Search Results
within category "Digestive Health & 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.
Interventions for Patients With Alzheimer's Disease and Dysphagia
The overall purpose of this project is to develop effective dysphagia rehabilitative
interventions for patients with Alzheimer's Disease and related dementias at risk for
pneumonia development.
Nicole Pulia, PhD, CCC-SLP
All
50 Years to 99 Years old
N/A
This study is NOT accepting healthy volunteers
NCT03682081
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Inclusion criteria (patients):
• Age 50-99
• English speaking
• Diagnosis of dementia or cognitive impairment or memory loss
• Clinical Dementia Rating (CDR) scale score between 0.5 and 2.0
• Actively involved caregiver
• Resides at home or an assisted living facility
Inclusion criteria (caregivers)
• English speaking
• Age 18 and older
• Contact with patient at least 1 time a week
• Has access to a working telephone
Exclusion criteria (patients):
• Dementia due to cerebrovascular disease as primary cause
• History of head and neck cancer or other structural deformity that can affect
swallowing
• Allergy to barium
• Currently breastfeed or pregnant or planning to become pregnant
Exclusion criteria (caregivers):
• Lacks ability to give consent
Dementia, Dysphagia, Alzheimer Disease, Dementia in other diseases classified elsewhere, Unspecified dementia, Alzheimer's disease, Mild Cognitive Impairment, Aphagia and dysphagia, Aging & Geriatrics, Food & Nutrition
Efficacy of Oral Vancomycin Prophylaxis for Prevention of Recurrent Clostridium Difficile Infection
This study evaluates the efficacy of prophylaxis with oral vancomycin for preventing
recurrent Clostridium difficile Infection (CDI) in patients who have experienced at least one
CDI episode in the last 180 days and are receiving antibiotics for a non CDI condition.
Participants will be randomized to receive either placebo or oral vancomycin in addition to
their prescribed antibiotic therapy.
Nasia Safdar, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03462459
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Inclusion Criteria:
• Willing to provide informed consent.
• Willing to comply with all study procedures and be available for the duration of the
study.
• Documented diagnosis of at least one CDI within the last 180 days with treatment
completed.
• Currently receiving systemic antibiotics for a non-CDI condition with anticipated
duration of no more than 2 weeks.
• Females of childbearing potential must have a negative pregnancy test prior to
randomization and agree to use adequate contraception prior to randomization, for the
duration of the study, and for 4 weeks following study completion.
• Have received no more than 72 hours of non-CDI antibiotics.
Exclusion Criteria:
• History of hypersensitivity or allergy to oral vancomycin.
• Current use of oral vancomycin
• Patients on concurrent treatment with metronidazole or tetracycline monotherapy for
any indication
• Patients diagnosed with inflammatory bowel disorder (Crohn's disease), or bacterial
gastrointestinal infection cause by agents other than C. difficile (e.g. Salmonella
sp.), toxic megacolon and/or known small bowel ileus.
• Dysphagia (inability to swallow capsules) or unwilling to swallow capsules.
• Major gastrointestinal surgery within 3 months of enrollment (does not include
appendectomy or cholecystectomy).
• Any history of total colectomy or bariatric surgery.
• Unable or unwilling to fulfill study requirements.
• Expected life expectancy < 6 months.
• Patients enrolled in another clinical trial with investigational drugs within 30 days
prior to randomization.
• Women who are pregnant or breast-feeding.
• Any patient deemed not suitable for study participation at the discretion of the study
investigator.
• Diarrhea (3 or more loose stools in a 24 hour period) at enrollment.
Technical Validation of MR Biomarkers of Obesity-Associated NAFLD (NAFLD)
The overall goal of this collaborative research program is to develop, validate and translate
advanced quantitative magnetic resonance (MR) biomarkers of obesity-associated non-alcoholic
fatty liver disease (NAFLD). This protocol represents the research plan for two distinct
phases. The first phase is an optimization phase. The second phase is designed to complete a
rigorous test of conventional and advanced MRE techniques. Complementary anthropometric,
laboratory, and MR measures will also be collected to characterize the cohort and identify
factors that affect MRE performance
Scott Reeder, MD, PhD in Biomedical Eng
All
18 Years and over
NA
This study is also accepting healthy volunteers
NCT03674528
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Inclusion Criteria (Phase 1 and 2 participants)
• Age of at least 18 years
• Severely obese (BMI ≥ 35 kg/m2) patient
Inclusion Criteria (Phase 2 participants only)
• Cleared for weight-loss surgery
• Willing and able to complete all safety and follow-up procedures
• Willing to allow for the banking of biological samples
Exclusion Criteria (Phase 1 and 2 participants)
• Contraindications to MRI
• Girth or weight that exceeds scanner capacity
• Women of childbearing potential that are pregnant or will be attempting to become
pregnant during the study duration.
Exclusion Criteria (Phase 2 participants only)
• Known liver malignancies
• Regular & excessive alcohol consumption within 2 years prior to recruitment
• Use of steatogenic or hepatotoxic drugs
• Clinical or laboratory evidence of liver disease other than Nonalcoholic fatty liver
disease (NAFLD)/ Nonalcoholic steatohepatitis (NASH) (e.g. HCV Ab, HBV Ab,
ceruloplasmin)
• The subject has increased bleeding risk (i.e., decreased platelets, von Willebrand
disease)
Oropharyngeal dysphagia, or difficulty swallowing, is a devastating condition that affects
physiological and psychosocial functioning in 1 in 25 adults. Many dysphagia treatments
exist, but our ability to adequately measure treatment outcomes is limited. Pharyngeal
high-resolution manometry (pHRM) directly measures swallowing pressures, providing an
objective measurement of physiology that characterizes the basic mechanisms of swallowing.
pHRM is well-poised to measure outcomes of dysphagia treatments due to its direct, objective,
and reproducible measures of swallowing function.
This proposed project will address a central hypotheses that objective swallowing measures
(including (pHRM) will reveal treatment-mediated swallowing changes, will align with
patient-reported outcome measures, and will be able to predict who will benefit from
treatment. The investigators will follow a cohort of participants with oropharyngeal
dysphagia as they undergo either pharyngeal strengthening therapy or relief of upper
esophageal sphincter outlet obstruction at three time points: baseline, mid-treatment (4-6
weeks) and post-treatment (10-12 weeks). The investigators will compare participants to
healthy controls using pHRM, videofluoroscopy, diet assessment, functional reserve tests, and
patient-reported outcome measures.
Timothy Mcculloch
All
18 Years to 99 Years old
NA
This study is also accepting healthy volunteers
NCT04130867
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Inclusion Criteria:
• Pathological Group
• Must have dysphagia as diagnosed by a licensed and certified otolaryngologist,
gastroenterologist, or speech-language pathologist AND must have a dysphagia
treatment plan that includes one of the following primary goals:
• Therapy to strengthen oropharyngeal musculature
• Medical or surgical management to relieve an obstruction at the upper
esophageal sphincter
• Must agree to comply with swallowing assessment, including interview and
manometry
• Must sign the Informed Consent form approved by the Health Sciences Institutional
Review Board of the University of Wisconsin
• Normal Group
• Having no swallowing disorders
• Must agree to comply with swallowing assessment, including interview and
manometry
• Must sign the Informed Consent form approved by the Health Sciences Institutional
Review Board of the University of Wisconsin.\
Exclusion Criteria:
• Pathological Group
• Therapeutic management plan already initiated prior to recruitment
• Therapy goals including only improvement of swallowing coordination
• Developmental disability, dementia, cognitive dysfunction, or difficulty
comprehending instructions
• Positive history of allergic response to topical anesthetic
• Allergy to food relevant to study participation (e.g. lactose intolerance)
• Normal Group
• Known swallowing disorder
• Developmental disability, dementia, cognitive dysfunction, or difficulty
comprehending instructions
• Positive history of allergic response to topical anesthetic
• Allergy to food relevant to study participation (e.g. lactose intolerance)
OAR-Based, Dose Escalated SBRT With Real Time Adaptive MRI Guidance for Liver Metastases
Stereotactic Body Radiation Therapy (SBRT) is a noninvasive local therapy with proven
efficacy in a number of solid tumor types. However, colorectal cancer (CRC) liver metastases
have been shown to be particularly resistant to SBRT, and often are found to have
significantly worse rates of control compared with other histologies. Higher SBRT dose was
recently shown to improve local control in CRC pulmonary metastases, however, increasing dose
delivery with SBRT has been limited based on the risk of toxicity to adjacent structures, and
the ability to visualize them during treatment. This is particularly relevant in treating
liver tumors, as tumor and small bowel movement can often make tumor targeting and
organs-at-risk (OAR) avoidance especially difficult. MRI-guided SBRT for liver tumors is both
safe and feasible and offers an as yet unprecedented opportunity to achieve the highest
possible safe dose to liver tumors.
The purpose of this trial is to identify a safe maximum tolerated dose level for MRI-guided
SBRT treatment of bowel and liver metastases, respectively.
Eligible participants will be on study for up to 12 months.
Michael Bassetti, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT04020276
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Inclusion Criteria:
• For Phase IA trial, have a diagnosis of histologically confirmed or clinically
suspected metastatic cancer to the liver; for Phase IB trial have have a diagnosis of
histologically confirmed or clinically suspected metastatic CRC to the liver.
• Participant must be a candidate for SBRT to at least one intrahepatic lesion but no
more than 6 intrahepatic lesions.
• Participant must be a candidate for treatment on the ViewRay treatment unit. Must be
screened to rule out implants and devices that are not MRI compatible.
• Be willing and able to provide written informed consent.
• Participants may be therapy-naïve or have had prior systemic therapy up to two weeks
prior to study entry.
• No active central nervous system (CNS) metastatic disease. NOTE: Subjects with CNS
involvement must meet all of the following to be eligible:
• At least 28 days from prior definitive treatment of their CNS disease by surgical
resection, SBRT or Whole Brain Radiation Therapy (WBRT) at the time of
registration
• AND asymptomatic and off systemic corticosteroids and/or enzyme-inducing
antiepileptic medications for brain metastases for >14 days prior to
registration.
• Demonstrate adequate organ function as defined in the following table; all screening
labs should be performed within 28 days of SBRT treatment initiation.
• Platelet count greater than or equal to 50000 /µL
• Absolute Neutrophil Count (ANC) greater than or equal to 1000 /µL
• Hemoglobin (Hgb) greater than or equal to 8 g/dL or greater than or equal to 5.6
mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of
assessment)
• Serum creatinine OR measured or calculated creatinine clearance (GFR can also be
used in place of creatinine or CrCl) Creatinine/Calculated creatinine clearance
(CrCl) greater than or equal to 30 mL/min for subject with creatinine levels
greater than 1.5 X institutional upper limit of normal (ULN)
• Bilirubin greater than or equal to 1. 5 × ULN OR direct bilirubin greater than or
equal to ULN for participants with total bilirubin levels greater than 1.5 ULN
• Aspartate aminotransferase (AST) and ALT (SGPT) greater than or equal to 5 × ULN
• International Normalized Ratio (INR) or Prothrombin Time (PT) greater than or
equal to 1.5 X ULN unless participant is receiving anticoagulant therapy as long
as PT or PTT is within therapeutic range of intended use of anticoagulants
• Activated Partial Thromboplastin Time (aPTT) greater than or equal to 1.5 X ULN
unless participant is receiving anticoagulant therapy as long as PT or PTT is
within therapeutic range of intended use of anticoagulants
• For participants enrolled on the liver dose escalation arm, screening labs must be
consistent with Child Pugh class A unless therapeutic anticoagulation places them in
Child Pugh B. In that case, trial entry or exclusion will be at the discretion of the
treating physician.
• Have a performance status of 2 or less on the Eastern Cooperative Oncology Group
(ECOG) performance scale.
• Life expectancy of > 12 weeks.
• Women of childbearing potential (WOCP) should have a negative urine or serum pregnancy
test prior to initiation of radiation therapy. If the urine test is positive or cannot
be confirmed as negative, a serum pregnancy test will be required.
• WOCP must not be pregnant or breast-feeding.
• WOCP must be willing to use an effective method of birth control such as an oral,
implantable, injectable, or transdermal hormonal contraceptive, an intrauterine device
(IUD), use of a double barrier method (condoms, sponge, diaphragm, or vaginal ring
with spermicidal jellies or cream), or total abstinence for the duration of the
radiotherapy and 60 days thereafter.
NOTE: A person of childbearing potential is anyone (regardless of sexual orientation,
gender identity, having undergone a tubal ligation, or remaining celibate by choice) who
was born with a uterus and at least one ovary and meets both of the following criteria:
• Is post-menarcheal (i.e., has had at least one prior menses)
• Has not undergone a hysterectomy or bilateral oophorectomy or has not been naturally
postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in
the preceding 12 consecutive months).
• Participant is willing and able to comply with the protocol for the duration of the
study including undergoing treatment and scheduled visits and examinations including
follow up.
Exclusion Criteria:
• Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of the initiation of SBRT.
• History of a second invasive cancer in the last 3 years (except for appropriately
treated low-risk prostate cancer, treated non-melanoma skin cancer, appropriately
treated ductal carcinoma in situ or early stage invasive carcinoma of breast
appropriately treated in situ/early stage cervical/endometrial cancer.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with participation for the
full duration of the trial, or is not in the best interest of the subject to
participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with follow up
scans or visits.
• Has a primary tumor histology of germ cell tumor, leukemia, or lymphoma.
• Has a primary liver cancer such as cholangiocarcinoma or hepatocellular carcinoma.
• Has had prior radiation therapy that significantly overlaps with the liver.
• Has a diagnosis of Crohn's disease, ulcerative colitis, or scleroderma.
• Participants with Gilbert's disease or other primary disorders of bilirubin metabolism
will not be allowed on the trial.
• For participants in the liver dose escalation arm only, has pre-existing liver disease
such that patients are classified as Child Pugh B or worse. If the participant is
anti-coagulated such that their INR places them in the CP-B classification, exclusion
or inclusion will be at the discretion of the treating physician.
• Pregnancy or women of childbearing potential and men who are sexually active and
refuse to use medically acceptable forms of contraception.
• Participants with implanted hardware that would preclude MRIs.
Liver Metastases, Stereotactic Body Radiation Therapy, MRI-guided Treatment, Breast, Colon, Lung, Colon and Rectum
Oxaliplatin and Liposomal Irinotecan (Plus Trastuzumab for HER2-positive Disease) in Advanced Esophageal and Gastric Adenocarcinoma
This is an open label, phase II, multi-site trial evaluating the efficacy and safety of the
combination of 5-FU, oxaliplatin, nal-IRI, and immunotherapy (plus trastuzumab for
HER2-positive tumors) as first-line therapy for participants with advanced Esophageal and
Gastric Adenocarcinoma (EGA). The investigators hypothesize that this drug combination will
be better tolerated than current first-line chemotherapy combinations for this disease.
Nataliya Uboha, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04150640
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Inclusion Criteria:
• Written informed consent and HIPAA authorization for release of personal health
information.
NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
• Histological or cytological confirmed locally advanced or metastatic EGA. Known HER2
status prior to treatment initiation required. Known PDL1 CPS status prior to
treatment initiation.
• Measurable disease according to RECIST v1.1.
• No prior lines of systemic therapy for advanced disease.
• Participants who had received neoadjuvant or adjuvant therapy or definitive
chemoradiation will be allowed to participate if recurrence occurred 6 months or
longer from the completion of all prior treatments.
• Demonstrate adequate organ function as defined below; all screening labs to be
obtained within 14 days prior to registration
• Absolute Neutrophil Count (ANC) ≥1,500 /μl without the use of hematopoietic
growth factors
• Hemoglobin (Hgb) ≥8 g/dL (blood transfusions are permitted for participants with
hemoglobin levels below 8 g/dL)
• Platelets ≥100,000 /μl
• Serum creatinine ≤1.5 X upper limit of normal (ULN) OR Measured or calculated
creatinine clearance (GFR can also be used in place of creatinine or CrCl). CrCl
calculation using the Cockcroft-Gault formula. ≥50 mL/min for participants with
creatinine levels > 1.5 X institutional ULN
• Bilirubin within normal range for the institution (biliary drainage is allowed
for biliary obstruction)
• Aspartate aminotransferase (AST) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver
metastases
• Alanine aminotransferase (ALT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver
metastases
• Albumin >3.0 g/dL
• International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless
subject is receiving anticoagulant therapy as long as PT or PTT is within
therapeutic range of intended use of anticoagulants
• Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is
receiving anticoagulant therapy as long as PT or PTT is within therapeutic range
of intended use of anticoagulants
• Women of childbearing potential should have a negative urine or serum pregnancy test
within 14 days of study registration. NOTE: Women are considered of child bearing
potential unless they are surgically sterile (have undergone a hysterectomy, bilateral
tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at
least 12 consecutive months
• Women of childbearing potential and males must be willing to abstain from heterosexual
activity or to use a form of effective method of contraception from the time of
informed consent until 30 days after treatment discontinuation.
• As determined by the enrolling physician or protocol designee, ability of the subject
to understand and comply with study procedures for the entire length of the study.
Exclusion Criteria:
• Known hypersensitivity to 5-FU, oxaliplatin or other platinum agents, or any of the
components of nal-IRI and other liposomal products.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency (testing not required prior to
enrollment).
• Other active malignancy requiring treatment within the last 2 years. Exceptions
include subjects with non-melanoma skin cancer, non-invasive/in situ cancer or
low-risk prostate cancer requiring hormonal therapy only.
• Current therapy with other investigational agents or participation in another clinical
study (supportive care and nontherapeutic trial participation allowed if not receiving
an investigational drug). Participants may participate in prescreening for other
therapeutic trials (prescreening of biologic sample for specific mutations, receptors,
etc.)
• Major surgery within 28 days or minor surgery within 14 days of the start of the study
treatment, except for tumor biopsy or placement of central infusion device (port
placement).
• Radiotherapy less than 7 days prior to the start of the study treatment
• Participants who receive nivolumab or pembrolizumab in addition to chemotherapy should
not have any contraindications to immune checkpoint inhibitors and should not have
received immunotherapy agents for the treatment of EGA prior to study enrollment.
• Participants must not have active autoimmune disease that has required systemic
treatment in the past 2 years. Participants are permitted to receive
immunotherapy l if they have vitiligo, type I diabetes mellitus, residual
hypothyroidism due to autoimmune condition only requiring hormone replacement,
psoriasis not requiring systemic treatment, or conditions not expected to recur
in the absence of an external trigger (precipitating event).
• Participants must not have a condition requiring systemic treatment with either
corticosteroids (>10 mg/day prednisone equivalents) or other immunosuppressive
medications within 14 days of study immunotherapy administration. Inhaled or
topical steroids and adrenal replacement doses (≤10 mg/day prednisone equivalent)
are permitted. Participants with prior immune mediated adverse events related to
immunotherapy that resulted in permanent treatment discontinuation with these
agents.
• Psychological, familial, or sociological condition potentially hampering compliance
with the study protocol and follow-up schedule.
• Active infection requiring systemic therapy.
• Pregnant or breastfeeding.
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Participants with previously treated brain metastases may participate provided they
are stable (without evidence of progression by imaging for at least four weeks prior
to the first dose of trial treatment and any neurologic symptoms have returned to
baseline), have no evidence of new or enlarging brain metastases, and are not using
steroids for at least 7 days prior to trial treatment. This exception does not include
carcinomatous meningitis, which is excluded regardless of clinical stability.
• Severe arterial thromboembolic events (myocardial infarction, unstable angina
pectoris, stroke) less than 6 months before inclusion.
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled
blood pressure.
• Known history of Human Immunodeficiency Virus (HIV).
Evaluation and Treatment of Iron Deficiency in Ovarian Cancer Patients
This study tests the hypothesis that IV iron sucrose infusions given to iron deficient
ovarian cancer patients prior to debulking surgery can improve pre-operative iron stores and
decrease transfusion of packed red blood cells in the peri-operative period. 21 participants
at least 18 years of age with epithelial ovarian cancer of any stage requiring neoadjuvant
chemotherapy and surgery will be enrolled. Participants will be on study for a period of up
to 3 months.
Lisa Barroilhet, MD
Female
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT03933813
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Inclusion Criteria:
• Provide written informed consent.
• Has a diagnosis of true or functional iron deficiency without anemia within 30 days of
treatment on this protocol
• Iron deficiency without anemia (normal Hgb >/= 11.6 g/dL but ferritin < 30 ng/mL)
• Functional iron deficiency without anemia (ferritin >30 ng/ml and iron saturation
of <50%)
• Has a clinical diagnosis of suspected epithelial ovarian cancer based on imaging
studies, exam findings and laboratory values
• Participants must be planning to receive neoadjuvant chemotherapy for their cancer
diagnosis (NACT is defined as chemotherapy prior to debulking surgery)
• Participants must be planning to undergo surgery for their cancer diagnosis
• Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test
within 7 days prior to administration of first dose of IV iron sucrose. WOCBP is
defined as patients who retain their reproductive structures and are not menopausal
(defined as > age 50 with no menses for at least 1 year)
• Participants of reproductive potential must agree to use effective birth control
during study participation. Effective birth control is defined as any FDA approved
contraceptive method
Exclusion Criteria:
• Currently taken any form of oral or intravenous iron therapy. Patients must have
discontinued iron therapy > 30 days from study entry
• Current untreated or unstable heart disease
• History of iron induced hypersensitivity or allergy
• History of leukemia, lymphoma, or other myelodysplastic disorders
• Prior diagnosis of hemochromatosis or hemoglobinopathy (e.g. thalassemia)
• Any subject with immediate requirement for radiotherapy
• Concomitant enrollment in another clinical trial interfering with endpoints on this
study
• Any medical condition which could compromise participation in the study according to
the investigator's assessment
• Female patient who is pregnant or breast-feeding
• Patients unwilling or unable to comply with the protocol or unable to give informed
consent
Epithelial Ovarian Cancer, Anemia, Iron Deficiency Anemia, Ovary
Treatment of Cytomegalovirus (CMV) Infections With Viral-Specific T Cells
The present trial will consist of the treatment of 20 pediatric and adult Hematopoietic Stem
Cell Transplantation (HSCT) recipients or immunocompromised participants diagnosed with
opportunistic Cytomegalovirus (CMV) infections with virus-specific, antigen-selected T-cells.
CMV-specific T-cells will be isolated from donor leukapheresis products using the CliniMACS®
Prodigy. Prior studies on transfer of CMV specific T-cells have been shown to be safe and
efficacious in the treatment of CMV infections.
The main trial objective is to evaluate the feasibility and safety of CMV-specific T-cell
transfer in adult and pediatric participants suffering from CMV infections or reactivation
following HSCT or due to other immunocompromised states (e.g.; primary immunodeficiency,
cytotoxic therapy).
Participants will be followed for one year.
Inga Hofmann, M.D.
All
1 Month and over
Phase 1
This study is NOT accepting healthy volunteers
NCT03798301
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Inclusion Criteria:
1. Adult or pediatric patient suffering from CMV reactivation/infections following HSCT
or due to other immunocompromised states (e.g.; primary immunodeficiency, cytotoxic
therapy).
• CMV reactivation/viremia defined as positive (>500 copies/ml) CMV qPCR and/or
• Presence of symptoms secondary to CMV infection or evidence of invasive CMV
infection (e.g. pneumonitis, colitis) AND
• Patients must have ONE OF THE FOLLOWING CRITERIA:
• Absence of an improvement of viral load after ≥ 14 days of antiviral therapy
with ganciclovir, valganciclovir or foscarnet (decrease by at least 1 log,
i.e. 10-fold), or
• New, persistent and/or worsening CMV-related symptoms, signs and/or markers
of end organ compromise while on antiviral therapy with ganciclovir,
valganciclovir or foscarnet, or
• Have contraindications or experience adverse effects of antiviral therapy
with ganciclovir, valganciclovir or foscarnet, or
• Known resistance to ganciclovir and/or foscarnet based on molecular testing.
2. Recipients of an allogeneic HSCT must be 28 days after stem cell infusion at the time
of T-cell transfer.
3. Written informed consent given by patient or legal representative.
4. Minimum patient age 1 month.
5. Minimum weight 7 lbs.
6. Female patients of childbearing age with negative pregnancy tests.
7. Patient Karnofsky/Lansky Performance Status >30%.
8. Donor eligible based on FACT infectious screening requirements.
Exclusion Criteria:
1. Patient with acute GVHD > grade 2 or active moderate or severe chronic GVHD at time of
T-cell transfer
2. Patient receiving steroids (>1.0 mg/kg body weight (BW) prednisone equivalent) at the
time of T-cell transfer
3. Patient received allogeneic HSCT less than 28 days prior to T-cell transfer
4. Patient treated with donor lymphocyte infusion (DLI) within 28 days prior to T-cell
transfer
5. Patient treated with Thymoglobulin (ATG), Alemtuzumab or T-cell immunosuppressive
monoclonal antibodies within 28 days.
6. Patient with organ dysfunction or failure as determined by Karnofsky (patients >16
years) or Lansky (patients ≤16 years) score ≤30% (Appendix 5)
7. Patients with CMV retinitis
8. Concomitant enrollment in another clinical trial with endpoints interfering with this
study
9. Any medical condition which could compromise participation in the study according to
the investigator's assessment
10. Known HIV infection
11. Female patient who is pregnant or breast-feeding, or adult of reproductive potential
not willing to use an effective method of birth control during study treatment. Note:
Women of childbearing potential must have a negative serum pregnancy test at study
entry.
12. Patients unwilling or unable to comply with the protocol or unable to give informed
consent.
Donor Eligibility:
The original donor will be the first choice as source of T cells. If the original donor is
not available for donation (such as NMDP donor, cord blood unit, or related donor not
available) of peripheral mononuclear cells or does not meet all donor eligibility criteria
(including donor selection criteria based on University of Wisconsin •Madison Standard
Operating Procedures for the selection of allogeneic donors), alternative related donors
will be selected, with preference for those who have full HLA matching in 6/6 loci over
those with partial HLA matching (≥ 3/6 HLA loci).
1. All donors must be ≥ 18 years old, available, CMV IgG positive, eligible and capable
of undergoing a single standard 2 blood volume leukapheresis. If original HSCT donor
is not available, CMV IgG negative or ineligible, a CMV IgG positive fully matched or
haploidentical family donor will be used.
2. Related donors must be at least partially HLA compatible, matching with recipient in
at least 3/6 HLA loci (HLA-A, HLA-B and HLA-DRB1 will be considered for this).
3. Donors must be CMV IgG seropositive.
4. Donors must show CMV T-cell activation after incubation with MACS GMP PepTivator
Peptide Pools of CMV pp65 before undergoing leukapheresis.
5. Donor must meet the criteria for donor selection defined in the Standard Operating
Procedures of the University of Wisconsin Hospitals and Clinics Stem Cell Transplant
Program and in FACT standards.
Anus, Any Site, Bones and Joints, Brain and Nervous System, Breast, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Hodgkin's Lymphoma, Ill-Defined Sites, Kaposi's Sarcoma, Kidney, Larynx, Leukemia, other, Lip, Oral Cavity and Pharynx, Liver, Lung, Lymphoid Leukemia, Melanoma, Skin, Multiple Myeloma, Mycosis Fungoides, Myeloid and Monocytic Leukemia, Non-Hodgkin's Lymphoma, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder, Head and Neck, Gastrointestinal cancers, other, Colon and Rectum, Anal, Sarcoma, Melanoma/Skin cancer, Hematologic cancers, other, Uterus, Genitourinary cancers, other, Bladder, Brain/Central Nervous System, Endocrine cancers, Lymphoma, Leukemia, CMV Infection, Cytomegalovirus Infections, CMV Viremia, Opportunistic Infections
The Effect of Methotrexate on Sperm Quality in Men With Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal
tract which includes Crohn's disease (CD) and ulcerative colitis (UC) which peak in incidence
(rate or frequency) during the reproductive years. An increasing number of young people will
face challenging decisions regarding medical management of this chronic disease during a
period of time when they are still completing schooling, establishing their career, and/or
are building a family.
Treatment options for IBD consist of immunosuppressive therapy, such as immunomodulators
(azathioprine and methotrexate). Methotrexate (MTX) is a folic acid antagonist (a substance
that interferes with or inhibits the action of another). It is thought that MTX works by
decreasing the inflammation in the gastrointestinal tract. MTX has been studied for many
years and in used as treatment in not only IBD, but also in conditions such as rheumatoid
arthritis and lupus. However, due to concerns about the safety of MTX, particularly in
regards to fertility and pregnancy has limited its current use.
Participants are invited to take part in this research project to determine whether the
treatment of IBD patients with MTX is associated with an increased risk for infertility.
Investigators will recruit 75 male IBD patients under MTX treatment for their IBD as well as
75 healthy male controls for a total of 150 patients at the University of Wisconsin Hospital
& Clinics.
Sumona Saha, M.D.
Male
18 Years to 40 Years old
Pilot
This study is NOT accepting healthy volunteers
NCT02461784
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Inclusion Criteria:
1. Cases: Men aged 18 to 40 years with a confirmed diagnosis of UC or CD based on
endoscopy, pathology, and/or radiology AND who regularly take MTX (per oral,
subcutaneous, or intramuscular) either as monotherapy or in combination with
mesalamine (any except sulfasalazine), corticosteroids, anti-TNF agents, or
anti-adhesion molecules for at least one month specifically for the treatment of IBD.
Controls: Men aged 18 to 40 years with a confirmed diagnosis of UC or CD based on
endoscopy, pathology, and/or radiology AND who do not take MTX (per oral,
subcutaneous, or intramuscular) either as monotherapy or in combination with other
IBD-specific drugs.
2. Individual able and willing to consent to donate their sperm to research.
Exclusion Criteria:
1. Men with previously documented problems with male reproductive health such as known
hypothalamic-pituitary disorders (e.g. pituitary macroadenomas, pituitary infarction),
primary hypogonadism (e.g. cryptorchidism, Klinefelter's syndrome), or disorders of
sperm transport (e.g. erectile dysfunction, history of vasectomy)
2. Current use of alkylating agents, ketoconazole, sulfalsalazine, H2-receptor
antagonists or spironolactone
3. Men who have undergone ileal pouch anal anastomosis within 3 months of study entry
Alpha/Beta CD19+ Depleted Haploidentical Transplantation + Zometa for Pediatric Hematologic Malignancies and Solid Tumors
This phase I trial studies the safety of transplantation with a haploidentical donor
peripheral blood stem cell graft depleted of TCRαβ+ cells and CD19+ cells in conjunction with
the immunomodulating drug, Zoledronate, given in the post-transplant period to treat
pediatric patients with relapsed or refractory hematologic malignancies or high risk solid
tumors.
Christian Capitini, MD
All
7 Months to 21 Years old
Phase 1
This study is NOT accepting healthy volunteers
NCT02508038
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Inclusion Criteria:
• Availability of an eligible haploidentical donor
• Hematologic malignancy or solid tumor
• Patients with more than one malignancy (hematologic or solid tumor) are eligible
• Patients with hematologic malignancy must have no HLA identical sibling or suitable
unrelated donor OR time needed to find an acceptable unrelated donor match would
likely result in disease progression such that the patient may become ineligible for
any type of potentially curative transplant
• Relapsed or primary therapy-refractory AML with bone marrow blast < 20%
• High-risk refractory or relapsed ALL in patients for whom transplantation is
deemed indicated (relapse occurring < 30 months from diagnosis, patients
relapsing after previous allogeneic transplant, relapse after 2nd remission,
primary induction failure or hypodiploidy)
• Relapsed Hodgkin lymphoma unable to achieve 2nd remission or Very Good Partial
Response (VGPR) and therefore ineligible to receive autologous hematopoietic stem
cell transplant (auto-HSCT)
• Hodgkin lymphoma relapsing after auto-HSCT
• Primary refractory or relapsed non-Hodgkin lymphoma unable to achieve 2nd
remission or VGPR and therefore ineligible to receive auto-HSCT
• Non-Hodgkin lymphoma relapsing after auto-HSCT
• Myelodysplastic Syndrome/Myeloproliferative Syndrome
Solid Tumor
• Patients with solid tumor must have failed or have been ineligible to receive
auto-HSCT or if auto-HSCT would not offer > 20% chance of cure
• Neuroblastoma
• high risk with relapsed or refractory disease
• Soft tissue sarcomas (Rhabdomyosarcoma, Ewing sarcoma, Primitive Neuroectodermal Tumor
or other high-risk extracranial solid tumors)
• Relapsed or primary refractory metastatic
• 1st complete remission, but very high-risk features (i.e., < 20% survival with
conventional therapy)
• Osteosarcoma
• Failure to achieve Complete Response (CR) following initial therapy
• Relapsed with pulmonary or bone metastases and did not achieve a CR with surgery
and/or chemotherapy
• Karnofsky (patients > 16 years) or Lansky (patients 16 years or older) performance
score of ≥ 60
• Life expectancy of ≥ 3 months
• Patient must have fully recovered from acute toxic effects of all prior chemotherapy,
immunotherapy, or radiotherapy prior to entering this study
• Study enrollment no earlier than 3 months after preceding HSCT
• Glomerular Filtration Rate (GFR) ≥ 60 ml/min/1.73m2
• Total bilirubin < 3 mg/dL
• ALT (alanine aminotransferase, SCPT) ≤ 5 x Upper LImit of Normal (ULN) for age
• Ejection fraction of > 40% by Multigated Acquisition Scan (MUGA) or echocardiogram
• No evidence of dyspnea at rest
• No supplemental oxygen requirement
• If measured, carbon monoxide diffusion capacity (DLCO) >50%
• No severe peripheral neuropathy, signs of leukoencephalopathy or active Central
Nervous System (CNS) infection
• Patients with seizure disorders may be enrolled if seizures are well controlled on
anticonvulsant therapy
• If of reproductive potential, negative pregnancy test and willing to use effective
birth control method
• Informed consent from patient or legal guardian (if patient is minor)
Inclusion Criteria for Donors:
• Donor must be 18 years of age minimum, 65 years of age maximum
• Donor must be in good general health as determined by evaluating medical provider
• Must meet donor criteria for human cells, tissues, and cellular and tissue-based
products per Code of Federal Regulations 21 CFR 1271, subpart C. Specifically:
• Donor screening in accordance with 1271.75 indicates that the donor:
• Is free from risk factors for, and clinical evidence of, infection due to
relevant communicable disease agents and diseases; and
• Is free from communicable disease risks associated with xenotransplantation;
and
• The results of donor testing for relevant communicable disease agents in
accordance with 1271.80 and 1271.85 are negative or nonreactive, except as
provided in 1271.80(d)(1).
• Haploidentical by HLA-typing
• Preference will be given to donors who demonstrate KIR incompatibility with recipient
HLA class I ligands defined as the donor expressing a KIR gene for which the
corresponding HLA class I ligand is not expressed by the recipient.
• Negative testing for relevant communicable diseases:
• Hepatitis B surface antigen (HBsAg)
• Hepatitis B core antibody (Anti-HBc)
• Hepatitis C antibody (Anti-HCV)
• HIV 1 & 2 antibody (Anti-HIV-1, 2 plus O)
• HTLV I/II antibody (Anti-HTLV I/II)
• RPR (Syphilis TP)
• CMV (Capture CMV)
• MPX for: HepB (HBV-PCR), HepC (HCV-PCR), HIV (HIV-PCR)
• NAT for West Nile Virus (WNV-PCR)
• T. Cruzi •EIA (Chagas)
Exclusion Criteria:
• Pregnant or breast-feeding
• HIV infection
• Heart failure or uncontrolled cardiac rhythm disturbance
• Uncontrolled, Serious Active Infection
• Prior organ allograft
• Significant serious intercurrent illness unrelated to cancer or its treatment not
covered by other exclusion criteria expected to significantly increase the risk of
HSCT
• Any mental or physical condition, in the opinion of the PI (or PI designee), which
could interfere with the ability of the subject (or the only parent or legal guardian
available to care for the subject) to understand or adhere to the requirements of the
study
• Enrollment in any other clinical study from screening up to Day 100 (unless PI judges
such enrollment would not interfere with endpoints of this study)
Exclusion Criteria for Donors:
• Lactating females
• Pregnant females
Bones and Joints, Brain and Nervous System, Colon, Esophagus, Eye and Orbit, Hodgkin's Lymphoma, Ill-Defined Sites, Kidney, Leukemia, other, Liver, Lung, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Non-Hodgkin's Lymphoma, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Urinary Bladder, Brain/Central Nervous System, Hematologic cancers, other, Leukemia, Lymphoma, Sarcoma, Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Myelodysplastic Syndrome, Myeloproliferative Syndrome, Rhabdomyosarcoma, Ewing Sarcoma, Primitive Neuroectodermal Tumor, Osteosarcoma, Neuroblastoma
Safety and Diagnostic Efficacy of Mangoral in Participants With Focal Liver Lesions and Reduced Kidney Function (SPARKLE)
The overall objective of this study is to evaluate the safety and diagnostic efficacy of
Mangoral in liver MRI in participants with known or suspected focal liver lesions and severe
renal impairment. The diagnostic efficacy of Mangoral will be assessed in terms of
visualization of detected focal liver lesions in combined MRI (CMRI: combined
Mangoral-enhanced and unenhanced MRI) compared to unenhanced MRI.
Scott Reeder, MD, PhD in Biomedical Eng
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04119843
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Inclusion Criteria:
• Male and female participants 18 years and older.
• Known or suspected focal liver lesions based on medical history and previous
laboratory and/or imaging examinations.
• Severe renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73
m^2) based on medical history and previous laboratory examinations, at least once,
within the last 3 months prior to the Baseline Visit, or participants with an increase
in serum creatinine ≥ 0.3 mg/dL within 48 hours or ≥ 50% within 7 days prior to the
Baseline Visit.
Exclusion Criteria:
• Participants with simple liver cysts only.
• Any investigational drug or device within 6 weeks prior to the Baseline Visit.
• Any magnetic resonance imaging (MRI) contrast media within 6 weeks prior to Baseline
Visit or scheduled to receive any contrast medium before the last study visit.
• Participants with severe hepatic impairment (according to Child-Pugh score C).
• Participants scheduled for surgery before last study visit.
• Participants with encephalopathy / neurodegenerative or acute neurological disorders.
• Participants with hemochromatosis.
Known or Suspected Focal Liver Lesions and Severe Renal Impairment, Liver disease unspecified, Chronic renal disease, Kidney Disease & Urinary
Dose Escalation Study of CLR 131 in Children, Adolescents, and Young Adults With Relapsed or Refractory Malignant Tumors Including But Not Limited to Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma (CLOVER-2)
The study evaluates CLR 131 in children, adolescents, and young adults with relapsed or
refractory malignant solid tumors and lymphoma and recurrent or refractory malignant brain
tumors for which there are no standard treatment options with curative potential.
Diane Puccetti, M.D.
All
2 Years to 25 Years old
Phase 1
This study is NOT accepting healthy volunteers
NCT03478462
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Inclusion Criteria:
All Patients
• Previously confirmed (histologically or cytologically) pediatric solid tumor (e.g.,
neuroblastoma, sarcoma), lymphoma (including Hodgkin's lymphoma), or malignant brain
tumors that are clinically or radiographically suspected to be relapsed, refractory,
or recurrent for which there are no standard treatment options with curative
potential. Note: patients with diffuse intrinsic pontine glioma (DIPG) may enroll
without histological or cytological confirmation.
• ≥ 2 years of age and ≤ 25 years of age at time of consent/assent
• If ≥ age 16 years, Karnofsky performance status of ≥ 60. If < age 16 years, Lansky
performance status ≥ 60
• Platelets ≥ 75,000/µL (last transfusion, if any, must be at least 1 week prior to
study registration, and, unless deemed medically necessary, no transfusions are
allowed between registration and dosing)
• Absolute neutrophil count ≥ 750/µL
• Hemoglobin ≥ 8 g/dL (last transfusion must be at least 1 week prior to study
registration, and, unless deemed medically necessary, no transfusions are allowed
between registration and dosing)
• Using the bedside Schwartz formula, estimated GFR (creatinine clearance) > 60
ml/min/1.73m2
• Alanine aminotransferase < 3 × ULN
• Bilirubin < 2 × ULN
• Patients who have undergone autologous or allogeneic bone marrow transplant must be at
least 3 months from transplant.
• Patients enrolling at total dose levels > 30 millicurie (mCi)/m2 must have
availability or ability to collect an autologous hematopoietic stem cell back-up
product prior to CLR 131 administration. At minimum, 2 x 10^6/kg cryopreserved CD34+
cells must be available.
• Patient or his or her legal representative is judged by the Investigator to have the
initiative and means to be compliant with the protocol.
Patients with Pediatric Solid Tumor or Lymphoma
• At least 1 measurable lesion with longest diameter of at least 10 mm. Patients with a
lesion(s) that are determined to be Metaiodobenzylguanidine (MIBG) or positron
emission tomography (PET) positive may be enrolled at the investigator's discretion,
even if not associated with a measurable lesion of at least 10 mm. Patients with
neuroblastoma who have detectable disease may enroll provided they meet the
requirements of the International Neuroblastoma Response Criteria.
• Patients with known brain metastases must have completed any radiotherapy or systemic
treatments for brain metastases prior to enrollment; by investigator assessment be
considered stable with no new signs or symptoms for at least 1 month, and on a stable
dose of steroids (unchanged for three weeks prior to registration or on a steroid
tapering regimen).
Patients with Recurrent or Refractory Brain Tumors
• At least 1 measurable lesion with longest diameter of at least 10 mm on any imaging
sequence.
• Patients with previously known neurological deficits must be clinically stable at time
of enrollment and able to complete all study related procedures. Patients with
documented or newly diagnosed neurological deficits will be enrolled at the
investigator's discretion.
• If patient receives steroids for neurological symptom control, the dose must be stable
(unchanged for three weeks prior to registration) or on a steroid tapering regimen.
Initiation of steroids per routine care immediately prior to CLR 131 dosing is
acceptable.
Exclusion Criteria:
• Patients receiving active treatment for central nervous system metastases or those
that are likely to require active treatment during anticipated participation in this
trial. Patients with stable brain metastases treated with steroids may enroll at the
investigator's discretion
• For solid tumor and lymphoma patients only, central nervous system involvement unless
previously treated with surgery, systemic therapy, or radiotherapy with the patient
neurologically stable. Patients with metastatic brain tumors that have been previously
treated are allowed, provided the patient is neurologically stable (determined at the
investigator's discretion).
• Antitumor therapy or investigational therapy, within 2 weeks of dosing. For certain
types of radiation (craniospinal, total abdominal, whole lung [spot irradiation to
skull-based metastases is not considered craniospinal radiation for the purposes of
this study]), at least 3 months must have elapsed. No washout is required for
palliative focal radiation. NOTE: Patients participating in non-interventional
clinical trials (i.e., non-drug) are allowed to participate in this trial
• Patients previously treated with iodine-131 (131I)-MIBG who have already received a
cumulative I-131 dose > 54 mCi/kg or who would exceed 54 mCi/kg by participating in
this trial, are not eligible.
Anus, Bones and Joints, Brain and Nervous System, Breast, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Hodgkin's Lymphoma, Ill-Defined Sites, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung, Non-Hodgkin's Lymphoma, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Urinary Bladder, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus, Pediatric Solid Tumor, Pediatric Lymphoma, Pediatric Brain Tumor, DIPG, Neuroblastoma, Ewing Sarcoma, Rhabdomyosarcoma, Osteosarcoma
DC/AML Fusion Cell Vaccine vs Observation in Patients Who Achieve a Chemotherapy-induced Remission
This research study is studying a cancer vaccine called Dendritic Cell/AML Fusion vaccine
(DC/AML vaccine) as a possible treatment for Acute Myelogenous Leukemia (AML).
The interventions involved in this study are:
-Dendritic Cell/AML Fusion vaccine (DC/AML vaccine)
Aric Hall, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03059485
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Step 1: Eligibility Criteria for Tumor Collection
Inclusion Criteria
• Patients must have AML at initial diagnosis or at first relapse
• Patients must be ≥ 55 years old
• ECOG performance status ≤2 (Appendix A)
• Patients must have normal organ and marrow function as defined below:
total bilirubin ≤ 2.0 mg/dL AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal
creatinine ≤ 2.0 mg/dl
• The effects of DC/AML fusion cells on the developing human fetus are unknown. For this
reason, 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 and for the duration of study participation. Should a woman become pregnant or
suspect she is pregnant while participating in this study, she should inform her
treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria
-Active or prior documented autoimmune or inflammatory disorders including but not limited
to the following:
--GI Disorders: (including inflammatory bowel disease [eg, ulcerative colitis, Crohn's
disease], diverticulitis (with the exception of a prior episode that has resolved), celiac
disease, or other serious gastrointestinal chronic conditions associated with diarrhea.
• Systemic lupus erythematosus
• Wegener's syndrome [granulomatosis with polyangiitis]
• Myasthenia gravis
• Graves' disease
• Rheumatoid arthritis
• Hypophysitis
• Uveitis
The following are exceptions to this criterion: subjects with vitiligo or alopecia;
subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone
replacement; or subjects with psoriasis not requiring systemic treatment..
• Because of compromised cellular immunity, patients who have a Known human
immunodeficiency virus (HIV), hepatitis C virus (HCV) or evidence of active hepatitis
B virus (HBV).
• Patients must not have significant cardiac disease characterized by symptomatic
congestive heart failure, unstable angina pectoris, clinically significant cardiac
arrhythmia
• Patients must not be pregnant. All premenopausal patients will undergo pregnancy
testing. Men will agree to not father a child while on protocol treatment. Men and
women will practice effective birth control while receiving protocol treatment.
• Individuals with a history of a different malignancy are ineligible except for the
following circumstances. Individuals with a history of other malignancies are eligible
if they have been disease-free for at least 5 years and are deemed by the investigator
to be at low risk for recurrence of that malignancy. Individuals with the following
cancers are eligible if diagnosed and treated within the past 5 years: non-invasive
cancer (such as, any in situ cancers) and basal cell or squamous cell carcinoma of the
skin.
• Prior allogeneic transplant
Step 2: Eligibility Criteria Prior to Randomization
Inclusion Criteria
• Patients must have obtained a complete remission with chemotherapy defined by the
absence of circulating blasts, and less than 5% blasts on bone marrow examination
following hematopoietic recovery
• Patient required no more than 2 cycles of chemotherapy or 4 cycles of a
hypomethylating agent (alone or in conjunction with venetoclax) to achieve remission.
• Resolution of all chemotherapy related grade III-IV toxicity as per CTC criteria 4.0
• Laboratories:
Absolute Neutrophil Count >1,000/uL Platelets > 50,000/uL Bilirubin < 2.0 mg/dL Creatinine
<2.0 mg/dL AST/ALT < 3.0 x ULN
•For patients with evidence of minimal residual disease prior to vaccination, assessment
of minimal residual disease status by cytogenetics or FISH will be followed post
vaccination.
Exclusion Criteria
• Patients must not have serious intercurrent illness such as infection requiring IV
antibiotics, or significant cardiac disease characterized by significant arrhythmia,
ischemic coronary disease or congestive heart failure
• Patients who, with their treating physician, choose to proceed with an allogeneic
transplant at the time of remission will not be eligible for randomization
• Active or prior documented autoimmune or inflammatory disorders including but not
limited to the following:
• GI Disorders: (including inflammatory bowel disease [eg, ulcerative colitis,
Crohn's disease], diverticulitis (with the exception of a prior episode that has
resolved), celiac disease, or other serious gastrointestinal chronic conditions
associated with diarrhea.
• Systemic lupus erythematosus
• Wegener's syndrome [granulomatosis with polyangiitis]
• Myasthenia gravis
• Graves' disease
• Rheumatoid arthritis
• Hypophysitis
• Uveitis
The following are exceptions to this criterion: subjects with vitiligo or alopecia;
subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone
replacement; or subjects with psoriasis not requiring systemic treatment.
• Current or prior use of immunosuppressive medication within 14 days prior to first
dose of vaccine. The following are exceptions to this criterion: intranasal, inhaled,
topical or local steroid injections (eg. intra-articular injection); steroids as
premedication for hypersensitivity reactions; systemic corticosteroid at physiologic
doses not to exceed 10mg/day of prednisone or equivalent
• Known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or evidence of
active hepatitis B virus (HBV).
• History of hypersensitivity to durvalumab or any excipient
• Receipt of live attenuated vaccination within 30 days prior the first vaccine
• Female subjects who are pregnant, breast-feeding or female patients of reproductive
potential who are not employing an effective method of birth control from starting
vaccine, including dosing interruptions through 90 days after receipt of the last
vaccine. Refrain from egg cell donation during vaccination and for at least 90 days
after the last vaccine.
• Male subjects who are not employing an effective method of birth control from starting
vaccine, including dosing interruptions through 90 days after receipt of the last
vaccine. Refrain from sperm donation during vaccination and for at least 90 days after
the last vaccine.
Step 3: Eligibility Criteria Prior to Treatment or Observation
• Resolution of all chemotherapy related grade III-IV toxicity as per CTC criteria 4.0
• Laboratories:
WBC > 2.0 X 103/uL Platelets > 50,000/uL Bilirubin < 2.0 mg/dL Creatinine <2.0 mg/dL
AST/ALT < 3.0 x ULN
•At least 2 doses of fusion vaccine were produced (Arm A only)
Acute Myelogenous Leukemia, Myeloid and Monocytic Leukemia, Leukemia
A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer (LIBRETTO-531)
The reason for this study is to see if the study drug selpercatinib is safe and more
effective compared to a standard treatment in participants with rearranged during
transfection (RET)-mutant medullary thyroid cancer (MTC) that cannot be removed by surgery or
has spread to other parts of the body. Participants who are assigned to the standard
treatment and discontinue due to progressive disease have the option to potentially crossover
to selpercatinib.
Justine Bruce, MD
All
12 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04211337
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• At least 18 years of age (participants as young as 12 years of age will be allowed if
permitted by local regulatory authorities).
• Histologically or cytologically confirmed, unresectable, locally advanced and/or
metastatic MTC and no prior history of treatment with kinase inhibitors for
advanced/metastatic disease.
• Radiographic progressive disease per Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1 at screening compared with a previous image taken within the prior 14
months as assessed by the BICR. Participants with measurable or non-measurable but
evaluable disease are eligible; however, participants with non-measurable disease may
not have disease limited to bone sites only.
• A defined/acceptable RET gene alteration identified in a tumor, germline
deoxyribonucleic acid (DNA) or blood sample.
• Tumor tissue in sufficient quantity to allow for retrospective central analysis
of RET mutation status
• Eastern Cooperative Oncology Group performance status score of 0 to 2.
• Adequate hematologic, hepatic, and renal function and electrolytes.
• Men and women of childbearing potential must agree to use a highly effective
contraceptive method during treatment with study drug and for 4 months following the
last dose of study drug.
• Ability to swallow capsules.
Exclusion Criteria:
• An additional validated oncogenic driver in MTC if known that could cause resistance
to selpercatinib treatment. Examples include, but are not limited to RAS or BRAF gene
mutations and NTRK gene fusions.
• Symptomatic central nervous system (CNS) metastases, leptomeningeal carcinomatosis, or
untreated spinal cord compression.
• Clinically significant active cardiovascular disease or history of myocardial
infarction within 6 months, history of Torsades de pointes, or prolongation of the
QTcF >470 milliseconds on more than one electrocardiogram (ECG) during screening.
Participants who are intended to receive vandetanib if randomized to the control arm
are ineligible if QTcF is >450 milliseconds.
• Active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing
uncontrolled intercurrent illness.
• Active hemorrhage or at significant risk for hemorrhage.
• Other malignancy unless nonmelanoma skin cancer, carcinoma in situ or malignancy
diagnosed ≥2 years previously and not currently active. Participants with multiple
endocrine neoplasia type 2 (MEN2) associated pheochromocytoma may be eligible.
Immunotherapy (Nivolumab or Brentuximab Vedotin) Plus Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage III-IV Classic Hodgkin Lymphoma
This phase III trial compares immunotherapy drugs (nivolumab or brentuximab vedotin) when
given with combination chemotherapy in treating patients with newly diagnosed stage III or IV
classic Hodgkin lymphoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may
help the body's immune system attack the cancer, and may interfere with the ability of tumor
cells to grow and spread. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked
to a toxic agent called vedotin. Brentuximab attaches to cancer cells in a targeted way and
delivers vedotin to kill them. Chemotherapy drugs, such as doxorubicin, vinblastine, and
dacarbazine, 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. The addition of
nivolumab or brentuximab vedotin to combination chemotherapy may shrink the cancer or extend
the time without disease symptoms coming back.
Vaishalee Kenkre, MD
All
12 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03907488
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Inclusion Criteria:
• All patients must have histologically confirmed newly diagnosed, previously untreated
stage III or IV classical Hodgkin lymphoma (nodular sclerosing, mixed cellularity,
lymphocyte-rich, or lymphocyte-depleted, or not otherwise specified [NOS]). Nodular
lymphocyte predominant Hodgkin lymphoma is not eligible.
• Patients must have bidimensionally measurable disease (at least one lesion with
longest diameter >= 1.5 cm) documented on the Lymphoma Baseline Tumor Assessment Form
in Rave.
• Patients must have a whole body or limited whole body PET-CT scan performed within 42
days prior to registration. (A contrast-enhanced [diagnostic] CT, MRI or MR-PET is
acceptable in event that PET-CT is contra-indicated, however if it is later possible
to administer a PET-CT, then PET-CT is strongly preferred for the interim scan (after
cycle 2) (if performed) and the EOT assessment. Otherwise, if PET-CT is not
subsequently possible, then the same modality as baseline must be used throughout the
trial.) NOTE: All images from PET-CT, CT, MRI or MR-PET scans performed as standard of
care to assess disease (within 42 days prior to registration) must be submitted and
associated radiology reports must be submitted.
• Patients must not have received any prior chemotherapy, radiation, or antibody-based
treatment for classical Hodgkin lymphoma. Steroid pre-treatment is permitted.
• Patients must not have had prior solid organ transplant.
• Patients must not have had prior allogeneic stem cell transplantation.
• Patients must not have received a live vaccine within 30 days prior to planned day 1
of protocol therapy (e.g. measles, mumps, rubella, varicella, yellow fever, rabies,
Bacillus Calmette-Guerin [BCG], oral polio vaccine, and oral typhoid).
• At registration, investigator must declare intent-to-treat with residual PET radiation
therapy (residual PET RT- RPRT) to be administered after patient completes 6 cycles of
therapy if, after end of treatment, the patient meets criteria specified for receiving
RT). Patients will be stratified by investigator's intent-to-treat with residual PET
RT.
• All pediatric patients (< 18 years of age) will be considered intent-to-treat
with Residual PET RT at time of registration.
• Patients must have a performance status corresponding to Zubrod scores of 0, 1 or 2.
Use Lansky for patients =< 17 years of age. *The conversion of the Lansky to Eastern
Cooperative Oncology Group (ECOG) scales is intended for National Cancer Institute
(NCI) reporting purposes only.
• Adults (age 18 or older): Creatinine clearance >= 30 mL/min, as estimated by the
Cockcroft and Gault formula. The creatinine value used in the calculation must have
been obtained within 28 days prior to registration. Estimated creatinine clearance is
based on actual body weight.
Pediatric Patients (age 12-17), the following must have been obtained within 14 days prior
to registration:
• Measured or calculated creatinine clearance or radioisotope glomerular filtration rate
(GFR) >= 70 ml/min/1.73 m^2, or
• Serum creatinine =< 1.5 x institutional upper limit of normal (IULN), or a serum
creatinine (SCr) based on age/gender as follows:
• Age < 13 maximum serum creatinine: Male 1.2 mg/dL; Female 1.2 mg/dL
• Age 13 to < 16 maximum serum creatinine: Male 1.5 mg/dL; Female 1.4 mg/dL
• Age 16-17 maximum serum creatinine: Male 1.7 mg/dL; Female 1.4 mg/dL
• Total bilirubin =< 2 x IULN (must be documented within 28 days prior to
registration for adults [age 18 or older]; must be documented within 14 days
prior to registration for pediatric patients [age 12-17]).
• Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile
duct syndrome
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x IULN
(must be documented within 28 days prior to registration for adults [age 18 or
older]; must be documented within 14 days prior to registration for pediatric
patients [age 12-17]).
• Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile
duct syndrome
• Patients must have an echocardiogram (ECHO), multigated acquisition (MUGA), or
functional cardiac imaging scan with a left ventricular ejection (LVEF) fraction
>= 50% or a shortening fraction of >= 27%. For all patients, the ECHO, MUGA, or
functional cardiac imaging scan must be performed within 42 days prior to
registration.
• Patients with known human immunodeficiency virus (HIV) infection must be
receiving anti-retroviral therapy and have an undetectable or unquantifiable
viral load at their most recent viral load test within 6 months prior to
registration.
• Patients must not have known active hepatitis B (HBV) or hepatitis C virus (HCV)
at date of registration. Patients with previously treated HBV or HCV that have an
undetectable viral load within 6 months prior to registration and no residual
hepatic impairment are eligible.
• Patients must not have any known central nervous system lymphoma.
• Patients must not have a history of or active interstitial pneumonitis or
interstitial lung disease.
• Patients must not have had a diagnosis of inherited or acquired immunodeficiency.
• Patients must not have any known uncontrolled intercurrent illness including, but
not limited to symptomatic congestive heart failure, unstable angina pectoris,
hemodynamically unstable cardiac arrhythmia, or psychiatric illness/social
situations that would limit compliance with study requirements.
• Patients must not have a condition requiring systemic treatment with either
corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive
medications within 14 days prior to registration. Inhaled or topical steroids,
and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted
in the absence of active autoimmune disease. Steroid use for the control of
Hodgkin lymphoma symptoms is allowable, but must be discontinued prior to cycle
1, day 1.
• Patients with peripheral neuropathy must have < grade 2 at date of registration.
• Patients must not have active autoimmune disease that has required systemic
treatment in past 2 years (i.e., with use of disease modifying agents,
immunosuppressive drugs, or corticosteroids with doses higher than prednisone 10
mg or equivalent). Autoimmune diseases include but are not limited to autoimmune
hepatitis, inflammatory bowel disease (including ulcerative colitis and Crohn's
disease), as well as symptomatic disease (e.g.: rheumatoid arthritis, systemic
progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune
vasculitis [e.g., Wegener's granulomatosis]); central nervous system (CNS) or
motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome
and myasthenia gravis, multiple sclerosis or glomerulonephritis). Vitiligo,
alopecia, hypothyroidism on stable doses of thyroid replacement therapy,
psoriasis not requiring systemic therapy within the past 2 years are permitted.
• No second prior malignancy is allowed except for adequately treated basal (or
squamous cell) skin cancer, any in situ cancer or other cancer for which the
patient has been disease free for two years.
• Females of childbearing potential must not be pregnant or nursing, and have a
negative pregnancy test within 28 days prior to registration. Women/men of
reproductive potential must have agreed to use an effective contraceptive method
while receiving study drug and for women until 6 months after receiving the last
dose of study drug or, for men, until 7 months after receiving the last dose of
study drug. A woman is considered to be of "reproductive potential" if she has
had menses at any time in the preceding 12 consecutive months. In addition to
routine contraceptive methods, "effective contraception" also includes
heterosexual celibacy and surgery intended to prevent pregnancy (or with a
side-effect of pregnancy prevention) defined as a hysterectomy, bilateral
oophorectomy or bilateral tubal ligation. However, if at any point a previously
celibate patient chooses to become heterosexually active during the time period
for use of contraceptive measures outlined in the protocol, he/she is responsible
for beginning contraceptive measures.
• Patients must have one formalin-fixed paraffin embedded (FFPE) diagnostic tumor
block or at least 1 diagnostic, 4-5 micron, hematoxylin and eosin (H&E) slide
collected prior to registration and available for submission.
• Patients must be offered participation in banking for planned translational
medicine and future research. With patient consent, any residuals from the
mandatory tissue submission will also be banked for future research.
• Patients who can complete Patient-Reported Outcome instruments in English,
Spanish, or French must complete the PROMIS Fatigue, the FACT/GOG-Ntx, and the
PROMIS Global prior to registration.
• Patients who can complete Patient-Reported Outcome instruments in English,
Spanish, or French must also agree to complete the PROMIS Fatigue, the
FACT/GOG-Ntx, the PROMIS Global, and the PRO-CTCAE (or Ped PRO-CTCAE) at the
scheduled on-study assessment timepoints.
• Patients must be informed of the investigational nature of this study and all
patients and/or their parents or legal guardians (for patients < 18 years of age)
must sign and give informed consent and assent (where appropriate) in accordance
with institutional and federal guidelines. For participants with impaired
decision-making capabilities, legally authorized representatives may sign and
give informed consent on behalf of study participants in accordance with
applicable federal, local, and Central Institutional Review Board Initiative
(CIRB) regulations.
• Note: 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.
Ann Arbor Stage III Hodgkin Lymphoma, Ann Arbor Stage III Lymphocyte-Depleted Classic Hodgkin Lymphoma, Ann Arbor Stage III Mixed Cellularity Classic Hodgkin Lymphoma, Ann Arbor Stage III Nodular Sclerosis Classic Hodgkin Lymphoma, Ann Arbor Stage IIIA Hodgkin Lymphoma, Ann Arbor Stage IIIB Hodgkin Lymphoma, Ann Arbor Stage IV Hodgkin Lymphoma, Ann Arbor Stage IV Lymphocyte-Depleted Classic Hodgkin Lymphoma, Ann Arbor Stage IV Mixed Cellularity Classic Hodgkin Lymphoma, Ann Arbor Stage IV Nodular Sclerosis Classic Hodgkin Lymphoma, Ann Arbor Stage IVA Hodgkin Lymphoma, Ann Arbor Stage IVB Hodgkin Lymphoma, Classic Hodgkin Lymphoma, Lymphocyte-Rich Classic Hodgkin Lymphoma, Hodgkin's Lymphoma, Lymphoma
Registry for Participants With Short Bowel Syndrome
This is a global prospective, observational, multi-center registry to evaluate the long-term
safety profile for participants with short bowel syndrome (SBS) who are treated with
teduglutide in a routine clinical setting. The registry will also evaluate the long-term
clinical outcomes in participants with SBS. SBS participants treated and not treated with
teduglutide will be enrolled.
Mark Reichelderfer, MD
All
Not specified
NA
This study is NOT accepting healthy volunteers
NCT01990040
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Inclusion Criteria:
1. Male and female participants, of any age, with a diagnosis of short bowel syndrome
(SBS).
2. Signed informed consent and medical records release by the participant or a legally
acceptable representative
3. Participants who have never received teduglutide treatment must be on parenteral
nutrition (PN)/intravenous (IV) fluids support for at least 6 months at the time of
enrollment.
Exclusion criteria:
1. Participants currently participating in a blinded clinical trial or their extension
studies.
2. Participants who have never been on PN/IV support.
3. Participants who are currently or previously exposed to any Glucagon-like peptide 2
(GLP-2) analogs other than teduglutide.
Short Bowel Syndrome, Postsurgical malabsorption, not elsewhere classified, Digestive Health & Liver Disease
Prospective, single-arm, multicenter study that will generate clinical data using the NEUWAVE
MicroWave Ablation System with AC (Ablation Confirmation) software in patients undergoing
ablation of a soft tissue liver lesion.
Timothy Ziemlewicz, MD
All
22 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT03753789
Show full eligibility criteria
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Inclusion Criteria:
1. A patient with at least one soft-tissue liver lesion less than or equal to 5cm
undergoing microwave ablation using the NEUWAVE Microwave Ablation System. Note: a
patient cannot have more than 3 lesions ablated during the procedure.
2. Intent to use Ablation Confirmation software (any AC software version permitted)
during the ablation procedure.
3. Written Informed Consent to voluntarily participate in the study, follow CT scan
schedule, and authorize the transfer of his/her data to the Sponsor
4. Patients greater than or equal to 22 years of age
5. Performance status 0-2 (Eastern Cooperative Oncology Group [ECOG]) classification
6. Class A or B functional hepatic reserve based on the Child-Pugh score.
7. Lesion must be visualized by non-contrast enhanced CT scan or the patient must
tolerate contrast and meet institutional guidelines for contrast use based on
glomerular filtration rate (GFR).
Exclusion Criteria:
1. Active bacterial infection or fungal infection on the day of the ablation.
2. Patients with implantable pacemakers or other electronic implants.
3. Platelet count less than 50,000/mm cubed.
4. Patients with uncorrectable coagulopathy at the time of ablation.
5. Currently breastfeeding or pregnant (latter confirmed by serum pregnancy test, per
site's SOC).
6. Physical or psychological condition which would impair study participation.
7. ASA (American Society of Anesthesiologists) score of great or equal to 4.
8. Use of hydrodissection.
9. Systemic chemotherapy or radiation therapy for the liver, within 30 days prior to the
study ablation procedure.
10. INR greater than 1.8.
11. Patient has participated in an investigational clinical study within 30 days of the
screening visit for this study.
12. Patient judged unsuitable for study participation by the performing physician for any
other reason.
Cancer of the Liver, Liver Cancer, Neoplasms, Liver, Malignant neoplasm of colon, unspecified, Liver cell carcinoma, Cancer, Digestive Health & Liver Disease
An Investigational Immuno-therapy Study Of Nivolumab In Combination With Trametinib With Or Without Ipilimumab In Participants With Previously Treated Cancer of the Colon or Rectum That Has Spread (CheckMate 9N9)
The purpose of this study is to investigate treatment with nivolumab in combination with
trametinib with or without ipilimumab in participants with previously treated cancer of the
colon or rectum that has spread.
Dustin Deming, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT03377361
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Inclusion Criteria:
• Histologically or cytologically confirmed previously treated metastatic colorectal
cancer with adenocarcinoma histology and in Stage IV per American Joint Committee on
Cancer (version 4.0) at study entry
• Microsatellite status should be performed per local standard of practice,
immunohistochemistry (IHC) and/or PCR. If IHC results are equivocal, PCR is required
for determining microsatellite stable (MSS) status
• Must have measurable disease per RECIST 1.1. Participants with lesions in a previously
irradiated field as the sole site of measurable disease will be permitted to enroll
provided the lesion(s) have demonstrated clear progression and can be measured
accurately
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 at screening and
on cycle 1 day 1 (C1D1)
Exclusion Criteria:
• BRAF V600 mutant colorectal cancer
• Active brain metastases or leptomeningeal metastases
• Active, known or suspected autoimmune disease
• Participants with a condition requiring systemic treatment with either corticosteroids
(> 10 mg daily prednisone equivalents) or other immunosuppressive medications within
14 days of study treatment administration
• History of interstitial lung disease or pneumonitis
• Prior treatment with immune checkpoint inhibitors and mitogen-activated protein kinase
enzymes (MEK) inhibitors
• History of allergy or hypersensitivity to study drug components
Other protocol defined inclusion/exclusion criteria apply
APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors (SPARTA)
The primary Phase 1 purpose of this study was to assess overall safety, tolerability and
recommended Phase 2 dose (RP2D) of APL-101.
The Phase 2 portion will assess efficacy of the dose determined in Phase 1 in individuals
with Non-Small Cell Lung Cancer with c-Met EXON 14 Skip Mutations; individuals with cancers
associated with c-Met amplifications; individuals with cancers associated with c-Met fusion
Mark Burkard, MD, PhD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT03175224
Show full eligibility criteria
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Major
Inclusion Criteria:
• Able to understand and comply with study procedures, understand the risks involved,
and provide written informed consent.
• For Phase 1, histologically and / or cytological confirmed unresectable or metastatic
solid malignancy, refractory to standard therapies with no more than three prior lines
of therapy (Completed).
• For Phase 2, seven cohorts will be enrolled:
Cohort A-1: NSCLC EXON 14 skip mutation (c-Met naïve) for first line treatment, Cohort A-2:
NSCLC EXON 14 skip mutation (c-Met naïve) pretreated subjects with no more than 3 lines of
prior therapy, Cohort B: NSCLC EXON 14 skip mutation (c-Met experienced; radiographic
progression on prior c-Met inhibitor), Cohort C: basket of tumor types with c-Met high
level amplification (except Primary CNS tumors), Cohort C-1: NSCLC harboring MET
amplification and wild-type epidermal growth factor receptor (EGFR) with no more than 3
lines of prior therapy (MET Naive), Cohort D: basket of tumor types except for primary CNS
tumors harboring MET gene fusions (e.g., NSCLC, upper GI, colorectal, hepatobiliary
cancer). Previously treated; or previously untreated but refused standard treatment, or if
treatment was unavailable or unfeasible (≤ 3 prior lines in unresectable or metastatic
setting). Met naive, Cohort E: Primary CNS tumors with MET alterations (single or
co-occurred MET fusion including PTPRZ1-MET [ZM] fusion, MET Exon 14 skipping mutation, or
MET amplification).Previously treated or previously untreated but refused standard
treatment, or if treatment was unavailable or unfeasible (≤ 3 prior lines), Met naive.
•Local/archival result (tissue and/or plasma) of a positive c-Met dysregulation is
required (except in Cohort A-1 in the US and Cohort C-1).
In Phase 2, provision of either archival or a fresh tumor biopsy sample (if safe and
feasible) either from the primary or a metastatic site is required for study entry for
Cohorts A-1, A-2, C, C-1, and D.
• Measurable disease according to relevant criteria (RECIST v1.1, RANO for CNS tumors,
or other relevant criteria per tumor type).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 and/or Karnofsky
Performance Scale (KPS) score.
• For all prior anticancer treatment, including radiotherapy, chemotherapy or targeted
agents or hormonal therapy, a duration of more than 30 days or 5 half-lives of the
agents used, whichever is shorter, must have elapsed, and any encountered toxicity
must have resolved to levels meeting all the other eligibility criteria prior to the
first dose of study treatment. Palliative radiotherapy to non-target lesions should be
completed within 2 weeks prior to APL-101 administration.
• No planned major surgery within 4 weeks of first dose of APL-101
• Expected survival (life expectancy) ≥ 3 months from C1D1.
Major
Exclusion Criteria:
• Hypersensitivity to APL-101, excipients of the drug product, or other components of
the study treatment regimen.
• Known actionable mutation/gene rearrangement of EGFR (except for Cohort C), ALK, ROS1,
RET, NTRK, KRAS, and BRAF.
• Unstable angina or myocardial infarction within 1 year prior to first dose of APL-101,
symptomatic or unstable arrhythmia requiring medical therapy, history of congenital
prolonged QT syndrome, prolonged QT interval corrected by Fridericia formula (QTcF) at
screening (> 450 msec based on the average of 3 measurements), or concurrent treatment
with a medication that is a known risk for prolonging the QT interval.
• Unable to swallow orally administered medication whole.
• Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter drug absorption (e.g., Crohn's, ulcerative colitis, active
inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption
syndrome).
Symptomatic and/or neurologically unstable CNS metastases, or who require an increase in
steroid dose to control CNS disease. Subjects who have been receiving a stable steroid dose
for at least 2 weeks prior to C1D1 may be allowed.
•Women who are breastfeeding.
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus, Solid Tumor, Advanced Cancer, Renal Cancer, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, NSCLC, Lung Cancer, Brain Tumor, Glioblastoma Multiforme
Assessing the Clinical Benefit of Molecular Profiling in Patients With Solid Tumors
Many patients are treated for advanced cancer without knowledge of underlying molecular
features that might indicate FDA approved therapies or potential eligibility for
biomarker-selected clinical trials.
The Strata Trial (STR-001-001) has been initiated by Strata Oncology to evaluate the clinical
benefit of systematic comprehensive genomic profiling for participants with advanced cancer
using real-world data and endpoints, while assessing the proportion of participants available
for clinical trials and approved targeted therapies in advanced and/or aggressive cancers.
The Strata Trial uses surplus, or leftover, tumor specimens for molecular profiling and does
not require additional study-specific procedures.
Mark Burkard, MD, PhD
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT03061305
Show full eligibility criteria
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Inclusion Criteria:
• Subjects must be ≥ 18 years of age.
• Subjects must have histologically documented solid tumors (including lymphoma and
multiple myeloma).
• Specific criteria for individual tumor types are as follows:
1. Participants with gliomas are eligible at any stage of disease
2. Participants with pancreatic carcinoma are eligible at any stage of disease
3. Participants with rare tumors (i.e. cancer started in an unusual place in the
body, it is unusual type and requires special treatment) are eligible at stages
II-IV.
4. Participants with other tumor types must have recurrent, relapsed, refractory,
metastatic, or advanced stages III or IV cancer.
• Must have an adequate formalin-fixed paraffin-embedded tumor specimen for genomic
sequencing.
Anus, Any Site, Bones and Joints, Brain and Nervous System, Breast, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Hodgkin's Lymphoma, Ill-Defined Sites, Kaposi's Sarcoma, Kidney, Larynx, Leukemia, other, Lip, Oral Cavity and Pharynx, Liver, Lung, Lymphoid Leukemia, Melanoma, Skin, Mycosis Fungoides, Myeloid and Monocytic Leukemia, Non-Hodgkin's Lymphoma, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder, Head and Neck, Gastrointestinal cancers, other, Colon and Rectum, Anal, Sarcoma, Melanoma/Skin cancer, Hematologic cancers, other, Uterus, Genitourinary cancers, other, Bladder, Brain/Central Nervous System, Endocrine cancers, Leukemia, Cancer, Adult Solid Tumor, Lymphoma, Multiple Myeloma
A Longitudinal Observational Study of the Natural History and Management of Patients With HCC
TARGET-HCC is a longitudinal, observational study of patients being managed for HCC in usual
clinical practice. TARGET-HCC will create a research registry of participants with HCC within
academic and community real-world practices in order to assess the safety and effectiveness
of the entire spectrum of current and future therapies across diverse populations.
Michael Lucey, MD
All
18 Years and over
NA
This study is NOT accepting healthy volunteers
NCT02954094
Show full eligibility criteria
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Inclusion Criteria:
1. Male or female patients, age ≥18 years
2. Patients with a histological/cytological or radiological diagnosis of HCC (mixed HCC
cholangiocarcinoma may be included; patients who are candidates for surgical and
non-surgical treatment, as well as those being followed without specific HCC therapy
may be included)
Exclusion Criteria:
1. Inability to provide written informed consent
Liver cell carcinoma, Digestive Health & Liver Disease, Hepatocellular Cancer
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.
Michael Lucey, MD
All
18 Years and over
NA
This study is NOT accepting healthy volunteers
NCT02932449
Show full eligibility criteria
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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
A Study to Assess Whether Etrolizumab is a Safe and Efficacious Treatment for Participants With Moderately to Severely Active Crohn's Disease (BERGAMOT)
This is a multicenter, Phase 3, double-blind, placebo-controlled study evaluating the
efficacy, safety, and tolerability of etrolizumab compared with placebo during induction and
maintenance treatment of moderately to severely active Crohn's Disease (CD). The target
population includes participants with CD who are refractory or intolerant to corticosteroids
(CS) and/or immunosuppressant (IS) therapy and who have either not received prior anti-tumor
necrosis factor (anti-TNF) therapy (TNF-naive) or who have had prior exposure to anti-TNF
therapies and demonstrated inadequate responses or intolerance to anti-TNFs.
The study period will consist of a Screening Phase (up to 35 days) plus (+) a 14-week
Induction Phase + a 52-week Maintenance Phase + a 12-week Safety Follow-up Phase. At Week 14
(end of Induction Phase), participants achieving a decrease from baseline of at least 70
points in the Crohn's Disease Activity Index (CDAI) score (CDAI-70 response) without the use
of rescue therapy will continue to the Maintenance Phase.
Sumona Saha, M.D.
All
18 Years to 80 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT02394028
Show full eligibility criteria
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Inclusion Criteria:
• Moderately to severely active Crohn's Disease (CD) as determined by the CDAI, patient
reported outcomes and endoscopically defined disease activity in the ileum and/or
colon
• Intolerance, refractory disease, or no response to corticosteroids (CS),
immunosuppressants (IS), or anti-TNF therapy within 5 years from screening.
Participants who have not previously demonstrated inadequate response or intolerance
to one or more anti-TNF therapies are eligible to participate in the study provided
they are intolerant or refractory to CS or IS therapy
• Use of effective contraception as defined by the protocol
Exclusion Criteria:
• A history of, or current conditions affecting the digestive tract, such as ulcerative
colitis, indeterminate colitis, fistulizing disease, abdominal or perianal abscess,
adenomatous colonic polyps not excised, colonic mucosal dysplasia, and short bowel
syndrome
• Planned surgery for CD
• Ileostomy or colostomy
• Has received non-permitted inflammatory bowel disease (IBD) therapies (including
natalizumab, vedolizumab, and efalizumab, as stated in the protocol)
• Any prior treatment with ustekinumab within 14 weeks prior to randomization
• Chronic hepatitis B or C infection, human immunodeficiency virus (HIV), active or
latent tuberculosis (participants with prior history of Bacillus Calmette-Guérin [BCG]
vaccination must pass protocol-defined screening criteria)
• Sinus tract with evidence for infection (e.g., purulent discharge) in the clinical
judgment of the investigator. Fistulas related to CD are not exclusionary
• Any prior treatment with anti-adhesion molecules (e.g., anti-mucosal addressin cell
adhesion molecule [anti-MAdCAM-1])
• Any major episode of infection requiring treatment with intravenous antibiotics ≤8
weeks prior to screening or oral antibiotics ≤4 weeks prior to screening. Treatment
with antibiotics as adjunctive therapy for CD in the absence of documented infection
is not exclusionary
• Hospitalization (other than for elective reasons) within 4 weeks prior to
randomization
A Study Evaluating Safety and Efficacy of Venetoclax in Combination With Azacitidine Versus Standard of Care After Allogeneic Stem Cell Transplantation (SCT) in Participants With Acute Myeloid Leukemia (AML) (VIALE-T)
The main objective of this study is to evaluate the efficacy of venetoclax in combination
with azacitidine to improve Relapse Free Survival (RFS) in Acute Myeloid Leukemia (AML)
participants compared to Best Supportive Care (BSC) when given as maintenance therapy
following allogeneic stem cell transplantation (SCT).
This study will have 2 parts: Part 1 (Dose Confirmation), which may include participants who
are greater than or equal to 18 years old; Part 2 (Randomization) which may include
participants who are greater than or equal to 12 years old. During Part 1, recommended Phase
3 dose of venetoclax in combination with azacitidine will be determined and during Part 2,
the efficacy and safety of venetoclax with azacitidine (Part 2 Arm A) will be compared with
BSC (Part 2 Arm B).
Aric Hall, MD
All
12 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04161885
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Inclusion Criteria:
• Participants must be at least 18 years old for Part 1 and, at least 12 years old for
Part 2.
• Participant must be diagnosed with Acute Myeloid Leukemia (AML) by World Health
Organization (WHO) criteria (2017) and either be planning for allogeneic stem cell
transplantation or have received allogeneic stem cell transplantation within the past
30 days.
• Blast percentage in bone marrow before transplant must be < 10%.
• Blast count in peripheral blood must be "0" and Blast percentage in bone marrow must
be < 5% after transplant.
• Participant meet adequate renal, hepatic and hematologic criteria as described in the
protocol.
• Participants >= 17 years old must have a Karnofsky Performance Scale (KPS) score > 50
and participants between 12 to 16 years old must have a Lansky Play Performance Scale
score > 40.
Exclusion Criteria:
• History of disease progression during prior treatment with venetoclax.
• History of any other malignancy within 2 years prior to study entry, except for:
Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of
breast; basal cell carcinoma of the skin or localized squamous cell carcinoma of the
skin; previous malignancy confined and surgically resected (or treated with other
modalities) with curative intent; Myelodysplastic Syndrome, Myeloproliferative
neoplasm (only allowed if it transformed to AML and AML should be the indication for
marrow transplantation).
• Participant has known infection with HIV or history of being positive for hepatitis B
virus (HBV) or hepatitis C virus (HCV) infection.
• Presence of clinical or laboratory symptoms/signs of extramedullary myeloid
malignancy.
Acute Myeloid Leukemia (AML), Cancer, Myeloid and Monocytic Leukemia, Leukemia
Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy
This phase III trial studies whether inotuzumab ozogamicin added to post-induction
chemotherapy for patients with High-Risk B-cell Acute Lymphoblastic Leukemia (B-ALL) improves
outcomes. This trial also studies the outcomes of patients with mixed phenotype acute
leukemia (MPAL), and B-lymphoblastic lymphoma (B-LLy) when treated with ALL therapy without
inotuzumab ozogamicin. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab,
linked to a type of chemotherapy called calicheamicin. Inotuzumab attaches to cancer cells in
a targeted way and delivers calicheamicin to kill them. Other drugs used in the chemotherapy
regimen, such as cyclophosphamide, cytarabine, dexamethasone, doxorubicin, daunorubicin,
methotrexate, leucovorin, mercaptopurine, prednisone, thioguanine, vincristine, and
pegaspargase 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. This trial will
also study the outcomes of patients with mixed phenotype acute leukemia (MPAL) and
disseminated B lymphoblastic lymphoma (B-LLy) when treated with high-risk ALL chemotherapy.
The overall goal of this study is to understand if adding inotuzumab ozogamicin to standard
of care chemotherapy maintains or improves outcomes in High Risk B-cell Acute Lymphoblastic
Leukemia (HR B-ALL). The first part of the study includes the first two phases of therapy:
Induction and Consolidation. This part will collect information on the leukemia, as well as
the effects of the initial treatment, in order to classify patients into post-consolidation
treatment groups. On the second part of this study, patients will receive the remainder of
the chemotherapy cycles (interim maintenance I, delayed intensification, interim maintenance
II, maintenance), with some patients randomized to receive inotuzumab. Other aims of this
study include investigating whether treating both males and females with the same duration of
chemotherapy maintains outcomes for males who have previously been treated for an additional
year compared to girls, as well as to evaluate the best ways to help patients adhere to oral
chemotherapy regimens. Finally, this study will be the first to track the outcomes of
subjects with disseminated B-cell Lymphoblastic Leukemia (B LLy) or Mixed Phenotype Acute
Leukemia (MPAL) when treated with B-ALL chemotherapy.
Kenneth Desantes, M.D.
All
1 Year to 24 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03959085
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Inclusion Criteria:
• B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to eligibility
studies (Part A) prior to treatment and enrollment on AALL1732. Note that central
confirmation of MPAL diagnosis must occur within 7 business days after enrollment for
MPAL patients. If not performed within this time frame, patients will be taken off
protocol.
• APEC14B1 is not a requirement for B-LLy patients but for institutional compliance
every patient should be offered participation in APEC14B1. B-LLy patients may directly
enroll on AALL1732.
• White blood cell count (WBC) criteria for patients with B-ALL (within 7 days prior to
the start of protocol-directed systemic therapy):
• Age 1-9.99 years: WBC >= 50,000/uL
• Age 10-24.99 years: Any WBC
• Age 1-9.99 years: WBC < 50,000/uL with:
• Testicular leukemia
• CNS leukemia (CNS3)
• Steroid pretreatment.
• White blood cell count (WBC) criteria for patients with MPAL (within 7 days prior to
the start of protocol-directed systemic therapy):
• Age 1-24.99 years: any WBC.
• Patient has newly diagnosed B-ALL or MPAL (by World Health Organization [WHO] 2016
criteria) with > 25% blasts on a bone marrow (BM) aspirate;
• OR If a BM aspirate is not obtained or is not diagnostic of acute leukemia, the
diagnosis can be established by a pathologic diagnosis of acute leukemia on a BM
biopsy;
• OR A complete blood count (CBC) documenting the presence of at least 1,000/uL
circulating leukemic cells if a bone marrow aspirate or biopsy cannot be
performed.
• Patient has newly diagnosed B-LLy Murphy stages III or IV.
• Patient has newly diagnosed B-LLy Murphy stages I or II with steroid pretreatment.
• Note: For B-LLy patients with tissue available for flow cytometry, the criterion for
diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e.,
paraffin blocks), the methodology and criteria for immunophenotypic analysis to
establish the diagnosis of B-LLy defined by the submitting institution will be
accepted.
• All patients and/or their parents or legal guardians must sign a written informed
consent.
• All institutional, Food and Drug Administration (FDA), and NCI requirements for human
studies must be met.
Exclusion Criteria:
• Patients with Down syndrome are not eligible (patients with Down syndrome and B-ALL
are eligible for AALL1731, regardless of NCI risk group).
• With the exception of steroid pretreatment or the administration of intrathecal
cytarabine, patients must not have received any prior cytotoxic chemotherapy for the
current diagnosis of B-ALL, MPAL, or B-LLy or for any cancer diagnosed prior to
initiation of protocol therapy on AALL1732.
• Patients who have received > 72 hours of hydroxyurea within one week prior to start of
systemic protocol therapy.
• Patients with B-ALL or MPAL who do not have sufficient diagnostic bone marrow
submitted for APEC14B1 testing and who do not have a peripheral blood sample submitted
containing > 1,000/uL circulating leukemia cells.
• Patients with acute undifferentiated leukemia (AUL) are not eligible.
• For Murphy stage III/IV B-LLy patients, or stage I/II patients with steroid
pretreatment, the following additional exclusion criteria apply:
• T-lymphoblastic lymphoma.
• Morphologically unclassifiable lymphoma.
• Absence of both B-cell and T-cell phenotype markers in a case submitted as
lymphoblastic lymphoma.
• Patients with known Charcot-Marie-Tooth disease.
• Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL,
regardless of blast immunophenotype.
• Patients requiring radiation at diagnosis.
• Female patients who are pregnant, since fetal toxicities and teratogenic effects have
been noted for several of the study drugs. A pregnancy test is required for female
patients of childbearing potential.
• Lactating women who plan to breastfeed their infants while on study and for 2 months
after the last dose of inotuzumab ozogamicin.
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of study participation. For those
patients randomized to inotuzumab ozogamicin, there is a minimum of 8 months after the
last dose of inotuzumab ozogamicin for females and 5 months after the last dose of
inotuzumab ozogamicin for males.
B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma, Central Nervous System Leukemia, Mixed Phenotype Acute Leukemia, Testicular Leukemia, Non-Hodgkin's Lymphoma, Lymphoid Leukemia, Leukemia, other, Leukemia, Lymphoma
De-intensified Radiation Therapy With Chemotherapy (Cisplatin) or Immunotherapy (Nivolumab) in Treating Patients With Early-Stage, HPV-Positive, Non-Smoking Associated Oropharyngeal Cancer
This phase II/III trial studies how well a reduced dose of radiation therapy works with
nivolumab compared to cisplatin in treating patients with human papillomavirus (HPV)-positive
oropharyngeal cancer that is early in its growth and may not have spread to other parts of
the body (early-stage), and is not associated with smoking. Radiation therapy uses
high-energy x-rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such as
cisplatin, 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. Immunotherapy with
monoclonal antibodies, such as nivolumab, may help the body's immune system attack the
cancer, and may interfere with the ability of tumor cells to grow and spread. This trial is
being done to see if a reduced dose of radiation therapy and nivolumab works as well as
standard dose radiation therapy and cisplatin in treating patients with oropharyngeal cancer.
Randall Kimple, MD, PhD
All
18 Years and over
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT03952585
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Pathologically (histologically or cytologically) proven diagnosis of squamous cell
carcinoma (including the histological variants papillary squamous cell carcinoma and
basaloid squamous cell carcinoma but not neuroendocrine phenotype) of the oropharynx
(tonsil, base of tongue, soft palate, or oropharyngeal walls); cytologic diagnosis
from a cervical lymph node is sufficient in the presence of clinical evidence of a
primary tumor in the oropharynx. Clinical evidence should be documented, may consist
of palpation, imaging, or endoscopic evaluation, and should be sufficient to estimate
the size of the primary (for T stage)
• Patients must have clinically or radiographically evident measurable disease at the
primary site or at nodal stations. Simple tonsillectomy or local excision of the
primary without removal of nodal disease is permitted, as is excision removing gross
nodal disease but with intact primary site. Limited neck dissections retrieving =< 4
nodes are permitted and considered as non-therapeutic nodal excisions
• P16-positive based on local site immunohistochemical tissue staining (defined as
greater than 70% strong diffuse nuclear or nuclear and cytoplasmic staining of tumor
cells). Fine needle aspiration (FNA) biopsy specimens may be used as the sole
diagnostic tissue. Centers are encouraged to contact the pathology chair for
clarification
• Note: Institutions must screen patients, whose tumors must be p16-positive by
immunohistochemistry (IHC) in order to be eligible for the trial using a Clinical
Laboratory Improvement Amendments (CLIA)-certified laboratory. A rigorous
laboratory accreditation process similar to the United States (U.S.) CLIA
certification, such as the provincial accreditation status offered by the Ontario
Laboratory Accreditation (OLA) Program in Canada, the College of American
Pathologists (CAP), or an equivalent accreditation in other countries, is
acceptable. The p16-positive results must be reported on the pathology report
being submitted
• Clinical stage T1-2, N1, M0 (American Joint Committee on Cancer [AJCC], 8th edition
[ed.]) or T3, N0-N1, M0 (AJCC, 8th ed.) including no distant metastases based on the
following diagnostic workup:
• General history and physical examination within 56 days prior to registration;
• Exam with laryngopharyngoscopy (mirror or in office direct procedure acceptable)
within 70 days prior to registration;
• One of the following imaging studies is required within 56 days prior to
registration:
• FDG-PET/CT of the neck and chest (with or without contrast); FDG-PET/CT scan
is strongly preferred and highly recommended to be used for eligibility OR
• Chest CT (with or without contrast)
• One of the following imaging studies is required within 28 days prior to
registration:
• A diagnostic CT scan of neck (with contrast and of diagnostic quality) OR
• An magnetic resonance imaging (MRI) of the neck (with contrast and of
diagnostic quality)
• Note: A diagnostic quality CT or MRI with contrast or FDG-PET/CT scan of
neck performed for the purposes of radiation planning may serve as both
staging and planning tools
• Patients must provide their personal smoking history prior to registration. The
lifetime cumulative history cannot exceed 10 pack-years. The following formula is used
to calculate the pack-years during the periods of smoking in the patient's life; the
cumulative total of the number of pack-years during each period of active smoking is
the lifetime cumulative history
• Number of pack-years = [Frequency of smoking (number of cigarettes per day) x
duration of cigarette smoking (years)] / 20
• Note: Twenty cigarettes is considered equivalent to one pack. The effect of
non-cigarette tobacco products on the survival of patients with p16-positive
oropharyngeal cancers is undefined. While there are reportedly increased risks of
head and neck cancer associated with sustained heavy cigar and pipe use (Wyss
2013), such sustained use of non-cigarette products is unusual and does not
appear to convey added risk with synchronous cigarette smoking. Cigar and pipe
tobacco consumption is therefore not included in calculating the lifetime
pack-years. Marijuana consumption is likewise not considered in this calculation.
There is no clear scientific evidence regarding the role of chewing
tobacco-containing products in this disease, although this is possibly more
concerning given the proximity of the oral cavity and oropharynx. In any case,
investigators are discouraged from enrolling patients with a history of very
sustained use (such as several years or more) of non-cigarette tobacco products
alone
• Zubrod performance status of 0-1 within 14 days prior to registration
• Absolute neutrophil count >= 1,500/mcL (within 14 days prior to registration)
• Platelets >= 100,000/mcL (within 14 days prior to registration)
• Hemoglobin >= 8.0 g/dL (within 14 days prior to registration) (Note: use of
transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dL is
acceptable)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 14 days
prior to registration)
• Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) or
alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x
institutional ULN (within 14 days prior to registration)
• Serum creatinine =< 1.5 x ULN OR creatinine clearance (CrCl) >= 50 mL/min (if using
the Cockcroft-Gault formula) (within 14 days prior to registration)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
• Note: Known positive test for hepatitis B virus surface antigen (HBV sAg)
indicating acute or chronic infection would make the patient ineligible unless
the viral load becomes undetectable on suppressive therapy. Patients who are
immune to hepatitis B (anti-hepatitis B surface antibody positive) are eligible
(e.g. patients immunized against hepatitis B)
• 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 for the
hepatitis, they are eligible if they have an undetectable HCV viral load.
• Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA)
indicating acute or chronic infection would make the patient ineligible unless
the viral load becomes undetectable on suppressive therapy
• For women of childbearing potential (WOCBP), negative serum or urine pregnancy test
within 24 hours prior to registration
• Women of childbearing potential (WOCBP) is defined as any female who has
experienced menarche and who has not undergone surgical sterilization
(hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause
is defined clinically as 12 months of amenorrhea in a woman over 45 in the
absence of other biological or physiological causes. In addition, women under the
age of 55 must have a documented serum follicle stimulating hormone (FSH) level
less than 40 mIU/mL
• Women of childbearing potential (WOCBP) and men who are sexually active with WOCBP
must be willing to use an adequate method of contraception during and after treatment
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry
• Only English, Spanish, or French speaking patients are eligible to participate as
these are the only languages for which the mandatory dysphagia-related patient
reported instrument (MDADI) is available
Exclusion Criteria:
• Clinical stages T0; T4; T1-2, N0; or any N2 (AJCC, 8th ed)
• Recurrent disease
• Definitive clinical or radiologic evidence of metastatic disease or adenopathy below
the clavicles
• Cancers considered to be from an oral cavity site (oral tongue, floor mouth, alveolar
ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if
p16-positive, or histologies of adenosquamous, verrucous, or spindle cell carcinomas
• Carcinoma of the neck of unknown primary site origin (T0 is ineligible, even if
p16-positive)
• Radiographically matted nodes, defined as 3 abutting nodes with loss of the
intervening fat plane
• Supraclavicular nodes, defined as nodes centered below the level of the cricoid
cartilage
• Gross total excision of both primary and nodal disease; this includes tonsillectomy,
local excision of primary site, and nodal excision that removes all clinically and
radiographically evident disease. In other words, to participate in this protocol, the
patient must have clinically or radiographically evident gross disease for which
disease response can be assessed
• Patients with simultaneous primary cancers or separate bilateral primary tumor sites
are excluded with the exception of patients with bilateral tonsil cancers
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for a minimum of 1095 days (3 years) (of note, the exclusion applies only for invasive
cancers such that carcinoma in situ of the breast, oral cavity, or cervix are all
permissible)
• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
different cancer is allowable
• Prior radiotherapy to the region of the study cancer that would result in overlap of
radiation therapy fields
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or
any other antibody or drug specifically targeting T-cell co-stimulation or immune
checkpoint pathways
• History of severe hypersensitivity reaction to any monoclonal antibody.
• Severe, active co-morbidity defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months
• Transmural myocardial infarction within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of registration
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within 30 days of
registration
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
• Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease
Control and Prevention (CDC) definition with immune compromise greater than that
noted; note, however, that HIV testing is not required for entry into this
protocol. The need to exclude patients with AIDS from this protocol is necessary
because the treatments involved in this protocol may be significantly
immunosuppressive. Protocol-specific requirements may also exclude
immuno-compromised patients
• Condition requiring systemic treatment with either corticosteroids (> 10 mg daily
prednisone equivalents) or other immunosuppressive medications within 14 days of
registration. Inhaled or topical steroids and adrenal replacement doses < 10 mg
daily prednisone equivalents are permitted in the absence of active autoimmune
disease
• Patients with active autoimmune disease requiring systemic treatment (i.e.
disease modifying agents, corticosteroids, or immunosuppressive drugs) should be
excluded. These include but are not limited to patients with a history of immune
related neurologic disease, multiple sclerosis, autoimmune (demyelinating)
neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune
disease such as systemic lupus erythematosus (SLE), rheumatoid arthritis,
connective tissue diseases, scleroderma, inflammatory bowel disease (IBD),
Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic
epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome
should be excluded because of the risk of recurrence or exacerbation of disease
• Note: Patients are permitted to enroll if they have vitiligo, type I diabetes
mellitus, residual hypothyroidism due to autoimmune condition only requiring
hormone replacement, psoriasis not requiring systemic treatment, or conditions
not expected to recur in the absence of an external trigger (precipitating event)
• Patients who are pregnant, nursing, or expecting to conceive or father children
• Prior allergic reaction to cisplatin
Basaloid Squamous Cell Carcinoma, Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Oropharyngeal Squamous Cell Carcinoma, Papillary Squamous Cell Carcinoma, Pathologic Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Pathologic Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Squamous Cell Carcinoma, Lip, Oral Cavity and Pharynx, Larynx, Head and Neck
Irinotecan Hydrochloride, Temozolomide, and Dinutuximab With or Without Eflornithine in Treating Patients With Relapsed or Refractory Neuroblastoma
This phase II trial studies how well irinotecan hydrochloride, temozolomide, and dinutuximab
work with or without eflornithine in treating patients with neuroblastoma that has come back
(relapsed) or that isn't responding to treatment (refractory). Drugs used in chemotherapy,
such as irinotecan hydrochloride and temozolomide, 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. Immunotherapy with monoclonal antibodies, such as dinutuximab, may
induce changes in the body's immune system and may interfere with the ability of tumor cells
to grow and spread. Eflornithine blocks the production of chemicals called polyamines that
are important in the growth of cancer cells. Giving eflornithine with irinotecan
hydrochloride, temozolomide, and dinutuximab, may work better in treating patients with
relapsed or refractory neuroblastoma.
Kenneth Desantes, M.D.
All
1 Year and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03794349
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patients must have had histologic verification of neuroblastoma or
ganglioneuroblastoma or demonstration of neuroblastoma cells in the bone marrow with
elevated urinary catecholamines (i.e. > 2 x upper limit of normal [ULN]), at the time
of initial diagnosis.
• For the purposes of this study, aggressive multidrug chemotherapy is defined as
chemotherapy including 2 or more agents that must include an alkylating agent and a
platinum-containing compound as intended to treat high-risk disease. The doses of
chemotherapy must be comparable to those used in frontline high-risk neuroblastoma
therapies (examples include A3973, ANBL0532, ANBL09P1, ANBL12P1, and ANBL1531).
Patients must have ONE of the following:
• First episode of recurrent high-risk disease following completion of aggressive
multi-drug frontline high-risk therapy.
• First episode of progressive high-risk disease during aggressive multi-drug
frontline therapy.
• Primary resistant/refractory disease (less than partial response by International
Neuroblastoma Response Criteria [INRC]) detected at the conclusion of at least 4
cycles of aggressive multidrug induction chemotherapy on or according to a
high-risk neuroblastoma protocol (examples include A3973, ANBL0532, ANBL09P1,
ANBL12P1, ANBL1531, etc.).
• Patients must have at least ONE of the following at the time of enrollment:
• Measurable tumor on magnetic resonance imaging (MRI) or computed tomography (CT)
scan. Measurable is defined as >= 10 mm in at least one dimension on
spiral/helical CT that is metaiodobenzylguanidine (MIBG) avid or demonstrates
increased fludeoxyglucose F-18 (FDG) uptake on positron emission tomography (PET)
scan.
• MIBG-avid lesion detected on MIBG scan with positive uptake at a minimum of one
site. This site must represent disease recurrence after completion of therapy,
progressive disease on therapy, or refractory disease during induction.
• Patients with resistant/refractory soft tissue disease that is not MIBG avid or
does not demonstrate increased FDG uptake on PET scan must undergo biopsy to
document the presence of viable neuroblastoma. Biopsy is not required for
patients who have a new site of soft tissue disease (radiographic evidence of
disease progression) regardless of whether progression occurs while receiving
therapy or after completion of therapy.
• Patients with bone marrow disease only will be eligible if they have more than 5%
disease involvement (documented neuroblastoma cells) in at least one sample from
bilateral bone marrow biopsies.
• Note: Patients with elevated catecholamines (i.e. > 2 x ULN) only are NOT
eligible for this study.
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age.
• Primary refractory/resistant patients must have received at least 4 cycles of
frontline high-risk chemotherapy. Frontline therapy may also have included surgery,
chemotherapy, autologous stem cell transplantation (SCT) +/- MIBG, immunotherapy,
radiotherapy, and retinoids but must NOT have received second line therapy for
resistant/refractory, relapsed, or progressive disease. Patients who received
intensified therapy for poor induction response or refractory disease (e.g. MIBG) will
be considered to have received second line therapy and will not be eligible.
• At least 14 days must have elapsed since completion of myelosuppressive therapy.
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced
platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of
agent.
• 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.
• No interim time prior to study entry is required following prior radiation therapy
(RT) for non-target lesions. However, patients must not have received radiation for a
minimum of 4 weeks prior to study entry at the site of any lesion that will be
identified as a target lesion to measure tumor response. Lesions that have been
previously radiated cannot be used as target lesions unless there is radiographic
evidence of progression at the site following radiation or a biopsy done following
radiation shows viable neuroblastoma. Palliative radiation while on study is not
permitted.
• Patients are eligible >= 6 weeks after autologous stem cell transplants or stem cell
infusions (including stem cell infusions given as supportive care following 131 I-MIBG
therapy) as long as hematologic and other eligibility criteria have been met.
• Patients are eligible >= 6 weeks after therapeutic 131 I-MIBG provided that all other
eligibility criteria are met.
• Subjects who have previously received anti-GD2 monoclonal antibodies with or without
retinoids for biologic therapy are eligible unless they have had progressive disease
while receiving prior anti-GD2 therapy or progressed/relapsed within 3 months of
receiving anti-GD2 therapy. However, eligible patients may NOT have received anti-GD2
monoclonal antibodies in combination with chemotherapy.
• Subjects who have received autologous marrow infusions or autologous stem cell
infusions that were purged using monoclonal antibody linked to beads are eligible.
• Subjects who have previously received DFMO are eligible for this study provided they
have not had progressive disease while receiving DFMO or progressed/relapsed within 3
months of completing DFMO.
• Patients must not have received long-acting myeloid growth factors (e.g.
pegfilgrastim) within 14 days of entry on this study. Seven days must have elapsed
since administration of a short-acting myeloid growth factor.
• For patients with solid tumors (without marrow involvement) including status post SCT:
peripheral absolute neutrophil count (ANC) >= 750/uL (within 7 days prior to
enrollment).
• For patients with solid tumors (without marrow involvement) including status post SCT:
platelet count >= 75,000/uL (transfusion independent) (within 7 days prior to
enrollment).
• Patients known to have bone marrow involvement with neuroblastoma are eligible
provided that minimum ANC and transfusion independent platelet count criteria are met
(as above). However, these patients are not evaluable for hematological toxicity.
• Creatinine clearance or radioisotope GFR >= 70 mL/min/1.73 m^2 or a serum creatinine
based on age/gender as follows:
• 1 to < 2 years (male 0.6 mg/dL, female 0.6 mg/dL)
• 2 to < 6 years (male 0.8 mg/dL, female 0.8 mg/dL)
• 6 to < 10 years (male 1 mg/dL, female 1 mg/dL)
• 10 to < 13 years (male 1.2 mg/dL, female 1.2 mg/dL)
• 13 to < 16 years (male 1.5 mg/dL, female 1.4 mg/dL)
• >= 16 years (male 1.7 mg/dL, female 1.4 mg/dL) (within 7 days prior to
enrollment).
• Total bilirubin =< 1.5 x ULN for age (within 7 days prior to enrollment).
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5.0 x
ULN for age (=< 225 U/L). For the purpose of this study, the ULN for SGPT is 45 U/L
(within 7 days prior to enrollment).
• Shortening fraction of >= 27% by echocardiography (ECHO) (within 7 days prior to
enrollment).
• Ejection fraction of >= 50% by ECHO or gated radionuclide study (within 7 days prior
to enrollment).
• No evidence of dyspnea at rest, no exercise intolerance, no chronic oxygen
requirement, and room air pulse oximetry > 94% if there is a clinical indication for
pulse oximetry. Normal pulmonary function tests in patients who are capable of
cooperating with testing (including diffusion capacity of the lung for carbon monoxide
[DLCO)] are required if there is a clinical indication for determination. For patients
who do not have respiratory symptoms, full pulmonary function tests (PFTs) are NOT
required.
• Patients with a history of central nervous system (CNS) disease must have no clinical
or radiological evidence of active CNS disease at the time of study enrollment.
• Patients with seizure disorders may be enrolled if seizures are well controlled on
anti-convulsants.
• CNS toxicity =< grade 2.
Exclusion Criteria:
• Men and women of childbearing potential and their partners must agree to use adequate
contraception while enrolled on this study. Based on the established teratogenic
potential of alkylating agents, pregnant women will be excluded from this study.
Because of potential risks to breastfed infants due to drug metabolites that could be
excreted in breast milk, female patients who are lactating must agree to stop
breastfeeding or will otherwise be excluded from this study. Females of childbearing
potential must have a negative pregnancy test to be eligible for this study.
• Patients with only elevated catecholamines (i.e. > 2 x ULN) are NOT eligible for this
study.
• Patients must have been off pharmacologic doses of systemic steroids for at least 7
days prior to enrollment. Patients who require or are likely to require pharmacologic
doses of systemic corticosteroids while receiving treatment on this study are
ineligible. The only exception is for patients known to require 2 mg/kg or less of
hydrocortisone (or an equivalent dose of an alternative corticosteroid) as
premedication for blood product administration in order to avoid allergic transfusion
reactions. The use of conventional doses of inhaled steroids for the treatment of
asthma is permitted, as is the use of physiologic doses of steroids for patients with
known adrenal insufficiency.
Patients on any other immunosuppressive medications (e.g. cyclosporine, tacrolimus) are not
eligible.
• Patients must not have received prior treatment with irinotecan and temozolomide.
• Patients must not have received enzyme-inducing anticonvulsants including phenytoin,
phenobarbital, or carbamazepine for at least 7 days prior to study enrollment.
Patients receiving non-enzyme inducing anticonvulsants such as gabapentin, valproic
acid, or levetiracetam will be eligible.
• Patients who have received drugs that are strong inducers or inhibitors of CYP3A4
within 7 days prior to study enrollment are not eligible.
• Patients must not have been diagnosed with myelodysplastic syndrome or with any
malignancy other than neuroblastoma.
• Patients with symptoms of congestive heart failure are not eligible.
• Patients must not have >= grade 2 diarrhea.
• Patients who are unable to tolerate oral/nasogastric/gastrostomy medications will not
be eligible for this trial. Additionally, patients with significant malabsorption will
not be eligible for this trial.
• Patients must not have uncontrolled infection.
• Patients with a history of grade 4 allergic reactions to anti-GD2 antibodies or
reactions that required permanent discontinuation of the anti-GD2 therapy are not
eligible.
• Patients with a significant intercurrent illness (any ongoing serious medical problem
unrelated to cancer or its treatment) that is not covered by the detailed exclusion
criteria and that is expected to interfere with the action of study agents or to
significantly increase the severity of the toxicities experienced from study treatment
are not eligible.
High Risk Neuroblastoma, Recurrent Neuroblastoma, Refractory Neuroblastoma, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Melanoma/Skin cancer, Sarcoma, Uterus
Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1
This study will evaluate the safety, tolerability, drug levels, molecular effects, and
clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors that have a
KRAS G12C mutation.
Nataliya Uboha, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT03785249
Show full eligibility criteria
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Inclusion Criteria:
• Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation
• Unresectable or metastatic disease
• Standard treatment is not available or patient declines; first-line treatment for
NSCLC for certain cohorts
• Adequate organ function
Exclusion Criteria:
• History of intestinal disease or major gastric surgery or inability to swallow oral
medications
• Other active cancer
Study of RP1 Monotherapy and RP1 in Combination With Nivolumab (IGNYTE)
RPL-001-16 is a Phase 1/2, open label, dose escalation and expansion clinical study of RP1
alone and in combination with nivolumab in adult subjects with advanced and/or refractory
solid tumors, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose
(RP2D), as well as to evaluate preliminary efficacy.
Hamid Emamekhoo, M.D.
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03767348
Show full eligibility criteria
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Inclusion Criteria:
• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
• At least one measurable and injectable lesion
• Have provided a former tumor pathology specimen or be willing to supply a new tumor
sample from a biopsy
• Have a predicted life expectancy of ≥ 3 months
• Measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST)
v1.1 criteria
• Subjects with MSI-H or dMMR tumors: has diagnosis of MSI-H or metatstatic dMMR tumor
(according to protocol definition) for whom anti PD-1 therapy is indicated, or have
refused, become intolerant to or have no further therapy options available
• Subjects with NMSC: has diagnosis of locally advanced or metastatic NMSC that are not
considered treatable by surgery including basal cell carcinoma, cutaneous squamous
cell carcinoma, basosquamous carcinoma, Merkel cell carcinoma and other non-melanoma
skin cancers (per protocol) for whom anti-PD1/PD-L1 therapy is indicated, or have
refused, become intolerant to or have no further therapy options available
• Subjects with anti-PD1 failed cutaneous melanoma: has confirmed progressive disease
while on anti-PD1 treatment for at least 8 weeks and documented BRAF mutation status
• Subjects with anti-PD1 failed NSCLC: has confirmed progressive disease after no more
than two prior systemic treatments including anti-PD1/PD-L1 treatment
Exclusion Criteria:
• Prior treatment with an oncolytic therapy
• History of viral infections according to the protocol
• Prior complications with herpes infections
• Chronic use of anti-virals
• Uncontrolled/untreated brain metastasis
• History of interstitial lung disease
• History of non-infectious pneumonitis
• History of clinically significant cardiovascular disease
Cancer, Melanoma (Skin), Mismatch Repair Deficiency, Microsatellite Instability, Non-melanoma Skin Cancer, Cutaneous Melanoma, NSCLC, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
Cisplatin and Combination Chemotherapy in Treating Children and Young Adults With Hepatoblastoma or Liver Cancer After Surgery
This partially randomized phase II/III trial studies how well, in combination with surgery,
cisplatin and combination chemotherapy works in treating children and young adults with
hepatoblastoma or hepatocellular carcinoma. Drugs used in chemotherapy, such as cisplatin,
doxorubicin, fluorouracil, vincristine sulfate, carboplatin, etoposide, irinotecan,
sorafenib, gemcitabine and oxaliplatin, work in different ways to stop the growth of tumor
cells, either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. Giving combination chemotherapy may kill more tumor cells than one type of
chemotherapy alone.
Kenneth Desantes, M.D.
All
up to 30 Years old
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT03533582
Show full eligibility criteria
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Inclusion Criteria:
• Patients in Group F must have a body surface area (BSA) >= 0.6 m^2
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age; patients who are unable to walk because of
paralysis, but who are up in a wheelchair, will be considered ambulatory for the
purpose of assessing the performance score
• Patients must be newly diagnosed with histologically-proven primary pediatric hepatic
malignancies including hepatoblastoma or hepatocellular carcinoma, except as noted
below; patients with a diagnosis of hepatocellular neoplasm, not otherwise specified,
should be classified and treated per hepatoblastoma treatment arms; note that rapid
central pathology review is required in some cases; please note: all patients with
histology as assessed by the institutional pathologist consistent with pure small cell
undifferentiated (SCU) HB will be required to have testing for INI1/SMARCB1 by
immunohistochemistry (IHC) according to the practices at the institution
• Patients with histology consistent with pure SCU must have positive INI1/SMARCB1
staining
• For all Group A patients, WDF status as determined by rapid review will be used to
further stratify patients to Group A1 or A2
• For Groups B, C and D, rapid review is required if patients are either >= 8 years
of age or have an alphafetoprotein (AFP) =< 100 at diagnosis
• For all Groups E and F patients, rapid central pathology review is required
• In emergency situations when a patient meets all other eligibility criteria and has
had baseline required observations, but is too ill to undergo a biopsy safely, the
patient may be enrolled without a biopsy
• Clinical situations in which emergent treatment may be indicated include, but are
not limited to, the following circumstances:
• Anatomic or mechanical compromise of critical organ function by tumor (e.g.,
respiratory distress/failure, abdominal compartment syndrome, urinary
obstruction, etc.)
• Uncorrectable coagulopathy
• For a patient to maintain eligibility for AHEP1531 when emergent treatment is
given, the following must occur:
• The patient must have a clinical diagnosis of hepatoblastoma, including an
elevated alphafetoprotein (AFP), and must meet all AHEP1531 eligibility
criteria at the time of emergent treatment
• Patient must be enrolled on AHEP1531 prior to initiating protocol therapy; a
patient will be ineligible if any chemotherapy is administered prior to
AHEP1531 enrollment
• Note: If the patient receives AHEP1531 chemotherapy emergently PRIOR to
undergoing a diagnostic biopsy, pathologic review of material obtained in the
future during either biopsy or surgical resection must either confirm the
diagnosis of hepatoblastoma or not reveal another pathological diagnosis to be
included in the analysis of the study aims
• Patients may have had surgical resection of the hepatic malignancy prior to
enrollment; all other anti-cancer therapy for the current liver lesion is prohibited
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 60
mL/min/1.73 m^2 or
• A serum creatinine based on age/gender as follows:
• Age: maximum serum creatinine (mg/dL)
• 1 month to < 6 months: 0.4 (male and female)
• 6 months to < 1 year: 0.5 (male and female)
• 1 to < 2 years: 06 (male and female)
• 2 to < 6 years: 0.8 (male and female)
• 6 to < 10 years: 1 (male and female)
• 10 to < 13 years: 1.2 (male and female)
• 13 to < 16 years: 1.5 (male), 1.4 (female)
• >= 16 years: 1.7 (male), 1.4 (female)
• Total bilirubin =< 5 x upper limit of normal (ULN) for age
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
< 10 x upper limit of normal (ULN) for age
• Shortening fraction of >= 28% by echocardiogram (for patients on
doxorubicin-containing regimens [Groups C, D, E2, and F] assessed within 8 weeks prior
to study enrollment) or
• Ejection fraction of >= 47% by echocardiogram or radionuclide angiogram (for patients
on doxorubicin-containing regimens [Groups C, D, E2, and F] assessed within 8 weeks
prior to study enrollment)
• Group F patients only: QT/corrected QT (QTc) interval =< 450 milliseconds for males
and =< 470 milliseconds for females (assessed within 8 weeks prior to study
enrollment)
• Normal pulmonary function tests (including diffusion capacity of the lung for carbon
monoxide [DLCO]) if there is clinical indication for determination (e.g. dyspnea at
rest, known requirement for supplemental oxygen) (for patients receiving chemotherapy
[Groups A, B, C, D, E2, F]); for patients who do not have respiratory symptoms or
requirement for supplemental oxygen, pulmonary function tests (PFTs) are NOT required
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Exclusion Criteria:
• Prior chemotherapy or tumor directed therapy (i.e. radiation therapy, biologic agents,
local therapy (embolization, radiofrequency ablation, and laser); therefore, patients
with a pre-disposition syndrome who have a prior malignancy are not eligible
• Patients who are currently receiving another investigational drug
• Patients who are currently receiving other anticancer agents
• Patients with uncontrolled infection
• Patients who previously received a solid organ transplant, other than those who
previously received an orthotopic liver transplantation (OLT) as primary treatment of
their hepatocellular carcinoma
• Patients with hypersensitivity to any drugs on their expected treatment arm
• Group C: Patients who have known deficiency of dihydropyrimidine dehydrogenase (DPD)
• Group D:
• Patients with chronic inflammatory bowel disease and/or bowel obstruction
• Patients with concomitant use of St. John's wort, which cannot be stopped prior
to the start of trial treatment
• Group F:
• Patients with peripheral sensitive neuropathy with functional impairment
• Patients with a personal or family history of congenital long QT syndrome
• These criteria apply ONLY to patients who may receive chemotherapy (all groups other
than Group E1):
• Female patients who are pregnant since fetal toxicities and teratogenic effects
have been noted for several of the study drugs; a pregnancy test is required for
female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation
• Note for Group F: patients of childbearing potential should use effective
birth control during treatment with sorafenib and for at least 2 weeks after
stopping treatment
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