Last updated on August 2011

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


Brief description of study

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.

Detailed Study Description

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.

Clinical Study Identifier: NCT00343694

Contact Investigators or Research Sites near you

Start Over

Clinical Trials Office - UAB ...

UAB Comprehensive Cancer Center
Birmingham, AL United States
  Connect »

Violet Shen

Children's Hospital of Orange County
Orange, CA United States
  Connect »

Neyssa M. Marina

Lucile Packard Children's Hospital at Stanford University Medical Center
Palo Alto, CA United States
  Connect »

Clinical Trials Office - Children's ...

Children's National Medical Center
Washington, WA United States
  Connect »

Stewart Goldman

Children's Memorial Hospital - Chicago
Chicago, IL United States
  Connect »

Clinical Trials Office - Indiana ...

Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, IN United States
  Connect »

Clinical Trials Office - Warren ...

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, MD United States
  Connect »

Suzanne Shusterman

Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
Boston, MA United States
  Connect »

Clinical Trials Office - C.S. ...

C.S. Mott Children's Hospital at University of Michigan Medical Center
Ann Arbor, MI United States
  Connect »

Clinical Trials Office - Masonic ...

Masonic Cancer Center at University of Minnesota
Minneapolis, MN United States
  Connect »

Robert J. Hayashi

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
St. Louis, MO United States
  Connect »

Clinical Trials Office - Herbert ...

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York, NY United States
  Connect »

Clinical Trials Office - SUNY ...

SUNY Upstate Medical University Hospital
Syracuse, NY United States
  Connect »

Clinical Trials Office - Cincinnati ...

Cincinnati Children's Hospital Medical Center
Cincinnati, OH United States
  Connect »

Clinical Trials Office - Knight ...

Knight Cancer Institute at Oregon Health and Science University
Portland, OR United States
  Connect »

Elizabeth Fox

Children's Hospital of Philadelphia
Philadelphia, PA United States
  Connect »

Clinical Trials Office - Children's ...

Children's Hospital of Pittsburgh of UPMC
Pittsburgh, PA United States
  Connect »

Clinical Trials Office - St. ...

St. Jude Children's Research Hospital
Memphis, TN United States
  Connect »

Clinical Trials Office - Simmons ...

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, TX United States
  Connect »

Patrick A. Thompson

Baylor University Medical Center - Houston
Houston, TX United States
  Connect »

Julie R. Park

Children's Hospital and Regional Medical Center - Seattle
Seattle, WA United States
  Connect »

Sylvain Baruchel

Hospital for Sick Children
Toronto, ON Canada
  Connect »

Yvan Samson

Hopital Sainte Justine
Montreal, QC Canada
  Connect »