Hyperpolarized Carbon-13 (13C) Pyruvate Imaging in Patients With Glioblastoma

Glioblastoma Multiforme (GBM) Clinical Trial

Official title:

Evaluating Hyperpolarized and Proton Brain Metabolism in Patients With Glioblastoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04019002
• Other study ID #: 19105
• Secondary ID: 2P50CA097257NCI-
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: November 19, 2019
• Est. completion date: September 30, 2025

Study information

• Verified date: October 2023
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 17
• Est. completion date: September 30, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme (GBM)

Intervention

Drug:
• Hyperpolarized 13C Pyruvate
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.

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Susan Chang	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From Day 1 through study completion, up to 4 months
Primary	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.	From Day 1 through study completion, up to 4 months
Primary	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	Day 1 and Week 8
Primary	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	Day 1 and Week 8
Primary	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.	Day 1, Week 1-2, and Week 6-8
Primary	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.	Day 1, Week 1-2, and Week 6-8
Primary	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.	From Day 1 until the date of documented disease progression, an average of 1 year
Primary	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.	From Day 1 until the date of documented disease progression, an average of 1 year
Primary	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.	From Day 1 until the date of documented disease progression, an average of 1 year
Primary	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.	From Day 1 until the date of death from any cause, up to 2 years
Primary	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.	From Day 1 until the date of death from any cause, up to 2 years
Primary	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.	From Day 1 until the date of death from any cause, up to 2 years