Sunitinib Malate in Treating Younger Patients With Recurrent, Refractory, or Progressive Malignant Glioma or Ependymoma
NCT ID: NCT01462695
Last Updated: 2015-08-27
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2
30 participants
INTERVENTIONAL
2012-01-31
2014-03-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Sorafenib in Treating Patients With Recurrent or Progressive Malignant Glioma
NCT00093613
Cilengitide in Treating Younger Patients With Recurrent or Progressive High-Grade Glioma That Has Not Responded to Standard Therapy
NCT00679354
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
NCT01089101
Leflunomide in Treating Patients With Anaplastic Astrocytoma in First Relapse
NCT00003775
Fenretinide in Treating Patients With Recurrent Malignant Glioma
NCT00006080
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
I. To estimate the objective response rate (partial response \[PR\] or complete response \[CR\] ≥ 8 weeks) to sunitinib in 2 strata (recurrent/progressive/refractory high-grade glioma vs ependymoma) of recurrent or progressive brain tumors in pediatric and young adult patients.
SECONDARY OBJECTIVES:
I. To explore and report descriptively the safety and tolerability of sunitinib in pediatric and young adult brain tumor patients who have not received prior anthracycline or radiotherapy involving the heart.
II. To describe the pharmacokinetic profile of pediatric and young adult patients taking sunitinib malate.
III. To describe the cumulative toxicities of sunitinib when administered over multiple courses to pediatric and young adult patients.
IV. To estimate progression-free survival (PFS) distributions for these cohorts of patients.
V. To evaluate changes in phosphorylation of PDGFR-α and -β, MEK/ERK, S6 kinase, and AKT in peripheral blood mononuclear cells and explore possible associations between these changes and outcome measures.
VI. To evaluate plasma levels of soluble isoforms of VEGFR-1 and -2 prior to initiation of therapy and at points during therapy as an exploration of possible biomarkers of clinical response.
VII. To evaluate and report descriptively the expression and ratio of VEGF isoforms in tumor tissue, as available.
VIII. To evaluate and report descriptively the genotype, expression, and possible amplification of KIT and PDGFR-α and -β in tumor tissue, as available.
OUTLINE: This is a multicenter study.
Patients receive sunitinib malate orally (PO) once daily (QD) on days 1-28. Treatment repeats every 42 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
Patients may undergo blood sample collection at baseline and during courses 1 and 2 for pharmacokinetic and pharmacodynamic studies. Tissue samples from diagnosis and surgical resection may be also collected.
After completion of study treatment, patients are followed up for up to 5 years.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Treatment (sunitinib)
Patients receive sunitinib malate orally (PO) once daily (QD) on days 1-28. Treatment repeats every 42 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
Diagnostic Laboratory Biomarker Analysis
Correlative studies
Pharmacological Study
Correlative studies
Sunitinib Malate
Given PO
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Diagnostic Laboratory Biomarker Analysis
Correlative studies
Pharmacological Study
Correlative studies
Sunitinib Malate
Given PO
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Stratum A: recurrent/progressive/refractory malignant glioma (i.e., anaplastic astrocytoma, glioblastoma multiforme \[including giant cell and gliosarcoma types\], anaplastic oligodendroglioma, anaplastic oligoastrocytoma, or anaplastic ganglioglioma) within the brain with or without spinal cord disease
* Stratum B: recurrent/progressive/refractory ependymoma (including ependymoma variants) within the brain with or without spinal cord disease
* Patients with diffuse intrinsic pontine glioma are not eligible
* A histological diagnosis from either the initial presentation or at the time of recurrence is required
* Patients must have radiographically documented measurable disease in the brain, defined as at least one lesion that can be accurately measured in at least 2 planes
* To document the degree of residual tumor, the following must be obtained:
* All patients must have a brain MRI with and without gadolinium and a spine magnetic resonance imaging (MRI), if clinically indicated,with and without gadolinium, performed within 2 weeks prior to study enrollment
* Patients with evidence of new central nervous system (CNS) hemorrhage of more than punctate size and/or more than 3 foci of punctate hemorrhage on baseline MRI obtained within 14 days prior to study enrollment are not eligible
* Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1, or 2 (use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age)
* Neurological deficits in patients must have been relatively stable for a minimum of 1 week prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* Peripheral absolute neutrophil count (ANC) ≥ 1,000/μL
* Platelet count ≥ 75,000/μL (transfusion independent, defined as not receiving platelet transfusions within the 7-day period prior to enrollment)
* Hemoglobin ≥ 8.0 g/dL (may receive red blood cell \[RBC\] transfusions)
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min OR serum creatinine based on age/gender as follows:
* 0.4 mg/dL (1 month to \< 6 months of age)
* 0.5 mg/dL (6 months to \< 1 year of age)
* 0.6 mg/dL (1 to \< 2 years of age)
* 0.8 mg/dL (2 to \< 6 years of age)
* 1.0 mg/dL (6 to \< 10 years of age)
* 1.2 mg/dL (10 to \< 13 years of age)
* 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to \< 16 years of age)
* 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)
* Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
* Serum glutamic oxaloacetic transaminase (SGOT/AST) and serum glutamic pyruvic transaminase (SGPT/ALT) ≤ 2.5 times ULN
* Shortening fraction of ≥ 27% by echocardiogram OR ejection fraction of ≥ 50% by radionuclide angiogram
* Corrected QT interval \< 450 msec (males) or \< 470 msec (females)
* Prothrombin time (PT) / international normalized ratio (INR) ≤ 1.5 times ULN
* Partial thromboplastin time (PTT) ≤ 1.5 times ULN
* Patients must not have a history of cardiac disease including, but not limited to:
* Uncontrolled hypertension within 12 months prior to enrollment; uncontrolled hypertension is defined as follows:
* Patients aged ≤ 17 years: greater than 95th percentile systolic and diastolic blood pressure based on age and height which is not controlled by one anti-hypertensive medication
* Patients aged \> 17 years: systolic blood pressure ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg which is not controlled by one anti-hypertensive medication
* Ongoing cardiac dysrhythmias ≥ grade 2 or atrial fibrillation of any grade
* Unstable angina, symptomatic congestive heart failure, or myocardial infarction
* Patients with a seizure disorder may be enrolled if on non-enzyme-inducing anticonvulsants and well controlled
* Commonly used non-enzyme-inducing anticonvulsants include: gabapentin, lamotrigine, levetiracetam, tiagabine, topiramate, valproic acid, and zonisamide
* Patients must not have had a cerebrovascular accident or transient is chemic attack within 12 months prior to enrollment
* Patients must not have had a pulmonary embolism or other significant thromboembolic event within 12 months prior to enrollment
* Patients must not have had grade ≥ 3 hemorrhage within 4 weeks prior to enrollment
* Patients must not have had any of the following diagnoses within 6 months prior to enrollment: peptic ulcer disease, inflammatory bowel disease, or diverticulitis
* Patients with a diagnosis of abdomen fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months prior to enrollment are not eligible
* Patients who have an uncontrolled infection are not eligible
* Patients with hypothyroidism that has not been well-controlled by medications for at least 2 weeks prior to study entry are not eligible
* Patients who have a personal history of genetic and/or congenital cardiac abnormalities are not eligible
* Patients who have a history of allergic reactions to compounds of similar chemical or biological composition to sunitinib are not eligible
* Patients who have any other condition that could result in an inability to swallow capsules/sprinkles or absorb oral sunitinib administered through a gastric tube are not eligible
* Patients with body surface area \< 0.55 m\^2 or \> 2.18 m\^2 are not eligible
* Female patients who are pregnant are not eligible
* Lactating females are not eligible unless they have agreed not to breastfeed their infants
* Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained within the past 4 weeks
* Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
* No concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs), clopidogrel, warfarin, heparin, low molecular weight heparin, dipyridamole, or aspirin therapy \> 81 mg/day
* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy (RT) prior to entering this study
* Must not have received myelosuppressive chemotherapy within 3 weeks of entry onto this study (6 weeks if prior nitrosourea)
* At least 7 days since the completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody
* At least 24 weeks must have elapsed if prior full-field RT
* ≥ 2 weeks must have elapsed if prior local palliative RT (small port) or limited-field RT
* ≥ 3 months must have elapsed since prior stem cell transplant (SCT) or rescue with total-body irradiation (TBI)
* No evidence of active graft-vs-host disease
* Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 7 days prior to enrollment
* Patients must not have received potent cytochrome P450-3A4 (CY3A4) inhibitors and/or inducers within 7 days prior to study enrollment and potent inducers within 12 days prior to study enrollment and during study
* At least 7 days must have elapsed since the completion of therapy with a hematopoietic growth factor
* Patients who have previously received sunitinib or who have received other VEGF-, PDGFR-, or KIT-targeted therapy are not eligible
* Patients who received bevacizumab as part of their prior therapy may enroll on study
* Patients must not have received more than 2 prior chemotherapy and/or RT regimens; for example, 1 initial treatment course of chemotherapy and/or RT (counts as 1 treatment course) and at relapse may have received 1 treatment course of chemotherapy and/or RT (counts as 1 treatment course)
* Patients who received prior therapy with known risk for cardiovascular complications (e.g., anthracycline therapy or prior RT that included the heart and/or craniospinal radiation) are not eligible
* Patients receiving ongoing treatment with therapeutic doses (i.e., therapeutic INR levels) of coumarin derivatives or oral anti-vitamin K agents are not eligible
* Patients receiving antiretroviral therapy for human immunodeficiency virus (HIV) disease are not eligible
* Patients who are started on protocol therapy on a phase II study prior to study enrollment are considered ineligible
* No other concurrent chemotherapy, investigational agents, or immunomodulating agents
* No concurrent RT
1 Year
21 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Cynthia Wetmore
Role: PRINCIPAL_INVESTIGATOR
Children's Oncology Group
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Children's Hospital of Alabama
Birmingham, Alabama, United States
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Southern California Permanente Medical Group
Downey, California, United States
Miller Children's and Women's Hospital Long Beach
Long Beach, California, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Children's Hospital Central California
Madera, California, United States
Children's Hospital of Orange County
Orange, California, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States
Rady Children's Hospital - San Diego
San Diego, California, United States
UCSF Medical Center-Parnassus
San Francisco, California, United States
Connecticut Children's Medical Center
Hartford, Connecticut, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Lee Memorial Health System
Fort Myers, Florida, United States
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, United States
Florida Hospital Orlando
Orlando, Florida, United States
Nemours Children's Clinic - Orlando
Orlando, Florida, United States
Nemours Children's Clinic - Pensacola
Pensacola, Florida, United States
All Children's Hospital
St. Petersburg, Florida, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States
Memorial University Medical Center
Savannah, Georgia, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
University of Illinois
Chicago, Illinois, United States
Saint Jude Midwest Affiliate
Peoria, Illinois, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
Saint Vincent Hospital and Health Services
Indianapolis, Indiana, United States
Blank Children's Hospital
Des Moines, Iowa, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
Kosair Children's Hospital
Louisville, Kentucky, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
The Childrens Mercy Hospital
Kansas City, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Mercy Hospital Saint Louis
St Louis, Missouri, United States
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Morristown Medical Center
Morristown, New Jersey, United States
Overlook Hospital
Summit, New Jersey, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Laura and Issac Perlmutter Cancer Center at NYU Langone
New York, New York, United States
Columbia University Medical Center
New York, New York, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
State University of New York Upstate Medical University
Syracuse, New York, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Children's Hospital Medical Center of Akron
Akron, Ohio, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Dayton Children's Hospital
Dayton, Ohio, United States
The Toledo Hospital/Toledo Children's Hospital
Toledo, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Oregon Health and Science University
Portland, Oregon, United States
Penn State Hershey Children's Hospital
Hershey, Pennsylvania, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Children's Oncology Group
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, United States
Greenville Cancer Treatment Center
Greenville, South Carolina, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
Dell Children's Medical Center of Central Texas
Austin, Texas, United States
Driscoll Children's Hospital
Corpus Christi, Texas, United States
Medical City Dallas Hospital
Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States
Cook Children's Medical Center
Fort Worth, Texas, United States
Baylor College of Medicine
Houston, Texas, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States
Primary Children's Hospital
Salt Lake City, Utah, United States
Naval Medical Center - Portsmouth
Portsmouth, Virginia, United States
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, United States
Seattle Children's Hospital
Seattle, Washington, United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, United States
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, United States
Saint Vincent Hospital
Green Bay, Wisconsin, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States
Sydney Children's Hospital
Randwick, New South Wales, Australia
The Children's Hospital at Westmead
Westmead, New South Wales, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia
Royal Children's Hospital-Brisbane
Herston, Queensland, Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia
IWK Health Centre
Halifax, Nova Scotia, Canada
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, Canada
Centre Hospitalier Universitaire de Quebec
Québec, Quebec, Canada
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Wang E, DuBois SG, Wetmore C, Verschuur AC, Khosravan R. Population Pharmacokinetics of Sunitinib and its Active Metabolite SU012662 in Pediatric Patients with Gastrointestinal Stromal Tumors or Other Solid Tumors. Eur J Drug Metab Pharmacokinet. 2021 May;46(3):343-352. doi: 10.1007/s13318-021-00671-7. Epub 2021 Apr 14.
Wang E, DuBois SG, Wetmore C, Khosravan R. Population pharmacokinetics-pharmacodynamics of sunitinib in pediatric patients with solid tumors. Cancer Chemother Pharmacol. 2020 Aug;86(2):181-192. doi: 10.1007/s00280-020-04106-z. Epub 2020 Jul 4.
Wetmore C, Daryani VM, Billups CA, Boyett JM, Leary S, Tanos R, Goldsmith KC, Stewart CF, Blaney SM, Gajjar A. Phase II evaluation of sunitinib in the treatment of recurrent or refractory high-grade glioma or ependymoma in children: a children's Oncology Group Study ACNS1021. Cancer Med. 2016 Jul;5(7):1416-24. doi: 10.1002/cam4.713. Epub 2016 Apr 25.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2011-03536
Identifier Type: REGISTRY
Identifier Source: secondary_id
CDR0000712861
Identifier Type: -
Identifier Source: secondary_id
COG-ACNS1021
Identifier Type: -
Identifier Source: secondary_id
ACNS1021
Identifier Type: OTHER
Identifier Source: secondary_id
ACNS1021
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2011-03536
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.