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

NCT04019002 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: 191052P50CA097257NCI-2019-07406
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioblastoma Multiforme (GBM)

Keywords

Glioblastoma Multiforme; Hyperpolarized Pyruvate; Magnetic Resonance; Magnetic Resonance Spectroscopic Imaging; Glioblastoma

Outcome Measures

Primary Outcomes (12)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

Study Arms (3)

Cohort 1: Newly Diagnosed- Standard Treatment

EXPERIMENTAL

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).

Drug: Hyperpolarized 13C Pyruvate

Cohort 2: Recurrent- Standard Surgical Resection

EXPERIMENTAL

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.

Drug: Hyperpolarized 13C Pyruvate

Cohort 3: Recurrent- Standard Treatment

EXPERIMENTAL

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.

Drug: Hyperpolarized 13C Pyruvate

Interventions

Hyperpolarized 13C Pyruvate DRUG

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.

Also known as: HP-13C

Cohort 1: Newly Diagnosed- Standard Treatment; Cohort 2: Recurrent- Standard Surgical Resection; Cohort 3: Recurrent- Standard Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• Subjects must be excluded from participating in this study if they are not able to comply with study and/or follow-up procedures.

Sponsors & Collaborators

• Susan Chang: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Susan Chang, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 11, 2019
• First Posted: July 15, 2019
• Study Start: November 19, 2019
• Primary Completion: September 30, 2025
• Study Completion: September 30, 2025
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)