Phase 2 Trial of Sorafenib in Children and Young Adults With Refractory Solid Tumors: A Report From the Children's Oncology Group

Pediatr Blood Cancer. 2015 Sep;62(9):1562-6. doi: 10.1002/pbc.25548. Epub 2015 Apr 27.


Background: Sorafenib is an oral small molecule inhibitor of multiple kinases controlling tumor growth and angiogenesis. The purpose of the phase 2 study was to determine the response rate of sorafenib and gain further information on the associated toxicities, pharmacokinetics, and pharmacodynamics of sorafenib in children and young adults with relapsed or refractory tumors including rhabdomyosarcoma, Wilms tumor, hepatocellular carcinoma (HCC), and papillary thyroid carcinoma (PTC).

Procedure: Sorafenib, 200 mg/m(2) /dose, was administered every 12 hr continuously for 28 day cycles using a two-stage design in two primary strata (rhabdomyosarcoma and Wilms tumor) and two secondary strata (HCC and PTC). Correlative studies in consenting patients included determination of sorafenib steady state trough concentrations and assessments of VEGF and sVEGFR2.

Results: Twenty patients (median age of 11 years; range, 5-21) enrolled. No objective responses (RECIST) were observed in the 10 evaluable patients enrolled in each of the two primary disease strata of rhabdomyosarcoma and Wilms tumor. No patients with HCC or PTC were enrolled. Sorafenib was not associated with an excessive rate of dose-limiting toxicity (DLT). The mean ± SD steady state concentration during cycle 1 day 15 was 6.5 ± 3.9 μg/ml (n = 10).

Conclusions: Sorafenib was well tolerated in children at 200 mg/m(2) /dose twice daily on a continuous regimen with toxicity profile and steady state drug concentrations similar to those previously reported. Single agent sorafenib was inactive in children with recurrent or refractory rhabdomyosarcoma or Wilms tumor.

Keywords: pediatrics; solid tumors; sorafenib.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / pharmacokinetics
  • Angiogenesis Inhibitors / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Kidney Neoplasms / blood
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / enzymology
  • Male
  • Neoplasm Proteins / blood
  • Niacinamide / adverse effects
  • Niacinamide / analogs & derivatives*
  • Niacinamide / pharmacokinetics
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / adverse effects
  • Phenylurea Compounds / pharmacokinetics
  • Phenylurea Compounds / therapeutic use*
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / therapeutic use*
  • Rhabdomyosarcoma / blood
  • Rhabdomyosarcoma / drug therapy*
  • Rhabdomyosarcoma / enzymology
  • Salvage Therapy*
  • Sorafenib
  • Treatment Failure
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor Receptor-2 / blood
  • Wilms Tumor / blood
  • Wilms Tumor / drug therapy*
  • Wilms Tumor / enzymology
  • Young Adult


  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Neoplasm Proteins
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Niacinamide
  • Sorafenib
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2