Hyperpolarized 13C MRI As a Biomarker in Advanced Solid Tumors

Robert Bok, MD, PhD

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Advanced Solid Tumor

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05599048

22924

5R01CA256740-02 (U.S. NIH Grant/Contract)

NCI-2022-09149 (Registry Identifier)

5U01EB026412-04 (U.S. NIH Grant/Contract)

P41EB013598-11 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 65 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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,

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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65 participants in 2 patient groups

Part A / Phase 1: Feasibility Run-In

Experimental group

Description:

Participants will undergo MR imaging at a single time point. Imaging will take one day and no follow up is planned.

Treatment:

Drug: 13C,15N-Urea

Drug: Hyperpolarized 13C-Pyruvate

Procedure: Magnetic Resonance Imaging (MRI)

Part B/ Phase II: Biomarker Cohort

Experimental group

Description:

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.

Treatment:

Drug: 13C,15N-Urea

Drug: Hyperpolarized 13C-Pyruvate

Procedure: Magnetic Resonance Imaging (MRI)