Sunitinib Malate in Treating Younger Patients With Recurrent, Refractory, or Progressive Malignant Glioma or Ependymoma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01462695
• Collaborator: (none)
• Enrollment: 30
• Locations: 96
• Arm: 1
• Duration (Months): 26
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Childhood Cerebellar Anaplastic Astrocytoma; Childhood Cerebral Anaplastic Astrocytoma; Childhood Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma	Other: Diagnostic Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Sunitinib Malate	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. 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.

2. To describe the pharmacokinetic profile of pediatric and young adult patients taking sunitinib malate.

3. To describe the cumulative toxicities of sunitinib when administered over multiple courses to pediatric and young adult patients.

4. To estimate progression-free survival (PFS) distributions for these cohorts of patients.

5. 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.

6. 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.

7. To evaluate and report descriptively the expression and ratio of VEGF isoforms in tumor tissue, as available.

8. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official 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
• Study Start Date: Jan 1, 2012
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
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: Diagnostic Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Drug: Sunitinib Malate; Given PO; Other Names: SU011248 SU11248 sunitinib Sutent

Outcome Measures

Primary Outcome Measures

1. Sustained Objective Response Rate [Up to 5 years]

   Sustained objective response was defined as a PR (Partial Response: ≥ 50% decrease in the sum of the products of the 2 perpendicular diameters of all target lesions (up to 5), taking as reference the initial baseline measurements) or CR (Complete Response: disappearance of all target lesions) lasting at least 8 weeks.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Alabama	Birmingham	Alabama	United States	35233
2	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
3	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	Southern California Permanente Medical Group	Downey	California	United States	90242
5	Miller Children's and Women's Hospital Long Beach	Long Beach	California	United States	90806
6	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
7	Children's Hospital Central California	Madera	California	United States	93636-8762
8	Children's Hospital of Orange County	Orange	California	United States	92868
9	Lucile Packard Children's Hospital Stanford University	Palo Alto	California	United States	94304
10	Rady Children's Hospital - San Diego	San Diego	California	United States	92123
11	UCSF Medical Center-Parnassus	San Francisco	California	United States	94143
12	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
13	Alfred I duPont Hospital for Children	Wilmington	Delaware	United States	19803
14	Children's National Medical Center	Washington	District of Columbia	United States	20010
15	Lee Memorial Health System	Fort Myers	Florida	United States	33901
16	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida	United States	33908
17	Nemours Children's Clinic-Jacksonville	Jacksonville	Florida	United States	32207
18	Florida Hospital Orlando	Orlando	Florida	United States	32803
19	Nemours Children's Clinic - Orlando	Orlando	Florida	United States	32806
20	Nemours Children's Clinic - Pensacola	Pensacola	Florida	United States	32504
21	All Children's Hospital	Saint Petersburg	Florida	United States	33701
22	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida	United States	33607
23	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia	United States	30322
24	Memorial University Medical Center	Savannah	Georgia	United States	31404
25	Lurie Children's Hospital-Chicago	Chicago	Illinois	United States	60611
26	University of Illinois	Chicago	Illinois	United States	60612
27	Saint Jude Midwest Affiliate	Peoria	Illinois	United States	61637
28	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
29	Saint Vincent Hospital and Health Services	Indianapolis	Indiana	United States	46260
30	Blank Children's Hospital	Des Moines	Iowa	United States	50309
31	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
32	Kosair Children's Hospital	Louisville	Kentucky	United States	40202
33	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
34	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
35	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota	United States	55404
36	University of Minnesota Medical Center-Fairview	Minneapolis	Minnesota	United States	55455
37	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
38	The Childrens Mercy Hospital	Kansas City	Missouri	United States	64108
39	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
40	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
41	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
42	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
43	Morristown Medical Center	Morristown	New Jersey	United States	07960
44	Overlook Hospital	Summit	New Jersey	United States	07902
45	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87106
46	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467-2490
47	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
48	Laura and Issac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
49	Columbia University Medical Center	New York	New York	United States	10032
50	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
51	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
52	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
53	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
54	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
55	Children's Hospital Medical Center of Akron	Akron	Ohio	United States	44308
56	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
57	Rainbow Babies and Childrens Hospital	Cleveland	Ohio	United States	44106
58	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
59	Dayton Children's Hospital	Dayton	Ohio	United States	45404
60	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio	United States	43606
61	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
62	Oregon Health and Science University	Portland	Oregon	United States	97239
63	Penn State Hershey Children's Hospital	Hershey	Pennsylvania	United States	17033
64	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
65	Children's Oncology Group	Philadelphia	Pennsylvania	United States	19104
66	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
67	BI-LO Charities Children's Cancer Center	Greenville	South Carolina	United States	29605
68	Greenville Cancer Treatment Center	Greenville	South Carolina	United States	29605
69	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
70	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
71	Dell Children's Medical Center of Central Texas	Austin	Texas	United States	78723
72	Driscoll Children's Hospital	Corpus Christi	Texas	United States	78411
73	Medical City Dallas Hospital	Dallas	Texas	United States	75230
74	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
75	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
76	Baylor College of Medicine	Houston	Texas	United States	77030
77	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
78	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
79	Naval Medical Center - Portsmouth	Portsmouth	Virginia	United States	23708-2197
80	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
81	Seattle Children's Hospital	Seattle	Washington	United States	98105
82	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington	United States	99204
83	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington	United States	98405
84	Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301
85	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
86	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226
87	Sydney Children's Hospital	Randwick	New South Wales	Australia	2031
88	The Children's Hospital at Westmead	Westmead	New South Wales	Australia	2145
89	Royal Brisbane and Women's Hospital	Herston	Queensland	Australia	4029
90	Royal Children's Hospital-Brisbane	Herston	Queensland	Australia	4029
91	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6008
92	IWK Health Centre	Halifax	Nova Scotia	Canada	B3K 6R8
93	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8N 3Z5
94	The Montreal Children's Hospital of the MUHC	Montreal	Quebec	Canada	H3H 1P3
95	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec	Canada	H3T 1C5
96	Centre Hospitalier Universitaire de Quebec	Quebec		Canada	G1V 4G2

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Cynthia Wetmore, Children's Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01462695
• Other Study ID Numbers: NCI-2011-03536; NCI-2011-03536; CDR0000712861; COG-ACNS1021; ACNS1021; ACNS1021; U10CA098543
• First Posted: Oct 31, 2011
• Last Update Posted: Aug 27, 2015
• Last Verified: Jun 1, 2015

• Additional relevant MeSH terms: Glioma; Astrocytoma; Ependymoma; Oligodendroglioma; Recurrence; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Stratum A: Recurrent High Grade Glioma	Stratum B: Recurrent Ependymoma
Arm/Group Description	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. sunitinib malate: Given PO diagnostic laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies	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. sunitinib malate: Given PO diagnostic laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies
Period Title: Overall Study
STARTED	17	13
COMPLETED	0	0
NOT COMPLETED	17	13

Baseline Characteristics

Arm/Group Title	Stratum A: Recurrent High Grade Glioma	Stratum B: Recurrent Ependymoma	Total
Arm/Group Description	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. sunitinib malate: Given PO diagnostic laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies	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. sunitinib malate: Given PO diagnostic laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies	Total of all reporting groups
Overall Participants	17	13	30
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	14.2	12.0	13.4
Age (Count of Participants)
<=18 years	16 94.1%	13 100%	29 96.7%
Between 18 and 65 years	1 5.9%	0 0%	1 3.3%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	4 23.5%	7 53.8%	11 36.7%
Male	13 76.5%	6 46.2%	19 63.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 17.6%	0 0%	3 10%
White	14 82.4%	11 84.6%	25 83.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	2 15.4%	2 6.7%
Region of Enrollment (participants) [Number]
United States	16 94.1%	11 84.6%	27 90%
Canada	1 5.9%	0 0%	1 3.3%
Australia	0 0%	1 7.7%	1 3.3%
Saudi Arabia	0 0%	1 7.7%	1 3.3%

Outcome Measures

1. Primary Outcome

Title	Sustained Objective Response Rate
Description	Sustained objective response was defined as a PR (Partial Response: ≥ 50% decrease in the sum of the products of the 2 perpendicular diameters of all target lesions (up to 5), taking as reference the initial baseline measurements) or CR (Complete Response: disappearance of all target lesions) lasting at least 8 weeks.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

One patient in Stratum A was excluded because the patient did not receive study drug and therefore was not evaluable for response.

Arm/Group Title	Stratum A: Recurrent High Grade Glioma	Stratum B: Recurrent Ependymoma
Arm/Group Description	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. sunitinib malate: Given PO diagnostic laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies	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. sunitinib malate: Given PO diagnostic laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies
Measure Participants	16	13
Number (95% Confidence Interval) [percentage of patients]	0	0

Adverse Events

Adverse Event Reporting Description	One stratum A patient did not receive any study drug and was excluded from the summary of adverse events. SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs) or grade 5 adverse events resulting in death. The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Arm/Group Title	Stratum A: Recurrent High Grade Glioma		Stratum B: Recurrent Ependymoma
Arm/Group Description	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. sunitinib malate: Given PO diagnostic laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies		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.
All Cause Mortality
	Stratum A: Recurrent High Grade Glioma		Stratum B: Recurrent Ependymoma
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Stratum A: Recurrent High Grade Glioma		Stratum B: Recurrent Ependymoma
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/16 (87.5%)		9/13 (69.2%)
General disorders
Death NOS	6/16 (37.5%)		4/13 (30.8%)
Gait disturbance	0/16 (0%)		1/13 (7.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	7/16 (43.8%)		5/13 (38.5%)
Nervous system disorders
Dysarthria	0/16 (0%)		1/13 (7.7%)
Facial nerve disorder	0/16 (0%)		1/13 (7.7%)
Headache	1/16 (6.3%)		0/13 (0%)
Hydrocephalus	2/16 (12.5%)		1/13 (7.7%)
Intracranial hemorrhage	2/16 (12.5%)		1/13 (7.7%)
Paresthesia	0/16 (0%)		1/13 (7.7%)
Peripheral motor neuropathy	0/16 (0%)		1/13 (7.7%)
Seizure	3/16 (18.8%)		0/13 (0%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/16 (6.3%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Stratum A: Recurrent High Grade Glioma		Stratum B: Recurrent Ependymoma
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/16 (50%)		6/13 (46.2%)
Gastrointestinal disorders
Diarrhea	0/16 (0%)		1/13 (7.7%)
Nausea	1/16 (6.3%)		0/13 (0%)
Vomiting	1/16 (6.3%)		0/13 (0%)
General disorders
Fatigue	1/16 (6.3%)		0/13 (0%)
Investigations
Alanine aminotransferase increased	1/16 (6.3%)		0/13 (0%)
Aspartate aminotransferase increased	1/16 (6.3%)		0/13 (0%)
Lipase increased	1/16 (6.3%)		0/13 (0%)
Lymphocyte count decreased	0/16 (0%)		1/13 (7.7%)
Neutrophil count decreased	2/16 (12.5%)		5/13 (38.5%)
Serum amylase increased	1/16 (6.3%)		0/13 (0%)
White blood cell decreased	0/16 (0%)		1/13 (7.7%)
Musculoskeletal and connective tissue disorders
Muscle weakness left-sided	1/16 (6.3%)		0/13 (0%)
Muscle weakness lower limb	1/16 (6.3%)		0/13 (0%)
Muscle weakness right-sided	1/16 (6.3%)		0/13 (0%)
Nervous system disorders
Paresthesia	0/16 (0%)		1/13 (7.7%)
Peripheral motor neuropathy	0/16 (0%)		1/13 (7.7%)
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other	1/16 (6.3%)		0/13 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.