Overview
This is a single center prospective imaging study investigating the utility of hyperpolarized 13C-pyruvate/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.
Description
PRIMARY OBJECTIVES:
Phase I/Part A
- To optimize the signal-to-noise ratio in detecting intra-tumoral hyperpolarized 13C pyruvate/lactate signal using metabolic MR imaging in participants 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 and pyruvate-to-lactate kinetic constant (kPL) after initiation of SOC treatment.
SECONDARY OBJECTIVES:
Phase I/Part A
- To further characterize the safety profile of hyperpolarized 13C-pyruvate.
- 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 after initiation of SOC treatment.
- To further characterize the safety profile of hyperpolarized 13C pyruvate.
- To determine the reproducibility of intra-tumoral HP lac/pyr ratio 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.
Eligibility
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:
- 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,