Sorafenib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Leukemia



Status:Archived
Conditions:Cancer, Blood Cancer, Leukemia
Therapuetic Areas:Oncology
Healthy:No
Age Range:Any
Updated:7/1/2011

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A Phase I/II Study of the Raf Kinase and Receptor Tyrosine Kinase Inhibitor Sorafenib (BAY 43-9006, NSC# 724772, IND# 69896) in Children With Refractory Solid Tumors or Refractory Leukemias


RATIONALE: Sorafenib may stop the growth of cancer cells by blocking some of the enzymes
needed for cell growth and by blocking blood flow to the cancer.

PURPOSE: This phase I trial is studying the side effects and best dose of sorafenib in
treating young patients with relapsed or refractory solid tumors or leukemia.


OBJECTIVES:

Primary

- Determine the maximum-tolerated dose (MTD) and recommended phase II dose of sorafenib
in pediatric patients with relapsed or refractory solid tumors.

- Determine whether pediatric patients with relapsed or refractory leukemia can tolerate
the MTD of sorafenib for solid tumors.

- Determine the tolerability, active N-oxide metabolite, pharmacodynamics, and activity
of sorafenib a the MTD in a subset of patients with acute myeloid leukemia (AML) and
FLT3-ITD mutation.

- Determine the toxicities of this drug in these patients.

- Determine the pharmacokinetics of this drug in these patients.

Secondary

- Determine, preliminarily, the antitumor activity of this drug within the confines of a
phase I trial.

- Assess the biologic effect of sorafenib on circulating endothelial cells (CEC),
circulating CEC precursors (CECP), VEGF, and VEGF-2 in peripheral blood.

- Assess the gene expression, proteomic profile, and ERK phosphorylation in blasts of
patients with refractory leukemia treated with this regimen.

- Assess the effect of sorafenib on solid tumor vascularity and tumor blood flow using
dynamic contrast-enhanced MRI (DEMRI) in patients with measurable soft tissue tumors.

- Analyze tumor samples and leukemic blasts for the presence of ras, raf, or FLT3
(leukemias) mutations.

- Analyze the plasma inhibitory activity for FLT3 phosphorylation in peripheral blood of
patients with AML and FLT3-ITD mutation.

- Determine the tolerability, pharmacokinetics of sorafenib and sorafenib's active
N-oxide metabolite, pharmacodynamics, and activity of sorafenib administered at the MTD
for refractory leukemias in a subset of patients with AML and FLT3-ITD mutation.

- Analyze the plasma inhibitory activity for FLT3 phosphorylation in peripheral blood
samples obtained at the time of PK studies in patients with FLT3-ITD mutation AML.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to
diagnosis (malignant solid tumor vs leukemia).

- Stratum 1 (refractory solid tumor patients): Patients receive oral sorafenib twice
daily on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence
of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of sorafenib until the maximum-tolerated
dose (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 (DLT). Once the MTD is determined, up to 6
additional patients under 12 years of age may be treated at the MTD. The MTD dose level is
also expanded to enroll up to 6 patients with refractory leukemia.

- Stratum 2 (refractory leukemia patients): A cohort of 3-6 patients with leukemia
receives treatment as in stratum 1 at the MTD determined in stratum 1. If 2 of 3 or 2
of 6 patients experience a DLT at the solid tumor MTD, sorafenib is reduced by one dose
level. The leukemia MTD is defined as the dose at which < 1/3 of patients experience
DLT during course 1 of treatment.

- Stratum 3 (acute myeloid leukemia and FLT3-ITD mutation patients): Patients receive
sorafenib as in stratum 1 at the MTD determined in stratum 2.

Patients undergo blood sample collection for pharmacokinetics, pharmacodynamics (in leukemia
blasts only), circulating endothelial cells (CEC), circulating CEC precursors (CECP), VEGF
and VEGF-2 , gene expression, proteomic profile, ERK phosphorylation, and FLT3
phosphorylation activity. Tumor tissue samples may also be analyzed for the presence of ras,
raf, or FLT3.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 77 patients will be accrued for this study.


We found this trial at
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Pittsburgh, Pennsylvania 15213
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Ann Arbor, MI 48109Bus: -
Ann Arbor, Michigan 48109
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1802 6th Avenue South
Birmingham, Alabama 35294
(205) 934-4011
UAB Comprehensive Cancer Center One of the nation’s leading cancer research and treatment centers, the...
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300 Longwood Avenue
Boston, Massachusetts 02115
617-355-6000
Children's Hospital - Boston Boston Children's Hospital is a 395-bed comprehensive center for pediatric health...
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Boston, MA
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450 Brookline Ave
Boston, Massachusetts 2215
(617) 632-3000
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute Founded in 1997, Dana-Farber/Harvard Cancer Center (DF/HCC) was...
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Boston, MA
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3333 Burnet Avenue # Mlc3008
Cincinnati, Ohio 45229
 1-513-636-4200 
Cincinnati Children's Hospital Medical Center Patients and families from across the region and around the...
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Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas From its...
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425 E River Pkwy # 754
Minneapolis, Minnesota 55455
612-624-2620
Masonic Cancer Center at University of Minnesota The Masonic Cancer Center was founded in 1991....
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Palo Alto, CA
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3181 SW Sam Jackson Park Rd
Portland, Oregon 97239
(503) 494-5058
Knight Cancer Institute at Oregon Health and Science University Cancer takes many forms. Although cancer...
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4800 Sand Point Way Northeast
Seattle, Washington 98105
(206) 987-2000
Children's Hospital and Regional Medical Center - Seattle Seattle Children
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9000 Rockville Pike
Bethesda, Maryland 20892
1-800-422-6237
National Cancer Institute (NCI) The National Cancer Institute (NCI) is part of the National Institutes...
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Brooklyn, New York 11203
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1 Baylor Plaza
Houston, Texas 77030
(713) 798-4951
Baylor School of Medicine Baylor College of Medicine is a health sciences university that creates...
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Indianapolis, Indiana 46202
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722 W 168th St
New York, New York 10032
(212) 305-2500
Columbia Presbyterian Med Ctr On January 1, 1998, The New York Hospital publicly announced its...
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660 S Euclid Ave
St. Louis, Missouri 63110
(800) 600-3606
Siteman Cancer Center The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University...
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