- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00387920
Sunitinib in Treating Young Patients With Refractory Solid Tumors
A Phase I Study of Sunitinib (SU11248), an Oral Multi-Targeted Tyrosine Kinase Inhibitor, in Children With Refractory Solid Tumors
Study Overview
Status
Conditions
- Unspecified Childhood Solid Tumor, Protocol Specific
- Central Nervous System Metastases
- Childhood Central Nervous System Germ Cell Tumor
- Childhood Central Nervous System Choriocarcinoma
- 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
- Childhood Central Nervous System Embryonal 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
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Ontario
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Toronto, Ontario, Canada, M5G 1X8
- Hospital for Sick Children
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Quebec
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Montreal, Quebec, Canada, H3T 1C5
- Centre Hospitalier Universitaire Sainte-Justine
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Alabama
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Birmingham, Alabama, United States, 35294
- University of Alabama At Birmingham
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California
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Orange, California, United States, 92868-3874
- Childrens Hospital of Orange County
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San Francisco, California, United States, 94143
- University of California San Francisco Medical Center-Parnassus
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San Francisco, California, United States, 94115
- UCSF-Mount Zion
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District of Columbia
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Washington, District of Columbia, United States, 20010
- Children's National Medical Center
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Dana-Farber Cancer Institute
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Michigan
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Ann Arbor, Michigan, United States, 48109
- C S Mott Children's Hospital
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
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New York
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New York, New York, United States, 10032
- Columbia University Medical Center
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Ohio
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Cincinnati, Ohio, United States, 45229
- Cincinnati Children's Hospital Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, United States, 15224
- Children's Hospital of Pittsburgh of UPMC
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Texas
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Dallas, Texas, United States, 75390
- University of Texas Southwestern Medical Center
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Houston, Texas, United States, 77030
- Baylor College of Medicine
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Washington
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Seattle, Washington, United States, 98105
- Seattle Children's Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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. |
Correlative studies
Correlative studies
Other Names:
Undergo DCE-MRI
Other Names:
Given orally
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
MTD and recommended phase II dose
Time Frame: During course 1 of therapy
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MTD will be the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT).
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During course 1 of therapy
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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
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Weekly during course 1, assessed up to 35 days
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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
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At baseline and days 1, 7, 14, 21, and 28 of course 1
|
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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
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At baseline and days 1, 7, 14, 21, and 28 of course 1
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Correlative studies
Time Frame: Days 1 and 28 of course 1
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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.
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Days 1 and 28 of course 1
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Steven DuBois, COG Phase I Consortium
Publications and helpful links
General 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Pregnancy Complications
- Pregnancy Complications, Neoplastic
- Trophoblastic Neoplasms
- Mesonephroma
- Neoplasms
- Neoplasms, Germ Cell and Embryonal
- Teratoma
- Choriocarcinoma
- Endodermal Sinus Tumor
- Germinoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Protein Kinase Inhibitors
- Sunitinib
Other Study ID Numbers
- NCI-2009-00361 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- U01CA097452 (U.S. NIH Grant/Contract)
- CDR0000507414
- COG-ADVL0612
- NCI-07-C-0220
- ADVL0612 (Other Identifier: CTEP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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