Hyperpolarized 13C MRI as a Biomarker in Advanced Solid Tumors

A Phase I/II Study of Hyperpolarized 13C MRI as a Biomarker of Aggressiveness & Response to Therapy in Patients With Advanced Solid Tumors

This is a single center prospective imaging study investigating the utility of hyperpolarized 13C-pyruvate +/-13C,15N-Urea/ metabolic MR imaging. The current protocol will serve as a companion imaging biomarker study paired with standard of care (SOC) therapeutics, as well as investigational therapies that participants may be scheduled to receive outside of this protocol.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: Hyperpolarized 13C-Pyruvate; Procedure: Magnetic Resonance Imaging (MRI); Drug: 13C,15N-Urea

Detailed Description

PRIMARY OBJECTIVES:

Phase I/Part A

1. To optimize the signal-to-noise ratio in detecting intra-tumoral hyperpolarized 13C pyruvate/lactate signal and hyperpolarized urea area under the curve (AUC) using metabolic magnetic resonance (MR) imaging in patients with advanced solid tumors.

Phase II/Part B

1. To determine the mean percent change from baseline in peak intra-tumoral hyperpolarized lactate-to-pyruvate ratio,pyruvate-to-lactate kinetic constant (kPL) and urea AUC after initiation of usual care/standard of care (SOC) treatment

SECONDARY OBJECTIVES:

Phase I/Part A

1. To further characterize the safety profile of hyperpolarized 13C-pyruvate +/- 13C,15N-urea.
2. To determine the reproducibility of intra-tumoral HP lac/pyr ratio with same-day repeated dose studies.

Phase II/Part B

1. To study the association between clinical outcomes and the percent change from baseline in peak intra-tumoral hyperpolarized lactate-to pyruvate ratio and kPL (+/-correction for HP urea AUC) after initiation of SOC treatment.
2. To further characterize the safety profile of hyperpolarized 13C pyruvate +/- 13C,15N-urea.
3. To determine the reproducibility of intra-tumoral HP lac/pyr ratio and/or HP urea AUC with same-day repeated dose studies.

OUTLINE:

Participants will be enrolled in Part A which is the feasibility, run-in study which includes the iterative adjustment of coil design to optimize imaging parameters within the target tumor lesion(s). If the data from Part A supports further investigation, additional participants will be enrolled in Part B which is a biomarker cohort which includes participants who are planning on being treated with either standard-of-care (SOC) or investigational therapies and will be followed until discontinuation of the treatment regimen outside of this protocol.

• Study Type: Interventional
• Enrollment (Estimated): 65
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Louise Magat; Phone Number: (415) 502-1822; Email: Louise.Magat@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco
      • Contact: Louise Magat; Phone Number: 415-502-1822; Email: Louise.Magat@ucsf.edu
      • Principal Investigator: Robert Bok, MD, PhD
      • Contact: Phone Number: 877-827-3222; Email: cancertrials@ucsf.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Presence of at least one target pelvic, abdominal, thoracic, neck or extremity lesion detected by standard staging scans that, in the judgment of study investigator, would be amenable to hyperpolarized C-13 pyruvate/metabolic MR imaging:

   a. Target lesion must measure at least 1.0 cm in long axis diameter on Computerized tomography (CT) or magnetic resonance imaging (MRI).

2. The participant is able and willing to comply with study procedures and provide signed and dated informed consent.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
4. Adequate renal function defined as creatinine < 1.5 x upper limit of normal (ULN) or estimated creatinine clearance >50 mL/min (by the Cockcroft Gault equation).

5. Participants age 18 and older.

   Part B only:

6. Planned treatment for disease with either standard of care regimen or an investigational agent.

Exclusion Criteria:

1. Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent.
2. Patients with contra- indications to MRI, such as cardiac pacemakers or non-compatible intracranial vascular clips.
3. Patients with a metallic implant or device that distorts local magnetic field and compromises the quality of MR imaging.

4. Patients with poorly controlled hypertension, defined as systolic blood pressure at study entry greater than 160mm Hg or diastolic blood pressure greater than 100mm Hg.

   Note: The addition of anti-hypertensives to control blood pressure is allowed.

5. Patients with congestive heart failure or New York Heart Association (NYHA) status >= 2.
6. Patients who are pregnant or lactating.

7. A history of clinically significant EKG abnormalities or myocardial infarction (MI) within 6 months of study entry.

   Note: Patients with rate-controlled atrial fibrillation/flutter will be allowed on study.

8. Any condition that, in the opinion of the Principal Investigator,

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A / Phase 1: Feasibility Run-In; Participants will undergo MR imaging at a single time point. Imaging will take one day and no follow up is planned.	Drug: Hyperpolarized 13C-Pyruvate; Given IV; Other Names: Hyperpolarized (HP) carbon^13 (13C)-pyruvate; HP-13C; Procedure: Magnetic Resonance Imaging (MRI); Imaging procedure; Other Names: MRI; Drug: 13C,15N-Urea; Given IV
Experimental: Part B/ Phase II: Biomarker Cohort; Participants will undergo paired 13C-pyruvate +/- 13C,15N-urea/metabolic MR imaging at baseline and again after approximately 21 days of therapy. Duration of the intervention period is approximately 21 days, and participants will be followed until discontinuation of their current SOC treatment regimen, about 6 months.	Drug: Hyperpolarized 13C-Pyruvate; Given IV; Other Names: Hyperpolarized (HP) carbon^13 (13C)-pyruvate; HP-13C; Procedure: Magnetic Resonance Imaging (MRI); Imaging procedure; Other Names: MRI; Drug: 13C,15N-Urea; Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Signal-to-noise ratio (Part A)	Signal-to-noise ratios is defined as a MR/spectroscopy parameter, consisting of the HP C13-Pyruvate or Lactate signal (peak) relative to background noise level (baseline) in MRI spectra of the tissue. For the analysis and interpretation of the HP 13C-pyruvate MR imaging data, DICOM software package (SIVIC) will be used to align, display and quantitatively interrogate serial multi-parametric imaging data.	Day of imaging (1 day)
Mean percent change from baseline in intratumoral HP pyruvate/lactate ratio	Intra-tumoral region of interest (ROI) will be used to quantify peak HP lactate/pyruvate ratio values in the selected volumes of interest. Descriptive statistics will be used to characterize the mean change from baseline in intra-tumoral HP pyruvate/lactate ratio for the study cohort, along with a 95% confidence interval	Up to 25 days
Mean percent change from baseline in Urea Area Under Curve (AUC)	Intra-tumoral region of interest (ROI) will be used to quantify urea AUC. Descriptive statistics will be used to characterize the mean change from baseline in Urea Area Under Curve (AUC)	Up to 25 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median percent change from baseline in peak intratumoral hyperpolarized lactate-to-pyruvate ratio (Part B)	Lactate/pyruvate ratio: hyperpolarized Lactate signal divided by the hyperpolarized pyruvate signal within the tumor region, for each injection/scan on the same day.	Up to 6 months
Objective response rate (ORR) (Part B)	ORR is defined as the proportion of treated patients who experience an objective response (confirmed complete response (CR) or confirmed partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST)	Up to 6 months
Clinical benefit rate (CBR) (Part B)	CBR is defined as the proportion of treated patients who experience clinical benefit (confirmed complete response (CR); confirmed partial response (PR); or stable disease (SD) for > 24 weeks per RECIST 1.1 criteria).	Up to 6 months
Radiographic progression-free survival (rPFS) (Part B)	rPFS is defined as the amount of time that elapses between initiation of standard of care treatment and the day of first documented radiographic disease progression per RECIST v.1.1 or death from any cause.	Up to 6 months
Lactate/pyruvate ratio (Part B)	Intra-patient reproducibility of HP lac/pyr ratio and kPL for patients who undergo repeated dose imaging studies will be descriptively reported using summary statistics (mean difference, standard deviation, range).	1 day
Number of participants reporting adverse events (Part A)	Safety analyses will be performed for all patients having received a dose of HP 13C pyruvate HP 13C-pyruvate +/- 13C,15N-urea. Adverse events will be classified and graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE)	Day of imaging (1 day)
Number of participants reporting adverse events (Part B)	Safety analyses will be performed for all patients having received a dose of HP 13C pyruvate HP 13C-pyruvate +/- 13C,15N-urea. Adverse events will be classified and graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE)	Up to 6 months
Median percent change from baseline in intra-tumoral HP Urea AUC (Part B)	HP urea AUC within the tumor region, for each injection/scan on the same day	Up to 6 months

Collaborators and Investigators

• Sponsor: Robert Bok, MD, PhD
• Collaborators: National Cancer Institute (NCI); National Institute for Biomedical Imaging and Bioengineering (NIBIB); Sigma-Aldrich
• Investigators: Principal Investigator: Robert Bok, MD, PhD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2022
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2027

Study Registration Dates

• First Submitted: October 25, 2022
• First Submitted That Met QC Criteria: October 25, 2022
• First Posted (Actual): October 31, 2022

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Biomarker
• Additional Relevant MeSH Terms: Neoplasms; Investigative Techniques; Chemistry Techniques, Analytical; Spectrum Analysis; Magnetic Resonance Spectroscopy
• Other Study ID Numbers: 22924; NCI-2022-09149 (Registry Identifier: NCI Clinical Trials Reporting Program (CTRP)); P41EB013598-11 (U.S. NIH Grant/Contract); 5U01EB026412-04 (U.S. NIH Grant/Contract); 5R01CA256740-02 (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