Magnetic Resonance (MR) Imaging With Hyperpolarized 13C-Pyruvate +/- 13C,15N-Urea in Patients With Prostate Cancer

A Phase 2 Study of Magnetic Resonance (MR) Imaging With Hyperpolarized 13C-Pyruvate +/- 13C,15N-Urea in Patients With Prostate Cancer Undergoing Radiation Therapy

This is a Phase 2 clinical study of hyperpolarized (HP) 13C-pyruvate (13C), 15N-urea (13C,15N) metabolic MR imaging in prostate cancer patients who are undergoing or have received radiation therapy for prostate cancer.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: hyperpolarized pyruvate +/-urea (13C/15N); Procedure: Multi-parametric magnetic resonance imaging (mpMRI); Procedure: Radiotherapy (RT); Biological: Non-interventional hormone therapy; Procedure: Prostate Biopsy; Radiation: Non-investigational External beam radiotherapy (EBRT)

Detailed Description

PRIMARY OBJECTIVES:

I. Part 1: To Optimize the imaging sequences that maximize signal-to-noise ratio (SNR) and intra-tumoral kPL and kPG in regions of tumor vs. adjacent benign tissue as assessed by mpMRI imaging characteristics.

II. Part 2A To perform HP 13C-MRI and measure the changes in tumoral kPL and kPG.

III. Part 2B: To perform HP 13C-MRI and study the metabolic effects (changes in tumor kPL and kPG).

IV. Part 3: To perform HP 13C-MRI at time of Biochemical Failure and measure tumoral kPL and kPG, in previously external beam radiation therapy (EBRT) treated patients.

SECONDARY OBJECTIVES:

I. To evaluate the intra-patient variability in intra-tumoral kPL and kPG with repeated dose studies (Part 1, 2 & 3).

II. To determine the association between peak intra-tumoral kPL observed on baseline imaging with serum PSA. (Part 2 & 3).

III. To determine the association between changes in intra-tumor kPL after 4-12 weeks of systemic hormone therapy and PSA response (Part 2B).

IV. To compare and contrast intra-tumoral kPL and kPG with Prostate Imaging Reporting and Data System (PI-RADS) version 2 and individual mpMRI parameters including apparent diffusion coefficient (ADC) on diffusion-weighted imaging (Part 1, 2 & 3).

V. To describe the frequency of up-grading of tumor with MR/US-guided fusion biopsy obtained following baseline HP-MRI exam. (Part 3).

VI. To further characterize the safety profile of HP C-13 pyruvate injections (Part 1, 2 & 3).

VII. For patients imaged with HP 13C-MRI at time of biochemical failure post-EBRT, correlate peak intra-tumoral kPL and kPG with radiotherapy dose distributions from EBRT course (Part 3).

VIII. For studies incorporating HP 13C-urea, the baseline and the on-treatment changes in urea AUC parameter will be measured and compared to kPL endpoints of the same lesions (Part 1, 2 & 3).

OUTLINE:

The study is divided into 3 parts. Part 1: Participants undergo imaging as part of a multi-parametric magnetic resonance imaging (mpMRI) exam to determine exact parameters for imaging.

Part 2A: Participants planned for external beam radiotherapy (EBRT) Part 2B: Participants with high-risk localized prostate cancer planned to receive primary radiation therapy with concurrent systemic hormone therapy Part 3: Evaluable EBRT participants scanned at time of biochemical failure and MR/US fusion-guided prostate biopsy within 12 weeks. Participants have the option of undergoing a follow up HP Pyruvate +/- Urea MR exam 6-15 months following the baseline scan.

All participants will receive a scan at baseline and other procedures may be performed as part of routine, non-interventional standard of care at the time of biochemical failure, including serial prostate-specific antigen (PSA) monitoring and gene expression profiling of tumor tissue. Participants will be followed for 24 months after last procedure or removal from study, or until death, whichever occurs first.

• Study Type: Interventional
• Enrollment (Estimated): 161
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Louise Magat; Phone Number: (415) 502-1822; Email: Louise.Magat@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco
      • Contact: Louise Magat; Phone Number: (415) 502-1822; Email: Louise.Magat@ucsf.edu
      • Principal Investigator: Robert Bok, MD, PhD
      • Contact: Phone Number: 877-827-3222; Email: cancertrials@ucsf.edu
      • Sub-Investigator: Anthony Wong, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants must have biopsy-proven adenocarcinoma of the prostate, as determined by medical chart review.

2. For:

   1. Part 1: Participants post-radiation therapy or currently considering EBRT.
   2. Part 2A: Participants currently scheduled for or considering EBRT (no neo-adjuvant therapy planned).
   3. Part 2B: Participants currently scheduled for or considering EBRT and neo-adjuvant therapy is planned. The participant has biopsy-proven adenocarcinoma of the prostate with high-risk disease, defined by the presence of at least two of following criteria: a tumor stage of T3 or T4, a Gleason score of 8 to 10, or a PSA level ≥40 ng/mL) and the participant must be planning to receive androgen deprivation therapy (ADT) with an Luteinizing hormone-releasing hormone (LHRH) agonist or antagonist. The addition of an androgen-receptor (AR) signaling inhibitor (e.g., abiraterone, bicalutamide,apalutamide, enzalutamide or darolutamide) will be allowed.
   4. Part 3: Participants who have previously received radiation treatment to the prostate and are exhibiting signs of biochemical failure, with planned fusion biopsy within 12 weeks following completion of baseline HP 13C pyruvate +/-urea mpMRI.
3. Participant is able and willing to comply with study procedures and provide signed and dated informed consent.
4. Eastern Cooperative Oncology Group (ECOG) performance status <= 1.
5. Age >= 18 years old at time of study entry.
6. Ability to understand and the willingness to sign a written informed consent document.

7. Demonstrates adequate organ function as defined below:

   1. White Blood Cell count (WBC) >=4000 cells/μL.
   2. Hemoglobin ≥9.0 gm/dL.
   3. Platelets ≥75,000 cells/μL.
   4. Renal Function > 30 Epithelial Growth Factor Receptor (eGFR).

Exclusion Criteria:

1. Evidence of pelvic regional or distant metastatic disease on conventional imaging (MRI, computed tomography or whole body bone scan) or prostate-specific membrane antigen (PSMA) Positron Emission Tomography (PET) imaging. PSMA-avid lymph nodes confined to the pelvis will be allowed if <1 centimeter (cm).
2. Prostate biopsy performed within 14 days prior to baseline C-13 HP pyruvate MRI.
3. Poorly controlled hypertension, with blood pressure at study entry > 160 mm Hg systolic or > 100 mm Hg diastolic. Treatment with anti-hypertensives and re-screening is permitted.
4. Contraindication to or inability to tolerate MRI with endorectal coil (e.g. severe claustrophobia, presence of cardiac pacemaker, aneurysm clip, severe or painful hemorrhoids, rectal stricture).
5. Congestive heart failure with New York Heart Association (NYHA) status >= 2.
6. History of clinically significant ECG abnormality, including QT prolongation, a family history of prolonged QT interval syndrome or myocardial infarction within 6 months of study entry.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Image Optimization Group; Participants will undergo Hyperpolarized 13C-Pyruvate +/- 13C,15N-Urea imaging as part of a multi-parametric magnetic resonance imaging (mpMRI) exam, with the primary objective of optimizing imaging sequences and techniques to maximize signal-to-noise ratio of imaging modality.	Drug: hyperpolarized pyruvate +/-urea (13C/15N); Given IV; Other Names: 13C-Pyruvate,15N-urea; Procedure: Multi-parametric magnetic resonance imaging (mpMRI); Imaging scan; Other Names: mpMRI
Experimental: Part 2B: Prospective imaging (High-risk localized prostate cancer); Participants with with high-risk localized prostate cancer and have pre-planned, non-interventional primary radiation therapy (RT) with concurrent, systemic, non-interventional hormone therapy will undergo HP Pyruvate+/-Urea mpMRI at baseline prior to the start of systemic hormone therapy, 4-12 weeks after the initiation of systemic hormone therapy (prior to radiation therapy), at 3 months post-radiation therapy, and at +1yr post-radiation therapy.	Drug: hyperpolarized pyruvate +/-urea (13C/15N); Given IV; Other Names: 13C-Pyruvate,15N-urea; Procedure: Multi-parametric magnetic resonance imaging (mpMRI); Imaging scan; Other Names: mpMRI; Procedure: Radiotherapy (RT); Radiation therapy given outside of this study; Other Names: RT; Biological: Non-interventional hormone therapy; Therapy given outside of this study as part of standard of care; Other Names: Non-interventional, systemic hormone therapy
Experimental: Part 2A: Prospective imaging (External beam radiotherapy (EBRT) Participants); Participants with pre-planned, non-interventional stereotactic body radiotherapy (EBRT) will undergo an HP Pyruvate +/-Urea mpMRI exam at baseline, at 3 months post-EBRT treatment and at 1yr post-treatment.	Drug: hyperpolarized pyruvate +/-urea (13C/15N); Given IV; Other Names: 13C-Pyruvate,15N-urea; Procedure: Multi-parametric magnetic resonance imaging (mpMRI); Imaging scan; Other Names: mpMRI; Radiation: Non-investigational External beam radiotherapy (EBRT); External beam radiotherapy given outside of this study; Other Names: EBRT
Experimental: Part 3: EBRT participants at time of biochemical recurrence (BCR); Evaluable EBRT participants who undergo HP Pyruvate +/-Urea mpMRI at time of biochemical failure, followed by magnetic resonance (MR) / ultrasound (US) fusion-guided prostate biopsy within 12 weeks following baseline MR exam. Participants in this group have the option of undergoing a follow up HP Pyruvate +/-Urea MR exam 6-15 months following the baseline scan, to evaluate for any interval change.	Drug: hyperpolarized pyruvate +/-urea (13C/15N); Given IV; Other Names: 13C-Pyruvate,15N-urea; Procedure: Multi-parametric magnetic resonance imaging (mpMRI); Imaging scan; Other Names: mpMRI; Procedure: Prostate Biopsy; Biopsies may be taken from Trans-rectal ultrasound (TRUS) -visible lesion at the urologist's discretion; Other Names: Biopsy; Radiation: Non-investigational External beam radiotherapy (EBRT); External beam radiotherapy given outside of this study; Other Names: EBRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Signal-to-noise ratio (Part 1)	A signal-to-noise ratio 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.	Day of MR imaging (1 day)
Mean kPL at time of biochemical failure (Part 3)	The mean kPL for participants with biochemical failure will be reported.	Up to 24 months
Mean kPG at time of biochemical failure (Part 3)	The mean kPG for participants with biochemical failure will be reported.	Up to 24 months
Mean HP 13C-pyruvate to lactate metabolic rate of conversion (kPL) over time (Part 2A)	The mean percent change in tumoral kPL between baseline and 1-year post-EBRT will be reported.	Up to 24 months
Mean HP 13C-pyruvate to glutamate metabolic rate of conversion (kPG) over time (Part 2A)	The mean percent change in tumoral kPG between baseline and 1-year post-EBRT will be reported.	Up to 24 months
Mean change in on-treatment kPL over time (Part 2B)	Mean percent change in tumoral kPL for participants receiving systemic hormone therapy between baseline and 1 -year post-EBRT will be reported.	Up to 24 months
Mean change in on-treatment kPG over time (Part 2B)	Mean percent change in tumoral kPG for participants receiving systemic hormone therapy between baseline and 1 -year post-EBRT will be reported.	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intra-patient variability of kPL	Intra-patient variability in the kPL will be summarized by the intraclass correlation and presented with a 90% confidence interval when multiple HP-MRI scans are obtained for a participant.	Up to 12 months
Intra-patient variability of kPG	Intra-patient variability in the kPG will be summarized by the intraclass correlation and presented with a 90% confidence interval when multiple HP-MRI scans are obtained for a participant.	Up to 12 months
Mean intra-tumoral kPL above and below the median PSA (Parts 2-3) and the mean serum PSA	The study cohort will be dichotomized by mean intra-tumoral kPL obtained at baseline with median serum PSA and will be compared between the two dichotomized subgroups using Mann-Whitney test.	Up to 24 months
Correlation of kPL with Prostate Imaging Reporting and Data System (PI-RADS) version 2 classification score	Spearman's rank order correlation coefficient will be used to determine the relationship between kPL with PI-RADS version 2 classification score (1 through 5; PI-RADS 1 - Very low (clinically significant cancer is highly unlikely to be present) PI-RADS 2 - Low (clinically significant cancer is unlikely to be present)). The Spearman's correlation coefficient (rs) measures the strength and direction of association between two variables. The Spearman correlation coefficient, rs, can take values from +1 to -1 where a value of +1 indicates a perfect association, an rs of 0 indicates no association and an rs of -1 indicates a perfect negative association. The closer rs is to 0, the weaker the association.	Up to 24 months
Correlation of kPG with PI-RADS version 2 classification score	Spearman's rank order correlation coefficient will be used to determine the relationship between kPL with PI-RADS version 2 classification score (1 through 5; PI-RADS 1 - Very low (clinically significant cancer is highly unlikely to be present) PI-RADS 2 - Low (clinically significant cancer is unlikely to be present)). The Spearman's correlation coefficient (rs) measures the strength and direction of association between two variables. The Spearman correlation coefficient, rs, can take values from +1 to -1 where a value of +1 indicates a perfect association, an rs of 0 indicates no association and an rs of -1 indicates a perfect negative association. The closer rs is to 0, the weaker the association.	Up to 24 months
Proportion of participants with concordant mismatch of low HP 13C-urea perfusion (ureaAUC)	A secondary endpoint will be to identify concordant mismatch of low HP 13C-urea perfusion (ureaAUC) in lesions assessed for kPL.	Up to 24 months
Mean percent change in kPL over time for participants with optional scan	For the subset of participants who undergo optional follow up MR scan following baseline MRI, the mean percent change from baseline in kPL will be descriptively reported using summary statistics.	Up to 24 months
Number of participants with reported treatment-related adverse events	The incidence of adverse events as graded by Common Toxicity Criteria version 5.0 will be determined	From start of HP 13C-pyruvate MR imaging to 20 minutes after the procedure for all scans

Collaborators and Investigators

• Sponsor: Robert Bok, MD, PhD
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Robert Bok, MD, PhD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): October 31, 2032

Study Registration Dates

• First Submitted: April 25, 2024
• First Submitted That Met QC Criteria: April 25, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): January 7, 2026
• Last Update Submitted That Met QC Criteria: January 6, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Imaging Studies; Hyperpolarized 13C-Pyruvate
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Investigative Techniques; Therapeutics; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Diagnostic Techniques, Surgical; Radiotherapy; Biopsy
• Other Study ID Numbers: 24922; 5R01CA238379 (U.S. NIH Grant/Contract); NCI-2024-03775 (Registry Identifier: NCI Clinical Trials Reporting Program)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No