Hyperpolarized 13C MRI as a Biomarker in Advanced Solid Tumors

NCT05599048 | Recruiting Phase 1 DMC FDA Drug

• 5 other identifiers: 22924NCI-2022-09149P41EB013598-115U01EB026412-045R01CA256740-02
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Solid Tumor

Keywords

Biomarker

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (8)

• Number of participants reporting adverse events (Part A)

  Day of imaging (1 day)

• Number of participants reporting adverse events (Part B)

  Up to 6 months

• Median percent change from baseline in peak intratumoral hyperpolarized lactate-to-pyruvate ratio (Part B)

  Up to 6 months

• Median percent change from baseline in intra-tumoral HP Urea AUC (Part B)

  Up to 6 months

• Objective response rate (ORR) (Part B)

  Up to 6 months

Study Arms (2)

Part A / Phase 1: Feasibility Run-In

EXPERIMENTAL

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; Procedure: Magnetic Resonance Imaging (MRI); Drug: 13C,15N-Urea

Part B/ Phase II: Biomarker Cohort

EXPERIMENTAL

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; Procedure: Magnetic Resonance Imaging (MRI); Drug: 13C,15N-Urea

Interventions

Hyperpolarized 13C-Pyruvate DRUG

Given IV

Also known as: Hyperpolarized (HP) carbon^13 (13C)-pyruvate, HP-13C

Part A / Phase 1: Feasibility Run-In; Part B/ Phase II: Biomarker Cohort

Magnetic Resonance Imaging (MRI) PROCEDURE

Imaging procedure

Also known as: MRI

Part A / Phase 1: Feasibility Run-In; Part B/ Phase II: Biomarker Cohort

13C,15N-Urea DRUG

Given IV

Part A / Phase 1: Feasibility Run-In; Part B/ Phase II: Biomarker Cohort

Eligibility Criteria

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

You may qualify if:

• 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).
• The participant is able and willing to comply with study procedures and provide signed and dated informed consent.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• 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).
• Participants age 18 and older.
• Part B only:
• Planned treatment for disease with either standard of care regimen or an investigational agent.

You may not qualify if:

• Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent.
• Patients with contra- indications to MRI, such as cardiac pacemakers or non-compatible intracranial vascular clips.
• Patients with a metallic implant or device that distorts local magnetic field and compromises the quality of MR imaging.
• 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.
• Patients with congestive heart failure or New York Heart Association (NYHA) status \>= 2.
• Patients who are pregnant or lactating.
• 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.
• Any condition that, in the opinion of the Principal Investigator,

Sponsors & Collaborators

• Robert Bok, MD, PhD: lead
• National Institute for Biomedical Imaging and Bioengineering (NIBIB): collaborator
• National Cancer Institute (NCI): collaborator
• Sigma-Aldrich: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

MeSH Terms

Interventions

Magnetic Resonance Spectroscopy

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Robert Bok, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Louise Magat

CONTACT

(415) 502-1822; Louise.Magat@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 25, 2022
• First Posted: October 31, 2022
• Study Start: December 15, 2022
• Primary Completion: January 31, 2026
• Study Completion: January 31, 2026
• Last Updated: March 24, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)