A Prospective Trial of Neural Progenitor Cell Sparing Radiation Therapy Plus Temozolomide for Newly Diagnosed Glioblastoma Multiforme
18 Years
N/A
Both
Glioblastoma Multiforme
Trial Information
A Prospective Trial of Neural Progenitor Cell Sparing Radiation Therapy Plus Temozolomide for Newly Diagnosed Glioblastoma Multiforme
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.
Inclusion Criteria:
- Patient must have newly diagnosed Glioblastoma Multifomre (GBM).
- Patient must have undergone surgical resection and must begin radiation within 12
weeks of this procedure.
- Patients must not have received previous irradiation to the brain.
- Patient must be at least 18 years of age
- Karnofsky performance status of greater than 60%
- Patient must receive temozolomide concurrent with and following radiation.
- If a woman is of child-bearing potential, a negative urine or serum pregnancy test
must be demonstrated prior to treatment. Women of childbearing potential and men must
agree to use adequate contraception for the duration of study participation and for
up to 12 weeks following the study. Should a women become pregnant or suspect she is
pregnant while participating in this study she should inform her treating physician
immediately.
- Patient must have the ability to understand and the willingness to sign a written
informed consent document.
- All patients must be informed of the investigational nature of this study and must be
given written informed consent in accordance with institutional and federal
guidelines.
Exclusion Criteria:
- Patients may not be receiving any other agents to treat their GBM
- No prior malignancy except for adequately treated basal cell or squamous cell skin
cancer, cervical carcinoma in situ, or other cancer from which the patient has been
disease free for at least 2 years.
- Patients with any other uncontrolled illness will be excluded.
- Pregnant and breastfeeding women are excluded. Women of child-bearing potential who
are unwilling or unable to use an acceptable method of birth control to avoid
pregnancy for the entire study period and up to 12 weeks after the study are
excluded. This applies to any woman who has not experienced menarche and who has not
undergone successful surgical sterilization or is not postmenopausal (defined as
amenorrhea for at least 12 consecutive months). Male subjects must also agree to use
effective contraception for the same period as above.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
NPC Sparing
Outcome Description:
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).
Outcome Time Frame:
1 year
Safety Issue:
Yes
Principal Investigator
Kristin Redmond, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
The Johns Hopkins University School of Medicine
Authority:
United States: Institutional Review Board
Study ID:
J-10100
NCT ID:
NCT01478854
Start Date:
May 2011
Completion Date:
May 2015
Related Keywords:
- Glioblastoma Multiforme
- Glioblastoma
Name | Location |
|---|---|
| The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231 |
