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
Showing posts with label new trial. Show all posts
Showing posts with label new trial. Show all posts
Tuesday, April 23, 2013
Monday, April 8, 2013
Hopkins New Trial for Progressive DIPG
Johns Hopkins has put up a new pilot study for children (age one month to 17 years) with progressive DIPGs using intra-arterial (IA) chemotherapy. This procedure will involve placing catheters into the arteries and guiding them to the blood vessels that directly feed the tumor. Melphalan hydrochoride, a chemotherapeutic agent, will be delivered directly into these vessels at two intervals 4 weeks apart. The hope is to increase the amount of drug to the tumor while decreasing the toxicity to the rest of the body.
An interesting part of this study in the interdepartmental nature of the panel which approves inclusion to the study. The panel included two neuro-oncologists- Ken Cohen and Eric Rabbe; a neurosurgeon- George Jallo; a radiation oncologist- Stephanie Tezakis; and a interventional neuroradiologist- Monica Pearl. A truly novel part of this study is that the primary investigator is the interventional neuroradiologist! It is exciting to see such a diverse team interested in novel ways to combat DIPG.
One of the hurdles for DIPG, and in fact all brain tumors, has been getting adequate drug to the tumor. There have been some attempts at trying to get chemotherapy directly to the tumor through the arteries in the past. In 2011, Cornell neurosurgeons published an article using the basilar artery to instill chemotherapy near recurrent pediatric ependymomas. Prior to that there was a publication on blood-brain barrier disruption chemotherapy specifically for diffuse pontine gliomas. Given the failures so far with DIPG treatment, it is good to see another institution interested in new ways to treat DIPG.
This pilot study is being funded by Solving Kids' Cancer. This organization, founded by two fathers of children with neuroblastoma, has a mission "to create more effective and less toxic treatment options for kids with the deadliest childhood cancers. Solving Kids' Cancer's therapeutic paths include genomics, tumor initiating cells, biotherapeutics, immunotherapeutics, embryonic development mechanisms, tumor cell surface receptor and implicated molecular pathways.
References:
Intra-arterial Chemotherapy for the Treatment of Progressive Diffuse Intrinsic Pontine Gliomas
http://www.hopkinsmedicine.org/interventional_neuroradiology/conditions_procedures/progressive_diffuse_intrinsic_pontine_glioma
Super-selective basilar artery infusion of bevacizumab and cetuximab for multiply recurrent pediatric ependymoma
http://www.ncbi.nlm.nih.gov/pubmed/22192550
Osmotic blood-brain barrier disruption chemotherapy for diffuse pontine gliomas
http://www.ncbi.nlm.nih.gov/pubmed/16314949
An interesting part of this study in the interdepartmental nature of the panel which approves inclusion to the study. The panel included two neuro-oncologists- Ken Cohen and Eric Rabbe; a neurosurgeon- George Jallo; a radiation oncologist- Stephanie Tezakis; and a interventional neuroradiologist- Monica Pearl. A truly novel part of this study is that the primary investigator is the interventional neuroradiologist! It is exciting to see such a diverse team interested in novel ways to combat DIPG.
One of the hurdles for DIPG, and in fact all brain tumors, has been getting adequate drug to the tumor. There have been some attempts at trying to get chemotherapy directly to the tumor through the arteries in the past. In 2011, Cornell neurosurgeons published an article using the basilar artery to instill chemotherapy near recurrent pediatric ependymomas. Prior to that there was a publication on blood-brain barrier disruption chemotherapy specifically for diffuse pontine gliomas. Given the failures so far with DIPG treatment, it is good to see another institution interested in new ways to treat DIPG.
This pilot study is being funded by Solving Kids' Cancer. This organization, founded by two fathers of children with neuroblastoma, has a mission "to create more effective and less toxic treatment options for kids with the deadliest childhood cancers. Solving Kids' Cancer's therapeutic paths include genomics, tumor initiating cells, biotherapeutics, immunotherapeutics, embryonic development mechanisms, tumor cell surface receptor and implicated molecular pathways.
References:
Intra-arterial Chemotherapy for the Treatment of Progressive Diffuse Intrinsic Pontine Gliomas
http://www.hopkinsmedicine.org/interventional_neuroradiology/conditions_procedures/progressive_diffuse_intrinsic_pontine_glioma
Super-selective basilar artery infusion of bevacizumab and cetuximab for multiply recurrent pediatric ependymoma
http://www.ncbi.nlm.nih.gov/pubmed/22192550
Osmotic blood-brain barrier disruption chemotherapy for diffuse pontine gliomas
http://www.ncbi.nlm.nih.gov/pubmed/16314949
Monday, March 18, 2013
New Trial- MGMT Cancer Gene Therapy Trial
One of the huge problems with chemotherapy is that it beats up normal cells- especially bone marrow. The toxicity limits how far the doctors can increase dosages before it is just too much for the body. One novel idea is to try to make the normal bone marrow cells more resistant to chemotherapy. This is exactly what researchers are trying to do with a gene therapy which effects MGMT. This will allow for increasing doses of temozolomide.
Dr Geoffrey McCowage at The Children's Hospital of Westmead in Sydney Australia has spent the last 15 years developing a trial which removes bone marrow stem cells, genetically modifies the NA repair protein and then reinserts them into the patient. The hope is that this modification will allow a patient to withstand escalating chemotherapy while better targeting the tumor. In fact, this is more than theory. This first of kind therapy for brain tumor kids is open in trial.
This Phase 1 intervention is open to several different types of brain tumors including brainstem glioma of diffuse pontine type and all the following recurrent tumors- medulloblastoma, ependymoma, atypical teratoid rhaboid, high and low grade glioma.
Erin is the first child enrolled. You can read at-
http://www.news.com.au/national-news/south-australia/brave-erins-inspirational-battle-against-cancer/story-fndo4dzn-122658419720
Last month she had reached a year from diagnosis- and in the picture she looks great.
The trial is being funded by the Kid's Cancer Project (formerly Oncology Children's Foundation), Sporting Chance Cancer Foundation and the Australian governmental funding agency, The Department of Innovation, Industry Science and Research.
Erin is hoping to raise $50,000 for The Cure Starts Now for DIPG research.
Note- A similar trial seems to be open in the US at the NIH for adult glioblastoma patients.
References:
Brave Erin's Inspirational Battle Against Cancer- http://www.news.com.au/national-news/south-australia/brave-erins-inspirational-battle-against-cancer/story-fndo4dzn-122658419720
MGMT Cancer Gene Therapy Project- http://www.thekidscancerproject.org.au/Research/Gene-Therapy-Trial.aspx
Cancer Gene Therapy Project (Westmead Research site)-
NIH Adult Trial with Newly Diagnosed GBM- http://www.clinicaltrials.gov/ct2/show/NCT01269424
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