Hyperpolarized 13C MRI as a Biomarker in Advanced Solid Tumors

PRIMARY OBJECTIVES:

Phase I/Part A

• 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

• 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

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

Phase II/Part B

• 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.
• To further characterize the safety profile of hyperpolarized 13C pyruvate +/- 13C,15N-urea.
• 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.

Inclusion criteria

• 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.

Exclusion criteria

• 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,