A Study of the Drugs Selumetinib Versus Carboplatin/Vincristine in Patients With Neurofibromatosis and Low-Grade Glioma

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Recruiting
CT.gov ID
NCT03871257
Collaborator
(none)
290
116
2
90.9
2.5
0

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Carboplatin
  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration
  • Drug: Selumetinib Sulfate
  • Drug: Vincristine Sulfate
Phase 3

Detailed Description

PRIMARY OBJECTIVES:
  1. To determine whether the efficacy of treatment with selumetinib sulfate (selumetinib) as measured by event-free survival (EFS) is non-inferior to treatment with carboplatin/vincristine sulfate (vincristine) (CV) in previously untreated neurofibromatosis type 1 (NF1)-associated low-grade glioma (LGG).

  2. To determine whether visual acuity (VA) using Teller acuity cards (TAC), in patients with NF1-associated LGG within the optic pathway, is better in those treated with selumetinib compared to CV.

SECONDARY OBJECTIVES:
  1. To estimate tumor response rates and overall survival (OS) in each treatment regimen in previously untreated NF1-associated LGG.

  2. To evaluate VA outcomes utilizing HOTV letter acuity testing in previously untreated NF1-associated LGG within the optic pathway in patients who are old enough to perform visual acuity testing utilizing HOTV (a recognition acuity measure).

  3. To describe the improvement in motor function as measured by the Vineland scale in patients with previously untreated NF1-associated LGG that have documented motor deficits at enrollment.

  4. To prospectively evaluate and compare the quality of life among patients treated with selumetinib or CV.

  5. To prospectively evaluate and compare the cognitive, social, emotional, and behavioral functioning of patients with NF1-associated LGG treated with either selumetinib or CV.

EXPLORATORY OBJECTIVES:
  1. To evaluate optical coherence tomography (OCT) measures of retinal axon and ganglion cell thickness as a marker of treatment response in previously untreated NF1-associated LGG within the optic pathway.

  2. To compare novel, semi-automated volumetric magnetic resonance imaging (MRI) measures to traditional measurements of treatment response (bi-dimensional MRI measurements) in NF1-associated optic pathway tumors.

  3. To obtain paired blood and tumor tissue to be banked for future NF1-LGG biology studies involving comprehensive molecular analysis, including but not limited to whole exome and ribonucleic acid (RNA) sequencing.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I:

INDUCTION: Patients receive carboplatin intravenously (IV) over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 and vincristine IV or IV push over 1 minute on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive carboplatin IV over 60 minutes on days 1, 8, 15, and 22 and vincristine IV or IV push over 1 minute on days 1, 8, and 15. Treatment repeats every 6 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive selumetinib sulfate orally (PO) twice daily (BID) on days 1-28. Treatment is continuous and repeats every 28 days for 27 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up with MRIs and physical exams every 3 months for 1 year, every 6 months for 2 years, and then once yearly for up to 10 years.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
290 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3 Randomized Study of Selumetinib Versus Carboplatin/Vincristine in Newly Diagnosed or Previously Untreated Neurofibromatosis Type 1 (NF1) Associated Low-Grade Glioma (LGG)
Actual Study Start Date :
Oct 4, 2019
Anticipated Primary Completion Date :
May 1, 2027
Anticipated Study Completion Date :
May 1, 2027

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Arm I (carboplatin, vincristine)

INDUCTION: Patients receive carboplatin IV over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 and vincristine IV or IV push over 1 minute on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive carboplatin IV over 60 minutes on days 1, 8, 15, and 22 and vincristine IV or IV push over 1 minute on days 1, 8, and 15. Treatment repeats every 6 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Names:
  • Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies

    Drug: Vincristine Sulfate
    Given IV or IV push
    Other Names:
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate
  • Experimental: Arm II (selumetinib sulfate)

    Patients receive selumetinib sulfate PO BID on days 1-28. Treatment is continuous and repeats every 28 days for 27 cycles in the absence of disease progression or unacceptable toxicity.

    Other: Quality-of-Life Assessment
    Ancillary studies
    Other Names:
  • Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies

    Drug: Selumetinib Sulfate
    Given PO
    Other Names:
  • AZD-6244 Hydrogen Sulfate
  • AZD6244 Hydrogen Sulfate
  • AZD6244 Hydrogen Sulphate
  • Koselugo
  • Selumetinib Sulphate
  • Outcome Measures

    Primary Outcome Measures

    1. Event-free survival (EFS) [From randomization to the first occurrence of any of the following events: clinical or radiographic disease progression, disease recurrence, second malignant neoplasm, or death from any cause, assessed up to 3 years after accrual completion]

      EFS is defined as time from randomization to the first occurrence of any of the following events: clinical or radiographic disease progression, disease recurrence, second malignant neoplasm, or death from any cause. Patients who are event-free will be censored at the time of last follow-up. Hazard ratio based on a stratified Cox proportional hazards model will be reported, along with a 90% confidence interval.

    2. Number of participants with visual acuity (VA) improvement per arm [Baseline and end of about 12 months of treatment]

      VA will be assessed using Teller acuity cards (TAC). A significant improvement in VA will be defined as a decrease of >= 0.2 logMAR (corrected for age) from baseline (pre-treatment baseline) to end of about 12 months of treatment. The primary analysis will be based on per subject outcome (rather than per eye).

    Secondary Outcome Measures

    1. Radiographic tumor response rate [Assessed up to 3 years after accrual completion]

      Tumors will be classified into complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Radiologic response rates will be summarized per arm and be tested for a difference between the two arms using an exact binomial test.

    2. Overall survival (OS) [From randomization until death from any cause or till the time of last follow-up for patients who are alive at the time of analysis, assessed up to 3 years after accrual completion]

      OS is defined as the time from randomization until death from any cause or till the time of last follow-up for patients who are alive at the time of analysis. Hazard ratio will be reported, along with a 90% confidence interval.

    3. Change in VA using HOTV letter acuity testing [Baseline and end of about 12 months of treatment]

      HOTV is a recognition acuity measure. It will be conducted on patients who are developmentally able to perform this testing.

    4. Change in motor function [Baseline and approximately 12 months of treatment]

      The Vineland-3 Motor Scale from the Comprehensive Parent Rating Form will be used to assess motor deficits. Change in Vineland motor scale from baseline to about 12 months of treatment will be compared between two treatment arms.

    5. Change in quality of life (QOL) [Baseline and 12 months of treatment]

      Will be measured by Pain and Hurt subscale score. QOL will be assessed by Pediatric Quality of Life (PedsQL) Generic and Brain Tumor modules. Analysis will be based on a 2-sample t-test comparing change in Pain and Hurt subscale score from baseline to 12 months for the two arms.

    6. Change in quality of life (QOL) [Baseline and 12 months of treatment]

      Will be measured by Movement and Balance subscale score. QOL will be assessed by Pediatric Quality of Life (PedsQL) Generic and Brain Tumor modules. Analysis will be based on a 2-sample t-test comparing change in Movement and Balance subscale score from baseline to 12 months for the two arms.

    7. Change in executive function [Baseline and 24 months of treatment]

      Will be measured by BRIEF Cognitive Regulation Index (CRI). Executive function will be measured by age-appropriate Behavior Rating Inventory of Executive Function (BRIEF) questionnaire. Analysis will be based on a 2-sample t-test comparing change in the designated score from baseline to 24 months for the two arms.

    8. Change in neurocognitive function [Baseline and 24 months of treatment]

      Will be measured by Cogstate composite score. Neurocognitive function will be measured by a computerized battery (Cogstate) testing. Analysis will be based on a 2-sample t-test comparing change in Cogstate composite score from baseline to 24 months for the two arms.

    Other Outcome Measures

    1. Change in circumpapillary retinal nerve fiber layer (cpRNFL) thickness by treatment arm [Baseline and 12 months]

      cpRNFL thickness is a measure of optical coherence tomography (OCT). This assessment will be conducted in a subgroup of consenting patients with optic pathway gliomas (OPGs) treated at select COG institutions with the expertise to utilize this technology. Analysis will be conducted on a per-eye basis.

    2. cpRNFL thickness at baseline by visual acuity (VA) treatment response [Baseline and 12 months]

      Data will be analyzed on a per-eye basis. Children with OPGs will be classified into decline in VA versus (vs.) stable/improved VA, depending on VA treatment response at 12 months. cpRNFL thickness prior to treatment initiation will be compared.

    3. cpRNFL thickness change over time by visual acuity (VA) treatment response [Baseline and 12 months]

      Data will be analyzed on a per-eye basis. Children with OPGs will be classified into decline in VA vs. stable/improved VA, depending on VA treatment response at 12 months. cpRNFL thickness change over time will be compared.

    4. Change in macular ganglion cell - inner plexiform layer (GCIPL) thickness by treatment arm [Baseline and 12 months]

      GCIPL thickness is another measure of optical coherence tomography (OCT). This assessment will be conducted in a subgroup of consenting patients with optic pathway gliomas (OPGs) treated at select COG institutions with the expertise to utilize this technology. Analysis will be conducted on a per-eye basis.

    5. GCIPL thickness at baseline by visual acuity (VA) treatment response [Baseline and 12 months]

      Data will be analyzed on a per-eye basis. Children with OPGs will be classified into decline in VA vs. stable/improved VA, depending on VA treatment response at 12 months. GCIPL thickness prior to treatment initiation will be compared.

    6. GCIPL thickness change over time by visual acuity (VA) treatment response [Baseline and 12 months]

      Data will be analyzed on a per-eye basis. Children with OPGs will be classified into decline in VA vs. stable/improved VA, depending on VA treatment response at 12 months. GCIPL thickness change over time will be compared.

    7. Novel semi-automated volumetric magnetic resonance imaging (MRI) measure at 3 months [3 months on study]

      Optic pathway tumors will be classified into progressive disease (PD), stable disease (SD), partial response (PR), and complete response (CR) using novel semi-automated volumetric MRI measurements. This assessment will include patients with OPGs consenting to volumetric MRI study.

    8. Percent change in tumor size between volumetric measure and traditional 2-dimentional (2-D) measure at 3 months [3 months on study]

      This assessment includes participants with OPGs consenting to volumetric MRI study.

    9. Novel semi-automated volumetric MRI measure at 6 months [6 months on study]

      Optic pathway tumors will be classified into progressive disease (PD), stable disease (SD), partial response (PR), and complete response (CR) using novel semi-automated volumetric MRI measurements. This assessment will include patients with OPGs consenting to volumetric MRI study.

    10. Percent change in tumor size between volumetric measure and traditional 2-dimentional (2-D) measure at 6 months [6 months on study]

      This assessment includes participants with OPGs consenting to volumetric MRI study.

    11. Novel semi-automated volumetric MRI measure at 9 months [9 months on study]

      Optic pathway tumors will be classified into progressive disease (PD), stable disease (SD), partial response (PR), and complete response (CR) using novel semi-automated volumetric MRI measurements. This assessment will include patients with OPGs consenting to volumetric MRI study.

    12. Percent change in tumor size between volumetric measure and traditional 2-dimentional (2-D) measure at 9 months [9 months on study]

      This assessment includes participants with OPGs consenting to volumetric MRI study.

    13. Novel semi-automated volumetric MRI measure at 12 months [12 months on study]

      Optic pathway tumors will be classified into progressive disease (PD), stable disease (SD), partial response (PR), and complete response (CR) using novel semi-automated volumetric MRI measurements. This assessment will include patients with OPGs consenting to volumetric MRI study.

    14. Percent change in tumor size between volumetric measure and traditional 2-dimentional (2-D) measure at 12 months [12 months on study]

      This assessment includes participants with OPGs consenting to volumetric MRI study.

    15. Novel semi-automated volumetric MRI measure at 15 months [15 months on study]

      Optic pathway tumors will be classified into progressive disease (PD), stable disease (SD), partial response (PR), and complete response (CR) using novel semi-automated volumetric MRI measurements. This assessment will include patients with OPGs consenting to volumetric MRI study.

    16. Percent change in tumor size between volumetric measure and traditional 2-dimentional (2-D) measure at 15 months [15 months on study]

      This assessment includes participants with OPGs consenting to volumetric MRI study.

    17. Tumor and blood banking [Up to 10 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    2 Years to 21 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • 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 7 days prior to enrollment

    • Corrected QT (QTc) interval =< 450 msec by electrocardiography (EKG) within 7 days 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Children's Hospital of Alabama Birmingham Alabama United States 35233
    2 Banner Children's at Desert Mesa Arizona United States 85202
    3 Phoenix Childrens Hospital Phoenix Arizona United States 85016
    4 Arkansas Children's Hospital Little Rock Arkansas United States 72202-3591
    5 Loma Linda University Medical Center Loma Linda California United States 92354
    6 Children's Hospital Los Angeles Los Angeles California United States 90027
    7 Kaiser Permanente-Oakland Oakland California United States 94611
    8 Lucile Packard Children's Hospital Stanford University Palo Alto California United States 94304
    9 Rady Children's Hospital - San Diego San Diego California United States 92123
    10 Naval Medical Center -San Diego San Diego California United States 92134
    11 UCSF Medical Center-Mission Bay San Francisco California United States 94158
    12 Children's Hospital Colorado Aurora Colorado United States 80045
    13 Connecticut Children's Medical Center Hartford Connecticut United States 06106
    14 Alfred I duPont Hospital for Children Wilmington Delaware United States 19803
    15 Children's National Medical Center Washington District of Columbia United States 20010
    16 University of Florida Health Science Center - Gainesville Gainesville Florida United States 32610
    17 Memorial Regional Hospital/Joe DiMaggio Children's Hospital Hollywood Florida United States 33021
    18 Nemours Children's Clinic-Jacksonville Jacksonville Florida United States 32207
    19 Nicklaus Children's Hospital Miami Florida United States 33155
    20 AdventHealth Orlando Orlando Florida United States 32803
    21 Arnold Palmer Hospital for Children Orlando Florida United States 32806
    22 Nemours Children's Hospital Orlando Florida United States 32827
    23 Sacred Heart Hospital Pensacola Florida United States 32504
    24 Johns Hopkins All Children's Hospital Saint Petersburg Florida United States 33701
    25 Children's Healthcare of Atlanta - Egleston Atlanta Georgia United States 30322
    26 Kapiolani Medical Center for Women and Children Honolulu Hawaii United States 96826
    27 Saint Luke's Cancer Institute - Boise Boise Idaho United States 83712
    28 Lurie Children's Hospital-Chicago Chicago Illinois United States 60611
    29 University of Chicago Comprehensive Cancer Center Chicago Illinois United States 60637
    30 Southern Illinois University School of Medicine Springfield Illinois United States 62702
    31 Riley Hospital for Children Indianapolis Indiana United States 46202
    32 Saint Vincent Hospital and Health Care Center Indianapolis Indiana United States 46260
    33 Blank Children's Hospital Des Moines Iowa United States 50309
    34 University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa United States 52242
    35 University of Kentucky/Markey Cancer Center Lexington Kentucky United States 40536
    36 Norton Children's Hospital Louisville Kentucky United States 40202
    37 Children's Hospital New Orleans New Orleans Louisiana United States 70118
    38 Ochsner Medical Center Jefferson New Orleans Louisiana United States 70121
    39 Eastern Maine Medical Center Bangor Maine United States 04401
    40 Maine Children's Cancer Program Scarborough Maine United States 04074
    41 Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland United States 21287
    42 Walter Reed National Military Medical Center Bethesda Maryland United States 20889-5600
    43 Massachusetts General Hospital Cancer Center Boston Massachusetts United States 02114
    44 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    45 C S Mott Children's Hospital Ann Arbor Michigan United States 48109
    46 Wayne State University/Karmanos Cancer Institute Detroit Michigan United States 48201
    47 Helen DeVos Children's Hospital at Spectrum Health Grand Rapids Michigan United States 49503
    48 Beaumont Children's Hospital-Royal Oak Royal Oak Michigan United States 48073
    49 Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis Minnesota United States 55404
    50 University of Minnesota/Masonic Cancer Center Minneapolis Minnesota United States 55455
    51 Mayo Clinic in Rochester Rochester Minnesota United States 55905
    52 University of Mississippi Medical Center Jackson Mississippi United States 39216
    53 Columbia Regional Columbia Missouri United States 65201
    54 Children's Mercy Hospitals and Clinics Kansas City Missouri United States 64108
    55 Cardinal Glennon Children's Medical Center Saint Louis Missouri United States 63104
    56 Washington University School of Medicine Saint Louis Missouri United States 63110
    57 Children's Hospital and Medical Center of Omaha Omaha Nebraska United States 68114
    58 University of Nebraska Medical Center Omaha Nebraska United States 68198
    59 Dartmouth Hitchcock Medical Center Lebanon New Hampshire United States 03756
    60 Morristown Medical Center Morristown New Jersey United States 07960
    61 Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital New Brunswick New Jersey United States 08903
    62 University of New Mexico Cancer Center Albuquerque New Mexico United States 87102
    63 Albany Medical Center Albany New York United States 12208
    64 Roswell Park Cancer Institute Buffalo New York United States 14263
    65 The Steven and Alexandra Cohen Children's Medical Center of New York New Hyde Park New York United States 11040
    66 Laura and Isaac Perlmutter Cancer Center at NYU Langone New York New York United States 10016
    67 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    68 UNC Lineberger Comprehensive Cancer Center Chapel Hill North Carolina United States 27599
    69 Carolinas Medical Center/Levine Cancer Institute Charlotte North Carolina United States 28203
    70 Duke University Medical Center Durham North Carolina United States 27710
    71 East Carolina University Greenville North Carolina United States 27834
    72 Wake Forest University Health Sciences Winston-Salem North Carolina United States 27157
    73 Sanford Broadway Medical Center Fargo North Dakota United States 58122
    74 Children's Hospital Medical Center of Akron Akron Ohio United States 44308
    75 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
    76 Rainbow Babies and Childrens Hospital Cleveland Ohio United States 44106
    77 Nationwide Children's Hospital Columbus Ohio United States 43205
    78 Dayton Children's Hospital Dayton Ohio United States 45404
    79 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    80 Legacy Emanuel Children's Hospital Portland Oregon United States 97227
    81 Oregon Health and Science University Portland Oregon United States 97239
    82 Geisinger Medical Center Danville Pennsylvania United States 17822
    83 Penn State Children's Hospital Hershey Pennsylvania United States 17033
    84 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    85 Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania United States 15224
    86 Rhode Island Hospital Providence Rhode Island United States 02903
    87 Medical University of South Carolina Charleston South Carolina United States 29425
    88 Prisma Health Richland Hospital Columbia South Carolina United States 29203
    89 BI-LO Charities Children's Cancer Center Greenville South Carolina United States 29605
    90 East Tennessee Childrens Hospital Knoxville Tennessee United States 37916
    91 Saint Jude Children's Research Hospital Memphis Tennessee United States 38105
    92 Vanderbilt University/Ingram Cancer Center Nashville Tennessee United States 37232
    93 Dell Children's Medical Center of Central Texas Austin Texas United States 78723
    94 UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas United States 75390
    95 El Paso Children's Hospital El Paso Texas United States 79905
    96 Cook Children's Medical Center Fort Worth Texas United States 76104
    97 Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center Houston Texas United States 77030
    98 M D Anderson Cancer Center Houston Texas United States 77030
    99 Covenant Children's Hospital Lubbock Texas United States 79410
    100 UMC Cancer Center / UMC Health System Lubbock Texas United States 79415
    101 Children's Hospital of San Antonio San Antonio Texas United States 78207
    102 Methodist Children's Hospital of South Texas San Antonio Texas United States 78229
    103 University of Texas Health Science Center at San Antonio San Antonio Texas United States 78229
    104 Primary Children's Hospital Salt Lake City Utah United States 84113
    105 Children's Hospital of The King's Daughters Norfolk Virginia United States 23507
    106 Virginia Commonwealth University/Massey Cancer Center Richmond Virginia United States 23298
    107 Seattle Children's Hospital Seattle Washington United States 98105
    108 Providence Sacred Heart Medical Center and Children's Hospital Spokane Washington United States 99204
    109 Mary Bridge Children's Hospital and Health Center Tacoma Washington United States 98405
    110 Madigan Army Medical Center Tacoma Washington United States 98431
    111 University of Wisconsin Carbone Cancer Center Madison Wisconsin United States 53792
    112 Children's Hospital of Wisconsin Milwaukee Wisconsin United States 53226
    113 IWK Health Centre Halifax Nova Scotia Canada B3K 6R8
    114 The Montreal Children's Hospital of the MUHC Montreal Quebec Canada H3H 1P3
    115 Centre Hospitalier Universitaire Sainte-Justine Montreal Quebec Canada H3T 1C5
    116 HIMA San Pablo Oncologic Hospital Caguas Puerto Rico 00726

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Jason R Fangusaro, Children's Oncology Group

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT03871257
    Other Study ID Numbers:
    • NCI-2019-01396
    • NCI-2019-01396
    • ACNS1831
    • ACNS1831
    • U10CA180886
    First Posted:
    Mar 12, 2019
    Last Update Posted:
    Aug 25, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 25, 2022