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Sunitinib in Treating Young Patients With Refractory Solid Tumors

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ClinicalTrials.gov Identifier: NCT00387920
Recruitment Status : Completed
First Posted : October 13, 2006
Last Update Posted : January 28, 2014
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE October 12, 2006
First Posted Date  ICMJE October 13, 2006
Last Update Posted Date January 28, 2014
Study Start Date  ICMJE October 2006
Actual Primary Completion Date September 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 20, 2012)
  • MTD and recommended phase II dose [ Time Frame: During course 1 of therapy ]
    MTD will be the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT).
  • Adverse events as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Weekly during course 1, assessed up to 35 days ]
  • Pharmacokinetics of sunitinib malate using liquid spectrometry/mass spectroscopy methods [ Time Frame: At baseline and days 1, 7, 14, 21, and 28 of course 1 ]
  • Tolerability and pharmacokinetic profile of capsule contents sprinkled over applesauce or yogurt [ Time Frame: At baseline and days 1, 7, 14, 21, and 28 of course 1 ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00387920 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 20, 2012)
Correlative studies [ Time Frame: Days 1 and 28 of course 1 ]
The laboratory, radiology, and pathology correlative studies are largely expected to be exploratory. Mean and median values will be reported at each time point for circulating endothelial cells, monocyte count, plasma angiogenic markers, and DCE-MRI vascular permeability. Depending on the distribution of data, either the paired t-test or Wilcoxon signed rank test will be used to evaluate for statistically significant changes in these markers from pre-treatment to post-treatment.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sunitinib in Treating Young Patients With Refractory Solid Tumors
Official Title  ICMJE A Phase I Study of Sunitinib (SU11248), an Oral Multi-Targeted Tyrosine Kinase Inhibitor, in Children With Refractory Solid Tumors
Brief Summary This phase I trial is studying the side effects and best dose of sunitinib in treating young patients with refractory solid tumors. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth and by blocking blood flow to the tumor.
Detailed Description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) and recommended phase II dose of sunitinib malate in pediatric patients with refractory solid tumors.

II. Determine the toxicity of this regimen in these patients. III. Characterize the pharmacokinetics of this regimen in these patients. IV. Evaluate the tolerability and pharmacokinetic profile of sunitinib malate capsule contents sprinkled over applesauce or yogurt using the recommended phase II dose.

SECONDARY OBJECTIVES:

I. Determine, preliminarily, the antitumor effects of this regimen in these patients.

II. Describe changes in peripheral blood monocyte counts, circulating endothelial cells, and plasma angiogenic factors during treatment with sunitinib malate.

III. Explore changes in tumor vascular permeability using dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) in patients receiving sunitinib malate.

OUTLINE: This is a multicenter, dose-escalation study (part A) followed by a pediatric-friendly formulation study (part B).

PART A: Patients receive oral sunitinib malate once daily on days 1-28 days. Treatment repeats every 42 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of sunitinib malate until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PART B: Patients receive sunitinib malate capsule contents sprinkled over applesauce or yogurt once daily on days 1-28. Treatment repeats every 42 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. After the first course, patients may switch to capsule formulation for convenience.

NOTE: Patients will not receive sunitinib malate on day 2 of the first course to allow for pharmacokinetic testing.

Blood is collected on days 1, 7, 14, 21, and 28 of course 1 for pharmacokinetic studies using liquid chromatography/mass spectrometry.

After completion of study treatment, patients are followed up for 30 days.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Central Nervous System Metastases
  • Childhood Central Nervous System Choriocarcinoma
  • Childhood Central Nervous System Embryonal Tumor
  • Childhood Central Nervous System Germ Cell Tumor
  • Childhood Central Nervous System Germinoma
  • Childhood Central Nervous System Mixed Germ Cell Tumor
  • Childhood Central Nervous System Teratoma
  • Childhood Central Nervous System Yolk Sac Tumor
  • Recurrent Childhood Central Nervous System Embryonal Tumor
  • Unspecified Childhood Solid Tumor, Protocol Specific
Intervention  ICMJE
  • Drug: sunitinib malate
    Given orally
    Other Names:
    • SU11248
    • sunitinib
    • Sutent
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
  • Procedure: dynamic contrast-enhanced magnetic resonance imaging
    Undergo DCE-MRI
    Other Name: DCE-MRI
  • Other: laboratory biomarker analysis
    Correlative studies
Study Arms  ICMJE Experimental: Treatment (enzyme inhibitor therapy)

PART A: Patients receive oral sunitinib malate once daily on days 1-28 days. Treatment repeats every 42 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

PART B: Patients receive sunitinib malate capsule contents sprinkled over applesauce or yogurt once daily on days 1-28. Treatment repeats every 42 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. After the first course, patients may switch to capsule formulation for convenience.

Interventions:
  • Drug: sunitinib malate
  • Other: pharmacological study
  • Procedure: dynamic contrast-enhanced magnetic resonance imaging
  • Other: laboratory biomarker analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 27, 2014)
35
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date September 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed solid tumor (not required for patients with intrinsic brain stem tumors or optic pathway gliomas)

    • Recurrent or refractory disease
  • Measurable or evaluable disease
  • No known curative therapy or therapy proven to prolong survival with an acceptable quality of life exists
  • Patients with metastatic bone marrow disease are eligible but are not evaluable for hematologic toxicity

    • Must not be refractory to red blood cell or platelet transfusions
  • Primary CNS tumors or known CNS metastases allowed

    • Neurological deficits must have been relatively stable for ≥ 1 week before study enrollment
    • No imaging evidence of prior intracranial hemorrhage
    • No evidence of new CNS hemorrhage on baseline MRI obtained within 14 days before study enrollment (ECHO gradient MRI sequences per institutional guidelines required for evaluation of CNS hemorrhage)

      • The presence of small punctuate CNS hemorrhage on these scans will exclude a patient from participation
  • No known bone marrow metastatic disease
  • No tumors involving the pleural surface
  • Karnofsky performance status (PS) 50-100% (> 10 years of age) OR Lansky PS 50-100% (≤ 10 years of age)
  • Absolute neutrophil count ≥ 1,000/mm³*
  • Platelet count ≥ 100,000/mm³ (transfusion independent)*
  • Hemoglobin ≥ 8.0 g/dL (transfusions allowed)*
  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine based on age/gender as follows:

    • No greater than 0.8 mg/dL (2 to 5 years of age)
    • No greater than 1 mg/dL (6 to 9 years of age)
    • No greater than 1.2 mg/dL (10 to 12 years of age)
    • No greater than 1.5 mg/dL (male) OR 1.4 mg/dL (female) (13 to 15 years of age)
    • No greater than 1.7 mg/dL (male) OR 1.4 mg/dL (female) (≥ 16 years of age)
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN for liver metastases)
  • Albumin ≥ 2 g/dL
  • LVEF or shortening fraction normal
  • Corrected QT interval ≤ 450 msec
  • Amylase ≤ 1.5 times ULN
  • Lipase ≤ 1.5 times ULN
  • Body surface area ≥ 0.5 m² (≥ 0.4 m² for part B)
  • Blood pressure within ULN
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No uncontrolled infection
  • Able to swallow sunitinib malate capsules (part A only)
  • No pre-existing thyroid abnormality (hyper- or hypothyroidism) with unstable thyroid function
  • No prior CNS hemorrhage
  • No history of allergic reaction attributed to sunitinib malate or component of sunitinib malate capsules
  • No allergy to both applesauce and yogurt (part B only)
  • Recovered from prior therapy
  • No prior sunitinib malate
  • No prior anthracycline (any dose)
  • No prior radiotherapy to a radiation field that included the heart(including total body or craniospinal irradiation)
  • At least 3 months since prior stem cell transplantation or rescue (without total-body irradiation) and no evidence of graft-vs-host disease
  • At least 2 weeks since prior local, palliative, small-port radiotherapy (at least 6 months for radiation to ≥ 50% of pelvis)
  • At least 6 weeks since other prior substantial bone marrow radiotherapy
  • At least 3 weeks since prior myelosuppressive therapy (6 weeks for nitrosoureas)
  • At least 1 week since prior antineoplastic biologic agents
  • At least 1 week since prior and no concurrent hematopoietic growth factors
  • At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the following:

    • Rifampin
    • Rifabutin
    • Carbamazepine
    • Phenobarbital
    • Phenytoin
    • Hypericum perforatum (St. John's wort)
    • Efavirenz
    • Tipranavir
  • At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:

    • Azole antifungals (e.g., itraconazole or ketoconazole)
    • Clarithromycin
    • Erythromycin
    • Diltiazem
    • Verapamil
    • HIV protease inhibitors (e.g., indinavir, saquinavir, ritonavir, atazanavir, or nelfinavir)
    • Delavirdine
  • No more than 1 concurrent antihypertensive agent
  • No concurrent major surgery
  • No concurrent antithrombotic or antiplatelet agents, including any of the following:

    • Warfarin
    • Heparin
    • Low molecular weight heparin
    • Acetylsalicylic acid (aspirin)
    • Ibuprofen
    • Other nonsteroidal anti-inflammatory drugs
  • No concurrent medication for the treatment of hypertension
  • No other concurrent investigational drugs
  • No other concurrent anticancer agents, including chemotherapy, radiotherapy, immunotherapy, or biologic therapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00387920
Other Study ID Numbers  ICMJE NCI-2009-00361
NCI-2009-00361 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000507414
COG-ADVL0612
NCI-07-C-0220
ADVL0612 ( Other Identifier: COG Phase I Consortium )
ADVL0612 ( Other Identifier: CTEP )
U01CA097452 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Steven DuBois COG Phase I Consortium
PRS Account National Cancer Institute (NCI)
Verification Date January 2014

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