Children's Hospital of Alabama |
Birmingham, Alabama, United States, 35233 |
Contact: Site Public Contact 205-638-9285 oncologyresearch@peds.uab.edu |
Principal Investigator: Matthew A. Kutny |
Phoenix Childrens Hospital |
Phoenix, Arizona, United States, 85016 |
Contact: Site Public Contact 602-546-0920 |
Principal Investigator: Lindsey M. Hoffman |
Arkansas Children's Hospital |
Little Rock, Arkansas, United States, 72202-3591 |
Contact: Site Public Contact 501-364-7373 |
Principal Investigator: David L. Becton |
Kaiser Permanente Downey Medical Center |
Downey, California, United States, 90242 |
Contact: Site Public Contact 626-564-3455 |
Principal Investigator: Hung N. Tran |
Loma Linda University Medical Center |
Loma Linda, California, United States, 92354 |
Contact: Site Public Contact 909-558-4050 |
Principal Investigator: Albert Kheradpour |
Miller Children's and Women's Hospital Long Beach |
Long Beach, California, United States, 90806 |
Contact: Site Public Contact 562-933-5600 |
Principal Investigator: Jacqueline N. Casillas |
Children's Hospital Los Angeles |
Los Angeles, California, United States, 90027 |
Contact: Site Public Contact 323-361-4110 |
Principal Investigator: Nathan J. Robison |
Cedars Sinai Medical Center |
Los Angeles, California, United States, 90048 |
Contact: Site Public Contact 310-423-8965 |
Principal Investigator: Fataneh (Fae) Majlessipour |
Kaiser Permanente-Oakland |
Oakland, California, United States, 94611 |
Contact: Site Public Contact 877-642-4691 Kpoct@kp.org |
Principal Investigator: Laura A. Campbell |
Lucile Packard Children's Hospital Stanford University |
Palo Alto, California, United States, 94304 |
Contact: Site Public Contact 800-694-0012 ccto-office@stanford.edu |
Principal Investigator: Jay Michael S. Balagtas |
University of California Davis Comprehensive Cancer Center |
Sacramento, California, United States, 95817 |
Contact: Site Public Contact 916-734-3089 |
Principal Investigator: Marcio H. Malogolowkin |
UCSF Medical Center-Mission Bay |
San Francisco, California, United States, 94158 |
Contact: Site Public Contact 877-827-3222 |
Principal Investigator: Alyssa T. Reddy |
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center |
Torrance, California, United States, 90502 |
Contact: Site Public Contact 310-222-3624 irb@lundquist.org |
Principal Investigator: Eduard H. Panosyan |
Children's Hospital Colorado |
Aurora, Colorado, United States, 80045 |
Contact: Site Public Contact 303-764-5056 josh.b.gordon@nsmtp.kp.org |
Principal Investigator: Kathleen M. Dorris |
Connecticut Children's Medical Center |
Hartford, Connecticut, United States, 06106 |
Contact: Site Public Contact 860-545-9981 |
Principal Investigator: Michael S. Isakoff |
Yale University |
New Haven, Connecticut, United States, 06520 |
Contact: Site Public Contact 203-785-5702 canceranswers@yale.edu |
Principal Investigator: Nina S. Kadan-Lottick |
Alfred I duPont Hospital for Children |
Wilmington, Delaware, United States, 19803 |
Contact: Site Public Contact 302-651-6884 dperry@nemours.org |
Principal Investigator: Scott M. Bradfield |
MedStar Georgetown University Hospital |
Washington, District of Columbia, United States, 20007 |
Contact: Site Public Contact 202-444-2223 |
Principal Investigator: Jeffrey A. Toretsky |
Golisano Children's Hospital of Southwest Florida |
Fort Myers, Florida, United States, 33908 |
Contact: Site Public Contact 239-343-5333 molly.arnstrom@leehealth.org |
Principal Investigator: Emad K. Salman |
University of Florida Health Science Center - Gainesville |
Gainesville, Florida, United States, 32610 |
Contact: Site Public Contact 352-273-8010 cancer-center@ufl.edu |
Principal Investigator: William B. Slayton |
Memorial Regional Hospital/Joe DiMaggio Children's Hospital |
Hollywood, Florida, United States, 33021 |
Contact: Site Public Contact 954-265-1847 OHR@mhs.net |
Principal Investigator: Iftikhar Hanif |
Nemours Children's Clinic-Jacksonville |
Jacksonville, Florida, United States, 32207 |
Contact: Site Public Contact 904-697-3529 |
Principal Investigator: Scott M. Bradfield |
University of Miami Miller School of Medicine-Sylvester Cancer Center |
Miami, Florida, United States, 33136 |
Contact: Site Public Contact 305-243-2647 |
Principal Investigator: Julio C. Barredo |
Nicklaus Children's Hospital |
Miami, Florida, United States, 33155 |
Contact: Site Public Contact 888-624-2778 |
Principal Investigator: Enrique A. Escalon |
AdventHealth Orlando |
Orlando, Florida, United States, 32803 |
Contact: Site Public Contact 407-303-2090 FH.Cancer.Research@flhosp.org |
Principal Investigator: Fouad M. Hajjar |
Arnold Palmer Hospital for Children |
Orlando, Florida, United States, 32806 |
Contact: Site Public Contact 321-841-2008 melissa.leffin@orlandohealth.com |
Principal Investigator: Amy A. Smith |
Nemours Children's Hospital |
Orlando, Florida, United States, 32827 |
Contact: Site Public Contact 407-650-7715 |
Principal Investigator: Scott M. Bradfield |
Johns Hopkins All Children's Hospital |
Saint Petersburg, Florida, United States, 33701 |
Contact: Site Public Contact 727-767-4784 Ashley.Repp@jhmi.edu |
Principal Investigator: Stacie L. Stapleton |
Tampa General Hospital |
Tampa, Florida, United States, 33606 |
Contact: Site Public Contact 813-844-7829 syapchanyk@tgh.org |
Principal Investigator: Juan F. Rico |
Saint Joseph's Hospital/Children's Hospital-Tampa |
Tampa, Florida, United States, 33607 |
Contact: Site Public Contact 813-357-0849 jennifer.manns@baycare.org |
Principal Investigator: Don E. Eslin |
Saint Mary's Hospital |
West Palm Beach, Florida, United States, 33407 |
Contact: Site Public Contact 561-881-2815 |
Principal Investigator: Narayana Gowda |
Children's Healthcare of Atlanta - Egleston |
Atlanta, Georgia, United States, 30322 |
Contact: Site Public Contact 404-785-2025 Leann.Schilling@choa.org |
Principal Investigator: Tobey J. MacDonald |
Memorial Health University Medical Center |
Savannah, Georgia, United States, 31404 |
Contact: Site Public Contact 912-350-7887 Lorraine.OHara@hcahealthcare.com |
Principal Investigator: Andrew L. Pendleton |
Kapiolani Medical Center for Women and Children |
Honolulu, Hawaii, United States, 96826 |
Contact: Site Public Contact 808-983-6090 |
Principal Investigator: Wade T. Kyono |
Saint Luke's Cancer Institute - Boise |
Boise, Idaho, United States, 83712 |
Contact: Site Public Contact 208-381-2774 eslinget@slhs.org |
Principal Investigator: Eugenia Chang |
Lurie Children's Hospital-Chicago |
Chicago, Illinois, United States, 60611 |
Contact: Site Public Contact 773-880-4562 |
Principal Investigator: Angela J. Waanders |
University of Illinois |
Chicago, Illinois, United States, 60612 |
Contact: Site Public Contact 312-355-3046 |
Principal Investigator: Mary L. Schmidt |
University of Chicago Comprehensive Cancer Center |
Chicago, Illinois, United States, 60637 |
Contact: Site Public Contact 773-702-8222 cancerclinicaltrials@bsd.uchicago.edu |
Principal Investigator: Wendy S. Darlington |
Saint Jude Midwest Affiliate |
Peoria, Illinois, United States, 61637 |
Contact: Site Public Contact 888-226-4343 |
Principal Investigator: Jaime M. Libes |
Riley Hospital for Children |
Indianapolis, Indiana, United States, 46202 |
Contact: Site Public Contact 800-248-1199 |
Principal Investigator: Sandeep Batra |
Saint Vincent Hospital and Health Care Center |
Indianapolis, Indiana, United States, 46260 |
Contact: Site Public Contact 317-338-2194 research@stvincent.org |
Principal Investigator: Jessica F. Goodman |
University of Iowa/Holden Comprehensive Cancer Center |
Iowa City, Iowa, United States, 52242 |
Contact: Site Public Contact 800-237-1225 |
Principal Investigator: Mariko Sato |
University of Kentucky/Markey Cancer Center |
Lexington, Kentucky, United States, 40536 |
Contact: Site Public Contact 859-257-3379 |
Principal Investigator: James T. Badgett |
Norton Children's Hospital |
Louisville, Kentucky, United States, 40202 |
Contact: Site Public Contact 502-629-5500 CancerResource@nortonhealthcare.org |
Principal Investigator: Ashok B. Raj |
Children's Hospital New Orleans |
New Orleans, Louisiana, United States, 70118 |
Contact: Site Public Contact CHResearch@lcmchealth.org |
Principal Investigator: Lolie C. Yu |
Ochsner Medical Center Jefferson |
New Orleans, Louisiana, United States, 70121 |
Contact: Site Public Contact 504-703-8712 Gregory.Johnstone@ochsner.org |
Principal Investigator: Craig Lotterman |
Eastern Maine Medical Center |
Bangor, Maine, United States, 04401 |
Contact: Site Public Contact 207-973-4274 |
Principal Investigator: Nadine P. SantaCruz |
Johns Hopkins University/Sidney Kimmel Cancer Center |
Baltimore, Maryland, United States, 21287 |
Contact: Site Public Contact 410-955-8804 jhcccro@jhmi.edu |
Principal Investigator: Kenneth J. Cohen |
Walter Reed National Military Medical Center |
Bethesda, Maryland, United States, 20889-5600 |
Contact: Site Public Contact 301-319-2100 |
Principal Investigator: Kenneth Lieuw |
Massachusetts General Hospital Cancer Center |
Boston, Massachusetts, United States, 02114 |
Contact: Site Public Contact 877-726-5130 |
Principal Investigator: David H. Ebb |
Dana-Farber Cancer Institute |
Boston, Massachusetts, United States, 02215 |
Contact: Site Public Contact 877-442-3324 |
Principal Investigator: Susan N. Chi |
C S Mott Children's Hospital |
Ann Arbor, Michigan, United States, 48109 |
Contact: Site Public Contact 800-865-1125 |
Principal Investigator: Carl J. Koschmann |
Helen DeVos Children's Hospital at Spectrum Health |
Grand Rapids, Michigan, United States, 49503 |
Contact: Site Public Contact 616-391-1230 crcwm-regulatory@crcwm.org |
Principal Investigator: Kathleen J. Yost |
Bronson Methodist Hospital |
Kalamazoo, Michigan, United States, 49007 |
April 17, 2019
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April 18, 2019
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June 7, 2021
|
October 2, 2019
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June 1, 2022 (Final data collection date for primary outcome measure)
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Event-free survival (EFS) for stratum 1 [ Time Frame: From the date of diagnosis until disease progression date, secondary malignant neoplasm occurrence date, death date of any cause, or last follow-up, assessed up to 5 years ] The EFS curve for the new treatment cohort (Stratum 1) will be estimated by Kaplan Meier estimates. A 2-sample, 1 sided log-rank test will be used to test whether the EFS distribution is better in new treatment compared with historical control. Calculation of the EFS will be based on the site determination as central review will be performed retrospectively.
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Event-free survival (EFS) [ Time Frame: From the date of diagnosis until disease progression date, secondary malignant neoplasm occurrence date, death date of any cause, or last follow-up, assessed up to 5 years ] The EFS curve for the new treatment cohort (Stratum 1) will be estimated by Kaplan Meier estimates. A 2-sample, 1 sided log-rank test will be used to test whether the EFS distribution is better in new treatment compared with historical control. Calculation of the EFS will be based on the site determination as central review will be performed retrospectively.
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- Overall survival (OS) for stratum 1, stratum 2, and stratum 3 [ Time Frame: From the date of diagnosis until death date of any cause or last follow up date, assessed up to 5 years ]
The OS curve for the new treatment cohort (stratum 1) will be estimated by Kaplan Meier estimates. A 2-sample, 1 sided log-rank test will be used to test whether the OS distribution is better in new treatment compared with historical control. For stratum 2 and stratum 3, Kaplan Meier estimates will be provided for OS distribution.
- Event-free survival (EFS) for stratum 2 and stratum 3 [ Time Frame: Follow up date, assessed up to 5 years ]
For stratum 2 and stratum 3, Kaplan Meier estimates will be provided for EFS distribution .
- Incidence of adverse events [ Time Frame: Up to 5 years ]
Graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Grade 3 and higher toxicities observed by cycle will be listed for each stratum separately. The grade 3 and higher toxicities observed by cycle and by system organ class for the eligible patients will also be listed for each stratum separately. Toxicity data will be reported separately for the radiation therapy phase versus the maintenance therapy phase for clarity of attribution. Toxicity monitoring will include toxicities such as grade 2 or higher pyrexia, uveitis, retinal vein occlusion, retinal pigment epithelial detachment, and decreased left ventricular ejection fraction.
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- Overall survival (OS) [ Time Frame: From the date of diagnosis until death date of any cause or last follow up date, assessed up to 5 years ]
The OS curve for the new treatment cohort (Stratum 1) will be estimated by Kaplan Meier estimates. A 2-sample, 1 sided log-rank test will be used to test whether the OS distribution is better in new treatment compared with historical control.
- Incidence of adverse events [ Time Frame: Up to 5 years ]
Graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Grade 3 and higher toxicities observed by cycle will be listed for each stratum separately. The grade 3 and higher toxicities observed by cycle and by system organ class for the eligible patients will also be listed for each stratum separately. Toxicity data will be reported separately for the radiation therapy phase versus the maintenance therapy phase for clarity of attribution. Toxicity monitoring will include toxicities such as grade 2 or higher pyrexia, uveitis, retinal vein occlusion, retinal pigment epithelial detachment, and decreased left ventricular ejection fraction.
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Not Provided
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Not Provided
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Dabrafenib Combined With Trametinib After Radiation Therapy in Treating Patients With Newly-Diagnosed High-Grade Glioma
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A Phase 2 Study of Dabrafenib (NSC# 763760) With Trametinib (NSC# 763093) After Local Irradiation in Newly-Diagnosed BRAF V600-Mutant High-Grade Glioma (HGG)
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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.
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PRIMARY OBJECTIVE:
I. To estimate the event-free survival (EFS) distribution for newly-diagnosed patients with BRAFV600-mutant high-grade glioma (HGG) without H3 K27M mutations excluding anaplastic pleomorphic xanthoastrocytoma (aPXA) and anaplastic ganglioglioma (aGG) treated with radiation therapy followed by a maintenance combination of dabrafenib mesylate (dabrafenib) and trametinib dimethyl sulfoxide (trametinib) and to compare this EFS to contemporary historical controls.
SECONDARY OBJECTIVES:
I. To describe the overall survival (OS) distribution for newly-diagnosed patients with BRAFV600-mutant HGG without H3 K27M mutations excluding aPXA and aGG treated with radiation therapy followed by a maintenance combination of dabrafenib and trametinib.
II. To describe the EFS and overall survival (OS) distribution for newly-diagnosed patients with BRAFV600E-mutant aPXA and aGG without H3 K27M mutations treated with radiation therapy followed by a maintenance combination of dabrafenib and trametinib.
III. To describe the EFS and overall survival (OS) distribution for newly-diagnosed patients with BRAFV600E-mutant HGG including aPXA and aGG with H3 K27M mutations treated with radiation therapy followed by a maintenance combination of dabrafenib and trametinib.
IV. To define and evaluate the toxicities of combination therapy with dabrafenib and trametinib after radiation therapy in newly-diagnosed patients with HGG.
EXPLORATORY OBJECTIVE:
I. To bank tumor specimens and body fluids (blood, urine and cerebrospinal fluid) for future studies.
OUTLINE:
Patients undergo standardized local radiation therapy (RT) 5 days a week (Monday-Friday) for 6-7 weeks. Four weeks after completion of RT, patients receive dabrafenib mesylate orally (PO) twice daily (BID) and trametinib dimethyl sulfoxide PO once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at disease relapse, every 3 months for year 1, every 4 months for year 2, every 6 months for year 3, then annually for years 4-5.
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Interventional
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Phase 2
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Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment
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- Anaplastic Astrocytoma
- Anaplastic Ganglioglioma
- Anaplastic Pleomorphic Xanthoastrocytoma
- Glioblastoma
- Malignant Glioma
- WHO Grade III Glioma
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- Drug: Dabrafenib Mesylate
Given PO
Other Names:
- Dabrafenib Methanesulfonate
- GSK2118436 Methane Sulfonate Salt
- GSK2118436B
- Tafinlar
- Radiation: Radiation Therapy
Undergo RT
Other Names:
- Cancer Radiotherapy
- ENERGY_TYPE
- Irradiate
- Irradiated
- Irradiation
- Radiation
- Radiation Therapy, NOS
- Radiotherapeutics
- Radiotherapy
- RT
- Therapy, Radiation
- Drug: Trametinib Dimethyl Sulfoxide
Given PO
Other Name: Mekinist
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Experimental: Treatment (radiation therapy, dabrafenib, trametinib)
Patients undergo standardized local RT 5 days a week (Monday-Friday) for 6-7 weeks. Four weeks after completion of RT, patients receive dabrafenib mesylate PO BID and trametinib dimethyl sulfoxide PO QD on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
Interventions:
- Drug: Dabrafenib Mesylate
- Radiation: Radiation Therapy
- Drug: Trametinib Dimethyl Sulfoxide
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Not Provided
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Recruiting
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58
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Same as current
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June 1, 2022
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June 1, 2022 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
- PRE-ENROLLMENT ELIGIBILITY SCREENING (STEP 0): Patient is suspected of having localized newly-diagnosed HGG, excluding metastatic disease
- PRE-ENROLLMENT ELIGIBILITY SCREENING (STEP 0): Patient and/or their parents or legal guardians have signed informed consent for eligibility screening on APEC14B1 Part A.
- PRE-ENROLLMENT ELIGIBILITY SCREENING (STEP 0): Specimens obtained at the time of diagnostic biopsy must be submitted through APEC14B1 as soon as possible (ASAP), preferably within 13 calendar days of the procedure.
- Patients must be >= 3 years and =< 21 years of age at the time of enrollment
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Patients must have eligibility confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1
- Newly diagnosed high-grade glioma with BRAFV600-mutation
- Positive or negative results for H3 K27M by immunohistochemistry (IHC)
- 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. Cerebrospinal fluid (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 magnetic resonance imaging (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
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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.
- 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.
- 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:
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Sexes Eligible for Study: |
All |
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3 Years to 25 Years (Child, Adult)
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No
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Puerto Rico, United States
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|
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NCT03919071
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NCI-2019-02289 NCI-2019-02289 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) ACNS1723 ( Other Identifier: Children's Oncology Group ) ACNS1723 ( Other Identifier: CTEP ) U10CA180886 ( U.S. NIH Grant/Contract )
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Plan to Share IPD: |
Yes |
Plan Description: |
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page. |
URL: |
https://grants.nih.gov/policy/sharing.htm |
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National Cancer Institute (NCI)
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National Cancer Institute (NCI)
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Not Provided
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Principal Investigator: |
Rishi R Lulla |
Children's Oncology Group |
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National Cancer Institute (NCI)
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January 2021
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