Clinical Trial: Sorafenib in Children and Young Adults With Recurrent or Progressive Low-Grade Astrocytomas

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Phase II Study of Sorafenib in Children and Young Adults With Recurrent or Progressive Low-Grade Astrocytomas

Brief Summary: The purpose of this study is to determine if a drug called sorafenib can shrink LGA tumors (low-grade astrocytomas) in children and adults. Previous research has given us a better understanding of this type of tumor by studying the genetic "make-up" of LGAs. From this research, the investigators found that a drug called sorafenib may stop the growth of tumor cells by blocking some of the molecules needed for cell growth and by blocking blood flow to the tumor. This trial is studying how well sorafenib works in treating patients with LGAs, and how the effects relate to the specific genetic "make-up" of your particular tumor. This testing of your tumor's genetic make-up is optional and requires available tumor tissue for testing. In summary, the aims of this study are: To see if sorafenib can shrink LGAs; how well sorafenib is tolerated in patients with LGAs; and, how the effects of sorafenib relate to the genetic make-up of individual LGAs (Optional Study)

Detailed Summary:

Novel therapies are urgently needed for children with relapsed LGA who are not surgical candidates and/or have exhausted standard chemotherapy approaches. Although a vast number of "molecular targeted" agents have been developed over the past decade for the treatment of cancer, none have been evaluated for the treatment of LGAs. Recently, genetic alterations resulting in oncogenic BRAF have been identified to be highly prevalent in LGAs, providing a rational target for therapeutic intervention.

The aims of this clinical trial are to estimate the efficacy, as well as safety and tolerability of sorafenib, a RAF and tyrosine kinase receptor inhibitor, in the treatment of pediatric patients with recurrent LGA. Sorafenib targets several pathways that, based on preliminary data from us and others, are likely contributing to the growth of LGAs: oncogenic BRAF, which is present in the majority of grade I LGAs and VEGFR2 and PDGFR, which are well-described mediators of tumor angiogenesis. Since sorafenib inhibits a number of additional kinases whose role in LGA growth has not yet been explored, it is possible that inhibition of pathways other than the primary targets may result in additional anti-tumor effects of sorafenib in LGA. Although the investigators hypothesize that LGAs with oncogenic BRAF should be most sensitive to sorafenib, the additional targets of sorafenib may also result in significant anti-tumor effects in LGAs with wild-type BRAF. Therefore, the investigators propose to evaluate the efficacy of sorafenib in children with LGAs in a translational clinical trial, stratified by BRAF status and tumor grade.

The investigators expect to learn the following from this clinical translational trial:

• The anti-tumor activity of sorafen
  Sponsor: New York University School of Medicine
  

  Current Primary Outcome:

  • Response Rate to Sorafenib [ Time Frame: one year ]
    To estimate the objective response rates to sorafenib in children and young adults with low-grade astrocytomas, including optic pathway gliomas.
  • Objective Response Rates [ Time Frame: MRIs performed after every 3rd 28-day cycle and off-study ]
    Determination of tumor response (CR, PR, SD) will be defined based on the comparison of the baseline MRI performed at study entry to the subsequent MRI which demonstrated best response. PR will be defined by a >15% decrease in tumor volume, as measured by 3D volumetric analysis.
  
  
  

  Original Primary Outcome: Response Rate to Sorafenib [ Time Frame: one year ]

  To estimate the objective response rates to sorafenib in children and young adults with low-grade astrocytomas, including optic pathway gliomas.
  
  
  

  Current Secondary Outcome:
  
  

  Original Secondary Outcome:
  
  Information By: New York University School of Medicine
  

  Dates:
  Date Received: April 18, 2011
  Date Started: April 2011
  Date Completion:
  Last Updated: December 28, 2016
  Last Verified: December 2016