Clinical trial NCT01478854: Neural Progenitor Cell Sparing Radiation Therapy Plus Temozolomide
Official title: A Prospective Trial of Neural Progenitor Cell Sparing Radiation Therapy Plus Temozolomide for Newly Diagnosed Glioblastoma Multiforme
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Glioblastoma Multiforme
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
First posted: 2011-11-23
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Patient must have newly diagnosed Glioblastoma Multiforme (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.

Primary outcomes:
measure: Number of Participants With Local Recurrence in the Spared NPC Niches
timeFrame: 1 year
Secondary outcomes:
measure: Extent of NPC Sparing
timeFrame: 1 year
measure: Distance of Tumor to Spared NPC Niches
timeFrame: 1 year
measure: Change in Neurocognitive Function as Measured by Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV) Coding Subtest
timeFrame: Change from baseline to 6 months
measure: Change in Neurocognitive Function as Measured by Trail Making Test
timeFrame: Change from baseline to 6 months
measure: Change in Neurocognitive Function (Verbal Fluency) as Measured by Controlled Oral Word Association Test (COWAT)
timeFrame: Change from baseline to 6 months
measure: Change in Neurocognitive Function (Total Recall, Delayed Recall, Recognition Discrimination) as Measured by Hopkins Verbal Learning Test-Revised (HVLT-R)
timeFrame: Change from baseline to 6 months
measure: Radiation Dose to Spared NPC Region
timeFrame: Day 1 of radiation therapy
measure: Volume (cc) of "NPC for Sparing" Region
timeFrame: day 1 of radiation therapy
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Kristin Redmond, M.D.
role: PRINCIPAL_INVESTIGATOR
References: