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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01462695
First received: October 27, 2011
Last updated: June 9, 2014
Last verified: June 2014

October 27, 2011
June 9, 2014
February 2012
December 2013   (final data collection date for primary outcome measure)
Sustained objective response rate, defined as a PR or CR lasting ≥ 8 weeks [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Response rate, defined as a PR or CR lasting ≥ 8 weeks [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01462695 on ClinicalTrials.gov Archive Site
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Sunitinib Malate in Treating Younger Patients With Recurrent, Refractory, or Progressive Malignant Glioma or Ependymoma
A Phase II Study of Sunitinib (NSC# 736511, IND# 74019) in Recurrent, Refractory or Progressive High Grade Glioma and Ependymoma Tumors in Pediatric and Young Adult Patients

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.

PRIMARY OBJECTIVES:

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.

EXPLORATORY OBJECTIVES I. To describe the pharmacokinetic profile of pediatric and young adult patients taking sunitinib malate.

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

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

IV. 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.

V. 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.

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

VII. 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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Childhood Cerebral Astrocytoma/Malignant Glioma
  • Childhood High-grade Cerebellar Astrocytoma
  • Childhood High-grade 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
  • Drug: sunitinib malate
    Given PO
    Other Names:
    • SU11248
    • sunitinib
    • Sutent
  • Other: diagnostic laboratory biomarker analysis
    Correlative studies
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
Experimental: Arm I
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.
Interventions:
  • Drug: sunitinib malate
  • Other: diagnostic laboratory biomarker analysis
  • Other: pharmacological study
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
30
Not Provided
December 2013   (final data collection date for primary outcome measure)

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 MRI, if clinically indicated,with and without gadolinium, performed within 2 weeks prior to study enrollment
    • Patients with evidence of new 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
  • 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 platelettransfusions within the 7-day period prior to enrollment)
  • Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)
  • Creatinine clearance or radioisotope 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)
  • SGOT (AST) and 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)
  • PT/INR ≤ 1.5 times ULN
  • 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: pepticulcer 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 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., anthracyclinetherapy 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 derivativesor oral anti-vitamin K agents are not eligible
  • Patients receiving antiretroviral therapy for 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
Both
1 Year to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada
 
NCT01462695
NCI-2011-03536, NCI-2011-03536, CDR0000712861, COG-ACNS1021, ACNS1021, ACNS1021, U10CA098543
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Cynthia Wetmore Children's Oncology Group
National Cancer Institute (NCI)
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP