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.
Genetic Analysis in Identifying Late-Occurring Complications in Childhood Cancer Survivors
This clinical trial studies cancer survivors to identify those who are at increased risk of
developing late-occurring complications after undergoing treatment for childhood cancer. A
patient's genes may affect the risk of developing complications, such as congestive heart
failure, avascular necrosis, stroke, and second cancer, years after undergoing cancer
treatment. Genetic studies may help doctors identify survivors of childhood cancer who are
more likely to develop late complications.
Kenneth Desantes, M.D.
All
up to 99 Years old
N/A
This study is NOT accepting healthy volunteers
NCT00082745
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Inclusion Criteria:
• ELIGIBILITY CRITERIA •CASES
• Diagnosis of primary cancer at age 21 or younger, irrespective of current age
• No prior history of allogeneic (non-autologous) hematopoietic cell transplant
• Development of one of the following key adverse events at any time following
initiation of cancer therapy:
• Cardiac dysfunction; please note: case enrollment has been closed due to
achievement of target accrual
• Ischemic stroke (IS)
• Subsequent malignant neoplasm (SMN)
• Avascular necrosis (AVN); please note: case enrollment has been closed due to
achievement of target accrual
• Submission of a blood specimen (or in certain cases a saliva specimen) to the
Coordinating Center at the University of Alabama at Birmingham as per the
requirements; please note: if a patient is currently receiving active cancer
treatment, it is preferable to obtain the blood sample at a time when the patient's
white blood cell (WBC) is > 2,000
• Written informed consent from the patient and/or the patient's legally authorized
guardian
• In active follow up by a COG institution; active follow up will be defined as date of
last visit or contact by a COG institution within the past 24 months; any type of
contact, including contact specifically for participation in ALTE03N1, qualifies as
active follow-up; please note: treatment on a COG (or legacy group) therapeutic
protocol for the primary cancer is NOT required
• ELIGIBILITY CRITERIA •CONTROLS
• CONTROL: Diagnosis of primary cancer at age 21 or younger, irrespective of current age
• CONTROLS: No prior history of allogeneic (non-autologous) hematopoietic cell
transplant
• CONTROLS: No clinical evidence of any of the following key adverse events:
• Cardiac dysfunction (CD); please note: if a patient is currently receiving active
cancer treatment, it is preferable to obtain the blood sample at a time when the
patient's WBC is > 2,000
• Ischemic stroke (IS)
• Avascular necrosis (AVN)
• Subsequent malignant neoplasm (SMN)
• CONTROLS: Submission of a blood specimen (or in certain cases a saliva specimen) to
the Coordinating Center Laboratory at the University of Alabama at Birmingham as per
the requirements
• CONTROLS: Written informed consent from the patient and/or the patient's legally
authorized guardian
• CONTROLS: In active follow up by a COG institution; active follow up will be defined
as date of last visit or contact by a COG institution within the past 24 months; any
type of contact, including contact specifically for participation in ALTE03N1,
qualifies as active follow-up; please note: treatment on a COG (or legacy group)
therapeutic protocol for the primary cancer is NOT required
Childhood Malignant Neoplasm, 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, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Leukemia, not otherwise specified, Other Hematopoietic, Ill-Defined Sites, Other
The purpose of the Registry is to provide continuing evaluation and periodic reporting of
safety and effectiveness of Medtronic market-released products. The Registry data is intended
to benefit and support interests of patients, hospitals, clinicians, regulatory bodies,
payers, and industry by streamlining the clinical surveillance process and facilitating
leading edge performance assessment via the least burdensome approach.
Micah Chan
All
Not specified
N/A
This study is NOT accepting healthy volunteers
NCT01524276
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Inclusion Criteria:
• Patient or legally authorized representative provides written authorization and/or
consent per institution and geographical requirements
• Patient has or is intended to receive or be treated with an eligible Medtronic product
• Patient within enrollment window relative to therapy initiation or meets criteria for
retrospective enrollment
Exclusion Criteria:
• Patient who is, or will be, inaccessible for follow-up
• Patient with exclusion criteria required by local law
• Patient is currently enrolled in or plans to enroll in any concurrent drug and/or
device study that may confound results
Cardiac Rhythm Disorders, Urological Disorders, Neurological Disorders, Cardiovascular Disorders, Digestive Disorders, Intracranial Aneurysm, Mechanical Circulatory Support, Respiratory Therapy, Aortic, Peripheral Vascular and Venous Disorders, Minimally Invasive Surgical Procedures, Diagnostic Techniques and Procedures, Surgical Procedures, Operative, Renal Insufficiency, Neurovascular, Coronary Artery Disease, Ear, Nose and Throat Disorder, Other
A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
This phase III trial compares the effect of selumetinib versus the standard of care treatment
with carboplatin and vincristine (CV) in treating patients with newly diagnosed or previously
untreated low-grade glioma (LGG) that does not have a genetic abnormality called BRAFV600E
mutation and is not associated with systemic neurofibromatosis type 1. Selumetinib works by
blocking some of the enzymes needed for cell growth and may kill tumor cells. Carboplatin and
vincristine are chemotherapy drugs that work in different ways to stop the growth of tumor
cells, either by killing the cells or by stopping them from dividing. The overall goal of
this study is to see if selumetinib works just as well as the standard treatment of CV for
patients with LGG. Another goal of this study is to compare the effects of selumetinib versus
CV in subjects with LGG to find out which is better. Additionally, this trial will also
examine if treatment with selumetinib improves the quality of life for subjects who take it.
Kenneth Desantes, M.D.
All
2 Years to 21 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04166409
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Inclusion Criteria:
• Patients must be >= 2 years and =< 21 years at the time of enrollment
• Patients must have a body surface area (BSA) of >= 0.5 m^2 at enrollment
• Patients must have non-neurofibromatosis type 1 (non-NF1) low-grade glioma (LGG)
without a BRAFV600E mutation as confirmed by Rapid Central Pathology and Molecular
Screening Reviews performed on APEC14B1 (NCT02402244) and that has not been treated
with any modality besides surgery. Note: Patients may be newly-diagnosed OR previously
diagnosed, and there is no required time frame between biopsy/surgery and treatment
initiation.
• Patients with residual tumor after resection or progressive tumor after initial
diagnosis (with or without surgery) who have not received treatment (chemotherapy
and/or radiation) are eligible
• Patients must have two-dimensional measurable tumor >= 1 cm^2 to be eligible
• Eligible histologies will include all tumors considered low-grade glioma or low-grade
astrocytoma (World Health Organization [WHO] grade I and II) by 5th edition WHO
classification of central nervous system (CNS) tumors with the exception of
subependymal giant cell astrocytoma
• Patients with metastatic disease or multiple independent primary LGG are eligible
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 OR a serum creatinine based on age/gender as follows (performed within
7 days prior to enrollment):
• Age: Maximum Serum Creatinine (mg/dL)
• 2 to < 6 years: 0.8 mg/dL (male); 0.8 mg/dL (female)
• 6 to < 10 years: 1 mg/dL (male); 1 mg/dL (female)
• 10 to < 13 years: 1.2 mg/dL (male); 1.2 mg/dL (female)
• 13 to < 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female)
• >= 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (performed within 7 days
prior to enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed
on study regardless of their total and indirect [unconjugated] bilirubin levels as
long as their direct [conjugated] bilirubin is < 3.1 mg/dL)
• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L
(performed within 7 days prior to enrollment). For the purpose of this study, the ULN
for SGPT is 45 U/L
• Albumin >= 2 g/dL (performed within 7 days prior to enrollment)
• Left ventricular ejection fraction (LVEF) >= 53% (or institutional normal; if the LVEF
result is given as a range of values, then the upper value of the range will be used)
by echocardiogram (performed within 4 weeks prior to enrollment)
• Corrected QT (QTc) interval =< 450 msec by electrocardiography (EKG) (performed within
4 weeks prior to enrollment)
• Absolute neutrophil count >= 1,000/uL (unsupported) (performed within 7 days prior to
enrollment)
• Platelets >= 100,000/uL (unsupported) (performed within 7 days prior to enrollment)
• Hemoglobin >= 8 g/dL (may be supported) (performed within 7 days prior to enrollment)
• Patients with a known seizure disorder should be stable and should not have
experienced a significant increase in seizure frequency within 2 weeks prior to
enrollment
• Patients 2-17 years of age must have a blood pressure that is =< 95th percentile for
age, height, and gender at the time of enrollment (with or without the use of
anti-hypertensive medications)
• Patients >= 18 years of age must have a blood pressure =< 130/80 mmHg at the time of
enrollment (with or without the use of anti-hypertensive medications)
• Note for patients of all ages: Adequate blood pressure can be achieved using
medication for the treatment of hypertension
• All patients must have ophthalmology toxicity assessments performed within 4 weeks
prior to enrollment
• For all patients, a magnetic resonance imaging (MRI) of the brain (with orbital cuts
for optic pathway tumors) and/or spine (depending on the site(s) of primary disease)
with and without contrast must be performed within 4 weeks prior to enrollment
• 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 must have the ability to swallow whole capsules
• All patients have signed an appropriate consent form and Health Insurance Portability
and Accountability Act (HIPAA) authorization form (if applicable)
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All patients have been consented and enrolled on APEC14B1 (NCT02402244) followed by
enrollment on the ACNS1833 Pre-Enrollment Eligibility Screening (Step 0) on the same
day to complete the Rapid Central Review
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Exclusion Criteria:
• Patients must not have received any prior tumor-directed therapy including
chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior
surgical intervention is permitted
• Patients with a concurrent malignancy or history of treatment (other than surgery) for
another tumor within the last year are ineligible
• Patients with diffuse intrinsic pontine tumors as seen on MRI (> 2/3 of pons
involvement on imaging) are not eligible even if biopsy reveals grade I/II histology
• Patients may not be receiving any other investigational agents
• Patients with any serious medical or psychiatric illness/condition, including
substance use disorders or ophthalmological conditions, likely in the judgment of the
investigator to interfere or limit compliance with study requirements/treatment
• Patients who, in the opinion of the investigator, are not able to comply with the
study procedures are not eligible
• Female patients who are pregnant are not eligible 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 are not eligible
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation and for
12 weeks after stopping study therapy are not eligible.
• Note: Women of child-bearing potential and males with sexual partners who are
pregnant or who could become pregnant (i.e., women of child-bearing potential)
should use effective methods of contraception for the duration of the study and
for 12 weeks after stopping study therapy to avoid pregnancy and/or potential
adverse effects on the developing embryo
• Known genetic disorder that increases risk for coronary artery disease. Note: The
presence of dyslipidemia in a family with a history of myocardial infarction is not in
itself an exclusion unless there is a known genetic disorder documented
• Symptomatic heart failure
• New York Health Association (NYHA) class II-IV prior or current cardiomyopathy
• Severe valvular heart disease
• History of atrial fibrillation
• Current or past history of central serous retinopathy
• Current or past history of retinal vein occlusion or retinal detachment
• Patients with uncontrolled glaucoma
• If checking pressure is clinically indicated, patients with intraocular pressure
(IOP) > 22 mmHg or ULN adjusted by age are not eligible
• Supplementation with vitamin E greater than 100% of the daily recommended dose. Any
multivitamin containing vitamin E must be stopped prior to study enrollment even if
less than 100% of the daily recommended dosing for vitamin E
• Surgery within 2 weeks prior to enrollment, with the exception of surgical biopsy,
placement of a vascular access device or cerebral spinal fluid (CSF) diverting
procedure such as endoscopic third ventriculostomy (ETV) and ventriculoperitoneal (VP)
shunt.
• Note: Patients must have healed from any prior surgery
• Patients who have an uncontrolled infection are not eligible
A Study of the Drugs Selumetinib Versus Carboplatin/Vincristine in Patients With Neurofibromatosis and Low-Grade Glioma
This phase III trial studies if selumetinib works just as well as the standard treatment with
carboplatin/vincristine (CV) for subjects with NF1-associated low grade glioma (LGG), and to
see if selumetinib is better than CV in improving vision in subjects with LGG of the optic
pathway (vision nerves). Selumetinib is a drug that works by blocking some enzymes that
low-grade glioma tumor cells need for their growth. This results in killing tumor cells.
Drugs used as chemotherapy, such as carboplatin and vincristine, work in different ways to
stop the growth of tumor cells, either by killing the cells, by stopping them from dividing,
or by stopping them from spreading. It is not yet known whether selumetinib works better in
treating patients with NF1-associated low-grade glioma compared to standard therapy with
carboplatin and vincristine.
Kenneth Desantes, M.D.
All
2 Years to 21 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03871257
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Inclusion Criteria:
• Patients must be >= 2 years and =< 21 years at the time of enrollment
• Patients must have a body surface area (BSA) of >= 0.5 m^2 at enrollment
• Patients must have neurofibromatosis type 1 (NF1) based on clinical criteria and/or
germline genetic testing
• Patients must be newly diagnosed or have previously diagnosed NF-1 associated LGG that
has not been treated with any modality other than surgery
• For patients with optic pathway gliomas (OPGs):
• Newly-diagnosed patients with OPG are eligible if there are neurologic symptoms
(including visual dysfunction, as defined below) or other exam findings
associated with the tumor
• Previously-diagnosed patients with OPG are eligible if they have new or worsening
neurologic symptoms (including visual dysfunction, as defined below) or have
tumor growth
• For both newly-diagnosed and previously-diagnosed OPG, the patient may be
eligible, irrespective of whether there has been tumor growth or other
neurological symptoms or worsening, if they meet at least one of the following
visual criteria:
• Visual worsening, defined as worsening of visual acuity (VA) or visual
fields (VF) documented within the past year (by examination or history); OR
• Significant visual dysfunction (defined as VA worse than normal for age by
0.6 logMAR [20/80, 6/24, or 2.5/10] or more in one or both eyes)
• For patients with LGG in other locations (i.e., not OPGs):
• Newly-diagnosed patients with LGG are eligible if there are neurologic symptoms
or other exam findings associated with the tumor
• NOTE: Newly-diagnosed patients with LGG without associated neurologic
symptoms or exam findings are not eligible
• Previously-diagnosed patients with LGG are eligible if they have new or worsening
neurologic symptoms or have tumor growth
• Although not required, if a biopsy/tumor resection is performed, eligible histologies
will include all tumors considered LGG or low-grade astrocytoma (World Health
Organization [WHO] grade I and II) by 5th edition WHO classification of central
nervous system (CNS) tumors with the exception of subependymal giant cell astrocytoma
• Patients must have two-dimensional measurable tumor >= 1 cm^2
• Patients with metastatic disease or multiple independent primary LGGs are allowed on
study
• Creatinine clearance or radioisotope glomerular filtration Rate (GFR) >= 70
mL/min/1.73 m^2 OR a serum creatinine based on age/gender (within 7 days prior to
enrollment) as follows:
• Age; maximum serum creatinine (mg/dL)
• 2 to < 6 years; 0.8 (male) and 0.8 (female)
• 6 to < 10 years; 1 (male) and 1 (female)
• 10 to < 13 years; 1.2 (male) and 1.2 (female)
• 13 to < 16 years; 1.5 (male) and 1.4 (female)
• >= 16 years; 1.7 (male) and 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed on study
regardless of their total and indirect [unconjugated] bilirubin levels as long as
their direct [conjugated] bilirubin is < 3.1 mg/dL)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x
upper limit of normal (ULN) = 135 U/L (within 7 days prior to enrollment). For the
purpose of this study, the ULN for SGPT is 45 U/L
• Albumin >= 2 g/dL (within 7 days prior to enrollment)
• Left ventricular ejection fraction (LVEF) >= 53% (or institutional normal; if the LVEF
result is given as a range of values, then the upper value of the range will be used)
by echocardiogram (within 4 weeks prior to enrollment)
• Corrected QT (QTc) interval =< 450 msec by electrocardiography (EKG) (within 4 weeks
prior to enrollment)
• Absolute neutrophil count >= 1,000/uL (unsupported) (within 7 days prior to
enrollment)
• Platelets >= 100,000/uL (unsupported) (within 7 days prior to enrollment)
• Hemoglobin >= 8 g/dL (may be supported) (within 7 days prior to enrollment)
• Patients with a known seizure disorder should be stable and should have not
experienced a significant increase in seizure frequency within 2 weeks prior to
enrollment
• Patients 2-17 years of age must have a blood pressure that is =< 95th percentile for
age, height, and gender at the time of enrollment. Patients >= 18 years of age must
have a blood pressure =< 130/80 mmHg at the time of enrollment (with or without the
use of antihypertensive medications).
• Note: Adequate blood pressure can be achieved using medication for the treatment
of hypertension
• All patients must have ophthalmology toxicity assessments performed within 4 weeks
prior to enrollment
• For all patients, an MRI of the brain (with orbital cuts for optic pathway tumors)
and/or spine (depending on the site(s) of primary disease) with and without contrast
must be performed within 4 weeks prior to enrollment
• For patients who undergo a surgery on the target tumor (not required), a pre- and
post-operative* MRI of the brain (with orbital cuts for optic pathway tumors) or spine
(depending on the site(s) of primary disease) with and without contrast must also be
performed within 4 weeks prior to enrollment
• The post-operative MRIs should be performed ideally within 48 hours after surgery
if possible
• 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 must have the ability to swallow whole capsules
• Patients must have receptive and expressive language skills in English or Spanish to
complete the quality of life (QOL) and neurocognitive assessments
• All patients and/or their parents or legal guardians must sign a written informed
consent.
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met.
Exclusion Criteria:
• Patients must not have received any prior tumor-directed therapy including
chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior
surgical intervention is permitted
• Patients with a concurrent malignancy or history of treatment (other than surgery) for
another tumor within the last year are ineligible
• Patients may not be receiving any other investigational agents
• Patients with any serious medical or psychiatric illness/ condition, including
substance use disorders likely in the judgement of the investigator to interfere or
limit compliance with study requirements/treatment are not eligible
• Patients who, in the opinion of the investigator, are not able to comply with the
study procedures are not eligible
• Female patients who are pregnant are not eligible 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 are not eligible
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation and for
12 weeks after stopping study therapy are not eligible
• Note: Women of child-bearing potential and males with sexual partners who are
pregnant or who could become pregnant (i.e., women of child-bearing potential)
should use effective methods of contraception for the duration of the study and
for 12 weeks after stopping study therapy to avoid pregnancy and/or potential
adverse effects on the developing embryo
• Cardiac conditions:
• Known genetic disorder that increases risk for coronary artery disease. Note: The
presence of dyslipidemia in a family with a history of myocardial infarction is
not in itself an exclusion unless there is a known genetic disorder documented
• Symptomatic heart failure
• New York Heart Association (NYHA) class II-IV prior or current cardiomyopathy
• Severe valvular heart disease
• History of atrial fibrillation
• Ophthalmologic conditions:
• Current or past history of central serous retinopathy
• Current or past history of retinal vein occlusion or retinal detachment
• Patients with uncontrolled glaucoma
• If checking pressure is clinically indicated, patients with intraocular
pressure (IOP) > 22 mmHg or ULN adjusted by age are not eligible
• Ophthalmological findings secondary to long-standing optic pathway glioma (such
as visual loss, optic nerve pallor, or strabismus) or longstanding
orbito-temporal plexiform neurofibroma (PN), such as visual loss, strabismus)
will NOT be considered a significant abnormality for the purposes of the study
• Treatments and/or medications patient is receiving that would make her/him ineligible,
such as:
• Supplementation with vitamin E greater than 100% of the daily recommended dose.
Any multivitamin containing vitamin E must be stopped prior to study enrollment
even if less than 100% of the daily recommended dosing for vitamin E
• Surgery within 2 weeks prior to enrollment, with the exception of surgical
placement for vascular access or cerebrospinal fluid (CSF) diverting procedures
such as endoscopic third ventriculostomy (ETV) and ventriculo-peritoneal (VP)
shunt.
• Note: Patients must have healed from any prior surgery prior to enrollment
• Patients who have an uncontrolled infection are not eligible
Low Grade Glioma, Neurofibromatosis Type 1, Visual Pathway Glioma, Brain and Nervous System, Brain/Central Nervous System
Dabrafenib Combined With Trametinib After Radiation Therapy in Treating Patients With Newly-Diagnosed High-Grade Glioma
This phase II trial studies how well the combination of dabrafenib and trametinib works after
radiation therapy in children and young adults with high grade glioma who have a genetic
change called BRAF V600 mutation. Radiation therapy uses high energy rays to kill tumor cells
and reduce the size of tumors. Dabrafenib and trametinib may stop the growth of tumor cells
by blocking BRAF and MEK, respectively, which are enzymes that tumor cells need for their
growth. Giving dabrafenib with trametinib after radiation therapy may work better than
treatments used in the past in patients with newly-diagnosed BRAF V600-mutant high-grade
glioma.
Kenneth Desantes, M.D.
All
12 Months to 21 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03919071
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Inclusion Criteria:
• PRE-ENROLLMENT ELIGIBILITY SCREENING: Patients must be =< 25 years of age at the time
of enrollment on APEC14B1 Part A CNS/HGG pre-enrollment eligibility screening.
• Note: This required age range applies to the pre-enrollment eligibility screening
for all HGG patients. Individual treatment protocols may have different age
criteria.
• PRE-ENROLLMENT ELIGIBILITY SCREENING: Patient is suspected of having localized
newly-diagnosed HGG, excluding metastatic disease.
• PRE-ENROLLMENT ELIGIBILITY SCREENING: Patient and/or their parents or legal guardians
have signed informed consent for eligibility screening on APEC14B1 Part A.
• PRE-ENROLLMENT ELIGIBILITY SCREENING: The specimens obtained at the time of diagnostic
biopsy or surgery must be submitted through APEC14B1 as soon as possible (ASAP),
preferably within 5 calendar days of the procedure.
• Please note: See the APEC14B1 Manual of Procedures for a full list of detailed
instructions for submitting required materials and for shipping details.
• Patients must be >= 3 years and =< 25 years of age at the time of enrollment.
• Patients must have eligibility confirmed by Rapid Central Pathology and Molecular
Screening Reviews performed on APEC14B1
• Newly diagnosed high-grade glioma with BRAF^V600-mutation
• Results for H3 K27M by immunohistochemistry (IHC) or sequencing
• Histologically confirmed high-grade glioma (World Health Organization [WHO] grade
III or IV) including but not limited to: anaplastic astrocytoma (AA), anaplastic
pleomorphic xanthoastrocytoma (aPXA), anaplastic gangliogliomas (aGG),
glioblastoma (GB), and high-grade astrocytoma, not otherwise specified (NOS).
• Patients must have had histologic verification of a high-grade glioma diagnosis. CSF
cytology by lumbar puncture must be done if clinically indicated and determined to be
safe prior to study enrollment. If cytology proves positive, the patient would be
considered to have metastatic disease and would, therefore, be ineligible.
• A pre- and post-operative brain MRI with and without contrast and a baseline spine MRI
with contrast must be obtained prior to enrollment. The requirement for a
post-operative MRI is waived for patients who undergo biopsy only. If the spine MRI is
positive, the patient would be considered to have metastatic disease and would be
ineligible.
• 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.
• Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to
enrollment).
• Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to
enrollment).
• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (within 7 days
prior to enrollment).
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 (within 7 days prior to enrollment) or
• A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
• Age 3 to < 6 years (Male 0.8 mg/dL, Female 0.8 mg/dL)
• Age 6 to < 10 years (Male 1 mg/dL, Female 1 mg/dL)
• Age 10 to < 13 years (Male 1.2 mg/dL, Female 1.2 mg/dL)
• Age 13 to < 16 years (Male 1.5 mg/dL, Female 1.4 mg/dL)
• Age >= 16 years (Male 1.7 mg/dL, Female 1.4 mg/dL)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment), and
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
U/L (within 7 days prior to enrollment). For the purpose of this study, the ULN for
SGPT is 45 U/L.
• Patients with a seizure disorder may be enrolled if their seizures are well controlled
while on non-enzyme inducing anticonvulsants permitted on this study.
• All patients and/or their parents or legal guardians must sign a written informed
consent
• Patients must be enrolled and protocol therapy must be projected to begin no later
than 31 days after definitive surgery (day 0). If a biopsy only was performed, the
biopsy date will be considered the date of definitive surgery. For patients who have a
biopsy or incomplete resection at diagnosis followed by additional surgery, the date
of the last resection will be considered the date of definitive surgery.
Exclusion Criteria:
• Patients with intrinsic brainstem or primary spinal cord tumors will be excluded.
• Patients with metastatic disease (defined as neuraxis dissemination either by imaging
or by cytology) will be excluded.
• Patients must not have received any prior tumor-directed therapy including
chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant for the
treatment of HGG other than surgical intervention and/or corticosteroids.
• Previous treatment with dabrafenib or another RAF inhibitor, trametinib or another MEK
inhibitor, or an ERK inhibitor.
• Patients with a history of a malignancy with confirmed activating RAS mutation.
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to dabrafenib, trametinib, and their excipients.
• Uncontrolled medical conditions (e.g., diabetes mellitus, hypertension, liver disease,
or uncontrolled infection), psychological, familial, sociological, or geographical
conditions that do not permit compliance with the protocol; or unwillingness or
inability to follow the procedures required in the protocol.
• Presence of active gastrointestinal (GI) disease or other condition (e.g., small bowel
or large bowel resection) that will interfere significantly with the absorption of
drugs.
• History of hepatitis B virus, or hepatitis C virus infection (patients with laboratory
evidence of cleared hepatitis B virus and/or hepatitis C virus may be enrolled).
• History or current diagnosis of cardiac disease indicating significant risk of safety
for patients participating in the study such as uncontrolled or significant cardiac
disease, including any of the following:
• Recent myocardial infarction (within the last 6 months);
• Uncontrolled congestive heart failure;
• Unstable angina (within last 6 months);
• Clinically significant (symptomatic) or known, uncontrolled cardiac arrhythmias
(e.g., sustained ventricular tachycardia, and clinically significant second or
third degree atrioventricular [AV] block without a pacemaker) except sinus
arrhythmia within the past 24 weeks prior to the first dose of study treatment;
• Coronary angioplasty or stenting (within last 6 months);
• Intra-cardiac defibrillators;
• Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram.
• Patients with a history or current evidence of retinal vein occlusion (RVO) or central
serous retinopathy (CSR), or predisposing factors to RVO or CSR (e.g., uncontrolled
glaucoma or ocular hypertension).
• Patients with presence of interstitial lung disease or pneumonitis.
• Female patients who are pregnant are ineligible since there is yet no available
information regarding human fetal or teratogenic toxicities.
• Lactating females are not eligible unless they have agreed not to breastfeed their
infants for the duration of the study and for 4 months following discontinuation of
study therapy.
• Female patients of childbearing potential are not eligible unless a negative pregnancy
test result has been obtained.
• Sexually active patients of reproductive potential (male or female) are not eligible
unless they have agreed to use an effective contraceptive method for the duration of
their study participation and for 4 months following discontinuation of study therapy.
Male patients (including those who have had a vasectomy) taking dabrafenib and
trametinib combination therapy must use a condom during intercourse while on study and
for 16 weeks after stopping treatment, and should not father a child during these
periods. Women of childbearing potential should use effective non-hormonal
contraception during therapy and for 4 weeks following discontinuation of dabrafenib
and at least 4 months following the last dose of trametinib in patients taking
combination therapy. Women should be advised that dabrafenib may decrease the efficacy
of hormonal contraceptives and an alternate method of contraception, such as barrier
methods, should be used.
Anaplastic Astrocytoma, Anaplastic Astrocytoma, Not Otherwise Specified, Anaplastic Ganglioglioma, Anaplastic Pleomorphic Xanthoastrocytoma, Glioblastoma, Malignant Glioma, WHO Grade 3 Glioma, Brain and Nervous System, Brain/Central Nervous System
Study to Evaluate Biological & Clinical Effects of Significantly Corrected CFTR Function in Infants & Young Children (BEGIN)
This is a two-part, multi-center, prospective longitudinal, exploratory study of highly
effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators and their
impact on children with cystic fibrosis (CF).
Christina Barreda
All
up to 5 Years old
NA
This study is NOT accepting healthy volunteers
NCT04509050
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Inclusion Criteria:
• Part A:
• Less than 5 years of age at the first study visit.
• Documentation of a CF diagnosis.
Part B:
• Participated in Part A OR less than 6 years of age at the first study visit.
• Documentation of a CF diagnosis.
• CFTR mutations consistent with FDA labeled indication of highly effective modulator
therapy (ivacaftor or elexacaftor/tezacaftor/ivacaftor).
• Physician intent to prescribe ivacaftor or elexacaftor/tezacaftor/ivacaftor.
Exclusion Criteria:
• Part A and Part B:
Use of an investigational drug within 28 days prior to and including the first study visit.
Use of ivacaftor or elexacaftor/tezacaftor/ivacaftor within the 180 days prior to and
including the first study visit.
Use of chronic oral corticosteroids within the 28 days prior to and including the first
study visit.
Cystic Fibrosis, Cystic fibrosis, Other, Children's & Adolescent Health
67Cu-SARTATE™ Peptide Receptor Radionuclide Therapy Administered to Pediatric Patients With High-Risk, Relapsed, Refractory Neuroblastoma
The aim of this study is to evaluate the safety and efficacy of 67Cu-SARTATE in pediatric
patients with high-risk neuroblastoma.
Kenneth Desantes, M.D.
All
Not specified
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04023331
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Inclusion Criteria:
1. Participant is able and willing to provide informed consent (≥18 years), or informed
consent is obtained by the parent or legal guardian for minor participants, with the
minor providing age appropriate assent, according to local law and regulations;
2. Life expectancy ≥ 12 weeks;
3. Known high-risk neuroblastoma OR previously intermediate-risk neuroblastoma that has
relapsed or progressed to high-risk, with failure to achieve complete response with
standard therapy (defined as at least 4 cycles of aggressive multi-drug induction
chemotherapy with or without radiation and surgery, or according to a standard
high-risk treatment/neuroblastoma protocol), OR who are medically ineligible to
receive standard treatment OR who are intolerant to standard treatment;
4. Adequate recovery from acute toxic effects of any prior therapy, as deemed by the
Investigator or treating Sub-Investigator;
5. Adequate liver function as defined by the following laboratory values obtained within
28 days prior to administration of 64Cu-SARTATE: Aspartate aminotransferase (AST) and
alanine aminotransferase (ALT) < 3.0 x upper limit of normal (ULN);
6. Adequate renal function;
7. Adequate laboratory parameters: Absolute neutrophil count > 1.0 x 10 9/L; Platelet
count > 50 x 10 9/L; Total bilirubin <1.5 x ULN;
8. Karnofsky or Lansky performance status ≥50;
9. All participants must have a hematopoietic stem cell product available (minimum CD34+
cell dose is ≥2 x 10 6 cells/kg);
10. Sexually active participants of reproductive potential must practice an effective
method of birth control while participating on this study, to avoid possible damage to
the fetus. Abstinence is considered acceptable;
11. 64Cu-SARTATE uptake on the 4 hour scan (SUVmax) of any lesion equal to or higher than
that of the liver in order to move on to the therapy phase of the study.
Exclusion Criteria:
1. Participants with disease of any major organ system that would compromise their
ability to tolerate therapy, as deemed by the Investigator or treating
Sub-Investigator;
2. Any other active malignancy, or a history of prior malignancy within the past 3 years;
3. History of cardiac failure as evidenced by: dyspnea at rest, exercise intolerance,
oxygen requirement, clinically significant cardiac dysfunction;
4. Planned administration of chemotherapy, anti-cancer cytokine therapy, immunotherapy or
radiotherapy within 2 weeks prior to the administration of 64Cu-SARTATE;
5. Administration of therapeutic dose of 131I-MIBG within 8 weeks prior to the
administration of 64Cu-SARTATE;
6. External beam radiation therapy (EBRT) to both kidneys or a single functioning kidney
within 12 months prior to the administration of 64Cu-SARTATE;
7. Administration of any investigational agents within 21 days prior to administration of
64Cu-SARTATE;
8. Treatment with long acting somatostatin analogues (administered within 28 days prior
to the administration of 64Cu-SARTATE), or short acting somatostatin analogues
(administered within 24 hours prior to the administration of 64Cu-SARTATE);
9. Known sensitivity or allergy to somatostatin analogues;
10. Previous peptide receptor radionuclide therapy (PRRT);
11. Female participants who are pregnant or lactating;
12. Participants who are on hemodialysis;
13. QTc interval ≥ 0.45 seconds as measured by Screening ECG;
14. Participants with uncontrolled infection(s);
15. Any medical condition which the Investigator feels may interfere with the procedures
or evaluations of the study;
16. Participants 12 months and younger will be excluded from cohorts where the planned
single or cumulative administered activity is modelled to deliver a radiation dose to
the marrow that exceeds 2 Gy.
Neuroblastoma, Relapsed 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
The primary purpose of this study is to discover new disease genes for rare Mendelian
disorders and its secondary purpose include diagnosing people with rare genetic disorders
that have not been previously diagnosed through conventional clinical means, learning more
about the pathobiology of genetic disorders, and developing novel diagnostic technologies and
analytics. 500 participants with undiagnosed and suspected genetic disorders will be
recruited over approximately 5 years time.
Stephen Meyn
All
up to 100 Years old
NA
This study is NOT accepting healthy volunteers
NCT04586075
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Inclusion Criteria:
• The applicant has a condition that remains undiagnosed despite thorough evaluation by
healthcare providers (including clinical genetic testing).
• The applicant has at least one objective finding that is likely to have an
identifiable genetic etiology.
• The applicant likely has a currently undescribed/new genetic condition or a known
genetic condition associated with a novel gene.
• The applicant/legal guardian agrees to the collection, storage and recurrent sharing
of coded information and biomaterials for research and diagnostic purposes both within
and outside of the University of Wisconsin-Undiagnosed Diseases Program (UW-UDP)
• The applicant/legal guardian agrees to receive secondary findings from genetic
testing.
• The applicant/legal guardian has sufficient proficiency in English to understand the
consent.
Exclusion Criteria:
• The applicant already has a diagnosis that explains the objective findings.
• A specific diagnosis is suspected and a standard clinical workup performed by the
referring/primary care provider would be appropriate.
• The UW-UDP is unlikely to improve on the comprehensive workup the applicant has
already received.
• The applicant's symptoms are likely multifactorial or due to a non-genetic cause.
Rare Diseases, Genetic Disease, Undiagnosed Disease, Other specified congenital malformation syndromes affecting multiple systems, Other
Making Informed Choices on Incorporating Chemoprevention Into Care (MiCHOICE)
This trial studies the implementation of web-based decision support tools for patients with
atypical hyperplasia or lobular carcinoma in situ and healthcare providers. Decision support
tools are designed to improve informed choice about breast cancer chemoprevention.
Recognizing barriers and facilitators that can influence the adoption of decision support
tools at recruitment centers may help researchers learn how to best implement them into
clinical practice.
Kari Wisinski, MD
All
Not specified
N/A
This study is also accepting healthy volunteers
NCT04496739
Show full eligibility criteria
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Inclusion Criteria:
• Patients must have histologically-confirmed atypical hyperplasia (AH) or lobular
carcinoma in situ (LCIS) documented by breast pathology report at any time in the
past. Patients with borderline breast lesions and pleomorphic LCIS are also eligible
• Patients must be women at least 35 and no more than 74 years of age at registration,
since the Breast Cancer Surveillance Consortium (BCSC) risk calculator is valid only
for this age range
• Both pre/perimenopausal and postmenopausal women are eligible
• Patients must be able to read and write in English or Spanish since study
questionnaires and educational materials are only available in English and Spanish
• Baseline questionnaires must be completed prior to patient registration
• The S1904 Patient Contact form must be completed prior to patient registration
• Patients must be able to access the internet and receive email or text messages. This
is required to access study materials and receive email/text message reminders from
the S1904 Study Team at Columbia University Irving Medical Center (CUIMC). The patient
decision aid, RealRisks, is accessible via smartphones, tablets, or personal
computers. If patients do not own these devices, local study personnel will provide
resources for patients to access RealRisks via computer kiosks or tablets in clinic
waiting rooms or public locations, such as community centers or public libraries
• Patients and healthcare providers must be informed of the investigational nature of
this study and must sign and give written informed consent in accordance with
institutional and federal guidelines
• 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
• IMPLEMENTATION: Providers who enrolled in S1904 at Group 2 (intervention) recruitment
center and consented to future contact are eligible to participate in the interviews
• IMPLEMENTATION EVALUATION: Patients who registered to S1904 at a Group 2
(Intervention) Recruitment Center and consented to be contacted for future research
are eligible to participate in the interviews
• Recruitment Centers must be National Clinical Trials Network (NCTN), National Cancer
Institute Community Oncology Research Program (NCORP) or Minority Underserved
(MU)-NCORP institutions
• Recruitment Centers must have an active EHR and patient portal used in the outpatient
clinics which is common and accessible across all sites belonging to the Recruitment
Center
• Recruitment Centers must be willing to allow the S1904 study team access to the site's
application program interface (API) for integration of the study materials (standard
educational materials and decision support tools) into the EHR and patient portal.
(NOTE: Both Group 1 (control) and Group 2 (intervention) recruitment centers may
access the standard educational materials via the patient portal or uniform resource
locator (URL)/website)
• Recruitment centers must see at least 50 AH and/or LCIS patients per year
• Recruitment centers must identify a lead principal investigator (PI) to facilitate
recruitment and retention of patients and healthcare providers and to participate in
quarterly stakeholder meetings/conference calls
• Recruitment centers must be willing to register at about 16 patients and 5 healthcare
providers to the study
• Recruitment Centers must be willing to submit monthly screening logs to CUIMC
• Providers must regularly see patients with AH or LCIS at an approved recruitment
center
• Providers must be willing to provide informed consent and complete an online baseline
questionnaire
• Providers who will register patients must be registered members of a Cooperative Group
• Providers who register patients to S1904 must be willing to see those same patients
for their 6-month study visits, as the provider intervention tools require that the
"treating investigator" as designated in OPEN and the provider at the 6-month study
visit be the same
Exclusion Criteria:
• Patients must not have a history of invasive breast cancer or ductal carcinoma in situ
• Patients must not have prior or current use of selective estrogen receptor modulators
(SERMs) or aromatase inhibitors (AIs)
• NOTE: The following are approved SERMS and AIs, however, the study is not limited
to these.
• SERMs: tamoxifen, raloxifene
• AIs: anastrozole, exemestane, letrozole
• Patients must not be currently taking hormone replacement therapy
• Patients must not have a history of bilateral mastectomies or breast implants since
the risk calculator is not applicable to these women
• Patients must not be pregnant or lactating
• Premenopausal patients must not have a history of thromboembolism, since it is a
contraindication to tamoxifen. Tamoxifen is the only Food and Drug Administration
(FDA)-approved drug for breast cancer chemoprevention among high-risk premenopausal
women, whereas postmenopausal women are eligible for both SERMs and AIs
Atypical Hyperplasia of the Breast, Lobular Breast Carcinoma In Situ, Pleomorphic Lobular Breast Carcinoma In Situ, Breast
A Study of Combination Chemotherapy for Patients With Newly Diagnosed DAWT and Relapsed FHWT
This phase II trial studies how well combination chemotherapy works in treating patients with
newly diagnosed stage II-IV diffuse anaplastic Wilms tumors (DAWT) or favorable histology
Wilms tumors (FHWT) that have come back (relapsed). Drugs used in chemotherapy regimens such
as UH-3 (vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan)
and ICE/Cyclo/Topo (ifosfamide, carboplatin, etoposide, cyclophosphamide, and topotecan) work
in different ways to stop the growth of tumor cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. This trial may help doctors find out
what effects, good and/or bad, regimen UH-3 has on patients with newly diagnosed DAWT and
standard risk relapsed FHWT (those treated with only 2 drugs for the initial WT) and regimen
ICE/Cyclo/Topo has on patients with high and very high risk relapsed FHWT (those treated with
3 or more drugs for the initial WT).
Kenneth Desantes, M.D.
All
up to 30 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT04322318
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Inclusion Criteria:
• Patients with newly diagnosed stages 2 •4 diffuse anaplastic Wilms tumor must be
enrolled on AREN03B2 and have received an initial risk assignment showing DAWT (if
anaplasia first identified at diagnostic, pre-treatment nephrectomy or biopsy) or a
delayed nephrectomy classification showing DAWT (if anaplasia first noted at delayed
nephrectomy) prior to enrollment on AREN1921. Prior enrollment on AREN03B2 is not an
eligibility requirement for patients with relapsed favorable histology Wilms tumor.
• Patients must be =< 30 years old at study enrollment
• Patients with the following diagnoses are eligible for this study:
• Newly diagnosed stages 2 •4 diffuse anaplastic Wilms tumor as confirmed by
central review
• Favorable histology Wilms tumor at first relapse. Relapsed FHWT patients must
have previously achieved remission for their initial FHWT diagnosis to be
eligible for this study. The relapse risk groups are defined as follows,
regardless of radiation therapy:
• Standard-Risk relapse: Patients who received two chemotherapy agents for
frontline therapy; primarily actinomycin D and vincristine
• High-Risk relapse: Patients who received three chemotherapy agents for
frontline therapy; primarily vincristine, actinomycin D and doxorubicin or
vincristine, actinomycin D and irinotecan
• Very High-Risk relapse: Patients who received four or more chemotherapy
agents as part of initial therapy; primarily regimen M or its variations
• Patients with newly diagnosed DAWT must have had histologic verification of the
malignancy. For relapsed FHWT patients, biopsy to prove recurrence is encouraged, but
not required
• Note: For relapsed FHWT patients, an institutional pathology report confirming
favorable histology Wilms tumor (from relapse, if available, or from original
diagnosis) must be available for upload prior to initiation of protocol therapy
• Patients with newly diagnosed Stages 2 •4 diffuse anaplastic Wilms tumor must be
enrolled on AREN1921 within 2 weeks of the tumor-directed surgery or biopsy procedure
that first confirms a diagnosis of DAWT, whether at initial diagnostic procedure or
delayed nephrectomy (such surgery/biopsy is day 0). For patients who received prior
therapy for presumed favorable histology Wilms tumor, later confirmed to have diffuse
anaplastic Wilms tumor at subsequent review of the initial biopsy
• Patients with newly diagnosed DAWT who undergo upfront nephrectomy must have at least
1 lymph node sampled prior to study enrollment
• 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 must have a life expectancy of >= 8 weeks
• Diffuse Anaplastic Wilms Tumor: Patients with diffuse anaplastic histology must have
had no prior systemic therapy, except in the following situations:
• Patients with diffuse anaplastic Wilms tumor who received no more than 12 weeks
of pre nephrectomy chemotherapy for what was originally presumed to be favorable
histology Wilms tumor, subsequently confirmed to be diffuse anaplastic Wilms
tumor at delayed nephrectomy
• Patients with diffuse anaplastic Wilms tumor who received no more than 6 weeks of
chemotherapy following upfront biopsy, initiated within 14 days of biopsy, for
presumed favorable histology Wilms tumor based on institutional review, but
subsequently corrected to diffuse anaplastic Wilms tumor based on the AREN03B2
initial risk assignment results (if available per current version of AREN03B2)
• Treatment consisting of vincristine/doxorubicin/cyclophosphamide initiated on an
emergent basis and within allowed timing as described
• Note: Patients who received prior therapy for presumed favorable histology Wilms
tumor, later identified to have diffuse anaplastic Wilms tumor as per above, must
begin study treatment starting at cycle 3 (week 7) of regimen UH 3. Patients who
received emergency radiation to preserve organ function are eligible as noted.
Patients who received radiation as part of standard of care for presumed newly
diagnosed favorable histology Wilms tumor, along with chemotherapy as noted
above, prior to identification of diffuse anaplasia, are also eligible
• Relapsed Favorable Histology Wilms Tumor: Patients must not have received prior
chemotherapy for their relapsed favorable histology Wilms tumor diagnosis. In
addition, patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry
onto this study
• Radiation therapy (RT): >= 2 weeks (wks) must have elapsed for local palliative
RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >=
50% radiation of pelvis; >= 6 wks must have elapsed if other substantial bone
marrow (BM) radiation. Patients with relapsed favorable histology Wilms tumor who
received emergency radiation to preserve organ function are eligible and do not
need to washout with the above criteria
• Patients may not be receiving any other investigational agents (within 4 weeks prior
to study enrollment)
• Peripheral absolute neutrophil count (ANC) >= 750/uL (performed within 7 days prior to
enrollment)
• Platelet count >= 75,000/uL (transfusion independent) (performed within 7 days prior
to enrollment)
• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (performed
within 7 days prior to enrollment)
• Patients with high-risk or very high-risk relapsed FHWT who will be treated with
regimen ICE/Cyclo/Topo, must have renal function assessed by creatinine clearance or
radioisotope glomerular filtration rate (GFR) and meet the following requirement:
• Creatinine clearance or radioisotope GFR >= 60 mL/min/1.73 m^2 (performed within
7 days prior to enrollment)
• Patients diagnosed with stage 2-4 DAWT or standard risk relapsed FHWT, who will be
treated with regimen UH 3, may either obtain a creatinine clearance, radioisotope GFR
(meeting the above criteria of GFR >= 60 mL/min/1.73 m^2), or an adequate serum
creatinine as per the following table:
• 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: 0.6 (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 =< 1.5 x upper limit of normal (ULN) for age or direct bilirubin =<
ULN for patients whose total bilirubin > 1.5 x ULN (performed within 7 days prior to
enrollment)
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x
upper limit of normal (ULN) for age or =< 5 x ULN for patients with liver metastases
(performed within 7 days prior to enrollment)
• Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by
radionuclide angiogram (obtained within 21 days prior to enrollment and start of
protocol therapy)
Exclusion Criteria:
• Patients with a history of bilateral Wilms tumor (synchronous or metachronous)
• Patients with any uncontrolled, intercurrent illness including, but not limited to,
ongoing or active infection, or symptomatic congestive heart failure (defined as grade
2 or higher heart failure per Common Terminology Criteria for Adverse Events [CTCAE]
version 5.0)
• Relapsed FHWT patients who did not receive frontline chemotherapy (e.g., very low risk
FHWT initially observed without chemotherapy) or received only one chemotherapy agent
for frontline therapy
• For patients with high-risk or very high-risk relapsed FHWT:
• Patients with renal tubular acidosis (RTA) as evidenced by serum bicarbonate < 16
mmol/L and serum phosphate =< 2 mg/dL (or < 0.8 mmol/L) without supplementation
• For stages 2-4 DAWT and standard-risk relapsed FHWT patients:
• Chronic inflammatory bowel disease and/or bowel obstruction
• Concomitant use of St. John's wort, which cannot be stopped prior to the start of
trial treatment
• 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
Anaplastic Kidney Wilms Tumor, Recurrent Kidney Wilms Tumor, Stage II Kidney Wilms Tumor, Stage III Kidney Wilms Tumor, Stage IV Kidney Wilms Tumor, Kidney
The goal of this study is to establish a birth cohort that collects prenatal and early life
biosamples and environmental samples and rigorously phenotypes young children for food
allergy and Atopic Dermatitis (AD) to identify prenatal and early life markers of high risk
for food allergy and AD, as well as biological pathways (endotypes) that result in these
conditions.
Primary Objectives:
- To study the role and interrelationships of established and novel clinical,
environmental, biological, and genetic prenatal and early-life factors in the
development of allergic diseases through age 3 years, with an emphasis on atopic
dermatitis and food allergy
- To apply systems biology to identify mechanisms and biomarkers underlying the
development of food allergy, atopic dermatitis, and their endotypes
- To collect, process, and assay or store environmental and biological samples for current
and future use in the study of allergic disease development
James Gern
All
0 Years and over
NA
This study is also accepting healthy volunteers
NCT04798079
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Inclusion Criteria:
Pregnant Women-
Pregnant women who meet all of the following criteria are eligible for enrollment as study
participants:
1. Age 18 years or older
2. Able to understand the oral and written instructions associated with study visits and
procedures and provide informed consent
3. Pregnant at any stage
4. Planning to give birth at a study-site designated center
5. Agrees to enroll offspring into the study at birth
6. In the case of multiple gestation, agrees to enroll only one child who will be
selected by randomized birth order
Biological Fathers-
Biological fathers who meet all of the following criteria are eligible for enrollment as
study participants:
1. Age 18 years or older
2. Able to understand the oral and written instructions associated with study visits and
procedures and provide informed consent
Exclusion Criteria:
Pregnant Women-
Pregnant women who meet any of these criteria are not eligible for enrollment:
1. Inability or unwillingness to comply with study protocol
2. Serious pregnancy complication (in the judgement of the investigator) prior to
enrollment
3. Fetus has a major chromosomal anomaly
4. Plans to move and would not be available for in-person visits at a study site
5. Plans to give up her child for adoption at birth
6. Pregnancy is the result of an egg donation
Infants-
Infants who meet any of these criteria are not eligible for enrollment:
1. Delivered earlier than 34 weeks of gestation
2. Sibling already enrolled
3. Born with a significant birth defect or medical condition, and in the judgment of the
investigators, participation is not in the infant's best interest
Biological Father-
1. Biological fathers who are unable or unwilling to comply with the study protocol as it
pertains to the biological father's participation are not eligible for enrollment
----Note Regarding Legal Guardians who are not the Biological Parents:
1. At screening for enrollment of either the mother or the child, if the biological
mother intends to give the infant up for adoption, neither the mother nor the child
are eligible for enrollment
2. If the biological mother gives up legal guardianship of the child during the child's
follow-up period, the child may remain enrolled as long as the new legal guardian:
• Agrees to meet the child's study requirements, and
• Provides written informed consent for the child's continued participation.
3. Throughout the protocol where it refers to the mother, father, or parent answering
questionnaires about the child or collecting samples from the child and the child's
primary home, the legal guardian who provides consent for the child's participation
may complete those procedures
Prospective Study of Pregnancy in Women With Cystic Fibrosis (MAYFLOWERS)
In this study, the investigators aim to evaluate changes in lung function in women with
cystic fibrosis (CF) during pregnancy and for 2 years after pregnancy based on exposure to
highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators.
Erin Lowery
Female
16 Years and over
NA
This study is NOT accepting healthy volunteers
NCT04828382
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Inclusion Criteria:
• Pregnant, intending to continue pregnancy, enrolled in the Cystic Fibrosis Foundation
Patient Registry (CFFPR)
Exclusion Criteria:
• None
Pregnancy Related, Cystic Fibrosis, Cystic fibrosis, Other
A Study of Encorafenib Plus Cetuximab With or Without Chemotherapy in People With Previously Untreated Metastatic Colorectal Cancer
The purpose of this study is to evaluate two study medicines (encorafenib plus cetuximab)
taken alone or together with standard chemotherapy for the potential treatment of colorectal
cancer that:
- has spread to other parts of the body (metastatic);
- has a certain type of abnormal gene called "BRAF"; and
- has not received prior treatment.
Participants in this study will receive one of the following study treatments:
- Encorafenib plus cetuximab: These participants will receive encorafenib by mouth at home
every day and cetuximab once every two weeks by intravenous (IV) infusion (an injection
into the vein) at the study clinic.
- Encorafenib plus cetuximab with chemotherapy: These participants will receive
encorafenib and cetuximab in the way described in the bullet above. Additionally, they
will receive standard chemotherapy by IV infusion and oral treatment at home.
- Chemotherapy alone: These participants will receive chemotherapy, the standard treatment
for this condition, by IV infusion at the study clinics and oral treatment at home.
This study is currently enrolling participants who will receive either encorafenib plus
cetuximab with chemotherapy or chemotherapy alone.
The study team will monitor how each participant responds to the study treatment for up to
about 3 years.
Dustin Deming, MD
All
16 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04607421
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Inclusion Criteria:
• Safety Lead-In = Male/female ≥ 18 years old
• Phase 3 and Cohort 3: Male/female ≥ 16 years old (where permitted locally)
• Histologically or cytologically confirmed Stage IV CRC that contains BRAF V600E
mutation
• Prior systemic treatment in metastatic setting: 0-1 regimens for Safety Lead In; none
for Phase 3 and Cohort 3. (Note: Prior adjuvant or neoadjuvant therapy considered
metastatic treatment if relapse/metastasis < 6 month from end of adj/neoadjuvant
treatment )
• Measurable disease (Phase 3 and Cohort 3)/ Measurable or evaluable disease (Safety
Lead-in)
• ECOG PS 0-1
• Adequate organ function
Exclusion Criteria:
• Tumors that are locally confirmed or unknown MSI-H or dMMR unless participant is
ineligible to receive immune checkpoint inhibitors due to a pre-existing medical
condition
• Active bacterial or viral infections in 2 weeks prior to starting dosing
• Symptomatic brain metastases
A Study to Compare Treatment With the Drug Selumetinib Alone Versus Selumetinib and Vinblastine in Patients With Recurrent or Progressive Low-Grade Glioma
This phase III trial investigates the best dose of vinblastine in combination with
selumetinib and the benefit of adding vinblastine to selumetinib compared to selumetinib
alone in treating children and young adults with low-grade glioma (a common type of brain
cancer) that has come back after prior treatment (recurrent) or does not respond to therapy
(progressive). Selumetinib is a drug that works by blocking a protein that lets tumor cells
grow without stopping. Vinblastine blocks cell growth by stopping cell division and may kill
cancer cells. Giving selumetinib in combination with vinblastine may work better than
selumetinib alone in treating recurrent or progressive low-grade glioma.
Kenneth Desantes, M.D.
All
2 Years to 25 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04576117
Show full eligibility criteria
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Inclusion Criteria:
• Feasibility phase: patients must be >= 2 years and =< 21 years of age at the time of
enrollment
• Efficacy phase: patients must be >= 2 years and =< 25 years of age at the time of
enrollment
• All patients > 21 years of age at the time of enrollment must have had initial
diagnosis of low-grade glioma by 21 years of age
• Patients must have a body surface area (BSA) of >= 0.5 m^2 at enrollment
• Patients must have eligibility confirmed by rapid central pathology and central
molecular screening reviews performed on APEC14B1
• Non-neurofibromatosis type 1 (non-NF1), non-tuberous sclerosis complex (non-TSC)
low-grade glioma (LGG) without a BRAFV600E or IDH1 mutation
• Patients must have progressive or recurrent LGG. Note: Biopsy may be at either
initial diagnosis or recurrence
• Patients must have measurable disease, defined as having a two-dimensional
measurable tumor volume of >= 1 cm^2
• Tumor size will be measured to include both solid and cystic components of
the tumor (whether or not tumor is enhancing) + fluid attenuated inversion
recovery (FLAIR) signal
• Eligible histologies will include all tumors considered low-grade glioma or
low-grade astrocytoma (World Health Organization [WHO] grade 1 and II) by the WHO
Classification of Tumors of the Central Nervous System •4th Edition Revised,
with the exception of subependymal giant cell astrocytoma
• Patients with metastatic disease or multiple independent primary LGGs are
eligible
• Patients must be progressive or recurrent after having been treated with at least one
prior tumor-directed therapy before enrollment
• Patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry
onto this study (4 weeks if prior nitrosourea);
• Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy
with a biologic agent;
• Radiation therapy (RT): >= 2 weeks (wks) for local palliative RT (small port); >=
6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of
pelvis; >= 6 wks must have elapsed if other substantial bone marrow (BM)
radiation;
• 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;
• MEK inhibitor or vinblastine: Must not have received treatment with a MEK
inhibitor or vinblastine within 6 months of study enrollment
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^ 2 or a serum creatinine based on age/gender as follows (within 7 days
prior to enrollment):
• 2 to < 6 years: 0.8 mg/dL (male) 0.8 mg/dL (female)
• 6 to < 10 years: 1 mg/dL (male) 1 mg/dL (female)
• 10 to < 13 years: 1.2 mg/dL (male) 1.2 mg/dL (female)
• 13 to < 16 years: 1.5 mg/dL (male) 1.4 mg/dL (female)
• >= 16 years: 1.7 mg/dL (male) 1.4 mg/dL (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed on study
regardless of their total and indirect [unconjugated] bilirubin levels as long as
their direct [conjugated] bilirubin is < 3.1 mg/dL)
• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L
(within 7 days prior to enrollment)
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L
• Albumin >= 2 g/L (within 7 days prior to enrollment)
• Left ventricular ejection fraction (LVEF) >= 53% (or institutional normal; if the LVEF
result is given as a range of values, then the upper value of the range will be used)
by echocardiogram (within 4 weeks prior to enrollment)
• Corrected QT interval (QTc interval) =< 450 msec by electrocardiogram (EKG) (within 4
weeks prior to enrollment)
• Absolute neutrophil count >= 1,000/uL (unsupported) (within 7 days prior to
enrollment)
• Platelets >= 100,000/uL (unsupported) (within 7 days prior to enrollment)
• Hemoglobin >= 8 g/dL (may be supported) (within 7 days prior to enrollment)
• Patients with a known seizure disorder should be stable and should not have
experienced a significant increase in seizure frequency within 2 weeks prior to
enrollment
• Stable neurological examination for >= 1 week
• HYPERTENSION:
• Patients 2-17 years of age must have a blood pressure that is =< 95th percentile
for age, height, and gender at the time of enrollment (with or without the use of
anti-hypertensive medications);
• Patients >= 18 years of age must have a blood pressure =< 130/80 mmHg at the time
of enrollment (with or without the use of anti-hypertensive medications)
• Note for patients of all ages: Adequate blood pressure can be achieved using
medication for the treatment of hypertension
• All patients must have ophthalmology toxicity assessments performed within 4 weeks
prior to enrollment
• For all patients, an MRI of the brain (with orbital cuts for optic pathway tumors)
and/or spine (depending on the site[s] of primary disease) with and without contrast
must be performed within 4 weeks prior to enrollment
• Note: If surgical resection or biopsy is performed at the time of progression or
recurrence, a post-operative MRI is required
• 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 must have the ability to swallow whole capsules
Exclusion Criteria:
• Prior therapy with vinblastine and/or a MEK inhibitor is permitted, with the following
exceptions:
• Patients must not have had progressive disease while on therapy with vinblastine
or a MEK inhibitor;
• Patients must not have discontinued vinblastine or selumetinib due to toxicity
• Patients with a concurrent malignancy or history of treatment (other than surgery) for
another tumor within the last year are ineligible
• Patients with diffuse intrinsic pontine tumors as seen on MRI (> 2/3 of pons
involvement on imaging) are not eligible even if biopsy reveals grade I/II histology
• Patients may not be receiving any other investigational agents
• Patients must not have known hypersensitivity to selumetinib, vinblastine, or similar
compounds
• CYP3A4 agents: Patients must not have received fluconazole or drugs that are strong
inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment
• Patients with any serious medical or psychiatric illness/condition, including
substance use disorders or ophthalmological conditions, likely in the judgment of the
investigator to interfere or limit compliance with study requirements/treatment
• Patients who, in the opinion of the investigator, are not able to comply with the
study procedures are not eligible
• PRE-EXISTING CONDITIONS (CARDIAC):
• Known genetic disorder that increases risk for coronary artery disease. Note: The
presence of dyslipidemia in a family with a history of myocardial infarction is
not in itself an exclusion unless there is a known genetic disorder documented;
• Symptomatic heart failure
• New York Heart Association (NYHA) class II-IV prior or current
cardiomyopathy
• Severe valvular heart disease
• History of atrial fibrillation
• PRE-EXISTING CONDITIONS (OPHTHALMOLOGIC CONDITIONS):
• Current or past history of central serous retinopathy
• Current or past history of retinal vein occlusion or retinal detachment
• Patients with uncontrolled glaucoma
• If checking pressure is clinically indicated, patients with intraocular
pressure (IOP) > 22 mmHg or upper limit of normal (ULN) adjusted by age are
not eligible
• Any multivitamin containing vitamin E must be stopped prior to study enrollment even
if it contains less than 100% of the daily recommended dosing for vitamin E
• Surgery within 2 weeks prior to enrollment, with the exception of a surgical biopsy,
placement of a vascular access device or cerebrospinal fluid (CSF) diverting procedure
such as endoscopic third ventriculostomy (ETV) and ventriculoperitoneal (VP) shunt
• Note: Patients must have healed from any prior surgery
• Patients who have an uncontrolled infection are not eligible
• Female patients who are pregnant are not eligible 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 and for
12 weeks after stopping study therapy are not eligible
• Note: Women of child-bearing potential and males with sexual partners who are
pregnant or who could become pregnant (i.e., women of child-bearing potential)
should use effective methods of contraception for the duration of the study and
for 12 weeks after stopping study therapy to avoid pregnancy and/or potential
adverse effects on the developing embryo
• 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
Recurrent Low Grade Astrocytoma, Recurrent WHO Grade 2 Glioma, Refractory Low Grade Astrocytoma, Refractory Low Grade Glioma, Refractory WHO Grade 1 Glioma, Brain and Nervous System, Brain/Central Nervous System
DNA-Guided Second Line Adjuvant Therapy For High Residual Risk, Stage II-III, Hormone Receptor Positive, HER2 Negative Breast Cancer (DARE)
A randomized, Phase II trial of circulating tumor DNA-guided second line Adjuvant therapy for
high Residual risk, stage II-III, Estrogen Receptor positive, HER-2 negative breast cancer
(DARE)
Mark Burkard, MD, PhD
All
Not specified
Phase 2
This study is NOT accepting healthy volunteers
NCT04567420
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Inclusion Criteria:
•4.1.1. Stage II or III, HER2 negative, ER positive invasive breast cancer in male or
female patients. For this study, ER positivity is defined as equal to or greater than 10%
ER positivity by immunohistochemistry, regardless of progesterone receptor (PR) status.
Patients with PR positive but ER negative cancer are not eligible. HER2 negative status is
defined as per the ASCO/CAP 2018 practice guidelines.
(i) if patients have synchronous bilateral ER+ breast cancer tissue from both sites should
be submitted to Natera to perform ctDNA testing.
(ii) patients with multifocal/multicentric tumors are eligible and the largest focus of
cancer should be submitted for testing. All tumors must meet pathological criteria for
HER2-and ER+ status.
(iii) For. patients who received neoadjuvant therapy and have discordant ER and HER2
results between the diagnostic biopsy (pre-treatment) and surgical pathology (post
neoadjuvant therapy), the ER+ and HER2- status of the post-treatment specimen determine
eligibility.
4.1.2. Currently taking an aromatase inhibitor, or tamoxifen, as adjuvant endocrine therapy
and have completed at least 6 months (i.e. 24 weeks), but no more than 7 years with 3 more
years planned, of endocrine therapy. Patients may register for the screening phase of the
study within the first 6 months of adjuvant endocrine therapy but the first ctDNA testing
must occur at, or after, 6 months of endocrine therapy.
(i) Adjuvant bisphosphonate therapy is allowed. (ii) LHRH analogues are required for
premenopausal patients randomized to receive fulvestrant.
4.1.3. Clinical and pathological high risk for recurrence defined as any one of the
following: (i) At least a 15% predicted risk of death within 10 years using ePREDICT V2.1
(https://breast.predict.nhs.uk/tool), or (ii) At least 15% or greater risk of distant
metastasis within 10 years using RSPC,
(https://tools.genomichealth.com/Tools/RSPCTool.aspx), or (iii) At least 15% or greater
risk of distant metastasis within 10 years CTS5 (https://www.cts5-calculator.com) for
patients who have completed a minimum of 4 years of adjuvant endocrine therapy, or (iv)
Tumor size > 5 cm, regardless of lymph node status, or (v) 1-3 involved axillary lymph
nodes and at least one of the following;
• Tumor size > 3 cm,
• High histological grade (e.g. grade 3).
• High genomic risk defined as Oncotype Dx Recurrence Score >26, EndoPredict score >4,
Prosigna risk of recurrence score ≥ 60, or Mammaprint high risk.
(vi) Patients who have received pre-operative (neoadjuvant) chemotherapy must have either:
• greater than or equal to 3 cm invasive residual cancer regardless of nodal status AND
grade 3 disease or RS>26/MammPrint High/Prosigna high/Endopredict high status, or
• greater than or equal to 1 cm invasive residual cancer (ypT1c) and at least 1 positive
lymph node (ypN+) AND grade 3 disease, or RS>26, or MammPrint High, or Endopredict
high or Prosigna high status.
4.1.4. Patients must have FFPE tissue from the primary tumor available for submission to
Natera to perform ctDNA assay (see Appendix B for tissue submission instructions).
4.1.5. Signed and dated informed consent, including willingness to be randomized to
standard of care versus fulvestrant + palbociclib.
4.2 Inclusion and exclusion criteria for treatment randomization
Inclusion criteria for randomization
4.2.1. ctDNA positivity by the Signatera assay, defined as 2 of the 16 cancer specific
markers positive in plasma.
4.2.2. Patients with positive Signatera results obtained in the context of commercial
testing, outside of the screening phase of this trial, are also eligible for randomization
if they meet other eligibility criteria.
4.2.3. No evidence of metastatic disease on CT scan of the chest, abdomen and pelvis.
• If imaging, after review with a radiologist, is low probability for metastatic
disease, patients may proceed to randomization.
• Patients with suspicious but inconclusive imaging results should undergo a diagnostic
biopsy, if biopsy is negative patients are eligible for randomization.
• Patients with positive imaging that is conclusive of metastatic disease, or with
biopsy proven metastatic disease, are not eligible for randomization.
4.2.4. Pre-menopausal women and male patients must be willing to use an adequate method of
contraception for the duration of trial treatment and for 4 additional weeks after
completion of treatment in the control arm, and for 2 years after the last dose of
fulvestrant, if randomized into the experimental arm.
Post-menopausal status is defined as:
• Documented bilateral oophorectomy.
• Age ≥ 60 years.
• Age < 60 years and amenorrhoeic for ≥ 12 consecutive months and FSH and estradiol
levels in the post-menopausal range according to the institutional reference range for
post-menopausal.
Adequate contraception is defined as ONE highly effective form (i.e. abstinence, surgical
sterilization through bilateral tubal ligation, vasectomy), or TWO effective forms (e.g.
non-hormonal IUD and condom / occlusive cap with spermicidal foam / gel / film / cream /
suppository).
•Abstinence is to be interpreted as "true abstinence" for heterosexual intercourse and
therefore, "periodic abstinence" (e.g. calendar, symptothermal, post-ovulation methods) and
withdrawal (coitus interruptus) are not considered highly effective.
Exclusion Criteria
4.1.5. Prior or current treatment with fulvestrant, or current treatment with a CDK4/6
inhibitor, or treatment in the prior 12 months, or participants in the PENELOPE and PALLAS
clinical trials.
4.1.6. Patients cannot start participation in another therapeutic clinical trial for breast
cancer after enrollment in this trial.
4.1.7. Patients with current or past invasive cancer, other than breast cancer are not
eligible, except:
• Adequately treated basal or squamous cell carcinoma of the skin are eligible.
• Cancer survivors of previously diagnosed invasive cancer, who were treated with a
curative intent, have no evidence of disease recurrence for 5 years or more, and are
considered low risk for future recurrence by the treating physician are also eligible.
4.1.8. Patients with a second HER2 positive or triple negative synchronous breast cancer
are not eligible.
Exclusion criteria for randomization
4.2.5. Patients with known contraindications to receive fulvestrant and palbociclib or
those who are unable to tolerate these drugs are not eligible.
• Absolute neutrophil count less than <1000/mm3;
4.2.6. Any concurrent severe and uncontrolled medical condition that would, in the
Investigator' opinion cause unacceptable safety risks or compromise compliance with the
protocol including but not limited to:
• Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of oral medication (e.g. Crohn's disease, ulcerative diseases,
uncontrolled chronic nausea, vomiting, diarrhea, malabsorption syndrome, or small
bowel resection).
• History of pneumonitis, interstitial lung disease or pulmonary fibrosis.
• Known history of Human Immunodeficiency Virus (HIV) (testing is not mandatory).
• Known active Hepatitis B or Hepatitis C (testing is not mandatory).
• Females who are pregnant or breastfeeding.
• History of bleeding diathesis (i.e. disseminated intravascular coagulation, clotting
factor deficiency) that preclude the IM injections of fulvestrant or LHRH agonist as
applicable.
4.2.7 Patients taking any CYPC3A4 strong inducers and inhibitors, that cannot be changed.
Study Assessing the Efficacy, Safety and PK of Alpelisib (BYL719) in Pediatric and Adult Patients With PIK3CA-related Overgrowth Spectrum (EPIK-P2)
This is a prospective Phase II multi-center study with an upfront 16-week, randomized,
double-blind, placebo-controlled period, and extension periods, to assess the efficacy,
safety and pharmacokinetics of alpelisib in pediatric and adult participants with
PIK3CA-related overgrowth spectrum (PROS).
Beth Drolet, MD
All
2 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04589650
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Inclusion Criteria:
1. Signed informed consent and assent (when applicable) from the patient, parent, legal
authorized representative or guardian prior to any study related screening procedures
are performed
2. Patients with diagnosis of PROS with symptomatic and /or progressive overgrowth and at
least one measurable PROS-related lesion confirmed by blinded independent review
committee (BIRC) assessment
3. Documented evidence of a somatic mutation(s) in the PIK3CA gene performed in local
laboratories
4. A tissue sample (fresh or archival) is be sent to a Novartis-designated central
laboratory. If archival tissue is not available, collection of a fresh tissue biopsy
is required for participants in Groups 1, 2 and 5, if it is not clinically
contraindicated. For participants in Groups 3 and 4, a fresh tissue biopsy is not
mandatory.
For China only: Tissue sample collection and biomarker assessments are not applicable.
For Germany only: If archival tissue is available, it must be sent to a Novartis
designated central laboratory. If no archival tissue is available, obtaining a fresh
tissue biopsy is recommended, if it is not clinically contraindicated, but is not
mandatory.
5. Karnofsky (in patients > 16 years old at study entry)/Lansky (≤16 yrs of age at study
entry) performance status index ≥50
6. Adequate bone marrow and organ function including Fasting plasma glucose (FPG) ≤ 140
mg/dL (7.7 mmol/L) and Glycosylated hemoglobin (HbA1c) ≤ 6.5% (both criteria have to
be met) (as assessed by central laboratory for eligibility)
7. Presence of at least one PROS-related measurable lesion defined as a lesion with
longest diameter ≥2 cm, when the volume can be accurately and reproducibly measured by
MRI (Magnetic resonance imaging), and associated with complaints, clinical symptoms or
functional limitations affecting the patient's everyday life. Measurability must be
confirmed by BIRC before randomization.
Exclusion Criteria:
1. Participant with only isolated macrodactyly, skin nevus/nevi and macroencephaly (the
only clinical feature or a combination of any of three of them), in absence of other
PROS-related lesions at the time of informed consent
2. Previous treatment with alpelisib and/or any other PI3K inhibitor(s) (except treatment
attempt, defined as the attempt to treat PROS with any of PI3K inhibitors, with
treatment duration less than 2 weeks and stopped at least 4 weeks prior to the first
dose of study medication with alpelisib)
3. Radiation exposure for PROS treatment purpose within the previous 12 months on those
PROS areas which are expected to qualify for target lesions (except lesion(s)
progressing after completion of radiotherapy) at time of informed consent.
4. Debulking or other major surgery performed within 3 months at time of informed consent
5. Clinically meaningful PROS-related thrombotic event (Grade 2 and more as per CTCAE
v.4.03) within 30 days before informed consent, and/or sclerotherapy/embolization for
vascular complications performed within 6 weeks before informed consent. Note:
Participants receiving anticoagulants for PROS-related coagulopathy, primary or
secondary prophylaxis of thrombosis may be included in the study
6. Participants in Groups 1, 2 ad 5 with documented pneumonitis or interstitial lung
disease at time of informed consent and with impaired lung function (e.g., FEV1 or
DLCO ≤ 70% of predicted) that is not related to PROS. Participants in Groups 3 and 4
with documented or suspicious pneumonitis or interstitial lung disease based on MRI
images at time of informed consent
7. History of acute pancreatitis within 1 year before informed consent or past medical
history of chronic pancreatitis at time of informed consent
8. Participants with an established diagnosis of type I diabetes mellitus or uncontrolled
type II diabetes mellitus at time of informed consent
9. Known history of seizure, or epilepsy, regardless of relatedness to PROS spectrum at
time of informed consent, when epilepsy is not controlled and/or the patient may not
be switched to non-enzyme inducing antiepileptic drug(s) at time of informed consent.
10. Participants with clinically significant worsening of PROS-related laboratory
anomalies, physical signs and symptoms (such as, but not limited to increase of
D-dimers, worsening of underlying pain, newly occurring swelling or redness)
indicating an uncontrolled condition during the screening phase, particularly if
systemic treatment with any other inhibitor of the PI3K/AKT/mTOR pathway was stopped
prior to the start of study treatment. This includes but is not limited to
hypercoagulability state in participants not receiving prophylactic treatment.
Other inclusion/exclusion criteria may apply
A Study to Compare Early Use of Vinorelbine and Maintenance Therapy for Patients With High Risk Rhabdomyosarcoma
This phase III trial compares the safety and effect of adding vinorelbine to vincristine,
dactinomycin, and cyclophosphamide (VAC) for the treatment of patients with high risk
rhabdomyosarcoma (RMS). High risk refers to cancer that is likely to recur (come back) after
treatment or spread to other parts of the body. This study will also examine if adding
maintenance therapy after VAC therapy, with or without vinorelbine, will help get rid of the
cancer and/or lower the chance that the cancer comes back. Vinorelbine and vincristine are in
a class of medications called vinca alkaloids. They work by stopping cancer cells from
growing and dividing and may kill them. Dactinomycin is a type of antibiotic that is only
used in cancer chemotherapy. It works by damaging the cell's deoxyribonucleic acid (DNA) and
may kill cancer cells. Cyclophosphamide is in a class of medications called alkylating
agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the
body's immune response. Vinorelbine, vincristine, dactinomycin and cyclophosphamide are
chemotherapy medications that 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 may have the potential to eliminate rhabdomyosarcoma for a long time or
for the rest of patient's life.
Kenneth Desantes, M.D.
All
up to 50 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04994132
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Inclusion Criteria:
• Patients must be =< 50 years of age at the time of enrollment
• Patients with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based
upon institutional histopathologic classification are eligible to enroll on the study
based upon stage, group, and age, as below. FOXO1 fusion status must be determined by
week 4 (day 28) of therapy. RMS types included under embryonal RMS (ERMS) include
those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as
ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the
2020 World Health Organization (WHO) Classification as ERMS (classic, dense and
botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical
spindle cell ERMS variant and the newly recognized sclerosing RMS variant).
Classification of alveolar RMS (ARMS) in the 2020 WHO Classification is the same as in
the ICR and includes classic and solid variants
• ERMS
• Stage 4, group IV, >= 10 years of age
• ARMS
• Stage 4, group IV Patients will be eligible to remain on protocol therapy
based upon stage, group, and age
• Bone marrow metastatic disease is based on morphologic evidence of RMS based on
hematoxylin and eosin (H&E) stains. In the absence of morphologic evidence of marrow
involvement on H&E, patients with bone marrow involvement detected ONLY by flow
cytometry, reverse transcriptase (RT)-polymerase chain reaction (PCR), fluorescence in
situ hybridization (FISH), or immunohistochemistry will NOT be considered to have
clinical bone marrow involvement for the purposes of this study
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (must be
performed within 7 days prior to enrollment):
• Age; Maximum serum creatinine (mg/dL)
• 1 month to < 6 months; 0.4 mg/dL (male); 0.4 mg/dL (female)
• 6 months to < 1 year; 0.5 mg/dL (male); 0.5 mg/dL (female)
• 1 to < 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)
• 2 to < 6 years; 0.8 mg/dL (male); 0.8 mg/dL (female)
• 6 to < 10 years; 1 mg/dL (male); 1 mg/dL (female)
• 10 to < 13 years; 1.2 mg/dL (male); 1.2 mg/dL (female)
• 13 to < 16 years; 1.5 mg/dL (male); 1.4 mg/dL (female)
• >= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (must be performed within
7 days prior to enrollment)
• If there is evidence of biliary obstruction by tumor, then total bilirubin must
be < 3 x ULN for age
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Exclusion Criteria:
• Patients with evidence of uncontrolled infection are not eligible
• RMS that is considered a second malignancy and previous cancer(s) that were treated
with chemotherapy and/or radiation. Surgical resection alone of previous cancer(s) is
allowed
• Patients with central nervous system involvement of RMS as defined below:
• Malignant cells detected in cerebrospinal fluid
• Intra-parenchymal brain metastasis separate and distinct from primary tumor
(i.e., direct extension from parameningeal primary tumors is allowed).
• Diffuse leptomeningeal disease
• Patients who have received any chemotherapy (excluding steroids) and/or radiation
therapy for RMS prior to enrollment.
• Note: the following exception:
• Patients requiring emergency radiation therapy for RMS. These patients are
eligible, provided they are consented to ARST2031 prior to administration of
radiation
• Note: Patients who have received or are receiving chemotherapy or radiation for
non-malignant conditions (e.g. autoimmune diseases) are eligible. Patients must
discontinue chemotherapy for non-malignant conditions prior to starting protocol
therapy
• Vincristine and vinorelbine are sensitive substrates of CYP450 3A4 isozyme. Patients
must not have received drugs that are moderate to strong CYP3A4 inhibitors and
inducers within 7 days prior to study enrollment
• 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
Alveolar Rhabdomyosarcoma, Botryoid-Type Embryonal Rhabdomyosarcoma, Embryonal Rhabdomyosarcoma, Metastatic Embryonal Rhabdomyosarcoma, Metastatic Rhabdomyosarcoma, Solid Alveolar Rhabdomyosarcoma, Spindle Cell Rhabdomyosarcoma, Spindle Cell/Sclerosing Rhabdomyosarcoma, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Soft Tissue, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Thyroid, Other Endocrine System, Bladder, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma
Phase 2 Basket Trial of Nab-sirolimus in Patients With Malignant Solid Tumors With Pathogenic Alterations in TSC1/TSC2 Genes (PRECISION 1)
A Phase 2 multi-center open-label basket trial of nab-sirolimus for adult and adolescent
patients with malignant solid tumors harboring pathogenic inactivating alterations in TSC1 or
TSC2 genes
Dustin Deming, MD
All
12 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05103358
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Inclusion Criteria:
1. Patients must have a malignant solid tumor with a pathogenic inactivating TSC1 or TSC2
alteration. Genetic alterations should be identified using NGS in tumor tissue or
liquid biopsy).
• Patients will be enrolled after the central evaluation of NGS report confirms
eligibility.
2. Patients must have solid tumors that are metastatic or locally advanced where surgical
resection is not an option or likely to result in severe morbidity.
3. Patients must have received all standard therapies appropriate for their tumor type
and stage of disease or, in the opinion of the Investigator, the patient would be
unlikely to tolerate or derive clinically meaningful benefit from appropriate standard
of care therapy, or the patient has no satisfactory alternative treatments.
4. Patients must have 1 or more measurable target lesions by computed tomography (CT)
scan or magnetic resonance imaging (MRI) (RECIST v1.1).
5. Age: 12 years or older.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 or Karnofsky
Performance Status (KPS) ≥80 or Lansky play-performance scale for pediatric patients
≥80.
7. Adequate liver function:
1. Total bilirubin ≤1.5 × upper limit of normal (ULN) (unless due to Gilbert's
syndrome, then ≤3 × ULN)
2. Aspartate aminotransferase (AST) ≤2.5 × ULN (≤5 × ULN if attributable to liver
metastases)
8. Adequate renal function: creatinine clearance ≥30 mL/min, Cockcroft-Gault CCr =
((140-age) × weight[kg]) / (72 × SCr[mL/min]) × 0.85, if female
9. Adequate hematologic parameters:
1. Absolute neutrophil count (ANC) ≥1.0 × 109/L (growth factor support allowed)
2. Platelet count ≥100,000/mm3 (100 × 109/L) (transfusion and/or growth factor
support allowed)
3. Hemoglobin ≥8.0 g/dL (transfusion and/or growth factor support allowed)
10. Fasting serum triglyceride must be ≤300 mg/dL; fasting serum cholesterol must be ≤350
mg/dL.
11. Minimum of 4 weeks since any major surgery, completion of radiation, or completion of
prior systemic anticancer therapy, or at least 5 half-lives if the prior therapy is a
single agent small-molecule therapeutic, and adequately recovered from the acute
toxicities of any prior therapy, including neuropathy, to Grade ≤1.
12. Male or non-pregnant and non-breastfeeding female:
1. Females of childbearing potential must agree to use effective contraception or
abstinence without interruption from 28 days prior to starting investigational
product (IP) throughout 3 months after last dose of IP and have a negative serum
pregnancy test (beta human chorionic gonadotropin, β-hCG) result at screening and
agree to ongoing pregnancy testing during the course of the study, and after the
end of study treatment. A second form of birth control is required even if she
has had a tubal ligation.
2. Male patients must agree not to donate sperm and must practice abstinence or
agree to use a condom during sexual contact with a pregnant female or a female of
childbearing potential while participating in the study and throughout 3 months
after last dose of IP. A second form of birth control is required even if he has
undergone a successful vasectomy.
13. The patient or the patient's parent(s) or legal guardian(s) understand(s) and sign(s)
the informed consent.
14. Willingness and ability to comply with scheduled visits, laboratory tests, and other
study procedures.
Exclusion Criteria:
1. Prior treatment with an mTOR inhibitor, including nab-sirolimus.
2. Severe (Grade ≥3) ongoing infection requiring parenteral or oral anti-infective
treatment, either ongoing or completed ≤7 days prior to enrollment.
3. Patients with primary brain tumors or PEComa.
4. Patients who have any severe and/or uncontrolled medical or psychiatric conditions or
other conditions that could affect their participation including:
1. Patients with meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal
cord compression, untreated brain metastases or symptomatic or unstable brain
metastases. Note: Patients with stable brain metastases (defined as asymptomatic
or no requirement for high-dose [defined as dexamethasone 10 mg daily or higher]
or increasing dose of systemic corticosteroids) and without imminent need of
radiation therapy are eligible. If applicable, patients must have completed brain
radiation therapy and recovered adequately from any associated toxicity and/or
complications prior to eligibility assessment. For patients who have received
prior radiation therapy, post-treatment MRI scan should show no increase in brain
lesion size/volume.
2. Unstable angina pectoris, symptomatic congestive heart failure (New York Heart
Association, NYHA class III or IV), myocardial infarction ≤6 months prior to
first study treatment, serious uncontrolled cardiac arrhythmia or any other
clinically significant cardiac disease.
3. Pre-existing severely impaired lung function. If a patient has a pre-existing
pulmonary condition, eligible patients should have a spirometry and diffusing
capacity for carbon monoxide (DLCO) that is >50% of the normal predicted value
and/or O2 saturation that is >88% at rest on room air (Note: spirometry and
pulmonary function tests [PFTs] not required to be performed unless clinically
indicated).
4. Nonmalignant medical illnesses that are uncontrolled or whose control may be
jeopardized by the treatment with the study therapy.
5. A history of malignancies other than the one under treatment unless the patient
is disease-free for more than 5 years from diagnosis. Note, controlled
non-melanoma skin cancers, carcinoma in situ of the cervix, resected incidental
prostate cancer, certain low grade hematologic malignancies (eg CLL, follicular
lymphoma, etc), or other adequately treated carcinoma-in-situ may be eligible,
after discussion with the medical monitor.
6. Uncontrolled hypertension (systolic blood pressure ≥160 mm-Hg and/or diastolic
blood pressure ≥100 mm Hg).
7. Patients with history of interstitial lung disease and/or pneumonitis, or
pulmonary hypertension.
8. Individuals with known human immunodeficiency virus (HIV) infection are excluded
from this study as combination antiretroviral therapy could potentially result in
significant pharmacokinetic interactions. In addition, these individuals are at
increased risk of serious infections due to the immunosuppressive effects of mTOR
inhibition.
9. Active Hepatitis B or Hepatitis C, with detectable viral load.
5. Regarding concomitant medications with significant CYP3A4 and P-gp interactions,
discontinuation of strong inhibitors (eg, ketoconazole, itraconazole, voriconazole,
erythromycin, clarithromycin, telithromycin, and others), strong inducers (eg,
rifampin, rifabutin), and known CYP3A4 substrates with a narrow therapeutic window
(eg, fentanyl, alfentanil, astemizole, cisapride, dihydroergotamine, pimozide,
quinidine, or terfenadine) is required at least 5 half lives prior to receiving the
first dose of nab-sirolimus, whichever is longer.
Tumor, Tumor, Solid, Metastasis, Metastatic Cancer, Cancer, Cancer Metastatic, Tumors, Neoplasms, Neoplasm Metastasis, Solid Tumor, Advanced Solid Tumor, Advanced Cancer, Malignant Solid Tumor, Malignant Solid Neoplasm, Malignant Neoplasm, Malignant Tumor, TSC, TSC1, TSC2, Metastatic Solid Tumor, Metastatic Neoplasm, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, 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, Lung, Melanoma/Skin cancer, Sarcoma, Uterus
The Pediatric Acute Leukemia (PedAL) Screening Trial - A Study to Test Bone Marrow and Blood in Children With Leukemia That Has Come Back After Treatment or Is Difficult to Treat - A Leukemia & Lymphoma Society and Children's Oncology Group Study
This study aims to use clinical and biological characteristics of acute leukemias to screen
for patient eligibility for available pediatric leukemia sub-trials. Testing bone marrow and
blood from patients with leukemia that has come back after treatment or is difficult to treat
may provide information about the patient's leukemia that is important when deciding how to
best treat it, and may help doctors find better ways to diagnose and treat leukemia in
children, adolescents, and young adults.
Kenneth Desantes, M.D.
All
up to 22 Years old
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04726241
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Inclusion Criteria:
• Patients must be less than 22 years of age at the time of study enrollment
• Patient must have one of the following:
• Patient has known or suspected relapsed/refractory (including primary refractory)
AML
• This includes isolated myeloid sarcoma
• Patient has known or suspected relapsed/refractory (including primary refractory)
myeloid leukemia of Down syndrome
• Patient has known or suspected relapsed ALL that meets one of the following
criteria:
• Second or greater B-ALL medullary relapse, excluding KMT2Ar.
• Any first or greater B-ALL medullary relapse involving KMT2Ar.
• Any first or greater T-ALL medullary relapse with or without KMT2Ar.
• Patient has known or suspected relapsed/refractory (including primary refractory)
mixed phenotype acute leukemia (MPAL)
• Patient has known or suspected de novo or relapsed/refractory (including primary
refractory) treatment-related AML (t-AML) or treatment-related myelodysplastic
syndrome (t-MDS)
• Patient has known or suspected de novo or relapsed/refractory (including primary
refractory) myelodysplastic syndrome (MDS)
• Patient has known or suspected de novo or relapsed/refractory (including primary
refractory) juvenile myelomonocytic leukemia (JMML)
• 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
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Acute Myeloid Leukemia Post Cytotoxic Therapy, Juvenile Myelomonocytic Leukemia, Mixed Phenotype Acute Leukemia, Myelodysplastic Syndrome, Myelodysplastic Syndrome Post Cytotoxic Therapy, Myeloid Leukemia Associated With Down Syndrome, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Leukemia
Study of Ravulizumab in Pediatric Participants With HSCT-TMA
This study will evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of
ravulizumab administered by intravenous infusion to pediatric participants, from 1 month to <
18 years of age, with HSCT-TMA. The treatment period is 26 weeks, followed by a 26-week
off-treatment follow-up period.
Kenneth Desantes, M.D.
All
1 Month to 17 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04557735
Show full eligibility criteria
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Inclusion Criteria:
1. 1 month of age up to < 18 years of age at the time of signing the informed consent.
2. Received HSCT within the past 6 months.
3. Diagnosis of TMA that persists despite initial management of any triggering condition.
4. Body weight ≥ 5 kilograms.
5. Female participants of childbearing potential and male participants with female
partners of childbearing potential must use highly effective contraception starting at
Screening and continuing until at least 8 months after the last dose of ravulizumab.
6. Participants must be vaccinated against meningococcal infections if clinically
feasible, according to institutional guidelines for immune reconstitution after HSCT.
Participants must be re-vaccinated against Haemophilus influenzae type b and
Streptococcus pneumoniae if clinically feasible, according to institutional guidelines
for immune reconstitution after HSCT. All participants should be administered coverage
with prophylactic antibiotics according to institutional post-transplant infection
prophylaxis guidances, including coverage against Neisseria meningitidis for at least
2 weeks after meningococcal vaccination. Participants who cannot receive meningococcal
vaccine should receive antibiotic prophylaxis coverage against Neisseria meningitidis
the entire Treatment Period and for 8 months following the final dose of ravulizumab.
Exclusion Criteria:
1. Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin
type 1 motif, member 13' deficiency (activity < 5%).
2. Known Shiga toxin-related hemolytic uremic syndrome.
3. Positive direct Coombs test.
4. Diagnosis or suspicion of disseminated intravascular coagulation.
5. Known bone marrow/graft failure.
6. Diagnosis of veno-occlusive disease (VOD).
7. Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody
titer).
8. Unresolved meningococcal disease.
9. Presence of sepsis requiring vasopressor support.
10. Pregnancy or breastfeeding.
11. Hypersensitivity to murine proteins or to 1 of the excipients of Ravulizumab.
12. Previously or currently treated with a complement inhibitor.
Thrombotic Microangiopathy, Other Hematopoietic, Hematologic cancers, other
Thoracotomy Versus Thoracoscopic Management of Pulmonary Metastases in Patients With Osteosarcoma
This phase III trial compares the effect of open thoracic surgery (thoracotomy) to
thoracoscopic surgery (video-assisted thoracoscopic surgery or VATS) in treating patients
with osteosarcoma that has spread to the lung (pulmonary metastases). Open thoracic surgery
is a type of surgery done through a single larger incision (like a large cut) that goes
between the ribs, opens up the chest, and removes the cancer. Thoracoscopy is a type of chest
surgery where the doctor makes several small incisions and uses a small camera to help with
removing the cancer. This trial is being done evaluate the two different surgery methods for
patients with osteosarcoma that has spread to the lung to find out which is better.
Kenneth Desantes, M.D.
All
up to 50 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05235165
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Inclusion Criteria:
• Patients must be < 50 years at the time of enrollment.
• Patients must have =< 4 nodules per lung consistent with or suspicious for metastases,
with at least one of which being >= 3 mm and all of which must be =< 3 cm size.
• Note: Patient must have eligibility confirmed by rapid central imaging review.
• Lung nodules must be considered resectable by either open thoracotomy or thoracoscopic
surgery. Determination of resectability is made by the institutional surgeon.
• Patients must have a histological diagnosis of osteosarcoma.
• Patients must have evidence of metastatic lung disease at the time of initial
diagnosis, or at time of 1st recurrence following completion of therapy for initially
localized disease.
• Patients with newly diagnosed disease must have completed successful gross tumor
resection for their primary tumor or surgical local control of primary tumor must be
planned to be performed simultaneously with thoracic surgery.
• Newly diagnosed patients must be receiving or recently completed (within 60 days)
systemic therapy considered by the treating physician to be standard treatment for
newly diagnosed osteosarcoma (eg, cisplatin-doxorubicin or ifosfamide-based drug
regimens) at the time of enrollment on this study. Dose and drug modifications for
toxicity do not exclude patients from participation.
• Patients at time of 1st recurrence must have completed systemic therapy for their
initial primary tumor, considered by the treating physician to be standard treatment
for newly diagnosed osteosarcoma (eg, cisplatin-doxorubicin or ifosfamide-based drug
regimens) at the time of enrollment on this study. Dose and drug modifications for
toxicity do not exclude patients from participation.
Exclusion Criteria:
• Patients with unresectable primary tumor.
• Patients with pulmonary metastatic lesions that would require anatomic resection
(lobectomy or pneumonectomy) or lesions that are defined as "central" (i.e., central
lesion involves or is proximal to segmental bronchi and peripheral is lesion distal to
segmental bronchi).
• Patients with chest wall or mediastinal based metastatic lesions, or with significant
pleural effusion.
• Patients with disease progression at either the primary or pulmonary metastatic site
while on initial therapy. Note: Once the patient has been enrolled on the study,
additional computed tomography (CT) scans are not anticipated prior to thoracic
surgery. Note: Some variation in nodule size measurements over the course of
pre-operative therapy is anticipated and does not qualify for exclusion unless deemed
true disease progression by the primary treatment team.
• Patients with evidence of extrapulmonary metastatic disease.
• Patients who received therapeutic pulmonary surgery for lung metastasis prior to
enrollment.
• All patients and/or their parents or legal guardians must sign a written informed
consent.
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met.
Metastatic Malignant Neoplasm in the Lung, Metastatic Osteosarcoma, Osteosarcoma, Bones and Joints, Sarcoma
A phase 3 randomized partial blind storage duration ranging study in patients undergoing
complex cardiac surgery that will compare the transfusion of cold stored platelets to
standard room temperature stored platelets. The primary objective is to establish that cold
stored platelets have a non-inferiority (or superiority) to room temperature platelets.
Eric Simon
All
0 Days to 84 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04834414
Show full eligibility criteria
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Inclusion Criteria:
• Viable neonates ≥ 3 kg at time of enrollment (as defined in Section 4.1) OR age
greater than 28 days and less than 85 years of age at time of consent; AND
• Planned complex cardiac surgery with planned use of cardiopulmonary bypass, with an
expectation of bleeding requiring platelet transfusion.
Exclusion Criteria:
• Expected order for washed or volume reduced platelets
• Patient with known anti-platelet antibodies
• Platelet transfusion refractoriness due to anti-HLA antibodies
• Known or suspected pregnancy
• Previously randomized in this study
• Conscious objection or unwillingness to receive blood products
• Known IgA deficiency
• Known congenital platelet disorder
• Known congenital bleeding disorder
• Planned post-operative extracorporeal membrane oxygenation (ECMO), ventricular assist
device (VAD), and/or continuous renal replacement therapy (CRRT)/ hemodialysis
• Patients intended to receive whole blood either intra-operative or post-operative for
bleeding
• Platelet transfusion (of any type) within 24 hours prior to the date of surgery
• Pre-operative thrombocytopenia, defined as platelet count <75x10(9)/L, based on the
most recent labs completed within 72 hours prior to the date of surgery.
Complications of heart transplant, Congenital malformation of heart, unspecified, Heart failure, Other acute ischemic heart diseases, Other, Heart & Vascular, Acute Blood Loss
A Study to See if Memantine Protects the Brain During Radiation Therapy Treatment for Primary Central Nervous System Tumors
This phase III trial compares memantine to usual treatment in treating patients with primary
central nervous system tumors. Memantine may block receptors (parts of nerve cells) in the
brain known to contribute to a decline in cognitive function. Giving memantine may make a
difference in cognitive function (attention, memory, or other thought processes) in children
and adolescents receiving brain radiation therapy to treat a primary central nervous system
tumors.
Kenneth Desantes, M.D.
All
4 Years to 17 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04939597
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Inclusion Criteria:
• >= 4 and < 18 years at time of study entry
• Patients must weigh 15 kg or greater at time of study entry
• Primary central nervous system tumors that have not received prior cranial
radiotherapy
• Planned focal, cranial or craniospinal radiation treatment for a primary central
nervous system tumor
• The patient must have receptive and expressive language skills in English, French or
Spanish since the neurocognitive function and quality of life (QOL) assessment
instruments are available in these languages only
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age: 4 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 male; 0.8 female
• Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 male; 1 female
• Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 male; 1.2 female
• Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 male; 1.4 female
• Age: >= 16 years; Maximum serum creatinine (mg/dL): 1.7 male; 1.4 female
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
U/L
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L
• The patient must be able to undergo magnetic resonance imaging
• 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:
• Life expectancy of less than 18 months
• Pre-existing conditions:
• Any contraindication or allergy to study drug (memantine or placebo)
• Intractable seizures while on adequate anticonvulsant therapy, defined as more
than one seizure per month for the past 2 months or since initiating
anticonvulsant therapy
• History of neurodevelopmental disorder such as Down syndrome, Fragile X,
William's Syndrome, intellectual disability (presumed intelligence quotient [IQ]
< 70), etc
• Co-morbid systemic illnesses, psychiatric conditions, social situations, or other
severe concurrent disease which, in the judgment of the investigator, would make
the patient inappropriate for entry into this study or interfere significantly
with the proper assessment of safety and toxicity of the prescribed regimens or
would limit compliance with the study requirements
• Patients with a motor, visual, or auditory condition that precludes participation
in computerized neurocognitive assessments
• Patients with any medical condition or taking medications that lead to
alterations of urine pH towards the alkaline condition (e.g., renal tubular
acidosis, carbonic anhydrase inhibitors, sodium bicarbonate)
• Personal history of prior cranial or craniospinal radiotherapy is not allowed
• Note: Prior anti-cancer therapy including surgery, chemotherapy, targeted agents
are allowed as per standard of care clinical treatment guidelines
• Female patients who are pregnant are excluded since fetal toxicities and teratogenic
effects have been noted for the study drug. 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 do not agree to use an
effective contraceptive method for the duration of their study participation
Central Nervous System Carcinoma, Brain and Nervous System, Brain/Central Nervous System
A Study Evaluating the Efficacy and Safety of IV L-Citrulline for the Prevention of Clinical Sequelae of Acute Lung Injury Induced by Cardiopulmonary Bypass in Pediatric Patients Undergoing Surgery for Congenital Heart Defects
This is a randomized, double-blind, placebo controlled, multicenter study to compare the
efficacy and safety of L-citrulline versus placebo in patients undergoing surgery for
congenital heart defects. Eligible patients undergoing repair of a large unrestrictive
ventricular septal defect (VSD), a partial or complete atrioventricular septal defect (AVSD),
or an ostium primum atrial septal defect (primum ASD) will be eligible for enrollment.
Petros Anagnostopoulos
All
up to 18 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05253209
Show full eligibility criteria
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Inclusion Criteria:
• Patients, parents, or legal guardian willing and able to sign informed consent
• Male and female subjects aged ≤18 years of age (females of child-bearing potential
willing to practice an acceptable form of birth control)
• Patients undergoing cardiopulmonary bypass for repair of a large unrestrictive
ventricular septal defect, an ostium primum/secundum atrial septal defect, or a
partial or complete atrioventricular septal defect
• Pre-operative echocardiogram confirming cardiovascular anatomy and defect to be
repaired
Exclusion Criteria:
• Evidence of pulmonary artery or vein abnormalities that will not be addressed
surgically. Specific abnormalities excluded include:
• significant pulmonary artery narrowing not amenable to surgical correction
• previous pulmonary artery stent placement
• significant left sided AV valve regurgitation not amenable to surgical correction
• pulmonary venous return abnormalities not amenable to surgical correction
• pulmonary vein stenosis not amenable to surgical correction
• Preoperative requirement for mechanical ventilation or IV inotrope support
• Presence of fixed or idiopathic pulmonary hypertension (i.e. Eisenmenger's Syndrome)
prior to surgical repair
• Pre-operative use of medications to treat pulmonary hypertension
• Pregnancy; Sexually active females of child-bearing potential must be willing to
practice an acceptable method of birth control for the duration of study participation
(e.g. oral contraceptive, hormonal implant, intra-uterine device)
• Participation in another clinical trial within 30 days of Screening or while
participating in the current study, including the 28 days of follow-up post study drug
administration.
• Any condition which, in the opinion of the investigator, might interfere with the
study objectives
Universal Rare Gene Study: A Registry and Natural History Study of Retinal Dystrophies Associated With Rare Disease-Causing Genetic Variants (Uni-Rare)
This is an international, multicenter study with two components:
Registry
- A standardized genetic screening and a prospective, standardized, cross-sectional
clinical data collection
- Enrollment is open to all genes on the RD Rare Gene List
Natural History Study
- A prospective, standardized, longitudinal Natural History Study
- Enrollment opens gene-by-gene, based on funding and within-gene Registry enrollment The
study objectives are as follows.
Registry Objectives
1. Genotype Characterization
2. Cross-Sectional Phenotype Characterization (within gene)
3. Establish a Link to My Retina Tracker Registry (MRTR)
4. Ancillary Exploratory Studies - Pooling of Genes
Natural History Study Objectives
1. Natural History (within gene)
2. Structure-Function Relationship (within gene)
3. Risk Factors for Progression (within gene)
4. Ancillary Exploratory Studies - Pooling of Genes
Kimberly Stepien, MD
All
4 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT05589714
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Inclusion Criteria:
Participants must meet all the following inclusion criteria at the
Registry/Screening Visit to be eligible to enroll into the genetic screening phase:
1. Willing to participate in the study and able to communicate consent during the consent
process
2. Willing and able to complete all applicable Registry/Screening Visit assessments
3. Age ≥ 4 years
4. Must have a single gene on the RD Rare Gene List which meets one of the Genetic
Screening Criteria below based on a genetic report* from a clinically certified lab
(or from a research lab which has been approved by the study Genetics Committee):
Inheritance Pattern is Recessive and has at least 2 disease-causing variants which are
homozygous or heterozygous in trans
OR
Inheritance Pattern is Recessive and has 2 disease-causing variants with unknown phase and
meets all the following additional informatic criteria that is consistent with likely
segregation in trans:
1. Investigator confirms genotype and phenotype are consistent with autosomal recessive
inheritance
2. The 2 disease-causing variants have not been reported in cis in variant databases
3. No additional potentially pathogenic variants were found on the gene (and the
sequencing data for the gene were sufficiently robust to detect any additional
potentially pathogenic variants)
4. No potentially pathogenic variants were found in other common, likely candidate genes
for the proposed condition
OR
Inheritance Pattern is Dominant, X-linked, or Mitochondrial and has at least 1
disease-causing variant
Both eyes must meet the following criteria at the Registry/Screening Visit to enroll into
the genetic screening phase:
1. Both eyes must have a clinical diagnosis of retinal dystrophy
2. Both eyes must permit good quality photographic imaging (e.g., but not limited to,
clear ocular media, adequate pupil dilation, stable fixation)
Exclusion Criteria:
Participants must not meet any of the following exclusion criteria at the
Registry/Screening Visit to be eligible to enroll into the genetic screening phase:
1. History of more than 1 year of cumulative treatment, at any time, with an agent
associated with pigmentary retinopathy including amiodarone, chloroquine, deferoxamine,
hydroxychloroquine, pentosan polysulfate, tamoxifen, and deferoxamine Note: Since this is
an observational study, pregnant women will not be specifically excluded from
participation. However, minors that are pregnant shall be precluded from participation
until they become the age of majority.
Ocular
Exclusion Criteria:
If either eye has any of the following ocular exclusion criteria at the Registry/Screening
Visit, then the participant is not eligible to enroll into the genetic screening phase:
1. Current vitreous hemorrhage
2. Current complications of pathological myopia (for example, but not limited to, myopic
maculopathy including atrophy, scar, choroidal neovascularization, schisis) that could
inhibit ability to obtain good quality photographic imaging
3. History of intraocular surgery (for example, but not limited to, cataract surgery,
vitrectomy, penetrating keratoplasty, or LASIK) within 3 months of Registry/Screening
Visit
4. Current or any history of confirmed diagnosis of glaucoma (for example, but not
limited to, glaucomatous VF changes or nerve changes, or history of glaucoma filtering
surgery)
5. Current or any history of retinal vascular occlusion or proliferative diabetic
retinopathy
6. History or current evidence of ocular disease that, in the opinion of the
Investigator, may confound assessment of visual function (for example, but not limited
to, tractional or rhegmatogenous retinal detachment, any vitreoretinal surgery,
retinal vascular occlusion, proliferative diabetic retinopathy)
7. The following medications and treatments are prohibited as they can affect progression
of retinitis pigmentosa (RP). The participant must not have received the following
treatments:
Any use of ocular stem cell or gene therapy Any treatment with ocriplasmin Treatment
with Ozurdex (dexamethasone), Iluvien, or Yutiq (fluocinolone acetonide) intravitreal
implant
8. The following medications and treatments are excluded within the specified timeframe:
Treatment with an ophthalmic oligonucleotide within the last 9 months (last treatment date
is less than 9 months prior to Registry/Screening Visit date)
Treatment with any other product within five times the expected half-life of the product
(time from last treatment date to Registry/Screening Visit date is at least 5 times the
half-life of the given product)
GD2-SADA:177Lu-DOTA Complex in Patients With Solid Tumors Known to Express GD2
Patients with Small Cell Lung Cancer, Sarcoma and Malignant Melanoma will be treated with
GD2-SADA:177Lu-DOTA complex(The IMP is a two-step radioimmunotherapy, delivered as two
separate products GD2-SADA and 177Lu-DOTA) to assess safety and tolerability
Vincent Ma, MD
All
16 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05130255
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Inclusion Criteria:
• Signed informed consent from patient, legal guardian(s) and/or adolescents obtained in
accordance with local regulations. Pediatric patients must provide assent as required
by local regulations.
• Age ≥18 years at the time of informed consent, for sarcoma age ≥16 years of age at
time of informed consent/assent
• Measurable disease according to RECIST 1.1
• ECOG performance status 0-1
• Expected survival >3 months
• Platelet counts ≥100,000 cells/mm3
• Hemoglobin ≥9 g/dL
• Adequate renal function with serum creatinine ≤1.5 mg/dL or creatinine clearance
≥60mL/min as calculated using the Cockcroft-Gault equation
• Patient willing and able to comply with the trial protocol
Exclusion Criteria:
• Systemic chemotherapy, radiotherapy, immunotherapy, or major surgery administered
within 3 weeks prior to the first planned dosing of the IMP per protocol
• Patients receiving any other investigational therapy for their cancer within 3 weeks
prior to the first planned dosing of the IMP per protocol
• Ongoing radiation toxicities from prior RT therapy
• Patients with a diagnosis of autoimmune diseases or immunodeficiencies or documented
infection with human immunodeficiency virus (HIV) or hepatitis B or C virus (active)
• Prior treatment with anti-GD2 antibody
Chemotherapy for the Treatment of Patients With Newly Diagnosed Very Low-Risk and Low Risk Fusion Negative Rhabdomyosarcoma
Rhabdomyosarcoma is a type of cancer that occurs in the soft tissues in the body. This phase
III trial aims to maintain excellent outcomes in patients with very low risk rhabdomyosarcoma
(VLR-RMS) while decreasing the burden of therapy using treatment with 24 weeks of vincristine
and dactinomycin (VA) and examines the use of centralized molecular risk stratification in
the treatment of rhabdomyosarcoma. Another aim of the study it to find out how well patients
with low risk rhabdomyosarcoma (LR-RMS) respond to standard chemotherapy when patients with
VLR-RMS and patients who have rhabdomyosarcoma with DNA mutations get separate treatment.
Finally, this study examines the effect of therapy intensification in patients who have RMS
cancer with DNA mutations to see if their outcomes can be improved.
Kenneth Desantes, M.D.
All
up to 21 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05304585
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Inclusion Criteria:
• All patients must be enrolled on APEC14B1 (NCT02402244) and consented to the Molecular
Characterization Initiative (Part A) prior to enrollment and treatment on ARST2032
(this trial).
• Patients must be =< 21 years at the time of enrollment.
• Patients must have newly diagnosed embryonal rhabdomyosarcoma (ERMS), spindle
cell/sclerosing RMS, or FOXO1 fusion negative alveolar rhabdomyosarcoma (ARMS)
(institutional FOXO1 fusion results are acceptable). RMS types included under ERMS
include those classified in the 1995 International Classification of Rhabdomyosarcoma
(ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified
in the 2020 World Health Organization (WHO) classification as ERMS (classic, dense and
botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical
spindle cell ERMS variant and the newly recognized sclerosing RMS variant). Enrollment
in APEC14B1 is required for all patients.
• All patients will be evaluated for stage and clinical group. Note that clinical
group designation assigned at the time of enrollment on study remains unchanged
regardless of any second-look operation that may be performed.
• Patients will be eligible for the very low-risk stratum (Regimen VA) if they
have Stage 1, CG I disease.
• Patients will be eligible for the low-risk stratum (Regimen VAC/VA) if they
have Stage 1, CG II disease, Stage 2, CG I or II disease, or Stage 1, CG III
(orbit only) disease.
• Paratesticular Tumors: Staging ipsilateral retroperitoneal lymph node sampling
(SIRLNS) is required for all patients >= 10 years of age with paratesticular
tumors who do not have gross nodal involvement on imaging.
• Extremity Tumors: Regional lymph node sampling is required for histologic
evaluation in patients with extremity tumors.
• Clinically or radiographically enlarged nodes must be sampled for histologic
evaluation.
• Patients must have a Lansky (for patients =< 16 years of age) or Karnofsky (for
patients > 16 years of age) performance status score of >= 50. Patients who are unable
to walk because of paralysis, but who are up in a wheelchair, will be considered
ambulatory for the purpose of assessing performance score.
• Peripheral absolute neutrophil count (ANC) >= 750/uL (within 7 days prior to
enrollment).
• Platelet count >= 75,000/uL (transfusion independent) (within 7 days prior to
enrollment).
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine (within 7 days prior to enrollment) based on
age/gender as follows:
• Age: 1 month to < 6 months; Maximum serum creatinine (mg/dL): 0.4 (male) : 0.4
(female)
• Age: 6 months to < 1 year; Maximum serum creatinine (mg/dL): 0.5 (male) : 0.5
(female)
• Age: 1 to < 2 years; Maximum serum creatinine (mg/dL): 0.6 (male) : 0.6 (female)
• Age: 2 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 (male) : 0.8 (female)
• Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 (male) : 1 (female)
• Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 (male) : 1.2
(female)
• Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 (male) : 1.4
(female)
• Age >= 16 years; Maximum serum creatinine (mg/dL): 1.7 (male) : 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment), and
• If there is evidence of biliary obstruction by the tumor, then the total
bilirubin must be < 3 x ULN for age.
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L.
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
U/L (within 7 days prior to enrollment).
• All patients and/or their parents or legal guardians must sign a written informed
consent.
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met.
Exclusion Criteria:
• Patients who have received prior chemotherapy and/or radiation therapy for cancer
prior to enrollment. Surgical resection alone of previous cancer(s) is permitted.
• Patients who have received chemotherapy or radiation for non-malignant conditions
(e.g., autoimmune diseases) are eligible. Patients must discontinue chemotherapy for
non-malignant conditions prior to starting protocol therapy.
• Vincristine is sensitive substrate of the CYP450 3A4 isozyme. Patients must not have
received drugs that are moderate to strong CYP3A4 inhibitors and inducers within 7
days prior to study enrollment.
• Patients unable to undergo radiation therapy, if necessary, as specified in the
protocol.
• Evidence of uncontrolled infection.
• Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs. A pregnancy test is required for female
patients of childbearing potential.
• Lactating females who plan to breastfeed their infants.
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation.
Embryonal Rhabdomyosarcoma, Fusion-Negative Alveolar Rhabdomyosarcoma, Spindle Cell/Sclerosing Rhabdomyosarcoma, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Soft Tissue, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Thyroid, Other Endocrine System, Bladder, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma
A Study of a New Way to Treat Children and Young Adults With a Brain Tumor Called NGGCT
This phase II trial studies the best approach to combine chemotherapy and radiation therapy
(RT) based on the patient's response to induction chemotherapy in patients with
non-germinomatous germ cell tumors (NGGCT) that have not spread to other parts of the brain
or body (localized). This study has 2 goals: 1) optimizing radiation for patients who respond
well to induction chemotherapy to diminish spinal cord relapses, 2) utilizing higher dose
chemotherapy followed by conventional RT in patients who did not respond to induction
chemotherapy. Chemotherapy drugs, such as carboplatin, etoposide, ifosfamide, and thiotepa,
work in different ways to stop the growth of tumor cells, either by killing the cells, by
stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high
energy x-rays or high-energy protons to kill tumor cells and shrink tumors. Studies have
shown that patients with newly-diagnosed localized NGGCT, whose disease responds well to
chemotherapy before receiving radiation therapy, are more likely to be free of the disease
for a longer time than are patients for whom the chemotherapy does not efficiently eliminate
or reduce the size of the tumor. The purpose of this study is to see how well the tumors
respond to induction chemotherapy to decide what treatment to give next. Some patients will
be given RT to the spine and a portion of the brain. Others will be given high dose
chemotherapy and a stem cell transplant before RT to the whole brain and spine. Giving
treatment based on the response to induction chemotherapy may lower the side effects of
radiation in some patients and adjust the therapy to a more efficient one for other patients
with localized NGGCT.
Kenneth Desantes, M.D.
All
3 Years to 29 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT04684368
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Inclusion Criteria:
• Patients must be >= 3 years and < 30 years at the time of study enrollment
• Patients must be newly diagnosed with localized primary CNS NGGCT of the suprasellar
and/or pineal region by pathology and/or serum or cerebrospinal fluid (CSF) elevation
of AFP above institutional normal or > 10 ng/mL or human chorionic gonadotropin (hCG)
beta > 100 mIU/mL as confirmed by Rapid Central Marker Screening Review on
APEC14B1-CNS. Suprasellar, pineal and bifocal tumors are included. (CSF tumor markers
and cytology must be within 31 days prior to enrollment and start of protocol therapy
[repeat if necessary]. Serum tumor markers, AFP and hCGbeta must be within 7 days
prior to enrollment and start of protocol therapy [repeat if necessary]). Basal
ganglia or other primary sites are excluded
• Patients with any of the following pathological elements are eligible: endodermal
sinus (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma
and mixed germ cell tumor (GCT) (i.e., may include some pure germinoma) if malignant
elements listed above are present. Patients with only mature teratoma are excluded.
Patients with pure germinoma admixed with mature teratoma are excluded (would be
eligible for pure germinoma protocols)
• Patients must have a cranial MRI with and without gadolinium at diagnosis/prior to
enrollment. If surgical resection is performed, patients must have pre-operative and
post operative brain MRI with and without gadolinium. The post operative brain MRI
should be obtained within 72 hours of surgery. If patient has a biopsy only,
post-operative brain MRI is recommended but not required (within 31 days prior to
study enrollment and start of protocol therapy )
• Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to
enrollment. Spine MRI with and without gadolinium is recommended (within 31 days prior
to study enrollment and start of protocol therapy)
• Lumbar CSF must be obtained prior to study enrollment unless medically
contraindicated. If a patient undergoes surgery and lumbar CSF cytology cannot be
obtained at the time of surgery, then it should be performed at least 10 days
following surgery and prior to study enrollment. False positive cytology can occur
within 10 days of surgery
• Patients must have RAPID CENTRAL TUMOR MARKER REVIEW CSF tumor markers obtained prior
to enrollment unless medically contraindicated. Ventricular CSF obtained at the time
of CSF diversion procedure (if performed) is acceptable for tumor markers but lumbar
CSF is preferred. In case CSF diversion and biopsy/surgery are combined, CSF tumor
markers should be collected first
• Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to
enrollment)
• Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to
enrollment)
• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (within 7 days
prior to enrollment)
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (within 7 days
prior to enrollment):
• Age: Maximum serum creatinine (mg/dL)
• 3 to < 6 years: 0.8 (male), 0.8 (female)
• 6 to < 10 years: 1 (male), 1 (female)
• 10 to < 13 years: 1.2 (male), 1.2 (female)
• 13 to < 16 years: 1.5 (male), 1.4 (female)
• >= 16 years: male (1.7), 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
U/L (within 7 days prior to enrollment)
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L
• Central nervous system function defined as:
• Patients with seizure disorder may be enrolled if on anticonvulsants and well
controlled
• Patients must not be in status epilepticus, coma or assisted ventilation prior to
study enrollment
• Protocol therapy must begin within 31 calendar days of definitive surgery or clinical
diagnosis, whichever is later. If a biopsy only was performed, the biopsy date will be
considered the date of definitive surgery. For patients who have a biopsy or
incomplete resection at diagnosis followed by additional surgery, the date of the last
resection will be considered the date of definitive surgery.
• 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
• NEUROCOGNITIVE FUNCTION AND QUALITY OF LIFE ASSESSMENT:
• English-, Spanish-, or French- speaking
• Note: Patients who speak a language other than English, Spanish, or French will
be allowed to participate in ACNS2021 but will not complete the neurocognitive
and quality of life assessments
• No known history of neurodevelopmental disorder prior to diagnosis of NGGCT (e.g.,
Down syndrome, fragile X, William syndrome, intellectual disability). Patients with
NF1 will be allowed to participate
• Additional eligibility criteria for the COG Standardized Neuropsychological Battery
only: must be at a site that has a psychologist to administer the battery
• Note: If not eligible for the COG Standardized Battery, patients should still
complete the Behavior Rating Inventory of Executive Function, Second Edition
(BRIEF-2), Pediatric Quality of Life Inventory (PedsQL), Adaptive Behavior
Assessment System Third Edition (ABAS-3), and Behavior Assessment System for
Children, Third Edition (BASC-3) questionnaires
Exclusion Criteria:
• Patients with tumors located outside the ventricles (i.e., basal ganglia, thalamus)
• Patients with only mature teratoma and non-elevated markers upon tumor sampling at
diagnosis
• Patients who have received any prior tumor-directed therapy for their diagnosis of
NGGCT other than surgical intervention and corticosteroids
• Patients with metastatic disease (i.e., MRI evaluation, lumbar CSF cytology or
intraoperative evidence of dissemination)
• Female patients who are pregnant, since fetal toxicities and teratogenic effects have
been noted for several of the study drugs
• Note: Serum and urine pregnancy tests may be falsely positive due to
HCGbeta-secreting germ cell tumors. Ensure the patient is not pregnant by
institutional standards
• 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
Central Nervous System Nongerminomatous Germ Cell Tumor, Choriocarcinoma, Embryonal Carcinoma, Immature Teratoma, Malignant Teratoma, Mixed Germ Cell Tumor, Pineal Region Germ Cell Tumor, Pineal Region Immature Teratoma, Pineal Region Yolk Sac Tumor, Suprasellar Germ Cell Tumor, Brain and Nervous System, Brain/Central Nervous System
This study will evaluate the effectiveness and safety of an investigational product (IP),
intravenous (IV) ganaxolone, to treat participants with status epilepticus (SE).
Aaron Struck, Medical Student
All
12 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04391569
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Inclusion Criteria:
1. Participant, participant's parent, guardian, or legal authorized representative (LAR)
must provide signed of informed consent/assent, and once capable (per institution
guidelines), there must be documentation of consent/assent by the participant
demonstrating they are willing and aware of the investigational nature of the study
and related procedures. Where allowed by law, where the participant lacks the capacity
to make informed decisions regarding his/her medical treatment options, the treating
clinician may follow their deferred consenting practices. The clinician will make the
final decision based on the best interests of the particiapant.
2. Male or females 12 years of age and older at the time of the first dose of IP
3. SE meeting the following criteria:
a. A diagnosis of SE with or without prominent motor features based on clinical and
EEG findings:
i. Diagnosis is established by:
• For SE with prominent motor features: Clinical and EEG seizure activity
indicative of convulsive, myoclonic or focal motor SE.
• For SE without prominent motor features (nonconvulsive SE): Appropriate clinical
features and an EEG indicative of non-convulsive status epilepticus (NCSE)
ii. For any type of SE:
• At least 6 minutes of cumulative seizure activity over a 30-minute period within
the hour before IP initiation, AND
• Seizure activity during the 30 minutes immediately prior to IP initiation
b. The treating clinician(s) anticipate that IV anesthesia is likely to be the
next treatment for SE that persists following initiation of IP
4. Participants must have received any two or more of the following agents for treatment
of the current episode of SE administered at an adequate dose and for a sufficient
duration, in the judgment of the investigator, to demonstrate efficacy
• Benzodiazepines,
• IV Fosphenytoin/phenytoin,
• IV Valproic acid,
• IV Levetiracetam,
• IV Lacosamide,
• IV Brivaracetam, or
• IV Phenobarbital
5. Body mass index (BMI) < 40 or, if BMI is not able to be calculated at screening,
participant is assessed by investigator as not morbidly obese
Exclusion Criteria:
1. Life expectancy of less than 24 hours
2. Anoxic brain injury or an uncorrected rapidly reversable metabolic condition as the
primary cause of SE (e.g., hypoglycemia < 50 milligram per deciliter [mg/dL] or
hyperglycemia > 400 mg/dL)
3. Participants who have received high-dose IV anesthetics (e.g., midazolam, propofol,
thiopental, or pentobarbital) during the current episode of SE for more than 18 hours,
or who continue to have clinical or electrographic evidence of persistent seizures
while receiving high-dose IV anesthetics.
4. Clinical condition or advance directive that would NOT permit use of IV anesthesia
5. Participants known or suspected to be pregnant
6. Participants with known allergy or sensitivity to progesterone or allopregnanolone
medications/supplements
7. Receiving a concomitant IV product containing Captisol®
8. Known or suspected hepatic insufficiency or hepatic failure leading to impaired
synthetic liver function.
9. Known or suspected stage 3B (moderate to severe; estimated glomerular filtration rate
[eGFR] 44-30 milliliter/minutes/1.73-meter square [mL/min/1.73m^2]), stage 4 (severe;
eGFR 29-15 mL/min/1.73m^2), or stage 5 (kidney failure; eGFR < 15 mL/min/1.73m^2 or
dialysis) kidney disease
10. Use of an investigational product for which less than 30 days or 5 half-lives have
elapsed from the final product administration. Participation in a non-interventional
clinical study does not exclude eligibility.
A Study Evaluating the Long-term Safety and Efficacy of VX-121 Combination Therapy
The purpose of this study is to evaluate the long-term safety, tolerability, and efficacy of
VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in participants with cystic fibrosis.
Andrew Braun
All
12 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05444257
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Key
Inclusion Criteria:
• Completed study drug treatment in a parent study VX20-121-102 (NCT05033080) and
VX20-121-103 (NCT05076149); or had study drug interruption(s) in a parent study but
did not permanently discontinue study drug, and completed study visits up to the last
scheduled visit of the Treatment Period in the parent study
Key
Exclusion Criteria:
• History of drug intolerance in a parent study
• Pregnant or breast-feeding females
Other protocol defined Inclusion/Exclusion criteria may apply.
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