Sunitinib in Treating Young Patients With Refractory Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00387920
First received: October 12, 2006
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
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
Drug: sunitinib malate
Other: pharmacological study
Procedure: dynamic contrast-enhanced magnetic resonance imaging
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Sunitinib (SU11248), an Oral Multi-Targeted Tyrosine Kinase Inhibitor, in Children With Refractory Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD and recommended phase II dose [ Time Frame: During course 1 of therapy ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Correlative studies [ Time Frame: Days 1 and 28 of course 1 ] [ Designated as safety issue: No ]
    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.


Enrollment: 35
Study Start Date: October 2006
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

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.

  Eligibility

Ages Eligible for Study:   2 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00387920

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Childrens Hospital of Orange County
Orange, California, United States, 92868-3874
University of California San Francisco Medical Center-Parnassus
San Francisco, California, United States, 94143
UCSF-Mount Zion
San Francisco, California, United States, 94115
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
C S Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, Canada, H3T 1C5
Sponsors and Collaborators
Investigators
Principal Investigator: Steven DuBois COG Phase I Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00387920     History of Changes
Other Study ID Numbers: NCI-2009-00361, NCI-2009-00361, CDR0000507414, COG-ADVL0612, NCI-07-C-0220, ADVL0612, ADVL0612, U01CA097452
Study First Received: October 12, 2006
Last Updated: January 27, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Choriocarcinoma
Endodermal Sinus Tumor
Neoplasms
Neoplasms, Germ Cell and Embryonal
Adenocarcinoma
Carcinoma
Gestational Trophoblastic Disease
Mesonephroma
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Pregnancy Complications
Pregnancy Complications, Neoplastic
Trophoblastic Neoplasms
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014