The purpose of this study is to evaluate whether new metabolic imaging will be useful to physicians and patients with glioblastoma for making treatment decisions and seeing how well various types of treatment work. The goal is to improve the way patient care is managed in the future. If you chose to be in this study, you will be receiving novel magnetic resonance (MR) metabolic imaging with standard MR imaging. The research component includes an injection of an investigational agent, called hyperpolarized 13C pyruvate, to obtain dynamic metabolic imaging.
The new metabolic imaging will use hyperpolarized 13C pyruvate, which allows for pictures of the brain that we won't be able to get with standard imaging. Hyperpolarized 13C pyruvate has not been approved for use by the Food and Drug Administration (FDA) and is available for research only. This investigational agent is a non-radioactive isotope of carbon. There are three groups in this study. Assignment to a study group depends on the status of your disease and the type of treatment you will be receiving. Subjects in Group 1 will have two MR examination time points. Each time point includes a hyperpolarized 13C pyruvate injection for research imaging as well as standard MR. The MR examinations will occur before receiving standard of care treatment with radiation and chemotherapy, and at the first post-radiation follow-up scan. Subjects in Group 2 will have one MR examination time point with hyperpolarized 13C pyruvate injection for research and standard MR. This MR examination occurs before surgery. Subjects in Group 3 will have three MR examination time points. Each time point includes a hyperpolarized 13C pyruvate injection for research imaging as well as standard MR. The MR examinations will occur prior to initiating therapy (baseline), at approximately 7-14 days after initiation of therapy, and 6-8 weeks after the initiation of therapy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
Given at 0.43 milliliters/kilogram body weight of a 250 millimolar (mM) solution via intravenous injection over a period of about 1 minute once prior to each research magnetic resonance imaging procedure.
University of California, San Francisco
San Francisco, California, United States
Number of Treatment Emergent Adverse Events (AEs) Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Patients will be monitored for the occurrence of AEs that occur during the course of study participation. AE monitoring occurs on each day of hyperpolarized 13C pyruvate administration and until 7 days after administration. Serious adverse events occurring more than 7 days after administration need only be reported if relationship to the investigational drug is suspected.
Time frame: From Day 1 through study completion, up to 4 months
Number of Dose-Limiting Toxicities (DLTs) Assessed by CTCAE Version 4.0
A DLT for this protocol is defined as any event grade 3 or higher in severity assessed by CTCAE version 4.0 that is possibly, probably, or definitely attributable to the investigational drug, excluding laboratory abnormalities determined to be clinically insignificant.
Time frame: From Day 1 through study completion, up to 4 months
Describe Changes in 13C pyruvate-to-lactate conversion rate (kPL) in Normal and Diseased Brain Tissues
The changes in 13C kPL from baseline to the post-RT scan will be compared in the normal appearing brain, enhancing lesion, and non-enhancing lesion
Time frame: Day 1 and Week 8
Describe Changes in 13C Lactate/Pyruvate Ratio in Normal and Diseased Brain Tissues
The changes in 13C lactate/pyruvate ratio from baseline to the post-RT scan will be compared in the normal appearing brain, enhancing lesion, and non-enhancing lesion
Time frame: Day 1 and Week 8
Compare 13C kPL Between Recurrent Lesions and Regions of Treatment Related Effects
The 13C kPL from the recurrent lesions will be compared to those in the regions of treatment related effects.
Time frame: Day 1, Week 1-2, and Week 6-8
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Compare 13C Lactate/Pyruvate Ratio Between Recurrent Lesions and Regions of Treatment Related Effects
The 13C lactate/pyruvate ratio from the recurrent lesions will be compared to those in the regions of treatment related effects.
Time frame: Day 1, Week 1-2, and Week 6-8
Determine the Association Between 13C kPL and Time to Disease Progression
Relationships between 13C kPL and time to disease progression will be compared. Time to disease progression is defined as the time from first study imaging until worsening of glioblastoma disease.
Time frame: From Day 1 until the date of documented disease progression, an average of 1 year
Determine the Association Between 13C Lactate/Pyruvate Ratio and Time to Disease Progression
Relationships between 13C lactate/pyruvate ratio and time to disease progression will be compared. Time to disease progression is defined as the time from first study imaging until worsening of glioblastoma disease.
Time frame: From Day 1 until the date of documented disease progression, an average of 1 year
Determine the Association Between Hydrogen-1 (1H) Choline-to-N-acetylaspartate (NAA) index (CNI) and Time to Disease Progression
Relationships between 1H CNI time to disease progression will be compared. Time to disease progression is defined as the time from first study imaging until worsening of glioblastoma disease.
Time frame: From Day 1 until the date of documented disease progression, an average of 1 year
Determine the Association Between 13C kPL and Overall Survival
Relationships between 13C kPL and overall survival will be compared. Overall Survival is defined as the time from first study imaging until death from any cause.
Time frame: From Day 1 until the date of death from any cause, up to 2 years
Determine the Association Between 13C Lactate/Pyruvate Ratio and Overall Survival
Relationships between 13C lactate/pyruvate ratio and overall survival will be compared. Overall Survival is defined as the time from first study imaging until death from any cause.
Time frame: From Day 1 until the date of death from any cause, up to 2 years
Determine the Association Between 1H CNI and Overall Survival
Relationships between 1H CNI and overall survival will be compared. Overall Survival is defined as the time from first study imaging until death from any cause.
Time frame: From Day 1 until the date of death from any cause, up to 2 years