Neural Progenitor Cell Sparing Radiation Therapy Plus Temozolomide
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Prospective Trial of Neural Progenitor Cell Sparing Radiation Therapy Plus Temozolomide for Newly Diagnosed Glioblastoma Multiforme|
- NPC Sparing [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]To estimate the local recurrence (LR) rate at 1 year in the spared neural progenitor cell (NPC) containing niches of the brain in patients treated with NPC sparing radiation therapy (RT) plus temozolomide for newly diagnosed glioblastoma multiforme (GBM).
- radiation dose sparing assessment [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]To quantify the extent of radiation dose sparing to the NPC containing regions that is possible without compromising tumor coverage in patients with newly diagnosed GBM
- Number of Participants with Cognitive Adverse Events [ Time Frame: 1 year ] [ Designated as safety issue: No ]To assess feasibility of evaluating cognitive function prospectively in patients undergoing NPC sparing RT for newly diagnosed GBM.
- Oral assessments after treatment [ Time Frame: 1 year ] [ Designated as safety issue: No ]To explore if the potential change from baseline to six months in neurocognitive function as measured by the Mini Mental State Exam, Trail Making Test, Controlled Oral Word Association test (COWAT), Hopkins Verbal Learning Test-Revised, Digit Symbol Substitution Test is related to radiation dose to the NPC containing regions in patients treated with NPC sparing radiation for newly diagnosed GBM.
|Study Start Date:||May 2011|
|Estimated Study Completion Date:||January 2016|
|Estimated Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
Experimental: Neural Progeniter Cell Sparing Radiation with Temozolomide
All subjects are treated with neural progenitor cell sparing radiation to 60 Gy in 2 Gy per day, 30 fractions Concurrent and adjuvant temozolomide chemotherapy
Patients will be treated to a total dose of 60 Gy with a once daily fractionation schedule of 2 Gy per fraction, administered five days per week. All patients will undergo CT simulation with intravenous contrast. In addition they will undergo MRI simulation with both T1 with gadolinium as well as FLAIR sequences. They will be treated in a supine position using an aquaplast mask system for immobilization. CT image data will be reconstructed in approximately 3 mm slice thickness and manually coregistered with T1 post-gadolinium and FLAIR sequence MRI.Drug: Chemotherapy
Radiation therapy (RT) is an integral component of the management of brain tumors, but cognitive deficits following cranial irradiation are well documented. There is an association between damage to neural progenitor cells (NPC) and neurocognitive dysfunction. NPC are similarly known to play an important role in recovery from damage to the brain, including radiation-induced damage. However NPC are extremely sensitive to radiation. In spite of this information, current RT planning techniques do not limit the radiation dose to the NPC containing regions. Recent human studies have demonstrated that it is possible to use intensity modulated radiation therapy to reduce the radiation dose to NPC containing regions during RT for brain tumors, without compromising coverage of the tumor. We hypothesize that NPC-sparing RT will reduce neurocognitive decline following treatment for brain tumors, without compromising tumor local control. However, there is conflicting data regarding the role of NPC in the development of glioblastoma multiforme (GBM). Some studies suggest that GBM are derived from NPC whereas others have associated NPC with improved tumor control following therapy for GBM. Prior to evaluation of neurocognitive outcomes with NPC-sparing RT, it is therefore imperative to evaluate whether NPC-sparing RT techniques lead to increased LR in the spared NPC containing niches of the brain.
The proposed study is designed to evaluate LR in the spared regions of the brain following NPC sparing RT in patients with newly diagnosed GBM. Our research will consist of 3 specific aims: 1) Determine the LR rate at 1 year in the spared NPC containing niches in patients treated with NPC sparing RT for GBM; 2) Quantify the extent of radiation dose sparing to the NPC containing regions that is possible without compromising tumor coverage in patients with GBM; 3) Determine if it is feasible to evaluate cognitive function prospectively in patients undergoing NPC sparing RT for GBM.
The long term goal of this research is to establish whether NPC sparing RT techniques improve neurocognitive outcomes compared to conventional RT for brain tumors. If the proposed study demonstrates that NPC sparing RT is not associated with increased LR in the spared regions of the brain compared to conventional RT, it will ideally serve as the foundation for a future multi-institutional randomized controlled trial comparing neurocognitive outcomes in patients treated with NPC-sparing RT versus conventional radiation therapy.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01478854
|United States, Maryland|
|The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231|
|Principal Investigator:||Kristin Redmond, M.D.||Johns Hopkins University|