A new Pediatric Brain Tumor Consortium phase 2 trial using a telomerase inhibitor, Imetelstat also known as GRN163L, for recurrent or refractory DIPG (as well as three other recurrent or refractory pediatric brain tumors) just went up on clinicaltrials.gov this week. This two section component study will be both a phase 2 study as well as a molecular analysis study. DIPGs will be excluded from the molecular analysis study component of this trial and will not require tissue/histological confirmation. The protocol will include a two hour IV infusion on day 1 and 8 followed by repeat infusions every 21 days for two years.
What are telomeres? I think of them like the plastic coating at the end of shoelaces which keeps the laces from fraying out.
Telomeres are thought to be an important in keeping a cell's DNA intact. They are located on the end of chromosomes and shorten with cell divisions. This shortening of telomeres protects the inner DNA as if it wasn't there the DNA could be affected. One can actually see how these telomere are at the end of chromosomes (image). When the telomeres in normal cells become too short the cell stops dividing and dies. However, there is an enzyme called telomerase which adds some bases to the end of telomeres to keep them from getting too short. This can be present in normal young cells; but is seems to be more prevalent in cancer cells. It is thought that telomerase might be one of the things that allows cancer cells to keep dividing and not die out.
For those that are interested in getting some background on telomeres check out these two article...
*New Telomere Discovery Could Help Explain Why Cancer Cells Never Stop Dividing
*Are Telomeres the Key to Aging and Cancer?
The hope is that if one can block telemorase activity in cancer that these cells will die out.
For those interested in work that has been done in pediatric brain tumors with telomeres/telomerase, check the work of Uri Tabori (Sick Kids) who published work about telomeres in pediatric low grade gliomas back in 2006 and ependymomas in 2008. In addition, St Jude made a study available in the end of 2012 using whole-genome sequencing to look at telomere content in pediatric cancer.
The Pediatric Brain Tumor Consortium (PBTC) is a group of US institutions banded together first in 1999 with the goal of improving treatment/outcomes with children with primary brain tumors by "rapidly conducting novel phase 1 and 2 clinical trials of new therapeutic drugs, new biological therapies, treatment delivery technologies and radiation treatment strategies in children" and a second goal of "characterizing reliable markers and predictors of response to new therapies". At this time there are 11 full members and 4 temporary members of the PBTC. Currently the PBTC is running 5 open trials of which two are related to DIPG- one is this trial and the other is ABT-888/temozolomide trial for newly diagnosed kids with DIPG. The primary investigator for this Imetelstat trial is Maryam Fouladi (Cincinnati). Contact information is available on the references below.
Reference:
A Molecular Biology and Phase II Study of Imetelstat (GRN163L) in Children With Recurrent High-Grade Glioma, Ependymoma, Medulloblastoma/Primitive Neuroectodermal Tumor and Diffuse Intrinsic Pontine Glioma
http://clinicaltrials.gov/ct2/show/NCT01836549?term=dipg&rank=24
Protocol Summary for Parents from PBTC
http://www.pbtc.org/public/PBTC-036_v1_1%20Summary%20for%20patients%20and%20families.pdf
Protocol Summary for Health Care Providers from PBTC
http://www.pbtc.org/public/PBTC-036%20Protocol%20Abstract%20and%20Schema%20for%20health%20prof_v3.pdf
COG Phase 1 Imetelstat Trial in Young Patients (appears to still be recruiting)
http://clinicaltrials.gov/ct2/show/NCT01273090?term=imetelstat&rank=6
