Pediatric Cancers
A Phase II Study of the Raf Kinase and Receptor Tyrosine Kinase Inhibitor Sorafenib (IND# 69896) in Children and Young Adults With Relapsed/Refractory Rhabdomyosarcoma, Wilms Tumor, Hepatocellular Carcinoma, and Papillary Thyroid Carcinoma
NCI-12-C-0098, NCT01502410
Print this page 
Investigator(s): |
Brigitte Widemann, M.D.
Principal Investigator
Phone: 301-496-7387
widemanb@mail.nih.gov
|
|
|
|
Pediatric Oncology
Phone: 301-496-4256
1-877-624-4878 (Toll free)
|
|
|
| |
Background:
- Sorafenib (Nexavar) is an orally bioavailable small molecule inhibitor of multiple kinases that are components of signaling pathways, which control tumor growth and angiogenesis including CRAF, BRAF, VEGFR-2, 3, PDGFRβ, FLT3, and c-KIT
- Sorafenib inhibits tumor growth by blocking neovascularization stimulated by VEGFs and PDGF, as well as by inhibiting tumor cell proliferation stimulated through the RAF/MEK/KER pathway
- Sorafenib is relatively well tolerated with manageable mild to moderate toxicities in children and adults in similar doses
- The pediatric Phase I trial of sorafenib in refractory solid tumors is complete and the maximum tolerated dose (MTD) and recommended dose in children with refractory solid tumors is 200 mg/m2/day every 12 hours, orally on a continuous dosing scheduled (90 percent of the adult recommended dose on the same schedule)
- Responses are described in a variety of adult tumors, including those that have not traditionally been described to harbor BRAF mutations; the drug is FDA approved for adults with advanced renal cell carcinoma (RCC) and HCC
Objectives:
- Primary Objectives:
- Determine the objective response rate to sorafenib in children with relapsed or refractory rhabdomyosarcoma, Wilms tumor, hepatocellular carcinoma (HCC), and papillary thyroid carcinoma (PTC)
- Secondary Objectives:
- Further define and describe the toxicities and characterize the pharmacokinetics of sorafenib administered orally, twice daily continuous schedule
- Estimate the progression-free survival, assess the biologic activity on VEGF and soluble VEGFR-2 in peripheral blood samples, and evaluate the presence of BRAF mutations and RET/PTC rearrangements in patients with PTC
Key Eligibility Criteria:
- Diagnosis of one of the following:
- Relapsed or refractory rhabdomyosarcoma or Wilms tumor
- ≥ 24 months and ≤ 30 years of age
- Relapsed or refractory hepatocellular carcinoma (HCC)
- ≥ 24 months and < 18 years of age
- Relapsed or refractory papillary thyroid carcinoma (PTC)
- ≥ 24 months and ≤ 21 years of age
- Performance level ≥ 50 percent (Lansky or Karnofsky) or ECOG ≤ 2
- Adequate hematologic, hepatic, renal, and cardiac status; must meet safety laboratory testing levels
Study Outline:
- This is a two-stage open-label Phase II trial for children and young adults in which sorafenib will be administered orally approximately every 12 hours at 200 mg/m2/day continuously for 28-day cycles
- Toxicity will be closely monitored
- Response will be assessed using RECIST prior to every odd cycle
- Patients may receive up to 24 cycles of therapy in the absence of progressive disease or unacceptable toxicity
Additional Information:
- This trial will be conducted at the NIH Clinical Center in Bethesda, MD. It is open to patients who meet the eligibility requirements, regardless of where they live in the United States.
- There is no charge for medical care received at NIH Clinical Center.
- PDQ (Physicians Data Query) - provides additional details about this study for health care providers.
Reviewed: 12/14/12
Updated: 12/27/12
Back to Top
