Search Results
within category "Digestive Systems & Liver Disease"
Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
Study of the Efficacy and Safety of Lonafarnib / Ritonavir With and Without Pegylated Interferon -Alfa-2a (D-LIVR)
Two LNF-containing regimens will be evaluated in the D-LIVR Phase 3 study: (1) LNF/RTV/PEG
IFN-alfa-2a and (2) LNF/RTV. Each of these arms will have efficacy endpoints that measure
clinical benefit with regard to viral suppression and alanine aminotransferase (ALT)
normalization. For each LNF-containing regimen, a composite endpoint of EOT (48 weeks)
virologic response and ALT normalization will be used. Virologic response will be defined as
a 2 log10 IU/mL reduction from baseline.
Call 214-648-5005 studyfinder@utsouthwestern.edu
William Lee
14217
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03719313
STU-2019-0768
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Inclusion Criteria:
1. Chronic HDV infection for at least 6 months in duration, documented by a positive HDV
antibody test and HDV RNA ≥ 500 IU/mL.
Note: All genotypes of HDV permitted.
2. Demonstrable suppression of HBV DNA following at least 12 weeks of anti-HBV
nucleos(t)ide treatment with entecavir or tenofovir prior to initiating therapy.
3. Serum ALT > 1.3 x upper limit of the normal range (ULN) and < 10 x ULN.
4. Baseline liver biopsy demonstrating evidence of chronic hepatitis.
5. ECGs demonstrating no acute ischemia or clinically significant abnormality.
6. Normal dilated retinal examination.
Exclusion Criteria:
General Exclusions
1. Previous use of LNF within 12 months.
2. Current or previous history of decompensated liver disease.
3. Co-infected with human immunodeficiency virus or hepatitis C virus (HCV) by detectable
HIV RNA and HCV RNA, respectively.
4. Evidence of significant portal hypertension.
5. Current evidence or history of ascites requiring diuretics or paracentesis, or hepatic
encephalopathy.
6. History of hepatocellular carcinoma.
7. Patients with any of the following:
• Current eating disorder
• Evidence of alcohol substance use disorder.
• Drug abuse within the previous 6 months before screening.
8. Prior history or current evidence of any of the following:
• Immunologically mediated disease,
• Retinal disorder or clinically relevant ophthalmic disorder,
• Any malignancy within 5 years before screening,
• Cardiomyopathy or significant ischemic cardiac or cerebrovascular disease,
• Chronic pulmonary disease,
• Pancreatitis or colitis,
• Severe or uncontrolled psychiatric disorder.
9. Other significant medical condition that may require intervention during the study.
10. Any condition that may impact proper absorption.
11. Therapy with an immunomodulatory agent, IFN-α (eg, IFN alfa-2a or IFN-alfa-2b, or
pegylated IFN-alfa-2a or alfa 2b), cytotoxic agent, or chronic systemic
corticosteroids within 12 months of screening.
12. Use of heparin or warfarin.
13. Systemic antibiotics, antifungals, or antivirals for treatment of active infection
other than HBV.
14. Receipt of systemic immunosuppressive therapy.
15. History or evidence for any intolerance or hypersensitivity to LNF, RTV, PEG
IFN-alfa-2a, tenofovir or entecavir.
A Study to Evaluate the Efficacy and Safety of Maralixibat in Subjects With Progressive Familial Intrahepatic Cholestasis (MARCH-PFIC) (MARCH-PFIC)
The purpose of this study is to determine if the investigational treatment (maralixibat) is
safe and effective in pediatric participants with Progressive Familial Intrahepatic
Cholestasis (PFIC).
Call 214-648-5005 studyfinder@utsouthwestern.edu
Amal Aqul
103693
All
1 Year to 17 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03905330
STU-2019-0942
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Key
Inclusion Criteria:
• Informed consent and assent (as applicable) per Institutional Review Board/Ethics
Committee (IRB/EC)
• Male or female subjects with a body weight ≥ 5.0 kg, who are ≥ 12 months and < 18
years of age at time of baseline
• Cholestasis as manifested by total sBA ≥ 3× Upper Limit of Normal (ULN) (applies to
primary cohort only)
• Moderate Pruritus
• Diagnosis of PFIC based on:
• Chronic cholestasis as manifested by persistent (>6 months) pruritus, in addition
to biochemical abnormalities and/or pathological evidence of progressive liver
disease and
• Primary Cohort: Subjects with genetic testing results consistent with biallelic
disease-causing variation in ABCB11 (PFIC2), based on standard of care genotyping
• Supplemental Cohort: i. Subjects with genetic testing results consistent with
biallelic disease-causing variation in ATP8B1 (PFIC1), ABCB4 (PFIC3), or TJP2
(PFIC4), based on standard of care genotyping ii. Subjects with PFIC phenotype
without a known mutation or with another known mutation not described above or
with intermittent cholestasis as manifested by fluctuating sBA levelsiii.
Subjects with PFIC after internal or external biliary diversion surgery or for
whom internal or external biliary diversion surgery was reversed
Exclusion Criteria:
• Predicted complete absence of bile salt excretion pump (BSEP) function based on the
type of ABCB11 mutation (PFIC2), as determined by a standard of care genotyping
(applies to primary cohort only). Subjects can enter the study in the Supplemental
Cohort (under inclusion criteria 6.ii or 6.iii).
• Recurrent intrahepatic cholestasis, indicated by a history of sBA levels <3x ULN or
intermittent pruritus (applies to primary cohort only)
• Current or recent history (<1 year) of atopic dermatitis or other non-cholestatic
diseases associated with pruritus
• History of surgical disruption of the enterohepatic circulation (applies to primary
cohort only)
• Chronic diarrhea requiring intravenous fluid or nutritional intervention for the
diarrhea and/or its sequelae at screening or during the 6 months prior to screening
• Previous or need for imminent liver transplant
• Decompensated cirrhosis (international normalized ratio [INR] > 1.5, and/or albumin <
30 g/L, history or presence of clinically significant ascites, and/or variceal
hemorrhage, and/or encephalopathy)
• Alanine aminotransferase (ALT) or total serum bilirubin (TSB) > 15× ULN at screening
• Presence of other liver disease
• Presence of any other disease or condition known to interfere with the absorption,
distribution, metabolism or excretion of drugs, including bile salt metabolism in the
intestine (e.g., inflammatory bowel disease), per Investigator discretion
• Possibly malignant liver mass on imaging, including screening ultrasound
• Known diagnosis of human immunodeficiency virus (HIV) infection
• Any prior cancer diagnosis (except for in situ carcinoma) within 5 years of the
screening visit (Visit 0)
• Any known history of alcohol or substance abuse
• Administration of bile acids or lipid binding resins, or phenylbutyrate during the
screening period
• Administration of any investigational drug, biologic, or medical device during the
screening period
• Previous use of an ileal bile acid transporter inhibitor (IBATi)
• History of non-adherence to medical regimens, unreliability, medical condition, mental
instability or cognitive impairment that, in the opinion of the Investigator or
Sponsor medical monitor, could compromise the validity of informed consent, compromise
the safety of the subject, or lead to nonadherence with the study protocol or
inability to conduct the study procedures.
Testing the Combination of Pevonedistat With Chemotherapy for Bile Duct Cancer of the Liver
This phase II trial studies how well pevonedistat alone or in combination with chemotherapy
(paclitaxel and carboplatin) works in treating patients with bile duct cancer of the liver.
Pevonedistat may stop the growth of tumor cells by blocking some of the enzymes needed for
cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in
different ways to stop the growth of tumor cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. This study may help the study doctors
find out how well pevonedistat shrinks bile duct cancer of the liver when given alone and
when in combination with paclitaxel and carboplatin.
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Patient must have a life expectancy >= 12 weeks
• Patient must have histologically confirmed intrahepatic cholangiocarcinoma or biphasic
hepatocellular carcinoma and cholangiocarcinoma that is metastatic or unresectable and
who have progressed on or been intolerant of one prior line of systemic gemcitabine
containing chemotherapy regimen.
• NOTE: Prior immunotherapy or targeted therapies are allowed and will not be
considered a line of therapy unless administered with cytotoxic chemotherapy
• Patient must have measurable disease. For patients who have received localized therapy
(embolization, chemoembolization, radiofrequency ablation or radiation) are eligible
if measurable disease is not within the treatment field or the treated disease has
clearly progressed since last localized therapy
• Leukocytes >= 3,000/mcL (obtained within 14 days prior to randomization)
• Absolute neutrophil count >= 1,500/mcL (obtained within 14 days prior to
randomization)
• Platelets >= 100,000/mcL (obtained within 14 days prior to randomization)
• Total bilirubin =< institutional upper limit of normal (ULN) except in patients with
Gilbert's syndrome. Patients with Gilbert's syndrome may enroll if direct bilirubin =<
1.5 x ULN of the direct bilirubin (obtained within 14 days prior to randomization)
• Hemoglobin >= 9 g/dL (obtained within 14 days prior to randomization)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional ULN (obtained within 14 days prior to randomization)
• Creatinine =< institutional ULN, OR glomerular filtration rate (GFR) >= 40 mL/min/1.73
m^2 (obtained within 14 days prior to randomization)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial.
Known HIV positive patients who meet the following criteria will be considered
eligible:
• CD4 count >= 350 cells/mm^3
• Undetectable viral load
• Maintained on modern therapeutic regimens utilizing non-CYP interactive agents
(i.e. excluding ritonavir)
• No history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic
infections
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
• Patients who received prior platinum or taxane chemotherapy are eligible
• Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better. In addition, patients
with any of the known cardiopulmonary disease, defined as follows, would be ineligible
for this trial:
• Unstable angina
• Congestive heart failure (New York Heart Association [NYHA] class III or IV;);
• Myocardial infarction within 6 months prior to randomization (patients who had
ischemic heart disease such as acute coronary syndrome [ACS], myocardial
infarction, and/or revascularization greater than 6 months before randomization
and who are without cardiac symptoms may enroll)
• Symptomatic cardiomyopathy
• Clinically symptomatic pulmonary hypertension requiring pharmacologic therapy
• Clinically significant arrhythmia, defined as:
• History of polymorphic ventricular fibrillation or torsade de pointes,
• Permanent atrial fibrillation, defined as continuous atrial fibrillation for
>= 6 months,
• Persistent atrial fibrillation, defined as sustained atrial fibrillation
lasting > 7 days and/or requiring cardioversion in the 4 weeks before
randomization,
• Grade 3 atrial fibrillation defined as symptomatic and incompletely
controlled medically, or controlled with device (e.g., pacemaker), or
ablation
• Patients with paroxysmal atrial fibrillation or grade < 3 atrial
fibrillation for period of at least 6 months are permitted to enroll
provided that their rate is controlled on a stable regimen
• Patients must have the ability to understand and the willingness to sign a written
informed consent document
• Participants with impaired decision-making capacity (IDMC) who have a legally
authorized representative (LAR) or caregiver and/or family member available will also
be considered eligible
Exclusion Criteria:
• Patients must not have had major surgery within 14 days before randomization. Patients
with surgery planned during study period are ineligible
• Women must not be pregnant or breast-feeding due to the potential harm to an unborn
fetus and possible risk for adverse events in nursing infants with the treatment
regimens being used. Patients must also not expect to conceive or father children from
the time of registration, while on study treatment, and until at least 4 months after
the last dose of study treatment. All females of childbearing potential must have a
blood test or urine study within 14 days prior to randomization to rule out pregnancy.
A female of childbearing potential is any woman, regardless of sexual orientation or
whether they have undergone tubal ligation, who meets the following criteria: 1) has
achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral
oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer
therapy does not rule out childbearing potential) for at least 24 consecutive months
(i.e., has had menses at any time in the preceding 24 consecutive months)
• Women of childbearing potential and sexually active males must not expect to conceive
or father children by using accepted and effective method(s) of contraception or by
abstaining from sexual intercourse for the duration of their participation in the
study and continue for at least 4 months after the last dose of protocol treatment
• Male patients must not donate sperm during the course of this study or within 4 months
after receiving their last dose of protocol treatment
• Female patients must not donate eggs (ova) during the course of this study or within 4
months after receiving their last dose of protocol treatment
• Patient must not have a prolonged rate corrected QT (QTc) interval >= 480 msec
calculated according to institutional guideline
• Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e. have residual toxicities > grade 1) are ineligible with the exception of
alopecia
• Patients with persistent >= grade 2 diarrhea lasting more than 3 days within 14 weeks
of randomization are ineligible
• Patients with known central nervous system (CNS) involvement are ineligible
• Patients must not be receiving any other investigational agents
• Patients must not have received chemotherapy or radiotherapy within 2 weeks prior to
randomization. Prior treatment with radiation therapy involving >= 25% of
hematopoietically active bone marrow will be ineligible
• Patients must not have received immunotherapy within 8 weeks prior to randomization
• Patients must not have a history of allergic reactions attributed to compounds of
similar chemical or biologic composition to pevonedistat, carboplatin, or paclitaxel
• Patient must not be receiving any treatment with clinically significant metabolic
enzyme inducers within 14 days before the first dose of the study drug as below.
Clinically significant metabolic enzyme inducers are not permitted during the study.
Patients must not be receiving any medications or substances that are strong inducers
of CYP3A4/5 (i.e. phenytoin, rifampin, St. Johns wort) or inhibitors of breast cancer
resistance protein (BCRP) (i.e. cyclosporine). Because the lists of these agents are
constantly changing, it is important to regularly consult a frequently-updated medical
reference. As part of enrollment/informed consent procedures, the patient will be
counseled on the risk of interactions with other agents, and what to do if a new
medication need to be prescribed or if the patient is considering a new
over-the-counter medicine or herbal product. Inhibitors of CYP3A4/5 are allowed
• Patients must not have uncontrolled intercurrent illness
• Patients must not have uncontrolled coagulopathy or bleeding disorder
• Patients must not have active, uncontrolled infection or severe infectious disease
such as severe pneumonia, meningitis, or septicemia
• Patients with known moderate chronic obstructive pulmonary disease, interstitial lung
disease, and pulmonary fibrosis are ineligible
• Patients must not have psychiatric illness/social situations that would limit
compliance with study requirements
• Participants must not have had prior pevonedistat treatment
Lower-Dose Chemoradiation in Treating Patients With Early-Stage Anal Cancer, the DECREASE Study
This phase II trial studies how well lower-dose chemotherapy plus radiation (chemoradiation)
therapy works in comparison to standard-dose chemoradiation in treating patients with
early-stage anal cancer. Drugs used in chemotherapy, such as mitomycin, fluorouracil, and
capecitabine, work in different ways to stop the growth of tumor cells, either by killing the
cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy
uses high-energy x-rays to kill tumor cells and shrink tumors. Giving chemotherapy with
radiation therapy may kill more tumor cells. This study may help doctors find out if
lower-dose chemoradiation is as effective and has fewer side effects than standard-dose
chemoradiation, which is the usual approach for treatment of this cancer type.
• Patient must have histologically proven T1-2N0M0 invasive anal canal or anal margin
squamous cell carcinoma with tumors measuring =< 4 cm within 4 weeks prior to
randomization. This may include tumors of non-keratinizing histology such as basaloid,
transitional cell or cloacogenic histology. Patients with T1N0M0 anal margin squamous
cell carcinoma who underwent surgical excision with negative margins are not eligible
• Patients who are human immunodeficiency virus (HIV)-negative must not have lymph nodes
that are radiographically-concerning for cancer involvement using computed tomography
(CT) and positron emission tomography (PET)/CT-based criteria. Measurable disease is
not required
• Patients who are HIV-negative and do not have lymph nodes classified as lymph
node positive, but are felt to be borderline for cancer involvement must undergo
central imaging review
• NOTE: Patients requiring central imaging review will be pre-registered to
Arm S. Upon central confirmation of no lymph node involvement, eligible
patients may proceed to randomization on Step 1
• Patients will be considered to be lymph node (LN) positive and thereby not
eligible in this study if the lymph nodes meet any of the following criteria:
• Mesorectal, presacral, internal iliac or obturator LN with:
• Short axis measuring > 5 mm based on CT / magnetic resonance imaging
(MRI) OR
• Morphologic features of irregular border or central necrosis if
assessed on MRI and LN measures > 3 mm OR
• Fludeoxyglucose F-18 (FDG) uptake > blood pool (Deauville 3-5) based on
PET/CT
• External Iliac and common Iliac:
• Short-axis measuring > 1 cm based on CT / MRI OR
• Morphologic features of irregular border or central necrosis based on
CT / MRI OR
• FDG uptake > blood pool (Deauville 3-5) based on PET/CT
• Inguinal LN (superficial and deep) meeting any of the following criteria will be
ineligible unless an FNA is performed and resulting cytology is negative.
• Morphologic features of irregular border or central necrosis based on CT /
MRI
• FDG uptake > liver (Deauville 4) based on PET/CT.
• Patients who are HIV-negative and have inguinal lymph nodes that do not meet
the above criteria must undergo fine needle aspiration and have negative
histology to be eligible.
• Patients who are HIV-positive must have
• A CD4 count >= 300
• Confirmation of no lymph node involvement by central real-time review of imaging
• NOTE: Patients will be pre-registered to Arm S. Upon central confirmation of
no lymph node involvement, eligible patients may proceed to randomization on
Step 1
• Patient must have Eastern Cooperative Oncology Group (ECOG) •American College of
Radiology Imaging Network (ACRIN) performance status of 0-2
• Patient must have no history of prior radiation or chemotherapy for this malignancy
• Patient must not have had prior potentially curative surgery (i.e. abdominal-perineal
resection) for carcinoma of the anus
• Patients with excisional biopsy procedure are eligible provided there was tumor
involvement of the anal canal and/or anal verge prior to resection
• Patient must not be receiving any other standard anti-cancer therapy or experimental
agent concurrently with the study drugs
• Patient must not have intercurrent illness including, but not limited to, ongoing or
active infection or psychiatric/social situations that, in the judgement of the
investigator, would limit compliance with study requirements
• Patient must not have had significant cardiovascular disease including myocardial
infarction, unstable angina, stroke, transient ischemic attack, symptomatic coronary
artery disease, symptomatic congestive heart failure, or uncontrolled cardiac
arrhythmia within 6 months of randomization
• Patient must not have a history of a different malignancy unless they have been
disease-free for at least 2 years and are deemed by the investigator to be at low risk
of recurrence
• Individuals with the following cancers are eligible if diagnosed and treated
within the past 5 years: cervical cancer in situ and basal cell or squamous cell
carcinoma of the skin
• Patient must not have active autoimmune or connective disease
• Patients who are on anti-coagulation with warfarin within 2 weeks prior to
registration and are considering the use of capecitabine, must use an alternative
anti-coagulant
• NOTE: Low molecular weight heparin is permitted provided the patient's
prothrombin time (PT)/international normalized ratio (INR) is < 1.5
• Patients who will receive capecitabine and are on Dilantin for a seizure disorder must
have Dilantin levels checked weekly
• Hemoglobin > 10 g/dL (within 2 weeks prior to registration)
• Platelets >= 100,000/mm^3 (within 2 weeks prior to registration)
• Absolute neutrophil count >= 1500/mm^3 (within 2 weeks prior to registration)
• Serum creatinine must be < 1.5 X upper limit of normal (ULN), or calculated creatinine
clearance must be > 60 ml/min (within 2 weeks prior to registration)
• Total bilirubin must be < 2 X ULN (within 2 weeks prior to registration)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 X institutional
ULN (within 2 weeks prior to registration)
• Albumin >= 3.0 g/dL (within 2 weeks prior to registration)
• Women must not be pregnant or breast-feeding because the study treatment administered
may cause harm to an unborn fetus or breastfeeding child. All females of childbearing
potential must have a blood test or urine study within 2 weeks prior to registration
to rule out pregnancy. A female of childbearing potential is any woman, regardless of
sexual orientation or whether they have undergone tubal ligation, who meets the
following criteria: 1) has achieved menarche at some point, 2) has not undergone a
hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal
(amenorrhea following cancer therapy does not rule out childbearing potential) for at
least 24 consecutive months (i.e., has had menses at any time in the preceding 24
consecutive months)
• Women of childbearing potential and sexually active males must be strongly advised to
use accepted and effective method(s) of contraception or to abstain from sexual
intercourse for the duration of their participation in the study and for at least 6
months after the completion of treatment
Comparing Two Treatment Combinations, Gemcitabine and Nab-Paclitaxel With 5-Fluorouracil, Leucovorin, and Liposomal Irinotecan for Older Patients With Pancreatic Cancer That Has Spread
This phase II trial compares two treatment combinations: gemcitabine hydrochloride and
nab-paclitaxel, or fluorouracil, leucovorin calcium, and liposomal irinotecan in older
patients with pancreatic cancer that has spread to other places in the body (metastatic).
Drugs used in chemotherapy, such as gemcitabine hydrochloride, nab-paclitaxel, fluorouracil,
leucovorin calcium, and liposomal irinotecan, work in different ways to stop the growth of
tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them
from spreading. This study may help doctors find out which treatment combination is better at
prolonging life in older patients with metastatic pancreatic cancer.
• Newly diagnosed untreated metastatic adenocarcinoma of the pancreas. However, previous
surgery, adjuvant chemotherapy and/or radiation therapy will be allowed, provided
radiation therapy is completed at least 2 weeks prior to registration and adjuvant
therapy was administered more than 6 months prior to registration. Patients with the
following histology are excluded: acinar cell; adenosquamous carcinoma
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Patient is an English speaker with the ability to understand and complete the informed
consent and questionnaires
• Leukocytes >= 3,000/mcL (obtained within 4 weeks of registration)
• Absolute neutrophil count >= 1,500/mcL (obtained within 4 weeks of registration)
• Platelets >= 100,000/mcL (obtained within 4 weeks of registration)
• Total bilirubin =< institutional upper limit of normal (ULN) (obtained within 4 weeks
of registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional ULN (obtained within 4 weeks of registration)
• Creatinine =< institutional ULN unless data exists supporting safe use at lower kidney
function values, no lower than 30 mL/min/1.73 m^2 (obtained within 4 weeks of
registration)
• Glomerular filtration rate (GFR) >= 40 mL/min/1.73 m^2 unless data exists supporting
safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2 (obtained
within 4 weeks of 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 protocol. HIV positive (+) patients who are on ritonavir or/and cobicistat-based
regimen must be switched to alternative anti-retroviral therapy (ART)
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
• Male patients must agree not to father children while on study
• Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association functional classification. To be
eligible for this protocol, patients should be class 2B or better
• Patients must have measurable disease and scans must be done within 4 weeks of
registration
• Patients classified to have mild-moderate abnormalities in any of the domains
evaluated in the screening geriatric assessment and are classified as "vulnerable" are
eligible. Patients classified without any abnormalities ("fit") or with severe
cognitive/functional impairment or high co-morbidity score ("frail") on the screening
geriatric assessment are ineligible
• Patients must agree not to take any medications or substances that are strong
inhibitors or inducers of CYP3A4. Those who are randomized to liposomal irinotecan
treatment arm should avoid drugs that are UGT1A1 inhibitors
Phase 4 Study of Obeticholic Acid Evaluating Clinical Outcomes in Patients With Primary Biliary Cholangitis (COBALT)
Primary Biliary Cholangitis (PBC) is a serious, life-threatening, bile acid related liver
disease of unknown cause. Without treatment, it frequently progresses to liver fibrosis and
eventual cirrhosis requiring liver transplantation or resulting in death. The investigational
drug, Obeticholic Acid (OCA) is a modified bile acid and FXR agonist that is derived from the
primary human bile acid chenodeoxycholic acid. The key mechanisms of action of OCA, including
its choleretic, anti-inflammatory, and anti-fibrotic properties, underlie its
hepatoprotective effects and result in attenuation of injury and improved liver function in a
cholestatic liver disease such as PBC. The study will assess the effect of OCA compared to
placebo, combined with stable standard care, on clinical outcomes in PBC patients.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Marlyn Mayo
14698
All
18 Years and over
Phase 4
This study is NOT accepting healthy volunteers
NCT02308111
STU 012015-021
Show full eligibility criteria
Hide eligibility criteria
Key
Inclusion Criteria:
1. Definite or probable PBC diagnosis (consistent with American Association for the Study
of Liver Diseases [AASLD] and the European Association for the Study of the Liver
[EASL] practice guidelines; Lindor 2009; EASL 2009), as demonstrated by the presence
of ≥2 of the following 3 diagnostic factors:
• History of elevated Alkaline phosphatase levels for at least 6 months
• Positive antimitochondrial antibody (AMA) titer or if AMA negative or in low
titer (<1:80) PBC-specific antibodies (anti-GP210 and/or anti-SP100 and/or
antibodies against the major M2 components [PDC-E2, 2-oxo-glutaric acid
dehydrogenase complex])
• Liver biopsy consistent with PBC
2. A mean total bilirubin >ULN and ≤5x ULN and/or a mean ALP >3x ULN
3. Either is not taking UDCA (no UDCA dose in the past 3 months) or has been taking UDCA
for at least 12 months with a stable dose for ≥3 months prior to Day 0
Exclusion Criteria:
1. History or presence of other concomitant liver diseases including:
• Hepatitis C virus infection
• Active Hepatitis B infection; however, subjects who have seroconverted (hepatitis
B surface antigen and hepatitis B e antigen negative) may be included in this
study after consultation with the medical monitor
• Primary sclerosing cholangitis (PSC)
• Alcoholic liver disease
• Definite autoimmune liver disease or overlap hepatitis
• Nonalcoholic steatohepatitis (NASH)
• Gilbert's Syndrome
2. Presence of clinical complications of PBC or clinically significant hepatic
decompensation, including:
• History of liver transplant, current placement on a liver transplant list, or
current Model of End Stage Liver Disease (MELD) score >12. Subjects who are
placed on a transplant list despite a relatively early disease stage (for example
per regional guidelines) may be eligible as long as they do not meet any of the
other exclusion criteria
• Cirrhosis with complications, including history (within the past 12 months) or
presence of:
• Variceal bleed
• Uncontrolled ascites
• Encephalopathy
• Spontaneous bacterial peritonitis
• Known or suspected HCC
• Prior transjugular intrahepatic portosystemic shunt procedure
• Hepatorenal syndrome (type I or II) or screening (Visit 1 or 2) serum creatinine
>2 mg/dL (178 μmol/L)
3. Mean total bilirubin >5x ULN
4. Subjects who have undergone gastric bypass procedures (gastric lap band is acceptable)
or ileal resection or plan to undergo either of these procedures
5. Other medical conditions that may diminish life expectancy, including known cancers
(except carcinomas in situ or other stable, relatively benign conditions)
6. If female: plans to become pregnant, known pregnancy or a positive urine pregnancy
test (confirmed by a positive serum pregnancy test), or lactating
7. Known history of human immunodeficiency virus infection
8. Medical conditions that may cause nonhepatic increases in ALP (eg, Paget's disease or
fractures within 3 months)
9. Other clinically significant medical conditions that are not well controlled or for
which medication needs are anticipated to change during the study
10. History of alcohol abuse or other substance abuse within 1 year prior to Day 0
11. Participation in another investigational product, biologic, or medical device study
within 30 days prior to Screening. Participation in a previous study of OCA is allowed
with 3 months washout prior to enrollment in this study
12. Mental instability or incompetence, such that the validity of informed consent or
ability to be compliant with the study is uncertain
13. History of known or suspected clinically significant hypersensitivity to OCA or any of
its components
14. UDCA naïve (unless contraindicated)
Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric Solid Tumors, Including Central Nervous System Tumors
Phase 1 of this study, utilizing a rolling 6 design, will be conducted to determine a maximum
tolerated dose (MTD) and recommended Phase 2 dose (RP2D), and to describe the toxicities of
lenvatinib administered in combination with everolimus once daily to pediatric participants
with recurrent/refractory solid tumors. Phase 2, utilizing Simon's optimal 2-stage design,
will be conducted to estimate the antitumor activity of lenvatinib in combination with
everolimus in pediatric participants with selected recurrent/refractory solid tumors
including Ewing sarcoma/peripheral primitive neuroectodermal tumor (pPNET), rhabdomyosarcoma,
and high grade glioma (HGG) using objective response rate (ORR) at Week 16 as the outcome
measure.
Inclusion Criteria
• ≥2 years and <18 years of age for enrolment in Phase 1 or ≥2 years and ≤21 years of
age for enrolment in Phase 2.
• Recurrent or refractory solid tumors
• Phase 1: All solid tumors (measurable or evaluable disease), including primary
central nervous system (CNS) tumors; exclusion of hepatoblastoma and lymphomas.
Participants with diffuse intrinsic pontine glioma, optic pathway glioma, or
pineal tumors with elevated tumor markers (alpha-fetoprotein [AFP] and beta-human
chorionic gonadotropin [ß-hCG][or human chorionic gonadotropin [hCG])do not
require histological or cytological confirmation of diagnosis
• Phase 2: Ewing sarcoma/peripheral primitive neuroectodermal tumor (pPNET),
Rhabdomyosarcoma, High Grade Glioma (HGG) (all must have measurable disease);
exclusion of Diffuse Intrinsic Pontine Glioma
• Histologically or cytologically confirmed diagnosis
• Measurable disease that meets the following criteria (Phase 2):
1. RECIST 1.1 (for all tumor types except HGG): At least 1 lesion of ≥1.0 cm in the
longest diameter for a non lymph node or ≥1.5 cm in the short-axis diameter for a
lymph node which is serially measurable according to RECIST 1.1 using computed
tomography /magnetic resonance imaging (CT/MRI)
2. Response Assessment in Neuro-Oncology (RANO) for high grade glioma (HGG): At
least one lesion must be measurable as defined as a bi dimensionally contrast
enhancing lesion with clearly defined margins by CT or MRI scan, with a minimal
diameter of 1 cm, and visible on 2 axial slices which are preferably at most 5 mm
apart with 0 mm skip
Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as
radiofrequency (RF) ablation must show evidence of progressive disease based on RECIST 1.1
to be deemed a target lesion
• Karnofsky performance score ≥50 for participants>16 year of age and Lansky play score
≥50 for participants ≤16 years of age. Neurologic deficits in participants with CNS
tumors must have been relatively stable for at least 7 days prior to study enrollment.
Participants 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
• Prior Therapy
• Participants must have fully recovered from the acute toxic effects of all prior
anti-cancer therapy
• Cytotoxic chemotherapy or other chemotherapy known to be myelosuppressive: ≥21
days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days
if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (eg, not associated with
reduced platelet or absolute neutrophil counts): ≥7 days after the last dose of
agent
• Monoclonal antibodies: ≥21 days or 3 half-lives (whichever is shorter) of the
antibody must have elapsed after the last dose of a monoclonal antibody
(including checkpoint inhibitors). Toxicity related to prior antibody therapy
must be recovered to Grade ≤1
• Corticosteroids: If used to modify immune adverse events related to prior
therapy, ≥14 days must have elapsed since last dose of corticosteroid.
Participants receiving corticosteroids, who have not been on a stable or
decreasing dose of corticosteroid for at least 7 days prior to enrollment, are
not eligible
• Hematopoietic growth factors: ≥14 days after the last dose of a long-acting
growth factor 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, interferons or cytokines
(other than hematopoietic growth factors)
• Stem cell infusions (with or without total body irradiation): Allogeneic
(non-autologous) bone marrow or stem cell transplant, or any stem cell infusion
including donor leukocytes infusion or boost infusion: ≥84 days after infusion
and no evidence of graft versus host disease; Autologous stem cell infusion
including boost infusion: ≥42 days
• Cellular Therapy: ≥42 days after the completion of any type of cellular therapy
(eg, modified T cells, natural killer cells, dendritic cells, etc)
• Radiotherapy (XRT)/External Beam Irradiation including Protons: ≥14 days after
local XRT; ≥150 days after total body irradiation, craniospinal XRT or if
radiation to ≥50% of the pelvis; ≥42 days if other substantial bone marrow
radiation.
• Radiopharmaceutical therapy: ≥42 days after systemically administered therapy.
• Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-targeted or
mammalian target of rapamycin (mTOR)-targeted therapies: Must not have received
prior exposure to lenvatinib; May have previously progressed on an mTOR
inhibitor; No more than 2 prior VEGF/VEGFR-targeted therapies (For Phase 2 only);
Must not have received prior VEGF/VEGFR-targeted therapy in combination with an
mTOR inhibitor (For Phase 2 only)
• Adequate bone marrow function for participants with solid tumors without known bone
marrow involvement
• Adequate bone marrow function for participants with known bone marrow metastatic
disease
• Adequate renal function
• Adequate liver function
• Adequate cardiac function
• Adequate neurologic function
• Adequate blood pressure (BP) control with or without antihypertensive medications
• Adequate coagulation
• Adequate pancreatic function
• Adequate metabolic function
• Adequate glycemic control
• Participants must have a minimum body surface area (BSA) of 0.6 m^2 at study entry.
Exclusion Criteria
• Participants who have had or are planning to have the following invasive procedures
• Major surgical procedure, laparoscopic procedure, open biopsy or significant
traumatic injury within 28 days prior to enrolment
• Central line placement or subcutaneous port placement is not considered major
surgery. External central lines must be placed at least 3 days prior to
enrollment and subcutaneous ports must be placed at least 7 days prior to
enrollment
• Fine needle aspirate within 7 days prior to enrolment
• Surgical or other wounds must be adequately healed prior to enrolment
• For purposes of this study, bone marrow aspirate and biopsy are not considered
surgical procedures and therefore are permitted within 14 days prior to start of
protocol therapy
• Participants who have non-healing wound, unhealed or incompletely healed fracture, or
a compound (open) bone fracture at the time of enrolment
• Participants having an active infection requiring systemic therapy.
• Participants with a known history of active hepatitis B (defined as hepatitis B
surface antigen reactive or hepatitis B virus- deoxyribonucleic [DNA] detected) or
known active hepatitis C virus (HCV, defined as HCV- Ribonucleic acid [RNA] detected).
Note: No testing for hepatitis B and hepatitis C is required unless mandated by the
local health authority.
• Known to be human immunodeficiency virus (HIV) positive. Note: HIV testing is required
at screening only when mandated by the local health authority
• Clinical evidence of nephrotic syndrome prior to enrolment
• Gastrointestinal bleeding or active hemoptysis (bright red blood of at least half
teaspoon) within 21 days prior to enrolment
• Thrombotic/ thromboembolic event requiring systemic anticoagulation within 90 days
prior to enrollment
• Evidence of new intracranial hemorrhage of more than punctate size on MRI assessment
obtained within 28 days prior to study enrollment for Participants with HGG
• Diagnosis of lymphoma
• Radiographic evidence of major blood vessel invasion/infiltration.
• Evidence of untreated CNS metastases (exception: participants with primary CNS tumors
and leptomeningeal disease)
• Participants who are currently receiving enzyme-inducing anticonvulsants
• Participants chronically receiving strong cytochrome P450 3A4 (CYP3A4)/P-glycoprotein
(P-gp) inhibitors or inducers within 7 days prior to study enrollment
• Females who are breastfeeding or pregnant. For females of childbearing potential, a
negative screening pregnancy test must be obtained within 72 hours before the first
dose of study drug
Drug: Lenvatinib, Drug: Everolimus
Sarcoma, Recurrent and Refractory Solid Tumors, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Kaposis sarcoma, Small Intestine, Soft Tissue
pediatrics, central nervous system tumors, lenvatinib, E7080, everolimus, Ewing sarcoma/peripheral primitive neuroectodermal tumor, rhabdomyosarcoma, high grade glioma, solid tumors
Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
This Pediatric MATCH screening and multi-sub-study phase II trial studies how well treatment
that is directed by genetic testing works in pediatric patients with solid tumors,
non-Hodgkin lymphomas, or histiocytic disorders that have progressed following at least one
line of standard systemic therapy and/or for which no standard treatment exists that has been
shown to prolong survival. Genetic tests look at the unique genetic material (genes) of
patients' tumor cells. Patients with genetic changes or abnormalities (mutations) may benefit
more from treatment which targets their tumor's particular genetic mutation, and may help
doctors plan better treatment for patients with solid tumors or non-Hodgkin lymphomas.
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients with recurrent or
refractory solid tumors, including non-Hodgkin lymphomas, histiocytoses (e.g.
langerhans cell histiocytosis [LCH], juvenile xanthogranuloma [JXG], histiocytic
sarcoma), and central nervous system (CNS) tumors are eligible; patients must have had
histologic verification of malignancy at original diagnosis or relapse except in
patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with
pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers
including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); in cases where
patient enrolls prior to histologic confirmation of recurrent disease, patient is
ineligible and should be withdrawn from study if histology fails to confirm
recurrence; please note: Patients with Hodgkin lymphoma and plexiform neurofibroma are
not eligible
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must have an
formalin-fixed paraffin-embedded (FFPE) tumor sample available for MATCH study testing
from a biopsy or surgery that was performed at any point after initial tumor
recurrence/progression, or be planned to have a procedure to obtain such a sample that
is considered to be of potential benefit by the treating clinicians; a tumor sample
from a clinically performed diagnostic (pre-treatment) biopsy will be acceptable for
enrollment onto Pediatric MATCH only for children with high-grade gliomas of the
brainstem (diffuse intrinsic pontine gliomas) or thalamus
• Please note: Samples that have been decalcified using standardly utilized
acid-based decalcification methods are not generally suitable for MATCH study
testing; the nucleic acids will have been degraded in the decalcification process
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Karnofsky >= 50% for patients >
16 years of age and Lansky >= 50 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
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must have
radiographically measurable disease; measurable disease based on imaging obtained less
than or equal to 56 days prior to enrollment; patients with neuroblastoma who do not
have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable
disease are eligible; measurable disease in patients with central nervous system (CNS)
involvement is defined as tumor that is measurable in two perpendicular diameters on
magnetic resonance imaging (MRI) and visible on more than one slice
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: NOTE: patient does not need to meet all
subprotocol criteria at time of enrollment onto the APEC1621SC screening protocol, but
will need to meet all criteria prior to enrollment on any assigned treatment
subprotocol. Patients must be enrolled onto a subprotocol within 8 weeks (56 days) of
treatment assignment
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Karnofsky >= 50% for patients > 16 years
of age and Lansky >= 50 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
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of treatment with subprotocol
specified therapy, the patients must have radiographically measurable disease;
patients with neuroblastoma who do not have measurable disease but have MIBG+
evaluable are eligible; measurable disease in patients with CNS involvement is defined
as tumor that is measurable in two perpendicular diameters on MRI and visible on more
than one slice
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
RECIST 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of enrollment onto a
subprotocol, the following general criteria for initiation of therapy will be
required:
• Patients must have fully recovered from the acute toxic effects of all prior
anticancer therapy and must meet the following minimum duration from prior
anticancer directed therapy prior to enrollment to the subprotocol; 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 anticancer agents known to be
myelosuppressive: 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 cytotoxic
or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anticancer agents not known to be myelosuppressive (e.g. not associated with
reduced platelet or absolute neutrophil counts [ANC]): >= 7 days after the
last dose of agent; 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
• Corticosteroids: If used to modify immune adverse events related to prior
therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a
long-acting growth factor (e.g. Neulasta) 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; the duration of this interval must
be discussed with the study chair and the study-assigned research
coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth
factors): >= 21 days after the completion of interleukins, interferon or
cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total-body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any
stem cell infusion including donor lymphocyte infusion (DLI) or boost
infusion: >= 84 days after infusion and no evidence of graft versus
host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular
therapy (e.g. modified T cells, NK cells, dendritic cells, etc.)
• X-ray therapy (XRT)/External Beam Irradiation including Protons: >= 14 days
after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to
>= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM)
radiation; note: radiation may not be delivered to "measurable disease"
tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42
days after systemically administered radiopharmaceutical therapy
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: For patients with solid tumors without
known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients with known bone marrow
metastatic disease will be eligible for study provided they meet the blood counts (may
receive transfusions provided they are not known to be refractory to red cell or
platelet transfusions); these patients will not be evaluable for hematologic toxicity
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Creatinine clearance or radioisotope
glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on
age/gender as follows:
• Age: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6
• Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
• Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Bilirubin (sum of conjugated +
unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Serum glutamate pyruvate transaminase
(SGPT) (alanine transferase [ALT]) =< 135 U/L (for the purpose of this study, the ULN
for SGPT is 45 U/L)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients must be able to swallow intact
capsules/tablets, unless otherwise specified in the subprotocol to which they are
assigned
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Agent specific limitations on prior
therapy will be included with specific treatment subprotocols
Exclusion Criteria:
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: 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 currently no available information
regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in
females who are post-menarchal; males or females of reproductive potential may not
participate unless they have agreed to use an effective contraceptive method
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Concomitant medications
• Corticosteroids: at the time of consent and enrollment to regimen specific
subprotocols, patients receiving corticosteroids who have not been on a stable or
decreasing dose of corticosteroid for at least 7 days prior to enrollment to the
subprotocol will not be eligible; if used to modify immune adverse events related
to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients must meet criteria for prior therapy at the time
of consent and enrollment to a subprotocol; other investigational agents may not
be administered to patients while they are receiving study drug as part of a
subprotocol
• Anticancer agents: patients must meet criteria for prior therapy at the time of
consent and enrollment to a subprotocol; other investigational agents may not be
administered to patients while they are receiving study drug as part of a
subprotocol
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine,
tacrolimus or other agents to prevent graft-versus-host disease post bone marrow
transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have an uncontrolled
infection are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have had a prior solid organ
transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Additional agent specific criteria will
be included with specific treatment subprotocols
Nivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy (PROSPER)
This phase III trial compares nephrectomy (surgery to remove a kidney or part of a kidney)
with nivolumab to the usual approach of nephrectomy followed by standard post-operative
follow-up and monitoring, in treating patients with kidney cancer that is limited to a
certain part of the body (localized). Nivolumab is a drug that may help stimulate the immune
system to attack any cancer cells that may remain after surgery. The addition of nivolumab to
the usual surgery could prevent the cancer from returning. It is not yet known whether
nivolumab and nephrectomy is more effective than nephrectomy alone in treating patients with
kidney cancer.
• ELIGIBILITY CRITERIA FOR RANDOMIZATION:
• Patients must have a renal mass consistent with a clinical stage >= T2Nx renal cell
carcinoma (RCC) or TanyN+ RCC for which radical or partial nephrectomy is planned
• Patients must have no clinical or radiological evidence of distant metastases (M0)
unless the presumed M1 disease is planned to be resected/definitively treated (e.g.,
thermal ablation, stereotactic radiation) at the same time or within a 12 week window
from the date of the initial procedure such that the patient is considered "no
evidence of disease" (M1 NED)
• Liver, bone, or brain metastases are not permitted
• No more than 3 metastases are permitted and all must be able to be removed or
definitively treated within 12 weeks of the primary tumor resection
• If histological confirmation of RCC has not been done within 12 months prior to
randomization, patient must be willing to undergo a core biopsy for this purpose if
randomized to Arm A
• NOTE: This histologic confirmation can be a (1) standard of care diagnostic
biopsy or (2) a research biopsy or a planned metastasectomy. Tissue must be
obtained with results available prior to the neoadjuvant dose
• Patients randomized to Arm A: core tumor biopsy must have demonstrated RCC
of any histology, including sarcomatoid, unclassified, or "unknown
histology" (if preoperative biopsy was uninformative) with exception below
for non-diagnostic biopsies
• If the biopsy performed following randomization clearly demonstrates a
benign condition, oncocytoma or a different type of cancer that is not RCC,
the patient is not eligible and must come off study
• A non-diagnostic biopsy is considered a good faith effort and does not need
to be repeated unless deemed clinically necessary by the treating
investigator
• Patient must not have any prior systemic or local anti-cancer therapy for the current
RCC
• Patient must not have undergone a partial nephrectomy for the current RCC
• Patient must not have had a metastasectomy for the current RCC diagnosis unless
performed to render patient NED (in addition to the planned nephrectomy) within 6
months of the current diagnosis
• Patient must not have received current or past antineoplastic systemic therapies
for RCC: i.e., chemotherapy, hormonal therapy, immunotherapy, or standard or
investigational agents for treatment of RCC
• Patient must not have received prior treatment with an anti-PD-1, anti-PD-L1,
anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug
specifically targeting T-cell co-stimulation or checkpoint pathways
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0
or 1
• Patient must not have a prior history of RCC that was treated with curative intent
within the past 5 years
• Patients with a prior RCC that was treated > 5 years before, are eligible if the
current tumor is consistent with a new primary in the opinion of the treating
investigator
• Patients with bilateral synchronous RCCs are eligible if they can be resected or
definitively treated at the same time or within a 12 week window from time of
initial nephrectomy (partial or radical) or procedure and maintain adequate
residual renal function; the patient is not eligible if both kidneys are to be
completely removed and subsequent hemodialysis will be required
• Permitted forms of local therapy for second tumor:
• Partial or radical nephrectomy
• If kidney tumor is =< 3 cm: thermal ablation (e.g., radiofrequency
ablation, cryoablation or stereotactic radiosurgery)
• Patients cannot have concurrent malignancies, with the following exceptions:
• Adequately treated basal cell or squamous cell skin cancer
• In situ cervical cancer
• A history of superficial Ta urothelial cancer is permitted (as long as not
currently undergoing treatment) whereas T1 or greater disease is excluded if
< 3 years from diagnosis; concurrent persistent disease is not permitted
• Adequately treated stage I or II cancer from which the patient is currently
in complete remission
• Any other cancer and stage from which the patient has been disease-free for
at least 3 years prior to the time of randomization and as long as they are
not receiving any current treatment (e.g. adjuvant or maintenance systemic
or local therapy)
• Concurrent low risk prostate cancer on active surveillance
• Patient must not have active known or suspected autoimmune disease. The following
autoimmune disorders are permitted: patients with vitiligo, type I diabetes mellitus,
controlled/stable hypo or hyperthyroidism due to autoimmune or non-autoimmune
conditions (hormone replacement is allowed), psoriasis not requiring systemic
treatment, or other conditions not expected to recur
• Patient must not have any ongoing condition requiring systemic treatment with either
corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive
medications with the exceptions outlined below; patient must not have received any
treatment with other immunosuppressive agents within 14 days prior to the first dose
of study drug with the following exceptions:
• Topical, ocular, intra-articular, intranasal, inhaled steroids and adrenal
replacement steroid doses > 10 mg daily prednisone or the equivalent are
permitted in the absence of active autoimmune disease
• A brief (less than 3 weeks) course of corticosteroids (any amount) for
prophylaxis (for example: contrast dye allergy) or for treatment of
non-autoimmune conditions (for example: nausea, delayed-type hypersensitivity
reaction caused by a contact allergen) is permitted
• Patient must not have uncontrolled adrenal insufficiency
• Patient must not have known evidence of chronic active liver disease or evidence of
acute or chronic hepatitis B Virus (HBV) or hepatitis C (HCV); HBV and HCV testing
must be completed within 8 weeks prior to randomization
• NOTE: If the patient has been treated and cured, and the HCV ribonucleic acid
(RNA) is undetectable, the patient is eligible for this study
• Patient must not have any serious intercurrent illness, including ongoing or active
infection requiring parenteral antibiotics
• Patient must not have known evidence of human immunodeficiency virus (HIV) infection,
since the effects of nivolumab on anti-retroviral therapy have not been studied; HIV
testing is only required if past or current history is suspected
• Patient must not have any known medical condition (e.g. a condition associated with
uncontrolled diarrhea such as ulcerative colitis or acute diverticulitis) that, in the
investigator's opinion, would increase the risk associated with study participation or
interfere with the interpretation of safety results
• Patient must not have had any major surgery within 28 days prior to randomization
• Patient must not be currently enrolled in other clinical trials testing a therapeutic
intervention
• Patient must not have any history of severe hypersensitivity to a monoclonal antibody
• Patient must have the ability to understand and the willingness to sign a written
informed consent document
• Women must not be pregnant or breast-feeding, as the effects of nivolumab on the
developing human fetus or in the nursing infant are unknown; all females of
childbearing potential must have a blood test or urine study within 2 weeks prior to
randomization to rule out pregnancy; a female of childbearing potential is defined as
any woman, regardless of sexual orientation or whether they have undergone tubal
ligation, who meets the following criteria: 1) has achieved menarche at some point 2)
has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been
naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at
any time in the preceding 24 consecutive months)
• Women of childbearing potential (WOCBP) and males who are sexually active with WOCBP
must use accepted and effective method(s) of contraception, as described in the
Informed Consent Form (ICF), or abstain from sexual intercourse for the duration of
their participation in the study; women of childbearing potential must use adequate
methods to avoid pregnancy for 5 months after the last dose of nivolumab; sexually
active males must use adequate methods to avoid pregnancy for 7 months after the last
dose of nivolumab
• White blood cells >= 2000/uL (within 8 weeks prior to randomization)
• Absolute neutrophil count (ANC) >= 1,500/mm^3 (within 8 weeks prior to randomization)
• Platelet count >= 100,000/mm^3 (within 8 weeks prior to randomization)
• Hemoglobin >= 9.0 g/dL (within 8 weeks prior to randomization)
• Serum creatinine =< 1.5 x upper limit of normal (ULN) or calculated creatinine
clearance (CrCl) >= 40mL/min (within 8 weeks prior to randomization)
• Total bilirubin =< 1.5 x ULN (except subjects with Gilbert syndrome, who can have
total bilirubin < 3.0 x ULN) (within 8 weeks prior to randomization)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
(within 8 weeks prior to randomization)
Combination Chemotherapy, Bevacizumab, and/or Atezolizumab in Treating Patients With Deficient DNA Mismatch Repair Metastatic Colorectal Cancer, the COMMIT Study
This phase III trial studies how well combination chemotherapy, bevacizumab, and/or
atezolizumab work in treating patients with deficient deoxyribonucleic acid (DNA) mismatch
repair colorectal cancer that has spread to other places in the body (metastatic).
Chemotherapy drugs, such as fluorouracil, oxaliplatin, and leucovorin calcium, work in
different ways to stop the growth of tumor cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. Bevacizumab may stop or slow
colorectal cancer by blocking the growth of new blood vessels necessary for tumor growth.
Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune
system attack the cancer, and may interfere with the ability of tumor cells to grow and
spread. Giving combination chemotherapy, bevacizumab, and atezolizumab may work better in
treating patients with colorectal cancer.
• The patient must have signed and dated an Institutional Review Board (IRB)-approved
consent form that conforms to federal and institutional guidelines
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Diagnosis of metastatic adenocarcinoma of colon or rectum without previous
chemotherapy or any other systemic therapy for metastatic colorectal cancer
• Tumor determined to be mismatch-repair deficient (dMMR) by Clinical Laboratory
Improvement Act (CLIA)-certified immunohistochemical (IHC) assay with a panel of all
four IHC markers, including MLH1, MSH2, PMS2, and MSH6; alternatively, MSI-H diagnosed
by polymerase chain reaction (PCR)-based assessment of microsatellite alterations
(either Bethesda markers or Pentaplex panel) or by next-generation sequencing (NGS)
are eligible
• Documentation by positron emission tomography(PET)/computed tomography (CT) scan, CT
scan, or magnetic resonance imaging (MRI) that the patient has measurable metastatic
disease per RECIST 1.1
• No immediate need for surgical intervention for the primary tumor or palliative
diversion/bypass
• Absolute neutrophil count (ANC) must be >= 1500/mm^3 (obtained within 28 days prior
randomization)
• Platelet count must be >= 100,000/mm^3 (obtained within 28 days prior randomization)
• Hemoglobin must be >= 8 g/dL (obtained within 28 days prior randomization)
• Total bilirubin must be =< 1.5 x ULN (upper limit of normal) for the lab unless the
patient has a bilirubin elevation > 1.5 x ULN to 3 x ULN due to Gilbert's disease or
similar syndrome involving slow conjugation of bilirubin (obtained within 28 days
prior randomization); and
• Alkaline phosphatase must be =< 2.5 x ULN for the lab with the following exception:
patients with documented liver metastases or bone involvement •alkaline phosphatase
must be =< 5 x ULN (obtained within 28 days prior randomization); and
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be =< 3 x ULN
for the lab with the following exception: for patients with documented liver
metastases, AST and ALT must be =< 5 x ULN (obtained within 28 days prior
randomization)
• Serum creatinine =< 1.5 x ULN for the lab or measured (24 hour urine collection) or
calculated creatinine clearance >= 30 mL/min (obtained within 28 days prior
randomization)
• A urine sample tested for proteinuria by either the dipstick method, urinalysis (UA),
or a urine protein creatinine (UPC) ratio:
• The dipstick method must indicate 0-1+ protein; if dipstick reading is >= 2+, a
24-hour urine must be done and it must demonstrate < 1.0 g of protein per 24
hours
• A urine protein creatinine (UPC) ratio must be < 1.0; if the UPC ratio is >= 1.0
a 24-hour urine must be done and it must demonstrate < 1.0 g of protein per 24
hours
• Urinalysis must indicate < 30 mg/dl. If urinalysis >= 30 mg/dl, a 24-hour urine
must be done and it must demonstrate < 1.0 g of protein per 24 hours
• International normalized ratio of prothrombin time (INR) and prothrombin time (PT)
must be =< 1.5 x ULN for the lab within 28 days before randomization; patients who are
therapeutically treated with an agent such as warfarin may participate if they are on
a stable dose and no underlying abnormality in coagulation parameters exists per
medical history, regardless of PT/INR results
• Pregnancy test done within 14 days prior randomization must be negative (for women of
childbearing potential only); pregnancy testing should be performed according to
institutional standards; administration of atezolizumab or
mFOLFOX6/bevacizumab/atezolizumab may have an adverse effect on pregnancy and poses a
risk to the human fetus, including embryo-lethality; should a woman become pregnant or
suspect she is pregnant while she or her partner is participating in this study, she
should inform her treating physician immediately
• Women of child-bearing potential and men must agree to use adequate contraception
methods that result in a failure rate of < 1% per year during the treatment period
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 5 months (150 days) after the last dose
of atezolizumab, 6 months after the last dose of bevacizumab, and 6 months after the
last dose of mFOLFOX6; a woman is considered to be of childbearing potential if she is
not postmenopausal, 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 with a failure rate of < 1% per year include: bilateral tubal ligation; male
partner sterilization; intrauterine devices; the reliability of sexual abstinence
should be evaluated in relation to the duration of the clinical study and the
preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar,
ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable
methods of contraception; men must refrain from donating sperm during this same period
Exclusion Criteria:
• Patients with central nervous system (CNS) metastases are excluded, with the following
exceptions:
• Patients with asymptomatic untreated CNS metastases may be enrolled, provided all
eligibility criteria are met, as well as the following:
• Evaluable or measurable disease outside the CNS
• No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within
10 mm of the optic apparatus (optic nerves and chiasm)
• No history of intracranial hemorrhage or spinal cord hemorrhage
• No ongoing requirement for dexamethasone for CNS disease; patients on a
stable dose of anticonvulsants are permitted.
• No neurosurgical resection or brain biopsy within 28 days prior to
randomization
• Patients with asymptomatic treated CNS metastases may be enrolled, provided all
eligibility criteria are met, as well as the following:
• No radiographic demonstration and no evidence of interim progression between
the completion of CNS-directed therapy and the screening radiographic study
• No stereotactic radiation or whole-brain radiation within 28 days prior to
randomization
• Screening CNS radiographic study >= 28 days from completion of radiotherapy
and >= 14 days from discontinuation of corticosteroids
• Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies, fluoropyrimidines, folic acid derivatives or oxaliplatin
• Uncontrolled high blood pressure defined as systolic blood pressure (BP) > 150 mmHg or
diastolic BP 90 mmHg with or without anti-hypertensive medication; patients with
initial BP elevations are eligible if initiation or adjustment of BP medication lowers
pressure to meet entry criteria
• Any of the following cardiac conditions:
• Documented New York Heart Association (NYHA) class III or IV congestive heart
failure
• Myocardial infarction within 6 months prior to randomization
• Unstable angina within 6 months prior to randomization
• Symptomatic arrhythmia
• Serious or non-healing wound, skin ulcer, or bone fracture
• History of transient ischemic attack (TIA), cerebrovascular accident (CVA),
gastrointestinal (GI) perforation or arterial thrombotic event within 6 months prior
to randomization, symptomatic peripheral ischemia, or other medical condition in the
opinion of the treating oncologist that makes the risk of cardiovascular or bleeding
complications with bevacizumab use unacceptably high
• Other malignancies are excluded unless the patient has completed therapy for the
malignancy >= 12 months prior to randomization and is considered disease-free;
patients with the following cancers are eligible if diagnosed and treated within the
past 12 months: in situ carcinomas or basal cell and squamous cell carcinoma of the
skin
• Known DPD (dihydro pyrimidine dehydrogenase) deficiency
• Symptomatic peripheral sensory neuropathy >= grade 2 (Common Terminology Criteria for
Adverse Events [CTCAE] version [v] 5.0)
• Prior treatment with oxaliplatin chemotherapy within 6 months prior to randomization
• Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or
pathway-targeting agents; patients who have received prior treatment with anti-CTLA-4
may be enrolled provided the following requirements are met:
• Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the
last dose to randomization
• No history of severe immune-related adverse effects (CTCAE Grade 3 and 4) from
anti-CTLA-4
• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events (other than alopecia) due to agents administered more
than 4 weeks earlier are excluded; however, the following therapies are allowed:
• Hormone-replacement therapy or oral contraception
• Herbal therapy > 7 days prior to randomization (herbal therapy intended as
anticancer therapy must be discontinued at least 1 week prior to randomization)
• Palliative radiotherapy for bone metastases > 14 days prior to randomization
• Treatment with systemic immunostimulatory medications (including, but not limited to
interferon [IFN]-alpha or interleukin [IL]-2 within 42 days prior to randomization
• Treatment with systemic immunosuppressive medications (including, but not limited to,
prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor
necrosis factor [anti-TNF] agents) within 14 days prior to randomization; however,
• Patients who have received acute, low dose, systemic immunosuppressant
medications (e.g., a one-time dose of dexamethasone for nausea; or chronic daily
treatment with corticosteroids with a dose of =< 10 mg/day methylprednisolone
equivalent) may be enrolled
• The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone)
for patients with orthostatic hypotension or adrenocortical insufficiency is
allowed
• Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of
bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is
allowed
• Patients requiring treatment with a receptor activator of nuclear factor kappa-B
ligand (RANKL) inhibitor (e.g., denosumab) who cannot discontinue it before treatment
with atezolizumab
• Treatment with any other investigational agent within 4 weeks prior to randomization
• Known clinically significant liver disease, including active viral, alcoholic, or
other hepatitis; cirrhosis; fatty liver; and inherited liver disease; however,
• Patients with past or resolved hepatitis B infection (defined as having a
negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc
[antibody to hepatitis B core antigen] antibody test) are eligible if polymerase
chain reaction (PCR) for HBV RNA is negative per local guidelines
• Patients positive for hepatitis C virus (HCV) antibody are eligible only if
polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA) per
local guidelines
• History or risk of autoimmune disease, including, but not limited to, systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's
syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune
thyroid disease, vasculitis, or glomerulonephritis; however,
• Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid
replacement hormone may be eligible
• Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may
be eligible
• Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis would
be excluded) are permitted provided that they meet the following conditions:
• Patients with psoriasis must have a baseline ophthalmologic exam to rule out
ocular manifestations
• 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%,
fluocinolone 0.01%, desonide 0.05%, alclometasone 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)
• History of idiopathic pulmonary fibrosis, pneumonitis (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; history of radiation pneumonitis in the radiation field
(fibrosis) is permitted
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins
• Patients with known active tuberculosis (TB) are excluded
• Severe infections within 28 days prior to randomization, including but not limited to,
hospitalization for complications of infection, bacteremia, or severe pneumonia
• Signs or symptoms of infection within 14 days prior to randomization
• Received oral or intravenous (IV) antibiotics within 14 days prior to randomization;
patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract
infection or chronic obstructive pulmonary disease) are eligible
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to randomization or anticipation of need for a major surgical procedure during
the course of the study
• Administration of a live, attenuated vaccine within 28 days prior to randomization or
anticipation that such a live, attenuated vaccine will be required during the study
and up to 5 months after the last dose of atezolizumab; Note: influenza vaccination
should be given during influenza season only (approximately October to March);
patients must not receive live, attenuated influenza vaccine within 28 days prior to
randomization or at any time during the study
• Psychiatric illness/social situations that would limit compliance with study
requirements
• Pregnant women are excluded from this study because atezolizumab is an agent with the
potential for teratogenic or abortifacient effects; because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with atezolizumab, breastfeeding should be discontinued if the mother is
treated with atezolizumab; these potential risks may also apply to other agents used
in this study; (Note: pr
Contrast-Enhanced Ultrasound Imaging in Diagnosing Liver Cancer in Patients With Cirrhosis
This clinical trial studies how well contrast-enhanced ultrasound imaging works in diagnosing
liver cancer in patients with cirrhosis. Diagnostic procedures, such as contrast-enhanced
ultrasound imaging, may help find and diagnose liver cancer.
• Capable of making informed decisions regarding his/her treatment
• Have known cirrhosis or other risk factors for HCC, based on American Association for
the Study of Liver Diseases (AASLD) and European Association for the Study of the
Liver (EASL) guidelines (applicable in each site jurisdictions)
• Patients with untreated focal liver observations on liver ultrasound or multiphase
contrast-enhanced CT or MRI performed as part of clinical standard of care within 4
weeks before patient enrollment.
OR
• Patients with untreated focal liver observations scheduled for follow-up multiphase
contrast-enhanced CT or MRI, biopsy or surgical excision as part of clinical standard of
care. CEUS should be performed within 4 weeks before or after follow-up imaging or within 4
weeks before biopsy or surgical excision.
Exclusion Criteria:
• Patients who are pregnant or lactating
• Patients with focal liver observations less than 5 mm or greater than 5 cm in size
• Patients with contraindications to CEUS
• Patients with contraindications to both CT and MRI
• Patients who are medically unstable, terminally ill, or whose clinical course is
unpredictable
• Liver nodule previously treated with trans-arterial or thermal ablation
• Patients who have received an investigational drug in the 30 days before CEUS, or will
receive one within 72 hour after their CEUS exam
A Study to Evaluate ONM-100, an Intraoperative Fluorescence Imaging Agent for the Detection of Cancer
This study is to evaluate diagnostic performance, safety and timing of post-dose imaging of
ONM-100, an intraoperative fluorescence imaging agent for the detection of cancer in patients
with solid tumors undergoing routine surgery.
• Biopsy-confirmed diagnosis of primary or recurrent respective tumor type and scheduled
to undergo surgical resection
• Part 1: Biopsy-confirmed diagnosis of head and neck squamous cell carcinoma (HNSCC) or
breast cancer
• Part 2: Biopsy-confirmed diagnosis of HNSCC, breast cancer, colorectal cancer,
prostate cancer, ovarian cancer, urothelial carcinoma and non-small cell lung cancer.
• Part 3: Stage 2 to 4 HNSCC Including T0 or Tx unknown Primary cancers
Exclusion Criteria:
• Histologically diagnosed by an excisional biopsy procedure
• Tumors at sites of which the surgeon would assess that in vivo intraoperative imaging
would not be feasible
• Life expectancy <12 weeks
• Hepatic impairment (Child-Pugh score >5) or significant liver disease including active
hepatitis or cirrhosis
Drug: ONM-100
Prostate Cancer, Non-Small Cell Lung Cancer, Breast Cancer, Colorectal Cancer, Ovarian Cancer, Head and Neck Squamous Cell Carcinoma, Urothelial Carcinoma, Breast - Female, Colon, Ovary, Prostate
Chemoradiotherapy With or Without Atezolizumab in Treating Patients With Localized Muscle Invasive Bladder Cancer
This phase III trial studies how well chemotherapy and radiation therapy work with or without
atezolizumab in treating patients with localized muscle invasive bladder cancer. Radiation
therapy uses high energy rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such
as gemcitabine, cisplatin, fluorouracil and mitomycin-C, work in different ways to stop the
growth of cancer cells, either by killing the cells, by stopping them from dividing, or by
stopping them from spreading. Giving chemotherapy with radiation therapy may kill more tumor
cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's
immune system attack the cancer, and may interfere with the ability of tumor cells to grow
and spread. Giving atezolizumab with radiation therapy and chemotherapy may work better in
treating patients with localized muscle invasive bladder cancer compared to radiation therapy
and chemotherapy without atezolizumab.
• STEP 1 REGISTRATION:
• If this will be the first patient from a registering site to receive a given RT
modality (3DCRT vs. IMRT), the site must first submit pre-RT planning documents within
3 days of Step 1 registration and receive approval from Imaging and Radiation Oncology
Core (IROC) before randomizing the patient to Step 2. If this will not be the first
patient to receive a specific RT modality, the patient should be immediately
randomized to Step 2 on the same day.
• STEP 2 RANDOMIZATION
• If patient required review of pre-RT planning, randomization must occur within 14 days
of initial registration.
• Patients must have histologically proven, T2-T4a N0M0 urothelial carcinoma of the
bladder within 120 days prior to randomization and no intervening treatment between
the histologic proof and randomization. Patients with mixed urothelial carcinoma will
be eligible for the trial, but the presence of small cell carcinoma will make a
patient ineligible. Patients with lymph nodes >= 1.0 cm in shortest cross-sectional
diameter on imaging (computed tomography [CT]/magnetic resonance imaging [MRI] of
abdomen and pelvis) must have a biopsy of the enlarged lymph node showing no tumor
involvement within 70 days prior to randomization. These patients may be suitable for
neoadjuvant chemotherapy and radical cystectomy and are eligible for this trial if
they seek out a bladder sparing treatment strategy, however patients who have received
prior systemic chemotherapy for bladder cancer are not eligible for the trial.
• Patients must undergo a transurethral resection of bladder tumor (TURBT) within 70
days prior to randomization. In a situation where a patient is referred from outside
to the enrolling institution, patient must have a repeat cystoscopy by the urologist
who will be following the patient on the clinical trial to assess the adequacy of the
prior TURBT. Patient may then undergo repeat TURBT if deemed necessary as standard of
care by the treating urologist. Patients may have either completely or partially
resected tumors as long as the treating urologist attempted maximal resection. Patient
must not have T4b disease.
• Patients must undergo radiological staging within 70 days prior to randomization.
Imaging of chest, abdomen, and pelvis must be performed using CT or MRI. Patients must
not have evidence of T4bN1-3 disease. Eligibility is based on the local radiology
report.
• Patients with hydronephrosis are eligible if they have unilateral hydronephrosis and
kidney function meets criteria specified.
• Patient must be planning to receive one of the protocol specified chemotherapy
regimens.
• All adverse events associated with any prior surgery and intravesical therapy must
have resolved to Common Terminology Criteria for Adverse Events (CTCAE) grade =< 2
prior to randomization.
• Patient may or may not be radical cystectomy candidates.
• Absolute neutrophil count (ANC) >=1,500/microliter (mcL) (within 28 days prior to
randomization).
• Platelets >= 100,000/mcL (within 28 days prior to randomization).
• Hemoglobin >= 9 g/dL (within 28 days prior to randomization).
• Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (except patients
with Gilbert's syndrome, who must have a total bilirubin < 3.0 mg/dL) (within 28 days
prior to randomization).
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x IULN
(within 28 days prior to randomization).
• Patients must have adequate renal function as evidenced by calculated creatinine
clearance >= 25 mL/min. The creatinine used to calculate the clearance result must
have been obtained within 28 days prior to randomization.
• Patients must have Zubrod performance status =< 2.
• Patients must have a baseline electrocardiography (ECG) performed within 30 days prior
to randomization.
• If patient has a known history of hepatitis B virus (HBV) or hepatitis C virus (HCV),
they must meet the following criteria within 28 days prior to randomization.
• Patients with past or resolved hepatitis B infection (defined as having a
negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc
[antibody to hepatitis B core antigen] antibody test) are eligible.
• Patients positive for hepatitis C virus (HCV) antibody are eligible only if
polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA).
• Patients who are known to be positive for human immunodeficiency virus (HIV) are
eligible only if they have all of the following:
• A stable regimen of highly active anti-retroviral therapy (HAART)
• No requirement for concurrent antibiotics or antifungal agents for the prevention
of opportunistic infections
• A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard
PCR-based tests within 28 days prior to randomization.
• No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
Stage I or II cancer from which the patient is currently in complete remission, or any
other cancer from which the patient has been disease free for two years. Patients with
localized prostate cancer who are being followed by an active surveillance program are
also eligible.
• Female patients of childbearing potential must have a serum pregnancy test prior to
randomization. Patients must not be pregnant or nursing due to the potential
teratogenic side effects of the protocol treatment. Women of child-bearing potential
and men must agree to use adequate contraception (hormonal or barrier method of birth
control; abstinence) prior to study entry, for the duration of protocol treatment, and
for 5 months (150 days) after the last dose of all study drugs. A woman is considered
to be of "reproductive potential" if she has had a menses at any time in the preceding
12 consecutive months.
• Patients must be offered the opportunity to participate in specimen banking for future
studies.
• Patients who can complete Patient-Reported Outcome instruments in English or Spanish
must agree to complete the EORTC QLQ-C30, the EORTC QLQ-BLM30, the EPIC-26 (bowel
domain only), and the EQ-5D-5L per protocol schedule of assessment.
• As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
treating institution's identity is provided in order to ensure that the current
(within 365 days) date of institutional review board approval for this study has been
entered in the system.
Exclusion Criteria:
• STEP 2 RANDOMIZATION EXCLUSION CRITERIA
• Patients must not have had urothelial carcinoma or histological variant at any site
outside of the urinary bladder within the previous 24 months except Ta/T1/carcinoma in
situ (CIS) of the upper urinary tract including renal pelvis and ureter if the patient
had undergone complete nephroureterectomy.
• Patients must not have diffuse CIS based on cystoscopy and biopsy.
• Patient must not have received any systemic chemotherapy for their bladder cancer.
• Patient must not have had prior pelvic radiation.
• Patients must not have received prior treatment for muscle invasive bladder cancer
including neoadjuvant chemotherapy for the current tumor.
• Patients must not have received any systemic therapy (including, but not limited to,
interferon alfa-2b, high dose IL-2, pegylated interferon [PEG-IFN], anti-PD-1,
anti-PD-L1), for non-muscle invasive bladder cancer. Prior intravesical BCG,
interferon, and intravesical chemotherapy are allowed.
• Patients must not have received any of the following prohibited therapies within 28
days prior to randomization or be planning to receive any of the following prohibited
therapies during protocol treatment:
• Anti-cancer systemic chemotherapy or biological therapy not specified in the
protocol.
• Immunotherapy not specified in this protocol.
• Systemic or intravesical use of any non-study anti-cancer agent (investigational
or non-investigational).
• Investigational agents other than atezolizumab.
• Live vaccines: Examples of live vaccines include, but are not limited to, the
following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies,
bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine. Seasonal influenza
vaccines for injection are generally killed virus vaccines and are allowed;
however, intranasal influenza vaccines (e.g. Flu-Mist) are live attenuated
vaccines, and are not allowed. Prior administration of intravesical BCG is
allowed.
• Glucocorticoids for any purpose other than to modulate symptoms from an event of
suspected immunologic etiology. The use of physiologic doses of corticosteroids
(defined as 10 mg prednisone) are acceptable, however site investigators should
consult with the study chair for any dose higher than 10 mg prednisone.
Dexamethasone 4 mg iv with chemotherapy to prevent nausea is allowed.
• RANKL infusion: Concurrent denosumab (which binds the cytokine RANKL) for any
known indication is prohibited due to interaction with study medication.
• Patients must not have a major surgical procedure within 28 days prior to
randomization. If patient had any surgical procedure then they should have recovered
to full presurgical performance status and surgical adverse events should have
resolved to grade =< 2. TURBT is not considered a major surgical procedure.
• Patients must not have received treatment with systemic immunosuppressive medications
(including, but not limited to, prednisone, cyclophosphamide, azathioprine,
methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 14
days prior to randomization. Exceptions:
• Patients may have received acute, low dose, systemic immunosuppressant
medications (e.g., a one-time dose of dexamethasone for nausea).
• The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone)
for patients with orthostatic hypotension or adrenocortical insufficiency is
allowed. Physiological doses equivalent of 10 mg prednisone daily are allowed.
Short term steroids given as antiemetic therapy, e.g. 4 mg dexamethasone or
equivalent once a week, is allowed.
• Patients must not have received a live, attenuated vaccine within 4 weeks prior to
randomization or anticipate that such a live, attenuated vaccine will be required
while on protocol treatment and up to 5 months after the last dose of protocol
treatment.
• Inactivated influenza vaccination should be given during influenza season only
(approximately October to March). Patients must not receive live, attenuated
influenza vaccine within 4 weeks prior to randomization or while on protocol
treatment and up to 5 months after the last dose of protocol treatment.
• Patients must not have undergone prior allogeneic bone marrow transplantation or prior
solid organ transplantation.
• Patients must not have clinically significant liver disease that precludes patient
from treatment regimens prescribed on the study (including, but not limited to, active
viral, alcoholic or other autoimmune hepatitis, cirrhosis or inherited liver disease).
• Patient must not have history of idiopathic pulmonary fibrosis, pneumonitis (including
drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic
organizing pneumonia, etc.), or evidence of active pneumonitis.
• Patients must not have an active infection requiring oral or IV antibiotics within 14
days prior to randomization. Patients receiving prophylactic antibiotics (e.g., for
prevention of a urinary tract infection or chronic obstructive pulmonary disease) are
not eligible. If patient develops urinary tract infection after TURBT they must have
recovered from the infection prior to registration.
• Patients must not have active autoimmune disease that has required systemic treatment
in past two years (i.e., with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
etc.) is not considered a form of systemic treatment. Autoimmune diseases include, but
are not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory
bowel disease, vascular thrombosis associated with antiphospholipid syndrome,
Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome,
multiple sclerosis, autoimmune thyroid disease, vasculitis, Graves' disease treated
with methimazole or glomerulonephritis.
• Patient must not have a history of active tuberculosis.
• Patients must not be known to be allergic to Chinese hamster egg or ovary cell
products and must not have any known major allergic reactions to any study drug.
Bladder Urothelial Carcinoma, Bladder Carcinoma Infiltrating the Muscle of the Bladder Wall, Stage II Bladder Cancer AJCC v8, Stage III Bladder Cancer AJCC v8, Stage IIIA Bladder Cancer AJCC v8
Study to Determine the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Eosinophilic Esophagitis (EoE)
The primary objectives of the study by study part are:
Part A:
To determine the treatment effect of dupilumab compared with placebo in adult and adolescent
patients with EoE after 24 weeks of treatment as assessed by histological and clinical
measures, and to inform/confirm the final sample size determination for Part B.
Part B:
To demonstrate the efficacy of dupilumab treatment compared with placebo in adult and
adolescent patients with EoE after 24 weeks of treatment as assessed by histological and
clinical measures.
Part C:
To assess the safety and efficacy of dupilumab treatment in adult and adolescent patients
with EoE after up to 52 weeks of treatment as assessed by histological and clinical measures.
The secondary objectives of the study are:
- To evaluate the safety, tolerability, and immunogenicity of dupilumab treatment for up
to 52 weeks in adult and adolescent patients with EoE
- To explore the relationship between dupilumab concentration and responses in adult and
adolescent patients with EoE, using descriptive analyses
Call 214-648-5005 studyfinder@utsouthwestern.edu
Christopher Parrish
168280
All
12 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03633617
STU-2019-0556
Show full eligibility criteria
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Key Inclusion Criteria (Parts A & B):
• A documented diagnosis of EoE by endoscopic biopsy
• Baseline endoscopic biopsies with a demonstration on central reading of
intraepithelial eosinophilic infiltration
• History (by patient report) of an average of at least 2 episodes of dysphagia (with
intake of solids) per week in the 4 weeks prior to screening
Key Exclusion Criteria (Parts A & B):
• Body weight ≤40 kg
• Prior participation in a dupilumab clinical trial, or past or current treatment with
dupilumab
• Initiation or change of a food-elimination diet regimen or re-introduction of a
previously eliminated food group in the 6 weeks prior to screening.
• Other causes of esophageal eosinophilia or the following conditions: hypereosinophilic
syndrome and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
• Active Helicobacter pylori infection
• History of achalasia, Crohn's disease, ulcerative colitis, celiac disease, and prior
esophageal surgery
• Any esophageal stricture unable to be passed with a standard, diagnostic, 9 to10 mm
upper endoscope or any critical esophageal stricture that requires dilation at
screening
• History of bleeding disorders or esophageal varices
• Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed
during the study
Key Exclusion Criteria (Part C):
• Participants who, during Part A or Part B, developed a serious adverse event (SAE)
and/or adverse event (AE) deemed related to study drug, which in the opinion of the
investigator could indicate that continued treatment with study drug may present an
unreasonable risk for the participant
• Participants who became pregnant during Part A or Part B
• Participants who are prematurely discontinued from study drug due to an AE (patients
who are prematurely discontinued from study drug due to lack of efficacy are eligible
to enter Part C)
• Patients who did not undergo endoscopy with biopsies prior to receiving rescue
treatment
Note: Other inclusion/ exclusion criteria apply
A Global Study to Evaluate Transarterial Chemoembolization (TACE) in Combination With Durvalumab and Bevacizumab Therapy in Patients With Locoregional Hepatocellular Carcinoma (EMERALD-1)
A global study to evaluate transarterial chemoembolization (TACE) in combination with
durvalumab and bevacizumab 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 to B7 and 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
Key Exclusion Criteria
• Any history of nephrotic or nephritic syndrome
• Clinically significant cardiovascular disease or history of arterioembolic event
including a stroke or myocardial infarction
• Any prior or current evidence of coagulopathy or bleeding diathesis or patients who
had any kind of surgery in the past 28 days (biopsies are exempt from this exclusion)
• History of abdominal fistula or GI perforation, non healed gastric ulcer that is
refractory to treatment, or active GI bleeding within 6 months prior to enrollment
• Patients with Vp3 and Vp4 portal vein thrombosis on baseline imaging are excluded
Trial of Anakinra (Plus Zinc) or Prednisone in Patients With Severe Alcoholic Hepatitis (AlcHepNet)
This multicenter, randomized, double blinded, placebo-controlled clinical trial is focused on
novel treatments for severe alcoholic hepatitis (AH), a life-threatening stage of alcoholic
liver injury that has a short-term mortality rate much higher than that of other liver
diseases.
The primary objective of the study is to determine the clinical efficacy and safety of
Anakinra (plus zinc) compared to the current standard medical treatment consisting of
prednisone in participants with clinically severe AH. Key secondary objectives broadly are as
follows: (a) to evaluate the use of biomarkers to assess disease severity and treatment
response; and (b) to develop novel endpoints to overcome the limitations of current
assessment strategies for severe AH.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Mack Mitchell
124226
All
21 Years to 65 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT04072822
STU-2019-1368
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Inclusion Criteria
1. AH, as defined by the NIAAA pan-consortia for AH6:
1. Onset of jaundice (defined as serum total bilirubin >3 mg/dL) within the prior 8
weeks to screening visit
2. Regular consumption of alcohol with an intake of > 40 gm daily or >280gm weekly
on average for women and > 60 gm daily or >420gm weekly on average for men for 6
months or more, with less than 8 weeks of abstinence before onset of jaundice
3. AST > 50 IU/l
4. AST:ALT > 1.5 and both values < 400 IU/l
5. and/or histological evidence of AH*
2. MELD 20-35 on day of randomization.
• In patients with possible AH or AH with confounding factors such as possible
ischemic hepatitis, possible DILI, uncertain history of alcohol use (e.g.,
patient denies excessive alcohol use), and atypical/abnormal laboratory tests
(e.g., AST < 50 IU/L or > 400 IU/L, AST/ALT ratio < 1.5), antinuclear antibody >
1:160 or SMA > 1:80, a standard of care liver biopsy may be performed during
current hospital admission to confirm AH and exclude competing etiologies 17
Exclusion Criteria
1. MELD SCORE <20 or > 35
2. Active sepsis (positive blood or ascitic cultures) with Systemic Inflammatory Response
Syndrome (SIRS) or hemodynamic compromise requiring intravenous pressors to maintain
tissue perfusion
3. Pneumonia as evidenced by radiological exam
4. Multi-organ failure
5. Renal failure defined by GFR <50 mL/min.
6. Clinically active C. diff infection
7. History of imaging of the liver (ultrasound, computerized tomography or magnetic
resonance) showing other causes of jaundice
8. History of other liver diseases including hepatitis B (positive HBsAg or HBV DNA),
hepatitis C (positive HCV RNA), autoimmune hepatitis, Wilson disease, genetic
\hemochromatosis, alpha1-antitrypsin deficiency or strong suspicion of Drug Induced
Liver Injury (DILI)
9. History of HIV infection (positive HIV RNA or on treatment for HIV infection)
10. History or presence of cancer (including hepatocellular carcinoma) other than non-
melanoma skin cancer
11. History of other significant medical problems such as autoimmune diseases, severe
asthma, psoriasis, Inflammatory Bowel Disease (IBD), etc. that might require
immunosuppressive treatments
12. Pregnancy or breastfeeding
13. Prior exposure to experimental therapies in last 3 months
14. Prior exposure to systemic corticosteroid (glucocorticoid) or immunosuppressive
therapy for more than 4 days within previous 30 days
15. Need for inotropic pressor support to maintain perfusion to critical organs within
prior 48 hours before randomization and initiation of experimental treatment
16. Clinically significant pancreatitis- abdominal pain, elevated lipase (> 3 X ULN) and
at least edema of pancreas with fat-stranding on CT scan
17. Total WBC count > 30,000/mm3
18. Known allergy or intolerance to therapeutic agents to be tested
19. Inability to voluntarily obtain informed consent from participant or guardian
20. Perceived inability to follow study procedures and comply with protocol
21. Platelet count < 50,000 k/cumm.
22. Positive PCR test for COVID -19 within 7 days prior to the baseline day 0 visit
*Positive test is exclusionary only during screening period. If a patient tests
positive any time after baseline randomization, a positive PCR test for COVID-19 will
be considered as a SAE.
Drug: Anakinra and Zinc, Drug: Prednisone, Drug: Placebos
ENhancing Recovery in CHildren Undergoing Surgery (ENRICH-US)
Initiated in the 1990s, perioperative Enhanced Recovery Protocols (ERPs) have progressively
gained traction in a wide range of adult surgical disciplines and have decreased hospital
length of stay (LOS), in-hospital costs, complications, and result in a markedly improved
patient care experience that mitigates the physiologic stress of surgery and hastens
recovery. Implementation of ERPs in pediatric surgery is lagging and concerted efforts to
demonstrate both clinical effectiveness and to examine obstacles to implementation are
needed. Specifically, pediatric patients with inflammatory bowel disease (IBD) undergoing
elective abdominal surgery represent an ideal population in which to study the implementation
of ERPs. Almost one third of patients with Crohn's disease (CD) and a quarter of patients
with Ulcerative Colitis (UC) present before age 20. Up to three-quarters of CD patients
require GI surgery for medically refractory disease and all patients with UC require
colectomy to either manage severe disease or to mitigate cancer risks. Over the past four
years, investigators modified existing adult ERPs to meet the needs of pediatric patients
undergoing elective GI surgery. Based on the positive results of a pilot study, the
investigators propose to conduct a multicenter, prospective, pragmatic, study using a
stepped-wedge, cluster, randomized controlled trial design to evaluate the effectiveness of
ERPs while assessing implementation fidelity, sustainability, and site-specific adaptations.
The cluster randomized trial design is ideally suited for this type of pragmatic intervention
implementation. The National Implementation Research Network's five Active Implementation
Frameworks (AIFs), which identifies competency, organization, and leadership as drivers of
implementation, empowers team collaboration, and facilitates rapid-cycle evaluation, will be
used to optimize implementation. The investigators propose to conduct the ENhancing Recovery
In CHildren Undergoing Surgery (ENRICH-US) Study in 18 US hospitals participating in the
Pediatric Surgical Research Collaborative (PedSRC) by implementing and evaluating the
effectiveness of the Pediatric ERP in GI Surgery on clinical outcomes for pediatric IBD
patients and by measuring by fidelity and sustainability of the intervention while
identifying organizational, leadership, and competency-based drivers of improved ERP
implementation and sustainability.
Entecavir/Pegylated Interferon in Immune Tolerant Children With Chronic Hepatitis B Virus (HBV) Infection
The purpose of this study is to determine the safety and efficacy of treatment using a
combination of drugs (entecavir and pegylated interferon) in children ages 3-<18 years old
with immunotolerant chronic hepatitis B.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Norberto Rodriguez-Baez
50856
All
3 Years to 18 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT01368497
STU 042011-031
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Inclusion Criteria:
• Enrolled in & completed the baseline evaluation in NCT01263600 OR completed necessary
components of NCT01263600 baseline evaluation by the end of the baseline visit.
• 3 to <18 years at time of randomization (day 0).
• Documented chronic HBV infection as evidenced by detection of HBsAg in serum for ≥ 24
weeks prior to baseline OR positive HBsAg and negative anti-HBc IgM within 24 weeks of
baseline visit.
• Presence of HBeAg in serum at the last screening visit within 6 weeks of baseline
visit.
• Serum HBV DNA level >10^7 IU/mL on at least 2 occasions at least 12 weeks apart during
the 52 weeks before baseline visit. The HBV DNA levels must be within 6 weeks of
baseline visit.
• ALT ≤60 U/l in males or ≤40 U/l in females, measured on at least 2 occasions, at
screening (within 6 weeks prior to baseline visit) & at least 12 weeks prior to the
screening visit & within the 52 weeks prior to baseline visit.
• Compensated liver disease, with normal total bilirubin (except if Gilbert's syndrome),
direct bilirubin ≤0.5 mg/dL, INR ≤1.5, and serum albumin ≥3.5 g/dL.
• Creatinine clearance 90 ml/min.
• Absence of hepatocellular carcinoma on liver ultrasound in the past 48 weeks.
Exclusion criteria:
• Presence of infection with HCV-RNA or anti-HCV, anti-HDV, or HIV at screening.
• Presence of another cause of liver disease or HCC (serum alpha-fetoprotein >50ng /ml).
• Evidence of decompensated liver disease (Childs B-C).
• History or other evidence of a medical condition associated with chronic liver disease
(e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin
exposures).
• Females who are pregnant or breastfeeding.
• Adolescent females unwilling or unable to use an acceptable method of contraception if
sexually active during the treatment period.
• Children currently breastfeeding while their mother is taking lamivudine, or those who
were exposed to lamivudine for ≥24 weeks via maternal lamivudine treatment during
pregnancy and/or while breastfeeding.
• Previous liver or other organ transplantation including engrafted bone marrow
transplant.
• Hematological abnormalities during the screening period that contraindicate full
dosing with study drugs, e.g absolute neutrophil count < 1.5 x 10^9 cells/L or
platelet count < 120 x 10^9 cells/L.
• Known allergy to study drugs; peginterferon alfa-2a or entecavir.
• Treatment with systemic acyclovir or famciclovir within the previous 6 months.
• Need for ongoing use of any antivirals with activity against HBV during the course of
the study or history of receiving treatment for HBV.
• Any use of illegal drugs OR use of alcoholic beverages which in the opinion of a study
physician is sufficient to prevent adequate compliance with study procedures or
increase the risk of pancreatitis or hepatotoxicity.
• History of immunologically mediated disease (e.g. inflammatory bowel disease,
idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic
anemia, scleroderma, severe psoriasis, rheumatoid arthritis).
• History or other evidence of bleeding from esophageal varices or consistent with
decompensated liver disease.
• History or other evidence of chronic pulmonary disease associated with functional
limitation.
• History of significant cardiovascular diseases.
• History of a severe seizure disorder or current anticonvulsant use.
• History or other evidence of severe retinopathy.
• History of thyroid disease poorly controlled on prescribed medications. Participants
with elevated thyroid stimulating hormone concentrations with elevation of antibodies
to thyroid peroxidase and any clinical manifestations of thyroid disease are excluded.
• Concomitant use or use during ≤ 6 months prior to the first dose of study drug of
anti-neoplastic, immunosuppressive, nephrotoxic or hepatotoxic medication, methadone,
theophylline or medications that may affect renal excretion or hepatic metabolism are
not permitted.
• Concomitant use of complementary or alternative medications purported to have
antiviral activity.
• A participant may not be co-enrolled in another clinical trial where an
investigational drug is administered.
• Any other condition or situation that in the opinion of a study physician would make
the participant unsuitable for enrollment or could interfere with the participant
participating in and completing the study.
A 5-year Longitudinal Observational Study of Patients With Nonalcoholic Fatty Liver (NAFL) or Nonalcoholic Steatohepatitis (NASH)
TARGET-NASH is a longitudinal observational cohort study of patients being managed for NAFL
or NASH in usual clinical practice. TARGET-NASH will create a research registry of patients
with NAFL or NASH within academic and community real-world practices in order to assess the
safety and effectiveness of current and future therapies.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Sarah Barlow
86752
All
2 Years and over
This study is NOT accepting healthy volunteers
NCT02815891
STU 042018-018
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Inclusion Criteria:
1. Adults and children (age 2 or older) being managed or treated for nonalcoholic fatty
liver disease. Diagnosis is based on the clinical judgement of the care provider.
Exclusion Criteria:
1. Inability to provide written informed assent/consent
2. Simultaneous enrollment in another registry, study, or clinical trial where NASH
treatment outcomes are reported, except where approved or conducted as an adjunct
project of TARGET-NASH. If a participant elects to enroll in an interventional
clinical trial during their enrollment in TARGET-NASH, records submissions for the
participant will be put 'on hold' for the trial duration. When participation in the
trial is complete, records submissions for TARGET-NASH will resume.
A 5-year Longitudinal Observational Study of Patients With Primary Biliary Cholangitis
This is a 5-year, longitudinal, observational study of patients with PBC designed to
specifically address important clinical questions that remain incompletely answered from
registration trials. In addition to the study database, a bio specimen repository will also
be included so that translational studies of genomics and biomarkers of response may be
performed.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Marlyn Mayo
14698
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT02932449
STU 032017-093
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Inclusion Criteria:
• Adult patients (age 18 or older) being treated or managed for PBC
Exclusion Criteria:
• Inability to provide written informed consent
• Simultaneous enrollment in another prospective registry or clinical trial or study
where PBC treatment outcomes are reported, except where approved or conducted as an
adjunct project of TARGET-PBC
PREA, PK And Safety PASS Study Of IV Pantoprazole In Pediatric Subjects
The purpose of this study is to characterize the pharmacokinetics (PK) and safety of
intravenous (IV) pantoprazole in patients 1 to 16 years old who are candidates for acid
suppression therapy.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Aakash Goyal
117056
All
1 Year to 16 Years old
Phase 4
This study is NOT accepting healthy volunteers
NCT02401035
STU 032017-112
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Inclusion Criteria:
• Subjects aged 1 to 16 years who in the judgment of the investigator are candidates for
gastric acid suppression therapy (ie, those with a presumptive diagnosis of GERD, a
clinical diagnosis of suspected GERD, symptomatic GERD, or endoscopically proven GERD)
and whom the investigator judges would need to receive IV PPI therapy for at least 4
days.
• Body weight > 5th percentile for age.
• Y-site or dedicated IV line for administration of pantoprazole sodium.
• Expected survival for at least 30 days.
• Fertile male and female subjects of childbearing potential at risk for pregnancy must
agree to use a highly effective method of contraception throughout the study and for
at least 28 days after the last dose of assigned treatment. Female subjects of
non-childbearing potential must be premenarchal, have undergone hysterectomy with
bilateral oophorectomy, have medically confirmed ovarian failure, or achieved
post-menopausal status.
Exclusion Criteria:
• Participation in other studies involving investigational drug(s) or treatment with an
investigational drug within 30 days or 5 half lives prior to study entry and/or during
study participation.
• Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or
investigational product administration or may interfere with the interpretation of
study results and, in the judgment of the investigator, would make the subject
inappropriate for entry into this study.
• Pregnant females; breastfeeding females; fertile male subjects, and female subjects of
childbearing potential who are unwilling or unable to use a highly effective method of
contraception for the duration of the study and for at least 28 days after last dose
of investigational product.
• Serum CK levels >3x ULN.
• Known history of HIV or clinical manifestations of AIDS.
• Known hypersensitivity to PPIs or to any substituted benzimidazole or to any of the
excipients.
• History of treatment with any PPI within 2 days (48 hours) before investigational
product dosing on Day 1.
• Use of H2RAs, sucralfate, misoprostol, or prokinetic agents, and bismuth preparations
within 1 day (24 hours) before investigational product dosing on Day 1.
• Any disorder requiring chronic (every day) use of warfarin, carbamazepine, or
phenytoin, methotrexate, atazanavir or nelfinavir, clopidogrel, and potent inhibitors
and inducers of CYP2C19.
• Chronic (daily) use of glucocorticoids. Steroid inhalers and topical steroids may be
used.
• Active malignancy of any type, or history of a malignancy (Subject with a history of
malignancies that have been surgically removed or eradicated by irradiation or
chemotherapy and who have no evidence of recurrence for at least 5 years before
Screening are acceptable).
• ALT or BUN >2.0 ULN or estimated creatinine >1.5 X ULN for age or any other laboratory
abnormality considered by the Investigator to be clinically significant within 14 days
before Screening.
• In the Investigator's opinion, a chronic condition (eg, diabetes, epilepsy), which is
either not stable or well controlled and may interfere with the conduct of the study.
• History of sensitivity to heparin or heparin induced thrombocytopenia.
Drug: IV pantoprazole
Gastroesophageal Reflux Disease
candidate for acid suppression therapy, presumptive diagnosis of GERD, clinical diagnosis of suspected GERD, symptomatic GERD, endoscopically proven GERD
Effect of Fatty Liver on TCA Cycle Flux and the Pentose Phosphate Pathway (HPFFF)
The investigators plan to evaluate sensitivity and specificity of HP 13C-pyruvate as an
imaging agent for detection of altered PDH flux in fatty liver.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Craig Malloy
14563
All
18 Years to 99 Years old
Early Phase 1
This study is also accepting healthy volunteers
NCT03480594
STU 082017-019
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Inclusion Criteria:
• Ages 18 to 99 years.
• All races, ethnicities and gender identification may be included. Subjects must meet
all of the inclusion and exclusion criteria to be included in the study.
• Either fatty liver diagnosis (defined as >5.6% fat content in the liver) or healthy
control
• While all races and ethnicities will be included, subjects must be able to read and
speak the English language. Once the protocol is established, Spanish-speaking
participants will be included.
• Women of child-bearing potential must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) prior to study entry, for the duration of
study participation. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately.
Exclusion Criteria:
Fatty Liver Subjects
• No subjects taking hypoglycemic agents or insulin will be enrolled. There is no
exclusion based on fasting glucose.
• Subjects with major mental health conditions such as schizophrenia and bipolar
disorder that would limit compliance with study requirements will not participate. In
general, subjects with any form of medical instability such as seizure disorders,
significant COPD, significant asthma, left ventricular dysfunction will not
participate.
• Medications for control of hypercholesterolemia, hypertriglyceridemia or
hyperglycemia.
Healthy Control Subjects
• Liver disease or other chronic illness
• Diagnosis of type I or type II diabetes
• No subjects taking hypoglycemic agents or insulin will be enrolled. There is no
exclusion based on fasting glucose.
• A potential subject with any major medical, surgical or psychiatric condition will not
participate. These conditions include but are not limited to thyroid disease, chronic
metabolic illness, known vascular disease, current cancer diagnosis and/or treatment.
• Subjects with major mental health conditions such as schizophrenia and bipolar
disorder that would limit compliance with study requirements will not participate. In
general, subjects with any form of medical instability such as seizure disorders,
significant COPD, significant asthma, left ventricular dysfunction will not
participate.
• Medications for control of hypercholesterolemia, hypertriglyceridemia or
hyperglycemia.
All Subjects
• No prior hepato-biliary surgery.
• Donated blood within the prior 4 weeks.
• Consume more than 10 grams of ethanol per day.
• Cirrhosis or any form of viral hepatitis.
• Prior documented hepatic reaction to drugs with a known hepatotoxicity profile such as
isoniazid, methotrexate, phenytoin, propylthiouracil, valproate, etc.
• Pregnant/Lactating
• Receiving any other investigational agents.
• Any contraindication noted on the UTSWMC MRI Screening Form including implants
contraindicated at 3T, pacemakers, Implantable Cardioverter Defibrillators (ICD),
etc., and significant claustrophobia.
A Multi-Center Trial to Study Acute Liver Failure in Adults (ALFSG)
The purpose of this study is to collect clinical and epidemiological data as well as serum,
plasma, urine, tissue and DNA samples on individuals who have acute liver failure and on
individuals who have acute liver injury, a less severe group of patients who have
coagulopathy but do not reach the threshold of encephalopathy.
Call 214-648-5005 studyfinder@utsouthwestern.edu
William Lee
14217
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT00518440
STU 062010-126
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ALF
Inclusion Criteria:
• Written Informed consent from patient's next of kin
• Altered mentation of any degree (encephalopathy)
• Evidence of moderately severe coagulopathy (INR ≥ 1.5)
• A presumed acute illness onset of less than 26 weeks
• The NIH guidelines on the inclusion of women and minorities as subjects in clinical
research will be observed
ALF
Exclusion Criteria:
• Cirrhosis patients
• Alcohol induced liver failure
• Known pre-existing chronic liver disease
ALI
NNITS-Nitazoxanide for Norovirus in Transplant Patients Study
This is a phase 2 multi-center, double-blind, placebo-controlled study of the efficacy and
safety of nitazoxanide for the treatment of solid organ and hematopoietic stem cell
transplant recipients with symptomatic diarrhea due to Norovirus. The study involves a total
of 160 Hematopoietic Stem Cell or Solid Organ transplant recipients, equal to or greater than
12 years of age with diagnosis of Norovirus who will be selected and randomly assigned (1:1)
to nitazoxanide or placebo group. The study duration is 60 months and subject participation
duration is 6 months. Given the safety of prolonged therapy with nitazoxanide, lack of
interactions with common post-transplant medications, putative antiviral activity and
prolonged duration of viral shedding we are assessing 56 doses of therapy. The longitudinal
monitoring phase will provide useful information on the course of host and viral responses in
subjects with chronic Norovirus infection with and without treatment. Randomization will be
stratified by age group (pediatric (12 through 17 years) vs. adult (greater than or equal to
18 years)), chronicity of Norovirus-associated symptoms (acute (less than 14 days) vs.
chronic (greater than or equal to 14 days)) and transplant type (solid organ (SOT)) vs.
hematopoietic stem cell transplant (HSCT)). Enrolled subjects will participate in 2 phases of
the study: Treatment Phase, which will include dosing with the assigned study agent for 28
days. Longitudinal Monitoring Phase which will include telephone call on Days 35, 53, 113,
173. Primary objective is 1) to assess the clinical efficacy of nitazoxanide for the
management of acute and chronic Norovirus in transplant recipients.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Pearlie Chong
170933
All
12 Years to 99 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03395405
STU 062017-022
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Inclusion Criteria:
Subjects should meet all of the following inclusion criteria:
1. Male or female age > / = 12 years.
2. Recipient of a solid organ or hematopoietic stem cell transplant.
3. Positive test result for Norovirus within 14 days of enrollment that is obtained as
part of routine clinical care using a Norovirus testing available to the site.
4. Active GI symptoms (diarrhea, or vomiting) that, in the opinion of the PI, are
secondary to Norovirus. Patients must have active diarrhea, which is defined as at
least 3 days of Bristol 6 or 7 stools in the past 2 weeks prior to enrollment per
patient report.
5. Willing and able to provide written informed consent and assent before initiation of
any study procedures, consistent with local IRB policy.
6. Subjects must be of non-childbearing potential or if of childbearing potential, must
be using an effective method of birth control or must be abstinent.
• Non-childbearing potential is defined as surgically sterile or postmenopausal for
> one year.
• Effective methods of birth control include the use of hormonal or barrier birth
control such as implants, injectable contraceptives, combined oral
contraceptives, intrauterine devices (IUDs),or condoms with spermicidal agents
during study period. Female subjects must be using an effective method of birth
control or practice abstinence and must agree to continue such precautions during
the study and for 30 days after the Day 28 study visit.
• A woman is eligible if she is monogamous with a vasectomized male.This subject is
considered low risk and not required to use contraception.
7. Agrees to complete all screening requirements, study visits and procedures.
Exclusion Criteria:
Subjects meeting any of the exclusion criteria at baseline will be excluded from study
participation:
1. Other identified infectious causes of diarrhea at screening. Alternative diagnosis
requiring treatment would be considered a co-infection; if the testing is positive for
a pathogen that the PI does not feel is causing the symptoms, they may be included but
the PI or his/her designee must document that the positive test is not clinically
significant, does not require treatment and is not causing the symptoms making the
patient eligible for enrollment.
2. Any condition that would, in opinion of the Site Investigator, place the subject at an
unacceptable risk of injury or render the subject unable to meet the requirements of
the protocol.
3. Subjects receiving oral or intravenous immunoglobulin therapy concurrently or in the
14 days prior to enrollment.
4. Nitazoxanide use for any illness in the previous 30 days prior to randomization.
5. Have received experimental products within 30 days prior to the study entry or plan to
receive experimental products at any time during the study
6. Known sensitivity to nitazoxanide or any of the excipients comprising the nitazoxanide
tablets.
7. Subjects unable to swallow oral medications.
8. Subjects with ostomy.
9. Women who are pregnant or lactating or have a positive urine pregnancy test at
screening/enrollment/Day 1.
A Study to Assess the Efficacy and Safety of Golimumab in Pediatric Participants With Moderately to Severely Active Ulcerative Colitis (PURSUIT 2)
The purpose of this study is to evaluate efficacy of golimumab in inducing clinical remission
as assessed by the Mayo score, in pediatric participants with moderately to severely active
ulcerative colitis (UC). In addition, the safety profile of golimumab, in pediatric
participants with moderately to severely active UC will be assessed.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Bhaskar Gurram
162197
All
2 Years to 17 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03596645
STU-2018-0101
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Inclusion Criteria:
• Must either be currently receiving treatment with, or have a history of having failed
to respond to, or have a medical contraindication to at least 1 of the following
therapies: oral or intravenous corticosteroids, 6-mercaptopurine, methotrexate or
azathioprine OR must either have or have had a history of corticosteroid dependency
(that is an inability to successfully taper corticosteroids without a return of the
symptoms of ulcerative colitis [UC]) OR required more than 3 courses of
corticosteroids in the past year
• Moderately to severely active UC (as defined by baseline Mayo score of 6 through 12
[endoscopy {sigmoidoscopy or colonoscopy} sub score assigned by local endoscopist],
inclusive), including a (sigmoidoscopy or colonoscopy) sub score greater than or equal
to (>=2)
• If receiving enteral nutrition, must have been on a stable regimen for at least 2
weeks prior to the first administration of study intervention at Week 0. Participants
who receive parenteral nutrition are not permitted to enroll in the trial
• No history of latent or active tuberculosis prior to screening
• Must be up to date with all immunizations (that is, measles, mumps, rubella, and
varicella) in agreement with current local immunization guidelines for
immunosuppressed participants before Week 0
Exclusion Criteria:
• History of liver or renal insufficiency; significant cardiac, vascular, pulmonary,
gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric
(including suicidality), or metabolic disturbances
• History of malignancy or macrophage activation syndrome or hemophagocytic
lymphohistiocytosis
• Have UC limited to the rectum only or to <20 percent (%) of the colon
• Presence of a stoma
• Presence or history of a fistula
• Contraindications to the use of golimumab or infliximab or anti-tumor necrosis factor
(TNF-alpha) therapy per local prescribing information
The purpose of this research study is to create a clinical database and bio-repository. To do
this, we will obtain blood, urine, and stool samples (e.g., biological samples) and personal
health information from you to use in future research studies related to alcoholic hepatitis
or other diseases. Part of your blood sample will be used to extract your DNA. DNA is the
genetic material that gives us unique characteristics. We are doing this research study
because we are trying to find out more about how and why illnesses related to alcoholic
hepatitis or other diseases occur in people. To do this, we will study the biological samples
and personal health information from healthy and sick people.
A "biological sample" is usually blood, but can be any body fluid. "Personal Health
Information" includes such items as your name, age, gender, race, and/or your medical
information. It can also include data from measurements and tests that you had while
participating in another research study or that were done during the course of your regular
medical care or doctor visits.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Mack Mitchell
124226
All
21 Years and over
This study is also accepting healthy volunteers
NCT03850899
STU-2019-0472
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CASES: Heavy drinkers with alcoholic hepatitis Inclusion criteria
1. A clinical diagnosis of alcoholic hepatitis
2. Serum total bilirubin >3 mg/dL
3. Subject or guardian ability to understand and willingness to provide written consent
4. Age greater or equal to 21 years
5. Re-enrolment of an alcoholic hepatitis donor is permissible up to 4 times if the donor
presents with a new episode of alcoholic hepatitis 24 weeks or longer after the most
recent enrolment in the study
Exclusion criteria
1. Liver disease significantly caused by hemochromatosis, autoimmune liver disease,
Wilson disease, NAFLD, and acute viral hepatitis
2. (NOTE: The presence of chronic hepatitis C, hepatitis B, or HIV is not exclusion to
participation.)Pregnant or breast feeding Based on the judgment of the investigator,
subject is not capable of understanding or complying with the study requirements.
CONTROLS: Heavy drinkers without significant liver disease Inclusion criteria
1. History of chronic alcohol consumption sufficient to cause liver damage. Generally,
this is considered to be >40 g/day or >280g/week on average for women and >60 g/day or
>420 g/week on average for men, for many years (usually decades). Judgement about
chronic alcohol consumption will be made by the site investigator.
2. Subject or guardian ability to understand and willingness to provide written consent
3. Age greater or equal to 21 years
Exclusion criteria
1. Past evidence of alcoholic liver disease, defined as a bilirubin > 2.0 mg/dL, an AST >
1.5 ULN, and any hospital admission for liver disease, or the presence of esophageal
varices or ascites (at any time in the past).
2. Liver disease significantly caused by hemochromatosis, autoimmune liver disease,
Wilson disease, NAFLD, and acute viral hepatitis (NOTE: The presence of chronic
hepatitis C, hepatitis B, or HIV is not exclusion to participation.)
3. Alcohol intake at less than 40 g/day or 280g/week on average for women and 60 g/day or
420 g/week on average for men for longer than the past 28 days
4. If liver stiffness has been assessed within the prior 90 days, then stiffness
suggesting fibrosis of F1 or greater is excluded. For Fibroscan, this is a fibrosis
score >7.0 kPa.
5. Pregnant or breast feeding
6. Any of the following laboratory abnormalities within 90 days prior to signing the
consent.
1. Total bilirubin: >ULN*
2. INR: > 1.4 5 *Individuals with a diagnosis of Gilbert's can have total bilirubin
up to 3.0 mg/dL and still be eligible for participation.
Healthy Controls
Inclusion criteria
1. AUDIT-C scores of <4 for men and <3 for women (signifying no alcohol misuse)
2. Abstinent (consumption of less than one standard drink/week) during the 6 months prior
to enrolment
3. Ability to understand and willingness to provide written consent.
Exclusion criteria
1. Clinical history or laboratory evidence of liver disease including alcoholic liver
disease, NAFLD, hemochromatosis, alcoholic hepatitis, autoimmune liver disease, Wilson
disease, hepatitis C, or hepatitis B.
2. Presence of diabetes (requiring treatment with oral agents or insulin).
3. Significant heart disease (prior history of heart disease, other than hypertension)
4. Chronic lung disease (requiring chronic treatment)
5. Immune related conditions (such as Crohn's disease, rheumatoid arthritis, ulcerative
colitis, systemic lupus erythematosus, severe psoriasis, etc.)
6. Known infection with HIV
7. Presumed infection, or use of antibiotics or other medications (e.g., corticosteroids)
that would affect immune function, within the past 14 days
8. BMI>35
9. Current or known history of cancer (except in situ carcinoma of the cervix or
adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior
to enrollment
10. Pregnant or breast feeding
11. Any of the following laboratory abnormalities within 90 days prior to signing the
consent.
1. Hemoglobin: <10 g/dL
2. Conjugated bilirubin: > ULN
3. INR: > 1.4
4. AST: >40 IU/mL
5. ALT: >40 IU/mL
12. Based on the judgment of the investigator, subject is not capable of complying with
the study requirements
Novel Therapies in Moderately Severe Acute Alcoholic Hepatitis (NTAH-Mod)
This study is being done to find out whether a diet supplemented with a probiotic nutrient
can improve alcoholic hepatitis and gut complications compared to routine standard care.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Mack Mitchell
124226
All
21 Years to 70 Years old
N/A
This study is NOT accepting healthy volunteers
NCT01922895
STU 092012-012
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Inclusion Criteria:
1. Ability to provide informed consent by subject or appropriate family member
2. Age between 21-70 years
3. Recent alcohol consumption > 50 g/d for > 6 months, continuing within two months
before enrollment
4. At least 2 of the following symptoms or signs of acute alcoholic hepatitis: Anorexia,
nausea, RUQ pain, jaundice, leukocytosis, hepatomegaly AND
5. Elevation of AST > 80 U/L, but < 500 U/L at the time of admission or within 3 days of
baseline visit; AST > ALT and ALT < 200 U/L; total bilirubin > 3 mg/dL AND
6. Liver biopsy showing alcoholic hepatitis (steatohepatitis) OR ultrasound of liver
showing increased echogenicity OR CT scan showing decreased attenuation of liver
compared to spleen OR MRI showing fatty liver (decreased signaling intensity on T1
weighted images). If the liver biopsy (done within 60 days of inclusion) confirms
diagnosis of AAH then inclusion e will be waived.
7. Model for End-Stage Liver Disease (MELD) <20
8. Willingness to utilize two reliable forms of contraception (both males and females of
childbearing potential) from screening through the first six weeks of study.
Exclusion Criteria:
1. Hypotension with BP < 80/50 after volume repletion
2. Pregnancy; incarceration; inability to provide consent or lack of appropriate family
member
3. Signs of systemic infection: Fever > 38o C and positive blood or ascites cultures on
appropriate antibiotic therapy for > 3 days within 3 days of inclusion
4. Acute gastrointestinal bleeding requiring > 2 units blood transfusion within the
previous 4 days
5. Undue risk from immunosuppression: Positive HBsAg; a positive skin PPD skin test or
history of treatment for tuberculosis; history of any malignancy including
hepatocellular carcinoma; known HIV infection
6. Treatment with corticosteroids or other immunosuppressive medications including
specific anti-TNF therapy (not including pentoxifylline), calcineurin inhibitors for >
3 days within the previous 3 months.
7. Evidence of acute pancreatitis: CT evidence and/or amylase or lipase > 5 X upper limit
of normal
8. Serious cardiac, respiratory or neurologic disease or evidence of autoimmune
hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilsons disease,
hemochromatosis, secondary iron overload due to chronic hemolysis, alpha-1-antitrypsin
deficiency
9. Acute or chronic kidney injury with serum creatinine > 3.0 mg/dl
Dietary Supplement: Lactobacillus Rhamnosus GG, Drug: Placebo for Probiotic
13C-Methacetin Breath Test for the Prediction of Outcome in in ALI or ALF (ALFSG-MBT)
The ALFSG-MBT protocol is for a multicenter, open label, non-randomized study to determine
the value of Breath Identification® (BreathID®) N-(4-Methoxy-13C-phenyl)acetamide
(13C-Methacetin) Breath Test System in predicting the outcome of patients diagnosed with
severe acute liver injury that is not related to acetaminophen overdose or acute liver
failure who meet inclusion/exclusion criteria.
Up to 200 evaluable patients will be enrolled. An evaluable patient is one who has completed
one or more breath tests for at least 30 minutes after administration of the 13C-Methacetin
solution (test substrate).
The Breath Test will be performed up to five times during the study period on all enrolled
patients. The first Breath Test will be performed upon admission into the study (Day 1) and
repeated on Days 2, 3, 5 and 7 provided no contra-indications are present. Each test
continuously measures changes in the metabolism of the 13C-Methacetin in order to assess the
improvement or deterioration in liver metabolic function about improvement or deterioration
in liver metabolic function. If an enrolled non-APAP ALI or ALF patient receives a liver
transplant, is discharged /transferred from the hospital or dies prior to Day 7, additional
Breath Tests will not be performed.
Patients will be contacted for the Day 21 follow up (21 days after enrollment into the trial)
to determine spontaneous survival, transplantation and occurrence of serious adverse events
since the patient's last study treatment.
Call 214-648-5005 studyfinder@utsouthwestern.edu
William Lee
14217
All
18 Years to 80 Years old
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT02786836
STU 122015-008
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Inclusion Criteria:
1. Adult men or women (18-80 years of age)
2. Severe acute liver injury not related to acetaminophen overdose: INR ≥2.0; no evidence
of HE
3. Acute liver failure: INR ≥1.5; presence of any degree of HE
4. Duration of illness <26 weeks
5. Enrolled into the ALFSG Registry.
6. Written informed consent from the patient or patient's legally authorized
representative or family member as defined in the Federal Register Number 21
Congressional Federal Register (CFR)50.3(m)
Exclusion Criteria:
1. Evidence of pre-existing chronic liver disease
2. Pre-existing New York Heart Association stage III/IV heart failure
3. Evidence of pre-existing chronic renal failure
4. Chronic hemodialysis prior to hospital admission
5. Evidence of cirrhosis (unless clinically acute Wilson disease or autoimmune non-APAP
ALI or ALF)
6. Severe obstructive lung disease (FEV1 <50% of predicted on previous spirometry)
7. Severe shock, defined as mean arterial pressure (MAP) <70 mmHg despite >15 µg/kg/min
dopamine, >0.1 µg/kg/min epinephrine, or >0.1 norepinephrine µg/kg/min
8. Extensive small bowel resection (>50 cm)
9. Any evidence of upper GI bleeding at enrollment requiring intervention (endoscopy or
red blood cell (RBC) transfusion specifically for upper GI bleeding)
10. Liver transplantation (LT) prior to enrollment. (Note: Listing for LT does not
preclude participation in the trial.)
11. Pregnancy or breastfeeding women (Note: Pregnancy related non-APAP ALI or ALF may be
considered for entry following the delivery of the baby and assuming the mother does
not wish to breastfeed or collect breast milk during the study period.)
12. Allergic to acetaminophen (such as Tylenol® or any other acetaminophen-containing
medications)
13. Participation in other clinical studies evaluating other experimental treatments or
procedures. (Note: Participation in observatory studies is not an exclusion.)
14. Patients in whom enteral drugs or fluids are contra-indicated or the patient either
does not have an appropriately placed naso-enteric/orogastric tube in situ or cannot
tolerate taking the drug preparation orally (200 ml)
15. Budd-Chiari Syndrome
16. Non-APAP ALI or ALF caused by malignancy
17. Moderate and severe adult respiratory distress syndrome (ARDS), as defined by Berlin
Criteria.
18. Subjects who have received amiodarone in the 30 days prior to study enrollment
19. Consumption of any food or beverage that contains caffeine in the 24 hours prior to
enrollment
20. Consumption of any of the following drugs that may interfere with the metabolism of
13C-Methacetin in the 48 hours prior to study enrollment including: allopurinol,
carbamazepine, cimetidine, ciprofloxacin, daidzein, disulfiram, Echinacea, enoxacin,
fluvoxamine, methoxsalen, mexiletine, montelukast, norfloxacin, phenylpropanolamine,
phenytoin, propafenone, rifampin, terbinafine, ticlopidine, thiabendazole, verapamil,
zileuton or oral contraceptives
21. Consumption of alcohol in the 24 hours prior to enrollment
22. Smoking cigarettes in the 8 hours prior to enrollment.
Mitochondrial Function in Patients With Severe Liver Disease (SLDglyc)
The researchers will recruit patients with liver disease at Parkland Hospital. Patients will
fast overnight, and the next morning will receive an oral mixture of [U-13C3]glycerol (25
mg/kg) plus unlabeled glycerol (25 mg/kg). The total dose of glycerol will be 50 mg/kg in 100
milliliters of water. The taste is slightly sweet. Blood will be drawn at 60 min and 120 min
after the ingestion. Blood glucose will be isolated and analyzed by NMR. The presence of
[5,6-13C2]- and [4,5-13C2]glucose indicates preserved mitochondrial function. The researchers
anticipate that patients with severe liver disease will show a decrease in mitochondrial
function and will inform biosynthetic function of liver mitochondria.
After the first 6 successful exams (see power analysis, below), healthy volunteers (age-,
gender-, and race-matched) will be studied at the AIRC and subject to the same protocol.
Call 214-648-5005 studyfinder@utsouthwestern.edu
Jeffrey Browning
51677
All
21 Years to 70 Years old
N/A
This study is also accepting healthy volunteers
NCT02457702
STU 022015-085
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Inclusion Criteria:
• Severe liver disease defined as known liver disease plus at least one of the
following: serum albumin less than 3.0 g/dL or INR more than 2.0.
Exclusion Criteria:
• Portal systemic encephalopathy
• Pregnancy or breastfeeding.
• Anemia (hematocrit < 32%)
• Significant weight loss or use of diet pills within previous 6 months.
• Cannot give informed consent, understand the protocol, or tolerate any aspect of the
protocol.
Neuromodulation for Accidental Bowel Leakage (NOTABLe)
This study is a multi-center, randomized clinical trial of women with refractory accidental
bowel leakage (ABL) symptoms who have failed to achieve satisfactory symptom control from 2
first-line treatments for ABL: supervised pelvic muscle training (PMT) and constipating
medication. The purpose of this study is to compare percutaneous tibial nerve stimulation
(PTNS) to a validated sham to determine if PTNS is effective for the treatment of fecal
incontinence (FI) in women.
The investigators will test the null hypothesis that change from baseline in St. Mark's
(Vaizey) score after 12 weeks of stimulation is not significantly different in women with
symptomatic ABL receiving PTNS treatments compared to women receiving sham PTNS treatments.
Call 214-648-5005 studyfinder@utsouthwestern.edu
David Rahn
49553
Female
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT03278613
STU 122017-009
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Inclusion Criteria:
• Women ≥ 18 years of age
• FI symptoms ≥ 3 months
• Baseline St. Mark's score of ≥ 12
• Attended ≥ 2 supervised PMT for ABL
• Intolerance, unwillingness, or inadequate response to constipating medications
• Current negative colon cancer screening based on the USPSTF's recommendation for
colorectal cancer screening (2016)
Exclusion Criteria:
• Previous PTNS treatment
• History of uncontrolled diarrhea in the past 3 months (usual or most common stool type
over the preceding 3 months of 7 on the Bristol Stool Form Scale)
• History of severe constipation in the past 3 months (usual or most common stool type
over the preceding 3 months of 1 on the Bristol Stool Form Scale)
• History of inflammatory bowel disease (includes Crohn's disease and ulcerative
colitis, but does not include irritable bowel disease)
• Unrepaired rectovaginal fistula/chronic 4th degree laceration
• Full thickness rectal prolapse
• History of congenital anorectal malformation
• History of bowel resection surgery for any indication
• Minor anal procedures within 6 months for treatment of ABL (injection of bulking agent
or radiofrequency energy) or ligation of hemorrhoids
• Prior pelvic or abdominal radiation
• Diagnosis of cancer of the descending colon or anus
• Diagnosis of cancer in the region where the PTNS or sham needles or surface electrodes
would be placed
• Pacemaker, implantable defibrillator
• Current use of Interstim sacral nerve stimulator or TENS in the pelvic region, back,
or legs
• Clinically significant neurological disorders known to affect anal continence
• Coagulopathy
• Severe peripheral edema preventing accurate placement of PTNS needles
• Chronic swollen, infected, inflamed skin or skin eruptions (e.g., phlebitis,
thrombophlebitis, varicose veins) in the region where the PTNS or sham needles or
surface electrodes would be placed
• Metal implant in foot/toes near TENS electrode location
• Marked sensory deficit (numbness) of feet or ankles in the region where the PTNS or
sham needles or surface electrodes would be placed
• Childbirth within the last 3 months
• Pregnant or planning to become pregnant during the study duration 1 year; a urine
pregnancy test will be performed and must be negative by the first intervention visit
if the participant is of childbearing potential
• Unwilling to use acceptable form of contraceptive if the participant is of
childbearing potential
• Participation in another intervention trial impacting bowel function
• Inability to provide informed consent, complete questionnaires independently, or to
attend intervention sessions
• Unable or unwilling to complete the bowel diary in Run-In Phase (valid diary defined
as data from ≥ 10 of 14 days with minimum of 3 consecutive days per week)
• Unwilling to download bowel diary app onto smartphone if the participant owns a
smartphone
• Visual impairment prohibiting reading the paper diary, the smart phone screen
• Unable to speak, read, or write in English or Spanish at a basic level