Back to resultsHyperpolarized Carbon-13 (13C) Pyruvate Imaging in Patients With Glioblastoma
Primary Purpose
Glioblastoma Multiforme (GBM)
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Hyperpolarized 13C Pyruvate
Sponsored by
About this trial
This is an interventional diagnostic trial for Glioblastoma Multiforme (GBM) focused on measuring Glioblastoma Multiforme, Hyperpolarized Pyruvate, Magnetic Resonance, Magnetic Resonance Spectroscopic Imaging, Glioblastoma
Eligibility Criteria
Inclusion Criteria:
- Cohort 1: Histologically proven newly diagnosed glioblastoma multiforme (GBM) who will undergo standard of treatment with radiation therapy (RT) and temozolomide (TMZ).
- Cohort 2: Histologically proven recurrent suspected GBM who will receive surgical resection for the recurrence.
- Cohort 3: Histologically proven recurrent suspected GBM who will undergo standard treatment for the recurrence.
- Patients must be >/= 18 years old and with a life expectancy > 16 weeks.
- Patients must have a Karnofsky performance status of ≥ 70.
- Patients must have adequate renal function: creatinine < 1.5 mg/dL before imaging. These tests must be performed within 60 days prior to Hyperpolarized Imaging scan.
- Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy, would compromise the patient's ability to tolerate the imaging examination or any disease that will obscure toxicity or dangerously alter response to the imaging agent.
- Patients must not have New York Heart Association (NYHA) Grade II or greater congestive heart failure
- Patients must not have a history of myocardial infarction or unstable angina within 12 months prior to study enrollment.
- This study was designed to include women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender. Minorities will actively be recruited to participate. No exclusion to this study will be based on race.
- Patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must sign an authorization for the release of their protected health information.
- Patients may not be known to be human immunodeficiency virus (HIV)-positive. HIV testing is not required for study participation.
- Patients must not have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years.
- Patients must not be pregnant or breast feeding. Women of childbearing potential are required to obtain a negative pregnancy test within 14 days of Hyperpolarized Imaging scan. Effective contraception (men and women) must be used in subjects of child-bearing potential.
Exclusion Criteria:
- Subjects must be excluded from participating in this study if they are not able to comply with study and/or follow-up procedures.
Sites / Locations
- University of California, San FranciscoRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Cohort 1: Newly Diagnosed- Standard Treatment
Cohort 2: Recurrent- Standard Surgical Resection
Cohort 3: Recurrent- Standard Treatment
Arm Description
This arm is for patients with histologically proven newly diagnosed glioblastoma who will undergo standard treatment with radiation therapy (RT) and temozolomide (TMZ). Patients will receive two injections of hyperpolarized 13C pyruvate for research imaging performed prior to standard imaging on the same day. Research imaging occurs at two time points: before receiving standard treatment with RT/TMZ and at the first post-radiation follow-up scan (8 weeks later).
This arm is for patients with histologically proven recurrent suspected glioblastoma who will receive surgical resection for the recurrence. Patients will receive one injection of hyperpolarized 13C pyruvate for research imaging performed prior to standard imaging on the same day. Research imaging occurs at one time point: before surgery.
This arm is for patients with histologically proven recurrent suspected glioblastoma who will undergo standard treatment for the recurrence. Patients will receive two injections of hyperpolarized 13C pyruvate for research imaging performed prior to standard imaging on the same day. Research imaging occurs at three time points: prior to treatment (baseline), approximately 7-14 days after the initiation of treatment, and 6-8 weeks after the initiation of treatment.
Outcomes
Primary Outcome Measures
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.
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.
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
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
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.
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.
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.
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.
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.
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.
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.
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT04019002
First Posted
July 11, 2019
Last Updated
March 29, 2023
Sponsor
Susan Chang
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT04019002
Brief Title
Hyperpolarized Carbon-13 (13C) Pyruvate Imaging in Patients With Glioblastoma
Official Title
Evaluating Hyperpolarized and Proton Brain Metabolism in Patients With Glioblastoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 19, 2019 (Actual)
Primary Completion Date
January 28, 2025 (Anticipated)
Study Completion Date
January 28, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Susan Chang
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma Multiforme (GBM)
Keywords
Glioblastoma Multiforme, Hyperpolarized Pyruvate, Magnetic Resonance, Magnetic Resonance Spectroscopic Imaging, Glioblastoma
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
90 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1: Newly Diagnosed- Standard Treatment
Arm Type
Experimental
Arm Description
This arm is for patients with histologically proven newly diagnosed glioblastoma who will undergo standard treatment with radiation therapy (RT) and temozolomide (TMZ).
Patients will receive two injections of hyperpolarized 13C pyruvate for research imaging performed prior to standard imaging on the same day. Research imaging occurs at two time points: before receiving standard treatment with RT/TMZ and at the first post-radiation follow-up scan (8 weeks later).
Arm Title
Cohort 2: Recurrent- Standard Surgical Resection
Arm Type
Experimental
Arm Description
This arm is for patients with histologically proven recurrent suspected glioblastoma who will receive surgical resection for the recurrence.
Patients will receive one injection of hyperpolarized 13C pyruvate for research imaging performed prior to standard imaging on the same day. Research imaging occurs at one time point: before surgery.
Arm Title
Cohort 3: Recurrent- Standard Treatment
Arm Type
Experimental
Arm Description
This arm is for patients with histologically proven recurrent suspected glioblastoma who will undergo standard treatment for the recurrence.
Patients will receive two injections of hyperpolarized 13C pyruvate for research imaging performed prior to standard imaging on the same day. Research imaging occurs at three time points: prior to treatment (baseline), approximately 7-14 days after the initiation of treatment, and 6-8 weeks after the initiation of treatment.
Intervention Type
Drug
Intervention Name(s)
Hyperpolarized 13C Pyruvate
Other Intervention Name(s)
HP-13C
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Treatment Emergent Adverse Events (AEs) Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Description
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
Title
Number of Dose-Limiting Toxicities (DLTs) Assessed by CTCAE Version 4.0
Description
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
Title
Describe Changes in 13C pyruvate-to-lactate conversion rate (kPL) in Normal and Diseased Brain Tissues
Description
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
Title
Describe Changes in 13C Lactate/Pyruvate Ratio in Normal and Diseased Brain Tissues
Description
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
Title
Compare 13C kPL Between Recurrent Lesions and Regions of Treatment Related Effects
Description
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
Title
Compare 13C Lactate/Pyruvate Ratio Between Recurrent Lesions and Regions of Treatment Related Effects
Description
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
Title
Determine the Association Between 13C kPL and Time to Disease Progression
Description
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
Title
Determine the Association Between 13C Lactate/Pyruvate Ratio and Time to Disease Progression
Description
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
Title
Determine the Association Between Hydrogen-1 (1H) Choline-to-N-acetylaspartate (NAA) index (CNI) and Time to Disease Progression
Description
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
Title
Determine the Association Between 13C kPL and Overall Survival
Description
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
Title
Determine the Association Between 13C Lactate/Pyruvate Ratio and Overall Survival
Description
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
Title
Determine the Association Between 1H CNI and Overall Survival
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Cohort 1: Histologically proven newly diagnosed glioblastoma multiforme (GBM) who will undergo standard of treatment with radiation therapy (RT) and temozolomide (TMZ).
Cohort 2: Histologically proven recurrent suspected GBM who will receive surgical resection for the recurrence.
Cohort 3: Histologically proven recurrent suspected GBM who will undergo standard treatment for the recurrence.
Patients must be >/= 18 years old and with a life expectancy > 16 weeks.
Patients must have a Karnofsky performance status of ≥ 70.
Patients must have adequate renal function: creatinine < 1.5 mg/dL before imaging. These tests must be performed within 60 days prior to Hyperpolarized Imaging scan.
Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy, would compromise the patient's ability to tolerate the imaging examination or any disease that will obscure toxicity or dangerously alter response to the imaging agent.
Patients must not have New York Heart Association (NYHA) Grade II or greater congestive heart failure
Patients must not have a history of myocardial infarction or unstable angina within 12 months prior to study enrollment.
This study was designed to include women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender. Minorities will actively be recruited to participate. No exclusion to this study will be based on race.
Patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must sign an authorization for the release of their protected health information.
Patients may not be known to be human immunodeficiency virus (HIV)-positive. HIV testing is not required for study participation.
Patients must not have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years.
Patients must not be pregnant or breast feeding. Women of childbearing potential are required to obtain a negative pregnancy test within 14 days of Hyperpolarized Imaging scan. Effective contraception (men and women) must be used in subjects of child-bearing potential.
Exclusion Criteria:
Subjects must be excluded from participating in this study if they are not able to comply with study and/or follow-up procedures.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wendy Ma
Phone
415-514-4418
Email
Wendy.Ma@ucsf.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susan Chang, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wendy Ma
Phone
415-514-4418
Email
Wendy.Ma@ucsf.edu
Phone
877-827-3222
Email
cancertrials@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Susan Chang, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Hyperpolarized Carbon-13 (13C) Pyruvate Imaging in Patients With Glioblastoma
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