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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01462695




Registration number
NCT01462695
Ethics application status
Date submitted
27/10/2011
Date registered
31/10/2011
Date last updated
27/08/2015

Titles & IDs
Public title
Sunitinib Malate in Treating Younger Patients With Recurrent, Refractory, or Progressive Malignant Glioma or Ependymoma
Scientific title
A Phase II Study of Sunitinib (NSC# 736511) in Recurrent, Refractory or Progressive High Grade Glioma and Ependymoma Tumors in Pediatric and Young Adult Patients
Secondary ID [1] 0 0
NCI-2011-03536
Secondary ID [2] 0 0
NCI-2011-03536
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Childhood Cerebellar Anaplastic Astrocytoma 0 0
Childhood Cerebral Anaplastic Astrocytoma 0 0
Childhood Cerebral Astrocytoma 0 0
Childhood Infratentorial Ependymoma 0 0
Childhood Mixed Glioma 0 0
Childhood Oligodendroglioma 0 0
Childhood Supratentorial Ependymoma 0 0
Recurrent Childhood Cerebellar Astrocytoma 0 0
Recurrent Childhood Cerebral Astrocytoma 0 0
Recurrent Childhood Ependymoma 0 0
Recurrent Childhood Subependymal Giant Cell Astrocytoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Children's - Brain
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Diagnostic Laboratory Biomarker Analysis
Other interventions - Pharmacological Study
Treatment: Drugs - Sunitinib Malate

Experimental: 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.


Other interventions: Diagnostic Laboratory Biomarker Analysis
Correlative studies

Other interventions: Pharmacological Study
Correlative studies

Treatment: Drugs: Sunitinib Malate
Given PO
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Sustained Objective Response Rate
Timepoint [1] 0 0
Up to 5 years

Eligibility
Key inclusion criteria
* Patients must be diagnosed with ependymoma or high-grade glioma (World Health Organization [WHO] grade III/IV):

* 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
Minimum age
1 Year
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2014
Sample size
Target
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [4] 0 0
Royal Children's Hospital-Brisbane - Herston
Recruitment hospital [5] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
6008 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Delaware
Country [6] 0 0
United States of America
State/province [6] 0 0
District of Columbia
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Georgia
Country [9] 0 0
United States of America
State/province [9] 0 0
Illinois
Country [10] 0 0
United States of America
State/province [10] 0 0
Indiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Iowa
Country [12] 0 0
United States of America
State/province [12] 0 0
Kentucky
Country [13] 0 0
United States of America
State/province [13] 0 0
Massachusetts
Country [14] 0 0
United States of America
State/province [14] 0 0
Michigan
Country [15] 0 0
United States of America
State/province [15] 0 0
Minnesota
Country [16] 0 0
United States of America
State/province [16] 0 0
Mississippi
Country [17] 0 0
United States of America
State/province [17] 0 0
Missouri
Country [18] 0 0
United States of America
State/province [18] 0 0
New Hampshire
Country [19] 0 0
United States of America
State/province [19] 0 0
New Jersey
Country [20] 0 0
United States of America
State/province [20] 0 0
New Mexico
Country [21] 0 0
United States of America
State/province [21] 0 0
New York
Country [22] 0 0
United States of America
State/province [22] 0 0
North Carolina
Country [23] 0 0
United States of America
State/province [23] 0 0
Ohio
Country [24] 0 0
United States of America
State/province [24] 0 0
Oklahoma
Country [25] 0 0
United States of America
State/province [25] 0 0
Oregon
Country [26] 0 0
United States of America
State/province [26] 0 0
Pennsylvania
Country [27] 0 0
United States of America
State/province [27] 0 0
South Carolina
Country [28] 0 0
United States of America
State/province [28] 0 0
South Dakota
Country [29] 0 0
United States of America
State/province [29] 0 0
Tennessee
Country [30] 0 0
United States of America
State/province [30] 0 0
Texas
Country [31] 0 0
United States of America
State/province [31] 0 0
Utah
Country [32] 0 0
United States of America
State/province [32] 0 0
Virginia
Country [33] 0 0
United States of America
State/province [33] 0 0
Washington
Country [34] 0 0
United States of America
State/province [34] 0 0
Wisconsin
Country [35] 0 0
Canada
State/province [35] 0 0
Nova Scotia
Country [36] 0 0
Canada
State/province [36] 0 0
Ontario
Country [37] 0 0
Canada
State/province [37] 0 0
Quebec

Funding & Sponsors
Primary sponsor type
Government body
Name
National Cancer Institute (NCI)
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This phase II trial studies how well sunitinib malate works in treating younger patients with recurrent, refractory, or progressive malignant glioma or ependymoma. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Trial website
https://clinicaltrials.gov/study/NCT01462695
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Cynthia Wetmore
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01462695