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Central Nervous System MetastasesPhase 1NCT00387920

Sunitinib in Treating Young Patients With Refractory Solid Tumors

A Phase 1 study testing sunitinib malate, pharmacological study and dynamic contrast-enhanced magnetic resonance imaging in people with Central Nervous System Metastases and Childhood Central Nervous System Choriocarcinoma, run by National Cancer Institute (NCI) at 17 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 2 to 21 years
What is being tested?
sunitinib malate, pharmacological study and dynamic contrast-enhanced magnetic resonance imaging
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
17 sitesin 2 countries
Study dates
Oct 2006to Sep 2012
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
Show all 79Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

17 sites in 2 countries.

17 sites in 2 countries

United States15 sites

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Columbia University Medical Center

    New York, New York, 10032

  • Childrens Hospital of Orange County

    Orange, California, 92868-3874

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • UCSF-Mount Zion

    San Francisco, California, 94115

  • University of California San Francisco Medical Center-Parnassus

    San Francisco, California, 94143

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

Canada2 sites

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

Other trials in Canada

About this study

Official title: A Phase I Study of Sunitinib (SU11248), an Oral Multi-Targeted Tyrosine Kinase Inhibitor, in Children With Refractory Solid Tumors

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
sunitinib malate, pharmacological study, dynamic contrast-enhanced magnetic resonance imaging, laboratory biomarker analysis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • sunitinib malateDrug

    Also called SU11248, sunitinib, Sutent

    Given orally

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • dynamic contrast-enhanced magnetic resonance imagingProcedure or surgery

    Also called DCE-MRI

    Undergo DCE-MRI

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00387920
Study groupRoleWhat they receive
Treatment (enzyme inhibitor therapy)ExperimentalPART 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.
Receives: Drug: sunitinib malate; Other: pharmacological study; Procedure: dynamic contrast-enhanced magnetic resonance imaging; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. MTD and recommended phase II dose

    MTD will be the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT).

    Measured: During course 1 of therapy

  2. Adverse events as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Measured: Weekly during course 1, assessed up to 35 days

  3. Pharmacokinetics of sunitinib malate using liquid spectrometry/mass spectroscopy methods

    Measured: At baseline and days 1, 7, 14, 21, and 28 of course 1

  4. Tolerability and pharmacokinetic profile of capsule contents sprinkled over applesauce or yogurt

    Measured: At baseline and days 1, 7, 14, 21, and 28 of course 1

Secondary outcomes (1)

  1. Correlative studies

    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.

    Measured: Days 1 and 28 of course 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Oct 2006 (estimated)
  2. Study startOct 2006
  3. Primary completionSep 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00387920
Sponsor's protocol ID
NCI-2009-00361
Other IDs
NCI-2009-00361, CDR0000507414, COG-ADVL0612, NCI-07-C-0220, ADVL0612, ADVL0612, U01CA097452
Status last verified
Jan 2014
First submitted
12 Oct 2006
Last updated
28 Jan 2014
Results posted
No

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.

    PubMed 33852135

  • 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.

    PubMed 32623479

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing sunitinib malate, pharmacological study and dynamic contrast-enhanced magnetic resonance imaging in people with Central Nervous System Metastases and Childhood Central Nervous System Choriocarcinoma, run by National Cancer Institute (NCI) at 17 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 79 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MTD and recommended phase II dose (time frame: During course 1 of therapy). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00387920, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2014.

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