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.
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
65
University of California, San Francisco
San Francisco, California, United States
RECRUITINGSignal-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.
Time frame: 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
Time frame: 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)
Time frame: Up to 25 days
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)
Time frame: 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)
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Time frame: Up to 6 months
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.
Time frame: 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
Time frame: 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)
Time frame: 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).
Time frame: 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.
Time frame: 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).
Time frame: 1 day