are acceptable
* Treatment with systemic immunosuppressive medication (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha \[TNF-alpha\] agents) must have concluded \>= 14 days prior to study enrollment
* For patients with solid tumors without known bone marrow involvement
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL (must be performed within 7 days prior to enrollment)
* For patients with solid tumors without known bone marrow involvement
* Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (must be performed within 7 days prior to enrollment)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts above (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity
* A creatinine based on age/gender as follows (must be performed within 7 days prior to enrollment):
* Age; Maximum Serum Creatinine (mg/dL)
* 1 to \< 2 years; Male: 0.6; Female: 0.6
* 2 to \< 6 years; Male: 0.8; Female: 0.8
* 6 to \< 10 years; Male: 1; Female: 1
* 10 to \< 13 years; Male: 1.2; Female: 1.2
* 13 to \< 16 years; Male: 1.5; Female: 1.4
* \>= 16 years; Male: 1.7; Female: 1.4 OR- a 24 hour urine creatinine clearance \>= 70 mL/min/1.73 m\^2 (must be performed within 7 days prior to enrollment) OR- a glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard) (must be performed within 7 days prior to enrollment)
* Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* Bilirubin (sum of conjugated + unconjugated or total) =\< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment)
* Patients with known Gilbert disease: Total bilirubin =\< 3 x ULN
* Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (must be performed within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L
* Albumin \>= 2 g/dL (must be performed within 7 days prior to enrollment)
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days
* Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] v5) resulting from prior therapy must be =\< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
* International normalized ratio (INR) =\< 1.5 (must be performed within 7 days prior to enrollment)
* Serum amylase =\< 1.5 x ULN (must be performed within 7 days prior to enrollment)
* Serum lipase =\< 1.5 x ULN (must be performed within 7 days prior to enrollment)
* Grade 1 or lower calcium level
* Note: can have history of hypercalcemia as long as controlled and asymptomatic
Exclusion Criteria:
* Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in female patients of childbearing potential. Female patients of childbearing potential are defined as those who are past the onset of menarche and are not surgically sterile (i.e., bilateral salpingectomy, bilateral oophorectomy, complete hysterectomy) or post-menopausal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of therapy and at least 90 days after final dose of tiragolumab and 150 days after final dose of atezolizumab, whichever is later. Abstinence is an acceptable method of birth control.
* It is not known if atezolizumab or tiragolumab are present in breast milk; however, IgG immunoglobulins are found in milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during therapy and for at least 150 days after the last dose of atezolizumab and 90 days after the last dose of tiragolumab, whichever is later
* Concomitant medications:
* Corticosteroids:
* Patients must not be receiving concomitant systemic steroid medications and \>= 14 days must have elapsed since last dose of systemic corticosteroid with the following exceptions:
* The use of physiologic doses of corticosteroids (5 mg/m\^2/day up to 10 mg/day of prednisone equivalent) is acceptable
* The use of topical, inhaled, or ophthalmic corticosteroids are acceptable
* The use of acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g. 48 hours of corticosteroids for a contrast allergy) are acceptable
* Investigational drugs: Patients who are currently receiving another investigational drug are not eligible
* Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible
* Systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, and thalidomide) during study treatment because these agents could potentially alter the efficacy and safety of study treatments would not be eligible
* Patients must not have a known hypersensitivity to any component of tiragolumab or atezolizumab injection
* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or tiragolumab formulation
* Patients who have undergone allogeneic bone marrow or allogeneic cell transplant are not eligible
* Patients with CNS metastases from non-CNS primary tumors are not eligible unless CNS metastases have been previously treated and sequential imaging shows no evidence for active disease in the CNS.
* Patients with primary CNS tumors (including ATRT) with involvement of the brainstem are not eligible. Note: Patients with ATRT with M0-M4 disease without involvement of the brain stem are allowed to participate
* Patients must not have active autoimmune disease that has required systemic treatment in the past 12 months, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy are not excluded. Replacement therapy (e.g. thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and these patients are eligible
* Patients who have active immune deficiency are not eligible
* Patients who have known active tuberculosis are not eligible
* Hepatitis B or C infection:
* Patients \< 18 years old at enrollment, who have known hepatitis B or C
* Patients \>= 18 years old at enrollment with:
* Positive hepatitis B surface antigen (HBsAg), OR
* Positive total hepatitis B core antibody (HBcAb) who have a quantitative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) \>= 500 IU/mL, OR
* Positive hepatitis C virus (HCV) antibody with a positive HCV ribonucleic acid (RNA) test
* Note: For adults (\>= 18 years old at enrollment), hepatitis B serology testing is required to determine eligibility. The HBV DNA test is required only for patients who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test. For adults (\>= 18 years old at enrollment), hepatitis C serology testing is required to determine eligibility. The HCV RNA test is required only for patients who have a positive HCV antibody test
* Patients who have a known, recent Epstein-Barr virus (EBV) infection or known history of chronic, active infection are not eligible
* Patients who have history of or active human immunodeficiency virus (HIV) are not eligible except patients who are stable on anti-retroviral therapy, have a CD4 count \>= 200/uL, and have an undetectable viral load
* Patients who have significant cardiovascular disease (such as New York Heart Association class III or IV congestive heart failure, myocardial infarction, or cerebrovascular accident) within 3 months prior to study enrollment, unstable arrhythmia, or unstable angina are not eligible
* Patients who have a major surgical procedure, other than for diagnosis, within 4 weeks prior to study enrollment, or the anticipation of the need for a major surgical procedure during the study are not eligible
* Patients who have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or known active pneumonitis are not eligible. History of radiation pneumonitis in the radiation field is permitted
* Patients who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) are not eligible. Patients with indwelling catheters (e.g., PleurX) are allowed
* Patients who have an uncontrolled infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
• Subject must be ≥ 18 and ≤ 95 years of age
• Clinical diagnosis of chronic limb-threatening ischemia, defined as any of the following clinical assessments: previous angiogram or hemodynamic evidence of severely diminished arterial inflow of the index limb (e.g., ABI ≤ 0.39, TP / TcPO2 \< 30 mm Hg) and
• Rutherford Classification 5, ischemic ulceration or
• Rutherford Classification 6, ischemic gangrene
• Subject has been assessed by the Principal Investigator and determined that no conventional distal bypass, surgical or endovascular therapy for limb salvage is feasible due to either a) absence of a usable pedal artery target (endovascular or surgical approach), or b) the presence of a pedal artery target with absence of a viable single-segment vein in either lower extremity or either arm that could be used for autogenous vein conduit.
• Proximally, the Target In-flow Artery at the cross-over point must fall within the recommended vessel diameter ranges for the LimFlow stent graft by visual estimation.
• Subject is willing and able to sign the informed consent form.
• Subject is enrolled in an acceptable wound care network and has an adequate support network to ensure that subject is compliant with medication regimen and follow-up study visits.
• Prior to enrollment (7-day window), women of childbearing potential must have a negative pregnancy test.
• Primary wound is stable (e.g., not rapidly deteriorating and/or showing signs of healing).
• Stable glycemic control, HbA1C \< 10% (\<269mg/dL)
• Subjects requiring dialysis may be included, provided they meet all the following requirements:
* On dialysis for \> 6 months
* Autologous arteriovenous (AV) fistula or peritoneal access used for hemodialysis
* Serum albumin \> 30 g/liter
* BMI \> 20
Exclusion Criteria:
• Concomitant hepatic insufficiency, thrombophlebitis in the target limb, or non-treatable coagulation disorder within the past 90 days.
• Active immunodeficiency disorder or currently receiving immunosuppressant therapy for an immunodeficiency disorder.
• Prior peripheral arterial bypass procedure above or below the knee which would inhibit proximal inflow to the stent graft.
• Absence of adequate viable tissue in target foot.
• Life expectancy less than 12 months.
• Documented myocardial infarction or stroke within previous 90 days.
• Active infection (e.g., fever, significantly elevated WBC count \>20.0 x 109/L, and/or positive blood culture) at the time of the index procedure that may preclude insertion of a prosthesis or require major amputation (e.g., osteomyelitis proximal to metatarsals).
• Known or suspected allergies or contraindications to aspirin or P2Y12 inhibitors, heparin, stainless steel, nitinol or contrast agent that cannot be adequately pre-treated.
• Subject is currently taking anti-coagulants, which in the opinion of the investigator, interferes with the subject's ability to participate in the study (i.e., intermittent interruption of therapy for procedure may compromise subject's safety).
• Lower extremity vascular disease that may inhibit the procedure and/or jeopardize wound healing (e.g., vasculitis, Buerger's disease, significant edema in the target limb, deep venous thrombus in the target vein, hyperpigmentation, or medial ulceration above the ankle).
• Significant acute or chronic kidney disease with a serum creatinine of \> 2.5 mg/dl in subjects not undergoing dialysis.
• Severe heart failure (e.g., NYHA Class IV), which in the opinion of the investigator may compromise subject's ability to safely undergo a percutaneous procedure.
• Any significant concurrent medical, psychological, or social condition, which may significantly interfere with the subject's optimal participation in the study, in the opinion of the investigator.
• The subject is currently participating in another investigational drug or device study that has not completed the primary endpoint or that clinically interferes with the endpoints of this study.
• Subject is unwilling, unable, or unlikely for cognitive or social reasons to comply with any of the protocol or follow-up requirements.
Noninvasive Brain Stimulation in Mild Cognitive Impairment and Dementia
The research objective of this study is to examine the efficacy of HD-tDCS to the preSMA/DACC
region and its influence on verbal episodic memory in patients with MCI or dementia after 10
sessions of HD-tDCS. There will be three treatment arms: two active HD-tDCS (1 mA or 2 mA)
and a sham group. A verbal episodic memory task will be completed at baseline, immediately
following the last HD-tDCS session, and a 2-month follow-up.
• Age 50 and older
• Fluent in English
• Active diagnosis of MCI or dementia
Exclusion Criteria:
• Substance use disorder
• Has metal fragments in head
• Taking medications that may interact with the HD-tDCS effect (i.e., amphetamines,
L-dopa, carbamazepine, sulpiride, pergolide, lorazepam, dextromethorphan,
D-cycloserine, flunarizine, or ropinirole)
Device: Active Transcranial direct current stimulation (STARStim 8), Device: Active Transcranial direct current stimulation (STARStim 8), Device: Sham Transcranial direct current stimulation (STARStim 8)
Dementia, Alzheimer Disease, Mild Cognitive Impairment, Brain and Nervous System
Transcranial direct current stimulation, Alzheimer Disease, Mild Cognitive Impairment, Dementia, MCI, Mild neurocognitive disorder, Amnestic, Pre- alzheimer
A Study to Evaluate the Effect of Venglustat Tablets on Left Ventricular Mass Index in Male and Female Adult Participants With Fabry Disease (CARAT)
studyfinder@utsouthwestern.edu
ALL
18 Years to 65 Years old
PHASE3
This study is NOT accepting healthy volunteers
NCT05280548
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
* Male and female participants aged 18 to 65 with previously confirmed diagnosis of Fabry disease and a history of clinical symptoms of Fabry disease.
* Participants may be receiving treatment with agalsidase alfa, agalsidase beta, or migalastat, or may be untreated.
* Left ventricular hypertrophy.
* Contraception for male or female participants: not pregnant or breastfeeding; no sperm donating for male participant.
* A signed informed consent must be provided prior to any study-related procedures.
Exclusion Criteria:
* History of transient ischemic attack, stroke, myocardial infarction, heart failure, major cardiovascular surgery or kidney transplantation.
* History of seizures currently requiring treatment.
* Underlying medical condition that may cause or contribute to left ventricular hypertrophy.
* Asymmetric hypertrophy by cardiac MRI at screening if considered by central reader to be not related to Fabry disease.
* Advanced cardiac fibrosis, defined as significant late gadolinium enhancement affecting 3 or more segments involving \>50% of myocardial thickness on screening cardiac MRI.
* History of clinically significant cardiac arrhythmia. Atrial fibrillation that is well controlled on a stable medical regimen for at least 12 months is not an exclusion if the CHA2DS2-VASc score is 0 for males or 1 for females.
* Estimated glomerular filtration rate \<45 mL/min/1.73m2.
* Presence of severe depression as measured by Beck's Depression Inventory (BDI)-II \>28 and/or a history of an untreated, unstable major affective disorder within 1 year of the screening visit.
* Patients with hepatitis C, HIV, or hepatitis B infection.
* Positive SARS-CoV-2 virus test within 2 weeks of enrollment, or COVID-19 requiring hospitalization within 6 months of enrollment.
* History of drug and/or alcohol abuse.
* Moderate to severe hepatic impairment.
* History of or active hepatobiliary disease.
* Liver enzymes (alanine aminotransferase/aspartate aminotransferase) or total bilirubin \>2 times the upper limit of normal.
* Strong or moderate inducers or inhibitors of cytochrome P450 CYP3A4 within 14 days or 5 half-lives, whichever is longer, prior to randomization.
* Known contraindication to undergoing MRI or known hypersensitivity to gadolinium-based contrast agents.
The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.
Addressing Risk Through Community Treatment for Infectious Disease and Opioid Use Disorder Now (ACTION) Among Justice-involved Populations (ACTION)
This is a 5-year Hybrid Type 1 Effectiveness-Implementation Randomized Control Trial (RCT)
that compares two models of linking and retaining individuals recently released from justice
involvement to the continuum of community-based HIV prevention and treatment, HCV treatment,
STI treatment, and opioid use disorder (OUD) prevention and treatment, medication for opioid
use disorder (MOUD) service cascades of care.
* Living in one of our research areas
* Age 18 or older
* Able to provide written informed consent in English or Spanish
* Involvement with the criminal justice system within the last 6 months
* Living with HIV or being at risk of acquiring HIV and willing to learn about PrEP
* Willing to be tested for HIV (unless already confirmed via medical record)
* Having a history of opioid and/or stimulant use within 12 months prior to being in a controlled setting and/or in the last 6 months within the community
* Having a history of condomless sexual intercourse, STI diagnosis, and/or IDU within 6 months prior to being in a controlled setting and/or in the last 6 months within the community
Exclusion Criteria:
* Severe medical or psychiatric disability making participation unsafe
* Unable to provide consent
* Not remaining in the local area after release from custody
* Being released to inpatient care
* Potential risk to research staff
BEHAVIORAL: Patient Navigator, BEHAVIORAL: Mobile Health Unit
Substance Abuse, Substance Use, Opioid Use Disorder, Stimulant Use Disorder, Infectious Disease, Risk Reduction Behavior
Justice involvement, HIV Prevention, Hepatitis C Prevention
Testing the Addition of Trastuzumab or Trastuzumab/Pertuzumab to the Usual Chemotherapy for HER2 Positive Endometrial Serous Carcinoma or Carcinosarcoma
This phase II/III trial tests whether adding trastuzumab and hyaluronidase-oysk (Herceptin
HylectaTM) or pertuzumab, trastuzumab and hyaluronidase-zzxf (PhesgoTM) to the usual
chemotherapy (paclitaxel and carboplatin) works to shrink tumors in patients with HER2
positive endometrial serous carcinoma or carcinosarcoma. Trastuzumab and pertuzumab are
monoclonal antibodies and forms of targeted therapy that attach to specific molecules
(receptors) on the surface of tumor cells, known as HER2 receptors. When trastuzumab or
pertuzumab attach to HER2 receptors, the signals that tell the cells to grow are blocked and
the tumor cell may be marked for destruction by the body's immune system. Hyaluronidase is an
endoglycosidase. It helps to keep pertuzumab and trastuzumab in the body longer, so that
these medications will have a greater effect. Hyaluronidase also allows trastuzumab and
trastuzumab/pertuzumab to be given by injection under the skin and shortens their
administration time compared to trastuzumab or pertuzumab alone. Paclitaxel is a taxane and
in a class of medications called antimicrotubule agents. It stops cancer cells from growing
and dividing and may kill them. Carboplatin is in a class of medications known as
platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin,
but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing
the growth of tumor cells. Giving Herceptin Hylecta or Phesgo in combination with paclitaxel
and carboplatin may shrink the tumor and prevent the cancer from coming back in patients with
HER2 positive endometrial serous carcinoma or carcinosarcoma.
* Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA-IVB, non-recurrent, chemotherapy (chemo)-naive, HER2-positive endometrial serous carcinoma or endometrial carcinosarcoma
* Histologic confirmation of the original primary tumor is required. Submission of surgical pathology report (or endometrial biopsy pathology report in patients who never undergo hysterectomy) is required
* Patients must be within 8 weeks of primary surgery (or endometrial biopsy in patients who never undergo hysterectomy) at the time of study registration
* Patients may have measurable disease, non-measurable disease, or no measurable disease. In patients with measurable disease, lesions will be defined and monitored by RECIST v 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be \>= 10 mm when measured by computed tomography (CT) or magnetic resonance imaging (MRI). Lymph nodes must be \>= 15 mm in short axis when measured by CT or MRI
* For patients with uterine-confined (stage I) disease, the tumor must be invasive into the myometrium. Any amount of myoinvasion is acceptable for eligibility. Patients with non-invasive disease, endometrial intraepithelial carcinoma alone, or disease confined to a polyp will be excluded
* All patients must have tumors that are HER2 positive as defined by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) 2018 Breast Cancer guidelines (https://documents.cap.org/documents/algorithim-evaluation-her2.pdf. In general HER2 positivity is defined as any of the following:
* 3+ immunohistochemistry (IHC),
* 2+ IHC with positive in situ hybridization (ISH)
* Average HER2 copy number \>= 6.0 signals/cell
* Average HER2 copy number \>= 4.0 and \< 6.0 signals/cell, with concurrent IHC 3+
* HER2/CEP17 ratio \>= 4.0 signals/cell
* HER2/CEP 17 ratio \>= 2.0 and \< 4.0, with concurrent IHC 3+ IHC and ISH testing will be done locally, at each participating institution and interpreted by local pathologists. Alternatively, patients could be eligible if next generation sequencing (NGS) demonstrates HER2 (ERBB2) amplification. NGS testing can be performed through any designated labs as per the National Cancer Institute (NCI) MATCH/NCI Combo-MATCH trial (https://ecog-acrin.org/nci-match-eay131-designated-labs).
Pathology report showing results of institutional HER2 testing (or NGS testing results) must be submitted.
Sites must submit all results available (IHC, ISH, and NGS)
* Additionally, patients must have the following histologic types to be eligible:
* Serous adenocarcinoma (may include =\< 10% non-serous histology)
* Carcinosarcoma with serous epithelial component (only the serous component needs to be HER2 positive; may include =\< 10% non-serous histology)
* In cases where determination of serous is equivocal or challenging, aberrant p53 immunohistochemistry (IHC) (defined as overexpression of p53 compared to internal controls) will be sufficient for inclusion
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
* Age \>= 18
* Platelets \>= 100,000/mcl (within 14 days prior to registration)
* Absolute neutrophil count (ANC) \>= 1,500/mcl (within 14 days prior to registration)
* Creatinine =\< 1.5 x institutional/laboratory upper limit of normal (ULN) or estimated Glomerular filtration rate (eGFR) \>= 50 mL/min using either the Cockcroft-Gault equation, the Modification of Diet in Renal Disease Study, or as reported in the comprehensive metabolic panel/basic metabolic panel (eGFR). (within 14 days prior to registration)
* Total serum bilirubin level =\< 1.5 x ULN (patients with known Gilbert's disease who have bilirubin level =\< 3 x ULN may be enrolled) (within 14 days prior to registration)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x ULN (within 14 days prior to registration)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial
* Although the uterus will have been removed in the vast majority of patients, for patients of child-bearing potential: negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required. Patients will be considered of non-reproductive potential if they are either:
* Postmenopausal (defined as at least 12 months with no menses without an alternative medical cause; in women \< 45 years of age, a high follicle stimulating hormone \[FSH\] level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient); OR
* Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion at least 6 weeks prior to registration
* Have a congenital or acquired condition that prevents childbearing
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Patients with evidence of chronic hepatitis B virus (HBV) infection must have an undetectable HBV viral load on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
Exclusion Criteria:
* Prior Therapy:
* Patients must NOT have received prior chemotherapy, biologic therapy, or targeted therapy for treatment of endometrial carcinoma
* Patients must NOT have received prior radiation therapy for treatment of endometrial carcinoma. Prior radiation includes external beam pelvic radiation therapy, external beam extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy
* NOTE: Vaginal brachytherapy for treatment of endometrial cancer is permitted during study treatment. Planned use of vaginal brachytherapy must be declared at time of registration
* Patients may have received prior hormonal therapy for treatment of endometrial carcinoma. All hormonal therapy must be discontinued at least one week prior to registration
* Patients may not have a planned interval cytoreduction or hysterectomy, prior to documentation of progression, after study registration
* Patients may not have planned external beam radiotherapy, prior to documentation of progression, after study registration
* Significant cardiovascular disease including:
* Uncontrolled hypertension, defined as systolic \> 150 mm Hg or diastolic \> 90 mm Hg despite antihypertensive medications
* Myocardial infarction or unstable angina within 6 months prior to registration
* New York Heart Association functional classification II, III or IV
* Serious cardiac arrhythmia requiring medication. This does not include asymptomatic, atrial fibrillation with controlled ventricular rate
* Significant lung disease: dyspnea at rest grade 2 or greater (resulting from extensive tumor involvement or other causes), pneumonitis grade 2 or greater, interstitial lung disease grade 2 or greater, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia)
* Patients with uncontrolled intercurrent illness including, but not limited to: ongoing or active infection (except for uncomplicated urinary tract infection), uncontrolled interstitial lung disease, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements
* Treatment with strong CYP2C8 or CYP3A4 inhibitors or inducers within 14 days or 5 drug-elimination half-lives, whichever is longer, prior to registration
* Women who are unwilling to discontinue nursing
4D-710 in Adult Patients With Cystic Fibrosis (CF)
This is a Phase 1/2 multicenter, open-label, single dose trial of 4D-710 investigational gene
therapy in adults with CF who are ineligible for or unable to tolerate CFTR modulator
therapy.
• 18 years and older
• Confirmed diagnosis of cystic fibrosis (CF) and CF lung disease including:
• Sweat chloride ≥ 60 mmol/L
• Mutation Status
• Bi-allelic mutations in the CFTR gene, or
• Single mutation in the CFTR gene and clinical manifestations of CF lung
disease
• Ineligible for CFTR modulator therapy, or previously received modulator therapy
but discontinued due to adverse effects.
• Forced expiratory volume in 1 second (FEV1) ≥50% and ≤100% of predicted (per Global
Lung Function Initiative) at Screening
• Resting oxygen saturation ≥ 92% on room air at Screening
Key
Exclusion Criteria:
• Any prior gene therapy for any indication (Exception: mRNA-based therapies are not
exclusionary)
• Active Mycobacterium abscessus infection requiring ongoing treatment at Screening
• Active allergic bronchopulmonary aspergillosis requiring management with systemic
corticosteroids or antifungal therapy
• Two or more pulmonary exacerbations requiring treatment with intravenous (IV)
antibiotics within 6 months prior to Screening
• Contraindication to systemic corticosteroid therapy
• Requires chronic use of systemic corticosteroids or immunosuppressants to treat
another condition
• If no known diagnosis of cystic fibrosis related diabetes (CFRD), Type I, or Type II
diabetes: Hemoglobin A1C ≥6.5% at Screening
• If known diagnosis of CFRD, Type I or Type II diabetes: Hemoglobin A1C >7.5% at
Screening
• Recent history of symptomatic hyperglycemia or unstable blood glucose levels as per
Investigator's assessment
• Other conditions that, in the Investigator's opinion, may interfere with management of
corticosteroid-related hyperglycemia
• Body Mass Index (BMI) <16
• Laboratory abnormalities at screening:
• ALT, AST or GGT ≥ 3 × the upper limit of normal (ULN)
• Total bilirubin ≥ 2 × ULN
• Hemoglobin < 10 g/dL
• Requirement for continuous or night-time oxygen supplementation
• Known CF liver disease with evidence of cirrhosis
• History of thrombosis (excluding catheter-related thrombosis) or conditions associated
with increased risk of thrombosis
A Study to Assess Adverse Events and Change in Disease Activity of Intravenously (IV) Infused ABBV-383 in Combination With Anti-Cancer Regimens for the Treatment of Adult Participants With Relapsed/Refractory Multiple Myeloma
Multiple myeloma (MM) is a plasma cell disease characterized by the growth of clonal plasma
cells in the bone marrow. The purpose of this study is to assess the safety and toxicity of
ABBV-383 when co-administered with pomalidomide-dexamethasone (Pd),
lenalidomide-dexamethasone (Rd), daratumumab-dexamethasone (Dd), or nirogacestat (Niro) in
adult participants with relapsed/refractory (R/R) multiple myeloma (MM). Adverse events and
change in disease activity will be assessed.
ABBV-383 is an investigational drug being developed for the treatment of R/R MM. Study
doctors put the participants in groups called treatment arms. ABBV-383 co-administered with
Pd, Rd, Dd, or Niro will be explored. Each treatment arm receives a different treatment
combination depending on stage of the study and eligibility. This study will include a dose
escalation phase to determine the best dose of ABBV-383, followed by a dose expansion phase
to confirm the dose. Approximately 270 adult participants with R/R MM will be enrolled in the
study in approximately 45 sites worldwide.
Participants will receive intravenous (IV) ABBV-383 co-administered with oral/IV Pd, oral/IV
Rd, oral/IV/subcutaneous (SC) Dd, or oral/IV Niro in 28-day cycles.
There may be higher treatment burden for participants in this trial compared to their
standard of care. Participants will attend regular visits during the study at an approved
institution (hospital or clinic). The effect of the treatment will be frequently checked by
medical assessments, blood tests, questionnaires and side effects.
* Eastern Cooperative Oncology Group (ECOG) performance of \<= 2.
* Must have confirmed diagnosis of Relapsed/Refractory (R/R) Multiple Myeloma (MM) with documented evidence of progression during or after the participant's last treatment regimen based on the investigator's determination of the International Myeloma Working Group (IMWG) criteria.
* Must have measurable disease as outlined in the protocol.
* Must be naïve to treatment with ABBV-383 and must have never received BCMA-targeted therapy. Participants who have received targeted therapy against non-BCMA targets will not be excluded.
* Has received prior MM treatment in Arms A, B, C, and D.
Exclusion Criteria:
* Received a peripheral autologous stem cell transplant (SCT) within 12 weeks, or an allogeneic SCT within 1 year of the first dose of study drug treatment.
* Unresolved adverse event (AE)s \>= Grade 2 (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0) from prior anticancer therapy.
* Known central nervous system involvement Multiple Myeloma (MM).
* Has any of the following conditions:
* Nonsecretory MM.
* Active Plasma cell leukemia i.e., either 20% of peripheral white blood cells or \> 2.0 × 10\^9L circulating plasma cells by standard differential.
* Waldenstrom's macroglobulinemia.
* Light chain amyloidosis.
* Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes (POEMS) syndrome.
* Major surgery within 4 weeks prior to first dose or planned study participation.
* Acute infections within 14 days prior to first dose of study drug requiring therapy (antibiotic, antifungal or antiviral).
* Uncontrolled diabetes or hypertension within 14 days prior to first dose.
* Peripheral neuropathy \>= Grade 3 or \>= Grade 2 with pain within 2 weeks prior to first dose.
* Known active infection of evidence of active hepatitis B, evidence of active hepatitis C, human immunodeficiency virus.
Safety and Feasibility of Robotic SP Nipple Sparing Mastectomy
This is a single arm, single-center, prospective clinical trial designed to track the peri,
post-operative and oncologic outcomes when utilizing the da-Vinci single port (SP) robotic
platform to perform robotic nipple sparing mastectomy (rNSM) and immediate breast
reconstruction with tissue expanders/implants and acellular dermal matrix (ADM - Alloderm),
for patients with breast cancer as well as those with a high risk for breast cancer.
Safety and feasibility measures will be measured as primary outcome measures. Oncological and
patient satisfaction outcome measures will be measured. Our hypothesis is that SPr-NSM is
equal to open NSM in terms of safety, feasibility and oncological outcomes with improved
patient satisfaction as measured by nipple sensation and patient reported outcomes.
• Candidates for open nipple sparing mastectomy, per standard of care with regards to
anatomic factors and tumor location including: nipple sparing resection and resection
OR prophylactic mastectomy for risk reduction OR treatment of ductal carcinoma in-situ
or clinically node negative cT1-T3 breast cancer
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Exclusion Criteria:
• Inability to provide informed consent
• Pregnant or nursing women
• Patients with:
• Inflammatory breast cancer
• Skin involvement with tumor
• Pre-operative diagnosis of Nipple Areolar Complex (NAC) tumor involvement
• Grade 3 or higher nipple ptosis
• Contraindicated for general anesthesia or surgery
• Heavy current smoking history (defined as > 20 cigarettes per day)
Device: da Vinci SP Surgical System
Breast Cancer, Breast - Female, High Risk of Breast Cancer
A Study of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Ciltacabtagene Autoleucel Versus Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Autologous Stem Cell Transplant (ASCT) in Participants With Newly Diagnosed Multiple Myeloma (CARTITUDE-6)
The purpose of this study is to compare the efficacy of Daratumumab, Bortezomib, Lenalidomide
and Dexamethasone (DVRd) followed by Ciltacabtagene Autoleucel versus Daratumumab,
Bortezomib, Lenalidomide and Dexamethasone (DVRd) followed by Autologous Stem Cell Transplant
(ASCT) in newly diagnosed multiple myeloma patients.
studyfinder@utsouthwestern.edu
ALL
18 Years and over
PHASE3
This study is NOT accepting healthy volunteers
NCT05257083
Show full eligibility criteria
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Inclusion Criteria:
* Participants with documented NDMM according to IMWG diagnostic criteria, for whom high-dose therapy and ASCT are part of the intended initial treatment plan.
* Measurable disease, as assessed by central laboratory, at screening as defined by any of the following:
• Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
• Light chain MM without measurable disease in serum or urine: serum Ig free-light chain (FLC) ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.
* ECOG performance status of grade 0 or 1
* Clinical laboratory values within prespecified range.
Exclusion Criteria:
* Prior treatment with CAR-T therapy directed at any target.
* Any prior BCMA target therapy.
* Any prior therapy for MM or smoldering myeloma other than a short course of corticosteroids
* Received a strong cytochrome P450 (CYP)3A4 inducer within 5 half-lives prior to randomization
* Received or plans to receive any live, attenuated vaccine (except for COVID-19 vaccines) within 4 weeks prior to randomization.
* Known active, or prior history of central nervous system (CNS) involvement or clinical signs of meningeal involvement of MM
* Stroke or seizure within 6 months of signing Informed Consent Form (ICF)
Thoracotomy Versus Thoracoscopic Management of Pulmonary Metastases in Patients With Osteosarcoma
This phase III trial compares the effect of open thoracic surgery (thoracotomy) to
thoracoscopic surgery (video-assisted thoracoscopic surgery or VATS) in treating patients
with osteosarcoma that has spread to the lung (pulmonary metastases). Open thoracic surgery
is a type of surgery done through a single larger incision (like a large cut) that goes
between the ribs, opens up the chest, and removes the cancer. Thoracoscopy is a type of chest
surgery where the doctor makes several small incisions and uses a small camera to help with
removing the cancer. This trial is being done evaluate the two different surgery methods for
patients with osteosarcoma that has spread to the lung to find out which is better.
• Patients must be < 50 years at the time of enrollment.
• Patients must have =< 4 nodules per lung consistent with or suspicious for metastases,
with at least one of which being >= 3 mm and all of which must be =< 3 cm size.
• Note: Patient must have eligibility confirmed by rapid central imaging review.
• Lung nodules must be considered resectable by either open thoracotomy or thoracoscopic
surgery. Determination of resectability is made by the institutional surgeon.
• Patients must have a histological diagnosis of osteosarcoma.
• Patients must have evidence of metastatic lung disease at the time of initial
diagnosis, or at time of 1st recurrence following completion of therapy for initially
localized disease.
• Patients with newly diagnosed disease must have completed successful gross tumor
resection for their primary tumor or surgical local control of primary tumor must be
planned to be performed simultaneously with thoracic surgery.
• Newly diagnosed patients must be receiving or recently completed (within 60 days)
systemic therapy considered by the treating physician to be standard treatment for
newly diagnosed osteosarcoma (eg, cisplatin-doxorubicin or ifosfamide-based drug
regimens) at the time of enrollment on this study. Dose and drug modifications for
toxicity do not exclude patients from participation.
• Patients at time of 1st recurrence must have completed systemic therapy for their
initial primary tumor, considered by the treating physician to be standard treatment
for newly diagnosed osteosarcoma (eg, cisplatin-doxorubicin or ifosfamide-based drug
regimens) at the time of enrollment on this study. Dose and drug modifications for
toxicity do not exclude patients from participation.
Exclusion Criteria:
• Patients with unresectable primary tumor.
• Patients with pulmonary metastatic lesions that would require anatomic resection
(lobectomy or pneumonectomy) or lesions that are defined as "central" (i.e., central
lesion involves or is proximal to segmental bronchi and peripheral is lesion distal to
segmental bronchi).
• Patients with chest wall or mediastinal based metastatic lesions, or with significant
pleural effusion.
• Patients with disease progression at either the primary or pulmonary metastatic site
while on initial therapy. Note: Once the patient has been enrolled on the study,
additional computed tomography (CT) scans are not anticipated prior to thoracic
surgery. Note: Some variation in nodule size measurements over the course of
pre-operative therapy is anticipated and does not qualify for exclusion unless deemed
true disease progression by the primary treatment team.
• Patients with evidence of extrapulmonary metastatic disease.
• Patients who received therapeutic pulmonary surgery for lung metastasis prior to
enrollment.
• All patients and/or their parents or legal guardians must sign a written informed
consent.
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met.
A Study of Daratumumab-Based Therapies in Participants With Amyloid Light Chain (AL) Amyloidosis (AQUARIUS)
The purpose of this study is to characterize cardiac safety of Daratumumab, Cyclophosphamide,
Bortezomib, and Dexamethasone (D-VCd) treatment regimens (Arm A: daratumumab + immediate VCd
treatment and Arm B: daratumumab + deferred VCd) in newly diagnosed systemic amyloid light
chain (AL) amyloidosis with cardiac involvement and to identify potential mitigation
strategies for cardiac toxicity (cohort 1); to characterize the pharmacokinetics of
subcutaneous (SC) daratumumab, among racial and ethnic minorities, including Black or African
American, with newly diagnosed AL amyloidosis treated with D-VCd (cohort 2).
* Cohort 1: Cardiac involvement (amyloid light chain \[AL\] amyloidosis Mayo Cardiac Stage II and Stage IIIa) with or without other organ(s) involved; Cohort 2: One or more organs impacted by systemic AL amyloidosis according to consensus guidelines
* Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2
* A female participant of childbearing potential must have a negative serum or urine test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study
* A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 6 months after receiving the last dose of cyclophosphamide or 100 days after discontinuation of daratumumab, whichever is longer
* Cohort 2 only: self-identified racial and ethnic minorities, including Black or African American
* Measurable disease at screening defined by one of the following:
Difference between iFLC and uninvolved FLC (dFLC) \>= 40mg/L per central laboratory Serum involved free light chain (iFLC) \>= 40 mg/L with an abnormal kappa:lambda ratio Serum M-protein \>= 0.5 g/dL
Exclusion Criteria:
* Prior therapy for systemic AL amyloidosis or multiple myeloma including medications that target cluster of differentiation 38 (CD38), with the exception of 160 milligrams(mg) dexamethasone or equivalent corticosteroid maximum exposure prior to randomization/enrollment
* Previous or current diagnosis of symptomatic multiple myeloma, including the presence of lytic bone disease, plasmacytomas, \>=60% plasma cells in the bone marrow, or hypercalcemia related to myeloma.
* Participant received any of the following therapies:
• treatment with an investigational drug or used an invasive investigational medical device within 14 days or at least 5 half-lives, whichever is less;
• vaccinated with an investigational vaccine (except for COVID-19) live, attenuated or replicating viral vector vaccines less than (\<) 4 weeks prior to randomization/enrollment. Participants who are taking strong Cytochrome P450 3A4(CYP3A4) inducers must discontinue their use at least 5 half-lives prior to the first dose of bortezomib
* Stem cell transplantation -Planned stem cell transplant during the first 9 cycles of protocol therapy are excluded. Stem cell collection during the first 9 cycles of protocol therapy is permitted
* Grade 2 sensory or Grade 1 painful peripheral neuropathy
Enfortumab Vedotin and Pembrolizumab in People With Bladder Cancer
This study will test whether enfortumab vedotin combined with pembrolizumab is an effective
treatment for people with bladder cancer (urothelial carcinoma) involving the lymph nodes who
are going to have surgery to remove their cancer (cystectomy). The researchers will look at
whether treatment with enfortumab vedotin and pembrolizumab before surgery can get rid of
cancer within the lymph nodes. They will also try to find out if this combination of drugs is
effective at shrinking participants' cancer before their surgery.
The researchers think that a combination of enfortumab vedotin and pembrolizumab may help
people with this disease because both drugs are designed to help the immune system attack and
kill cancer cells. The researchers think the drugs may be more effective if given in
combination rather than on their own.
* Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of muscle invasive bladder cancer (previously known as transitional cell) carcinoma (i.e., cancer of the bladder, renal pelvis, ureter, or urethra)
* Clinical Stage T2-T4, N1-N3, M0 OR cT1, N2-N3, M0
* Pathology:
* Representative urothelial carcinoma FFPE tumor specimens (tumor blocks or 20 unstained slides). Patients with \< 20 slides may be enrolled after discussion with the principal investigator.
* Muscle invasive urothelial carcinoma of the bladder histologically confirmed at the enrolling institution from TURBT. (Urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed provided the extent of disease is confirmed via imaging and/or EUA.)
* Evidence of urothelial carcinoma from FNA of lymph node OR lymphadenopathy suspicious for nodal disease on cross-sectional imaging, MRI, or u/s.
* Node positivity for eligibility will be defined as imaging read with suspicious lymph node ≥ 1.0 cm in the short axis, with biopsy, as documented by the radiologist at the treating center. While biopsy to confirm lymph node involvement is preferred, patients without biopsy proven urothelial carcinoma in lymph nodes may be enrolled if imaging shows a lymph node ≥ 1.0 cm in the short axis, and with confirmation from the study principal investigator.
* Deemed medically appropriate for radical cystectomy with treatment response achieved, as per MSK or participating site Attending Urologic Oncologist
* Platinum eligible and ineligible patients are permitted on study
* No prior treatments for muscle invasive or metastatic urothelial carcinoma
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
* Estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m2 using the CKD-EPI equation: eGFR = 141 x min(Scr/k, 1)a x max (Scr/k, 1)-1.209 x 0.993Age x 1.018 \[if female\] x 1.159 \[if black\]
°Scr is serum creatinine, k is 0.7 for females and 0.9 for males, a is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1
* Be willing and able to provide written informed consent for the trial
* Contraception requirements:
• Male participants:
A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days following the last dose of treatment, corresponding to time needed to eliminate any study treatment(s) (e.g. 5 terminal half-lives for pembrolizumab and enfortumab vedotin) plus an additional 90 days (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants:
A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
i. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR ii. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least \[90 days (corresponding to time needed to eliminate any study treatment(s) (pembrolizumab and enfortumab vedotin) plus 30 days (a menstruation cycle)\] after the last dose of study treatment.
* Have adequate organ function as defined in the following table (Table 1). Specimens must be collected within 14 days prior to the start of study treatment either prior to consent or at the study screening visit.
* Hematological
* Absolute neutrophil count (ANC) ≥1500/μL
* Platelets ≥100 000/μL
* Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La
* Renal
°Measured or calculatedb creatinine clearance (GFR can also be used in place of creatinine or CrCl) GFR or CrCl of ≥ 30 mL/min
* Hepatic
* Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN
* AST (SGOT) and ALT (SGPT) ≤ 2.5 × ULN
* Coagulation °International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.
a Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks. b eGFR as calculated by the CKD-EPI equation can be used in place of the creatinine clearance
Note: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies
Exclusion Criteria:
* Evidence of NYHA functional class III or IV heart disease
* Any of the following within 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
* On-going cardiac dysrhythmias of NCI CTCAE Version 5.0 grade ≥ 2. However, stable atrial fibrillation controlled medically or with a device (i.e. pacemaker) or prior ablation is allowed
* Pre-existing sensory grade ≥ 2 neuropathy
* Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure aside from cystectomy during the course of the study. Transurethral resection or other urinary tract diagnostic procedures, excisional biopsy, IR-guided biopsy, or MEDIPORT placement are NOT defined as major surgical procedures.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
* A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
* Is currently enrolled in another therapeutic trial. Patients cannot receive concurrent treatment on another clinical trial; Patients are allowed to enroll on supportive care trials or non-treatment trials (e.g. QOL, dietary survey studies) concurrently
* 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 (eg, CTLA-4, OX 40, CD137).
* Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to allocation.
* Prior treatment with an antibody drug conjugate for bladder cancer directed therapy
* Prior systemic chemotherapy (prior intravesical therapy is allowed)
* Prior radiation therapy to the bladder
* Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
* Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. 1. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. Administration of killed vaccines is allowed. COVID-19 vaccination is permitted.
°Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist®) within 4 weeks prior to Cycle 1, Day 1 or at any time during the study.
* Has receieved intravesical bacillus Calmette-Guerin (BCG) within 4 weeks before Cycle 1, Day 1 14.
* 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 to the first dose of study drug.
* Has a history of poorly controlled human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) related illness. Patients with a history of an aids-defining opportunistic infection within the last 12 months or who are on prophylactic antimicrobials related to underlying HIV are not eligible. Patients with a history of HIV and a CD4 T cell count of ≥350 are eligible to enroll in this study with the approval of the study PI.
* Subjects with uncontrolled diabetes. Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥8% or HbA1c 7% to \<8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
* Has a history of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, vascular thrombosis associated with antiphospholipid syndrome, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, systemic vasculitis, or glomerulonephritis.
* Patients with history of autoimmune related hypothyroidism on stable dose of thyroid replacement hormone may be eligible for this study
* Patients with controlled Type I diabetes mellitus on a stable dose of insulin may be eligible for this study
* Has a history of idiopathic pulmonary fibrosis, pneumonitis/interstitial lung disease that requires steroids or has current pneumonitis/interstitial lung disease (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan
* Patients with active hepatitis B virus (HBV, chronic or acute, defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C antibody
* Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody \[HBc Ab\] and absence of HBsAg) are eligible. HBV DNA must be obtained in these patients prior to Cycle 1, Day 1 and confirmed to be negative.
* Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
* Active tuberculosis or BCG infection
* Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
* Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1. Abnormal urinalysis does not constitute signs/symptoms of infection unless urine culture obtained at screening grows ≥ 100,000 colonies of bacteria.
* Therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1
* Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible.
* Patients receiving antibiotics for active infection are not eligible
* Prior allogeneic stem cell or solid organ transplant
* AEs from prior anticancer therapy that have not resolved to Grade ≤ 1 except for alopecia
* Patients with a history of or active bone marrow disorders expected to interfere with study therapy (e.g. acute leukemias, accelerated/blast-phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma)
* Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; and inherited liver disease
* Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
* Patients with active keratitis or history of corneal ulcers are excluded
* Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
* Rash must cover less than 10% of body surface area (BSA)
* Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
* No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation \[PUVA\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
* Malignancies other than the disease under study within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-ofcare management (e.g. prostate cancer with Gleason score ≤ 7, and prostate-specific antigen \[PSA\] ≤ 10 mg/mL, etc).
• Men or women 50-85 years of age (inclusive), meeting criteria for probable Dementia
with Lewy Bodies (DLB).
• MRI, or CT scan due to contraindication of MRI if approved by medical monitor)
obtained during screening consistent with the clinical diagnosis of DLB and without
findings of significant exclusionary abnormalities. An historical MRI (or CT scan), up
to 1 year prior to screening, may be used if there is no history of intervening
neurologic disease or clinical events (such as a stroke, head trauma etc.) and the
subject is without clinical symptoms or signs suggestive of such intervening events.
• MMSE 18-27 inclusive
Exclusion Criteria:
• Any neurological condition that may be contributing to cognitive impairment above and
beyond those caused by the subject's DLB, including any co-morbidities detected by
clinical assessment or MRI (or CT scan due to contraindication of MRI, if approved by
medical monitor)
• Screening MRI (or historical MRI or CT scan due to contraindication of MRI if approved
by medical monitor) or historical MRI/CT scan, if applicable. of the brain indicative
of significant abnormality, including, but not limited to, prior hemorrhage or infarct
> 1 cm3, >3 lacunar infarcts, cerebral contusion, encephalomalacia, aneurysm, vascular
malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g. abscess
or brain tumor such as meningioma). If a small incidental meningioma is observed, the
medical monitor may be contacted to discuss eligibility.
• Clinical, laboratory findings or medical history consistent with:
• Other primary degenerative dementia (fronto-temporal dementia, Huntington's
disease, Creutzfeldt-Jakob Disease, Down syndrome, etc.).
• Other neurodegenerative condition (amyotrophic lateral sclerosis, etc.).
• Seizure disorder.
• Other infectious, metabolic or systemic diseases affecting the central nervous
system (syphilis, present hypothyroidism, present vitamin B12 or folate
deficiency, other laboratory values etc.).
• Any major psychiatric diagnosis, including schizophrenia, bipolar disorder, and
current major depressive disorder as per Diagnostic and Statistical Manual of Mental
Disorders Fifth Edition
• Clinically significant, advanced or unstable disease that may interfere with outcome
evaluations.
Phase 3 Study to Evaluate the Efficacy and Safety of HER2/Neu Peptide GLSI-100 (GP2 + GM-CSF) in HER2/Neu Positive Subjects (FLAMINGO-01)
This is a prospective, randomized, double-blinded, placebo-controlled, multi-center, Phase 3
study of GLSI-100 immunotherapy in HLA-A*02 positive and HER2/neu positive subjects who are
at high risk for disease recurrence and have completed both neoadjuvant and postoperative
adjuvant standard of care therapy. Treatment consists of 6 intradermal injections, Primary
Immunization Series (PIS), over the first 6 months of treatment and 5 booster intradermal
injections spaced 6 months apart. A third open-label arm will explore GLSI-100 immunotherapy
in non-HLA-A*02 positive and HER2/neu positive subjects.
* HLA-A\*02-positive, unless being enrolled in the third non-HLA-A\*02 arm
* Histologically confirmed diagnosis of HER2/neu positive primary breast cancer
* Completion of both neoadjuvant and adjuvant trastuzumab-based standard of care breast cancer therapy
* Stage I, II, or III at presentation with pathologic evidence of residual invasive carcinoma in the breast or axillary lymph nodes (residual disease) at surgery following completion of neoadjuvant therapy -OR- Stage III at presentation with pathologic complete response (pCR) at surgery following completion of neoadjuvant therapy
* The subject can begin study therapy within one year of completion of adjuvant trastuzumab-based therapy and any other standard therapies, but, study therapy can be administered concurrently with endocrine therapy.
* No clinical evidence of residual or persistent breast cancer per treating physician assessment
* ECOG 0-2
* Adequate organ function
* Negative pregnancy test or evidence of post-menopausal status
* If of childbearing potential, willing to use a form of highly effective contraception
Exclusion Criteria:
* Stage IV cancer or metastatic breast cancer at any time
* Inflammatory breast cancer
* Receiving other investigational agents
* Receiving chemotherapy
* Requiring long-term systemic treatment with corticosteroids or other immunosuppressive therapy
* History of immunodeficiency or active autoimmune disease
* A history of serious allergic reactions, including anaphylaxis, to human granulocyte-macrophage colony-stimulating factors such as sargramostim, yeast-derived products, or any component of the investigational product
* Other malignancies except adequately treated in situ carcinoma of the cervix or basal cell or squamous cell carcinoma of the skin
* Active infection
* Known HIV infection with a detectable viral load within 6 months of the anticipated start of treatment. Note: Subjects on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial.
A Study of Ivaltinostat Plus Capecitabine or Capecitabine in Metastatic Pancreatic Adenocarcinoma
This study is a Phase 1b/2, dose-escalation, randomized, multicenter study to assess the
efficacy, safety, tolerability, and PK of ivaltinostat in combination with capecitabine and
capecitabine monotherapy in patients with metastatic pancreatic adenocarcinoma whose disease
has not progressed on a first line fluoropyrimidine-based chemotherapy (e.g., FOLFIRINOX).
In Phase 1b, 3 dose levels of ivaltinostat will be studied in combination with a fixed dose
of capecitabine to determine the RP2D of ivaltinostat.
In Phase 2, patients will be randomized in a 1:1 ratio to the combination of ivaltinostat and
capecitabine or to capecitabine monotherapy. A fixed dose for capecitabine 1000 mg/m2 orally
twice daily will be taken on Days 1 to 14, and the RP2D of ivaltinostat will be administered
intravenously once a week for 2 weeks, followed by 1 week of rest. One cycle consists of 21
days. Tumor response during study treatment will be assessed every 6 weeks up to Cycle 10,
then every 9 weeks afterwards using RECIST v1.1 criteria.
* Age: ≥18 years
* For Phase 1b, histologically or cytologically confirmed pancreatic adenocarcinoma (locally advanced or metastatic) with at least 1 prior therapy in either the advanced or perioperative setting
* For Phase 1b, measurable disease and/or non-measurable disease per RECIST v1.1
* For Phase 2, histologically or cytologically confirmed pancreatic adenocarcinoma without evidence of disease progression while receiving initial chemotherapy for metastatic disease (e.g., must have had a demonstrated CR, PR, or SD following initial chemotherapy).
* For Phase 2, measurable disease and/or non-measurable or no evidence of disease assessed by baseline CT (or MRI where CT is contraindicated). RECIST v1.1 will be used to allow for assessment of disease progression due to new lesions in patients with no evidence of disease at baseline. Patients with no evidence of disease following FOLFIRINOX chemotherapy will be deemed to have radiographic disease progression if new lesions are detected.
* For Phase 2, treatment with FOLFIRINOX for metastatic pancreatic adenocarcinoma at full or modified doses, for a minimum of 16 weeks, and no evidence of progression based on the radiographic imaging.
* a. Randomization must occur within 6 weeks of the last dose of chemotherapy.
* b. Patients who have received at least 16 weeks of FOLFIRINOX combination regimen but had non-fluoropyrimidine chemotherapeutic agents discontinued prior to 16 weeks due to toxicity are eligible if they have no radiographic evidence of disease.
* For Phase 2, patients who received prior chemotherapy or prior chemoradiation for a prior cancer or as adjuvant/neoadjuvant treatment for pancreatic adenocarcinoma are eligible provided at least 12 months have elapsed between the last dose of treatment and initiation of the FOLFIRINOX chemotherapy for metastatic pancreatic adenocarcinoma.
* Prior radiation therapy is allowed, provided \>14 days have elapsed since completion of radiation prior to randomization.
* Adequate organ function
* ECOG Performance Status 0-1 at the date of signing the informed consent.
Exclusion Criteria:
* For Phase 2, radiographic progression of tumor per RECIST 1.1 between start of first line FOLFIRINOX chemotherapy for metastatic pancreatic adenocarcinoma and randomization.
* Cytotoxic chemotherapy or non-hormonal targeted therapy within 28 days of Cycle 1 Day 1 is not permitted. Palliative radiotherapy must have been completed 14 or more days before Cycle 1 Day 1. The patient can receive a stable dose of bisphosphonates or RANKL directed therapy for bone metastases before and during the study as long as these were initiated at least 2 weeks prior to study treatment
* For Phase 2, not receiving FOLFIRINOX as initial therapy for metastatic PDAC. Patients who received FOLFIRINOX initially and who needed to discontinue irinotecan or oxaliplatin due to toxicity are eligible, provided they received at least 4 weeks (2 cycles) of FOLFIRINOX
* For Phase 2, more than 1 prior line of therapy for metastatic PDAC
* Exposure to an investigational agent within 30 days or 5 half-lives (whichever is longer) prior to randomization
* Any previous treatment with a HDAC inhibitor, including ivaltinostat