Hyperpolarized Carbon C 13 Pyruvate Magnetic Resonance Spectroscopic Imaging in Detecting Lactate and Bicarbonate in Participants With Central Nervous System Tumors

A Pilot Study to Assess Lactate and Bicarbonate Detection Within Malignant Brain Tumors Using [1-13C]-Pyruvate DNP Magnetic Resonance Spectroscopy (MRS)

This early phase I trial studies how well hyperpolarized carbon C 13 pyruvate magnetic resonance imaging works in detecting lactate and bicarbonate in participants with central nervous system tumors. Hyperpolarized carbon C 13 pyruvate magnetic resonance imaging may be used to measure the metabolic state of malignant brain tumors.

Study Overview

• Status: Completed
• Conditions: Malignant Central Nervous System Neoplasm; Metastatic Malignant Neoplasm in the Central Nervous System
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; Procedure: Magnetic Resonance Spectroscopic Imaging; Drug: Hyperpolarized Carbon C 13 Pyruvate; Other: Gadolinium

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the safety of intravenous (IV) injection of hyperpolarized carbon C 13 pyruvate (hyperpolarized [1-13C] pyruvate) for magnetic resonance imaging (MRI).

II. To assess the frequency and sensitivity with which lactate and bicarbonate signals can be detected in malignant brain tumors after IV injection of hyperpolarized [1-13C] pyruvate.

OUTLINE:

Participants undergo MRI over 45 minutes at baseline. Participants then receive hyperpolarized carbon C 13 pyruvate IV over 30-40 seconds. Within 1 minute, participants undergo magnetic resonance spectroscopic imaging (MRSI) over 3 minutes and MRI over 10 minutes (participants may receive gadolinium at the discretion of the protocol director).

After completion of study, participants are followed up periodically.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with a known diagnosis of central nervous system (CNS) malignancy, including metastases, with known enhancement on magnetic resonance (MR) who are otherwise eligible to undergo MRI
• Glomerular filtration rate (GFR) > 30 ml/min
• No allergy to gadolinium
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Refusal to have an IV placed for injection
• Acute major illness (e.g., unstable angina, etc.) or other condition that makes participation unsafe, per the investigator?s judgement
• Total bilirubin > 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2.5 x ULN
• Gamma-glutamyltransferase (GGT) > 2.5 x ULN
• Pregnant or breast-feeding

• Cardiovascular risk, including:

  • Poorly controlled hypertension, defined as either systolic > 170 or diastolic > 110
  • Congestive heart failure
  • Myocardial infarction within the past year
  • QT prolongation, defined as pretreatment corrected QT interval (QTc) > 440 msec in males or > 460 msec in females

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Volunteers; Participants undergo MRI over 45 minutes at baseline. Participants then receive hyperpolarized carbon C 13 pyruvate IV over 30-40 seconds. Within 1 minute, participants undergo MRSI over 3 minutes and MRI over 10 minutes.	Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Procedure: Magnetic Resonance Spectroscopic Imaging; Undergo MRSI; Other Names: 1H- Nuclear Magnetic Resonance Spectroscopic Imaging; 1H-nuclear magnetic resonance spectroscopic imaging; Magnetic Resonance Spectroscopy; MRS; MRS Imaging; MRSI; Proton Magnetic Resonance Spectroscopic Imaging; Drug: Hyperpolarized Carbon C 13 Pyruvate; Given IV; Other Names: Hyperpolarized 13C-Pyruvate; Hyperpolarized Pyruvate (13C)
Experimental: Known CNS Malignancy; Participants undergo MRI over 45 minutes at baseline. Participants then receive hyperpolarized carbon C 13 pyruvate IV over 30-40 seconds. Within 1 minute, participants undergo MRSI over 3 minutes and MRI over 10 minutes (participants may receive gadolinium at the discretion of the protocol director).	Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Procedure: Magnetic Resonance Spectroscopic Imaging; Undergo MRSI; Other Names: 1H- Nuclear Magnetic Resonance Spectroscopic Imaging; 1H-nuclear magnetic resonance spectroscopic imaging; Magnetic Resonance Spectroscopy; MRS; MRS Imaging; MRSI; Proton Magnetic Resonance Spectroscopic Imaging; Drug: Hyperpolarized Carbon C 13 Pyruvate; Given IV; Other Names: Hyperpolarized 13C-Pyruvate; Hyperpolarized Pyruvate (13C); Other: Gadolinium; gadolinium enhanced MRI; Other Names: Gd

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Grade 2 or Higher Toxicities	The measurement of this drug is the number of participants with Grade 2 or higher related adverse events (except for asymptomatic lab increases)	2 days (+/-2) after the scan

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lactate and Bicarbonate Production in Tumor and Normal Brain Tissue	The outcome is defined as the frequency of hyperpolarized carbon C 13 pyruvate magnetic resonance signal detection above background noise level of both lactate and bicarbonate in all tumors screened.	Day 4

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lactate and Bicarbonate Production in Tumor and Normal Brain Tissue	The outcome is defined as the number of participants with hyperpolarized carbon C 13 pyruvate magnetic resonance signal detection above background noise level of both lactate and bicarbonate in all tumors screened.	Imaging timepoint (up to 15 minutes to obtain scan)

Collaborators and Investigators

• Sponsor: Daniel M. Spielman
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Lawrence Recht, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2018
• Primary Completion (Actual): June 20, 2019
• Study Completion (Actual): June 20, 2019

Study Registration Dates

• First Submitted: June 11, 2018
• First Submitted That Met QC Criteria: June 11, 2018
• First Posted (Actual): June 21, 2018

Study Record Updates

• Last Update Posted (Estimated): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms
• Other Study ID Numbers: IRB-39845 (Other Identifier: Stanford IRB); NCI-2018-01122 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); BRN0036 (Other Identifier: OnCore); R01CA245097-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No