Pilot Study of (MR) Imaging With Pyruvate (13C) to Detect High Grade Prostate Cancer (pyruvate)

A Pilot Study of Magnetic Resonance (MR) Imaging With Hyperpolarized Pyruvate (13C) to Detect High Grade Localized Prostate Cancer

This pilot clinical trial studies how well magnetic resonance spectroscopic imaging (MRSI) with hyperpolarized carbon 13 (13C) pyruvate alone or in combination with 13C 15N2 Urea works in finding prostate cancer that exhibits poorly differentiated or undifferentiated cells (high-grade) and that is restricted to the site of origin, without evidence of spread (localized) in patients undergoing radical prostatectomy. Diagnostic procedures, such as MRSI with hyperpolarized carbon (13C) pyruvate, may aid in the diagnosis of prostate cancer and in discriminating high-grade from low-grade prostate cancer and benign adjacent prostate tissue

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Localized Prostate Carcinoma
• Intervention / Treatment: Drug: Hyperpolarized 13C-Pyruvate; Procedure: Magnetic Resonance Spectroscopic Imaging; Drug: Hyperpolarized 13C,15N2-urea

Detailed Description

PRIMARY OBJECTIVES:

I. To investigate the association between hyperpolarized (HP) pyruvate-to-lactate conversion (kPL) and HP urea perfusion with histologic grade of prostate cancer, including benign prostate tissue, low grade disease (primary Gleason score < 4), and high grade (primary Gleason score >= 4) prostate cancer (Cohort A).

II. To investigate the association between HP pyruvate-to-lactate conversion (kPL) and HP urea perfusion with in-field clinically significant (Gleason score >3+3) recurrent/residual prostate cancer following non-investigational High-Intensity Focused Ultrasound (HIFU) focal therapy (Cohort B)

SECONDARY OBJECTIVES:

I. Safety.

II. To determine the optimal cut-off value of peak lactate to pyruvate ratio (lac/pyr), lac/pyr area under the curve (AUC), 13C pyruvate to lactate (kPL) rate, urea AUC, and urea transfer constant (ktrans) on magnetic resonance imaging (MRI) that accurately detects primary Gleason 4 component cancer (Cohort A).

III. To determine the optimal cut-off value of peak lac/pyr, lac/pyr AUC, kPL Urea AUC, Urea ktrans and kPL-urea product (kUP) on MRI that accurately detects in-field clinically significant (ie. Gleason score >3+3) recurrent/residual prostate cancer (Cohort B only).

IV. To determine the reproducibility of peak lac/pyr, lac/pyr AUC and kPL, urea AUC and urea transfer constant (ktrans) with same-day repeated dose studies. with same-day repeated dose studies.

V. To compare peak lac/pyr, lac/pyr AUC and kPL, urea AUC, urea transfer constant (ktrans) on MRI with Prostate Imaging-Reporting and Data System (PI-RADS) assessment of multiparametric MRI in predicting regions of cancer versus benign tissue.

EXPLORATORY OBJECTIVES:

I. To correlate histologic markers, including lactate dehydrogenase A (LDHA) expression and activity level, along with Ki-67, MYC, and MCT 1 and 4 expression, with peak intra-tumoral lac/pyr ratio, lactate AUC, and kPL detected using anatomically aligned magnetic resonance (MR) cross-sectional images of the prostate gland.

II. To test for an association between mean intra-tumoral lac/pyr signal and lactate AUC, kPL, urea AUC, and urea transfer constant (ktrans) with adverse clinical and pathologic characteristics including extracapsular extension, positive nodal involvement, and failure to achieve undetectable prostate specific antigen (PSA) nadir following prostatectomy.

OUTLINE:

Participants receive either hyperpolarized carbon pyruvate (13C) or co-polarized 13C pyruvate and 13C, 15N2urea intravenously (IV) and undergo MRSI within 12 weeks of undergoing non-investigational radical prostatectomy (cohort A) or non-investigational systematic and MR-targeted biopsies (cohort B). Participants may receive optional second hyperpolarized 13C injection and dynamic 13C MRI scan performed within 15 to 60 minutes following completion of first scan.

After completion of study, participants are followed up at 24 hours.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Early Phase 1

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
      • Contact: Phone Number: 877-827-3222; Email: cancertrials@ucsf.edu
      • Principal Investigator: Hao Nguyen, MD
      • Principal Investigator: Ivan de Kouchkovsky, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Biopsy-proven adenocarcinoma of the prostate. Biopsy may be performed outside of University of California, San Francisco (UCSF), if detailed results of sextant biopsy are available. For Cohort A only, a minimum of 20 participants out of a planned enrollment of 50 patients must have high-risk disease as defined by primary Gleason score of 4 or 5 on prior prostate biopsy.
• Cohort A only: Planned radical prostatectomy at UCSF within 12 weeks following protocol MRI/MRSI.
• Cohort B only: HIFU focal therapy completed within 18 months of protocol MRI/MRSI, and planned systematic and MR-guided biopsy at UCSF within 12 weeks following protocol MRI/MRSI.
• 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

Exclusion Criteria:

• Participants who because of age less than 18 years old, general medical or psychiatric condition, or physiologic status cannot give valid informed consent.
• Participants unwilling or unable to undergo MR imaging, including patients with contraindications to MRI, such as cardiac pacemakers or non-compatible intracranial vascular clips.
• Participants who cannot tolerate or have contra-indications to endorectal coil insertion; for example, participants with a prior abdominoperineal resection of the rectum or latex allergy.

Note: The use of an endorectal coil may be waived at the discretion of the Principal Investigator upon review of available imaging with radiology, in which case this exclusion criterion will not apply.

• Patients with contra-indications to injection of gadolinium contrast; for example patients with prior documented allergy or those with inadequate renal function.
• Metallic hip implant or any other metallic implant or device that distorts local magnetic field and compromises the quality of MR imaging.
• Cryosurgery, surgery for prostate cancer, prostatic or pelvic radiotherapy prior to study enrollment. For Cohort B, HIFU focal therapy is allowed. No limit on number of prior prostate biopsies; prior transurethral prostatic resection (TURP) is not allowed.
• Current or prior androgen deprivation therapy. For Cohort A, a history of use of a 5-alpha reductase inhibitor is allowed, provided it was discontinued at least one month prior to study entry. For cohort B, a history of use of 5-α reductase inhibitor is allowed, provided it is discontinued at least 14 days to protocol MRI/MRSI.
• Poorly controlled hypertension, with blood pressure at study entry > 160/100; the addition of anti-hypertensives to control blood pressure is allowed for eligibility determination.
• Congestive heart failure or New York Heart Association (NYHA) status >= 2.
• A history of clinically significant electrocardiography (EKG) abnormalities, including QT prolongation, a family history of prolonged QT interval syndrome, or myocardial infarction (MI) within 6 months of study entry; patients with rate-controlled atrial fibrillation/flutter will be allowed on study.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: Pre-surgical Prostate Cancer patients; Participants will receive an infusion of hyperpolarized 13C-pyruvate alone or co-hyperpolarized 13C pyruvate with hyperpolarized 13C, 15N urea injection prior to metabolic/perfusion high spatial resolution MRI/1H MRSI staging exam (PROSE) with endorectal coil using both a phased-array abdominal coil and an endorectal coil will be performed within 12 weeks of subsequent non-investigational radical prostatectomy.	Drug: Hyperpolarized 13C-Pyruvate; Given IV; Other Names: Hyperpolarized Pyruvate (13C); Procedure: Magnetic Resonance Spectroscopic Imaging; Undergo MRSI; Other Names: 1H- Nuclear Magnetic Resonance Spectroscopic Imaging; MRS; MRS Imaging; MRSI; Drug: Hyperpolarized 13C,15N2-urea; Given IV; Other Names: Urea C-13; C13 Urea
Experimental: Cohort B: Post-HIFU Participants; Participants will receive an infusion of hyperpolarized 13C-pyruvate alone or co-hyperpolarized 13C pyruvate with hyperpolarized 13C, 15N urea injection prior to metabolic/perfusion high spatial resolution MRI/1H MRSI staging exam (PROSE) with endorectal coil using both a phased-array abdominal coil and an endorectal coil will be performed for participants with planned post-HIFU surveillance systematic and MR-targeted non-investigational biopsies	Drug: Hyperpolarized 13C-Pyruvate; Given IV; Other Names: Hyperpolarized Pyruvate (13C); Procedure: Magnetic Resonance Spectroscopic Imaging; Undergo MRSI; Other Names: 1H- Nuclear Magnetic Resonance Spectroscopic Imaging; MRS; MRS Imaging; MRSI; Drug: Hyperpolarized 13C,15N2-urea; Given IV; Other Names: Urea C-13; C13 Urea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean peak intra-tumoral lactate/pyruvate (lac/pyr) ratio by pathological grade (Cohort A)	Means and standard deviations for lactate area under curve will be calculated by pathologic grade (benign, low grade (primary Gleason score <4) and high grade (primary Gleason score >4)).	Baseline, 1 day
Mean peak intra-tumoral lactate/pyruvate (lac/pyr) ratio (Cohort B)	Means and standard deviations for lactate area under curve will be calculated for those with in-field recurrent/residual clinically significant prostate cancer.	Baseline, 1 day
Mean lactate area under curve (AUC) by pathological grade (Cohort A)	Means and standard deviations for lactate area under curve will be calculated by pathologic grade (benign, low grade (primary Gleason score <4) and high grade (primary Gleason score >4)). A One-way ANOVA model will be used to compare lactate area under curve by pathologic grade (benign, low grade (primary Gleason score <4) and high grade (primary Gleason score >4)).	Baseline, 1 day
Mean lactate area under curve (AUC) (Cohort B)	Means and standard deviations for lactate area under curve will be calculated for those with in-field recurrent/residual clinically significant prostate cancer.	Baseline, 1 day
Mean peak conversion of HP 13C pyruvate to lactate (kPL) by pathological grade (Cohort A)	Means and standard deviations for kPL will be calculated by pathologic grade (benign, low grade (primary Gleason score <4) and high grade (primary Gleason score >4)).	Baseline, 1 day
Mean peak conversion of HP 13C pyruvate to lactate (kPL) (Cohort B)	Means and standard deviations for kPL will be calculated for those with in-field recurrent/residual clinically significant prostate cancer.	Baseline, 1 day
Mean Urea AUC by pathological grade (Cohort A)	Means and standard deviations for Urea AUC will be calculated by pathologic grade (benign, low grade (primary Gleason score <4) and high grade (primary Gleason score >4)).	Baseline, 1 day
Mean Urea AUC (Cohort B)	Means and standard deviations for Urea AUC will be calculated for those with in-field recurrent/residual clinically significant prostate cancer.	Baseline, 1 day
Mean urea transfer constant (Ktrans) by pathological grade (Cohort A)	Means and standard deviations for Ktrans will be calculated by pathologic grade (benign, low grade (primary Gleason score <4) and high grade (primary Gleason score >4)).	Baseline, 1 day
Mean urea transfer constant (Ktrans) (Cohort B)	Means and standard deviations for Ktrans will be calculated for those with in-field recurrent/residual clinically significant prostate cancer.	Baseline, 1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with Treatment-Related Adverse Events	Assessment of the occurrence of clinically significant changes in safety variables from baseline. Safety endpoints include monitoring for the occurrence of treatment-emergent AEs. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology (Toxicity) Criteria for Adverse Events (CTCAE) version 4.0.	Baseline, 1 day
Compare lactate/pyruvate area under curve (AUC) with Prostate Imaging Reporting and Data System (PI-RADS)	To compare lactate/pyruvate AUC on MRI with PI-RADS assessment of multiparametric MRI in predicting regions of cancer versus benign tissue. Radiologists use the PI-RADS to report how likely it is that a suspicious area is a clinically significant cancer. PI-RADS scores range from 1 (most likely not cancer) to 5 (very suspicious).	Baseline, 1 day
Compare peak lactate/pyruvate with PI-RADS	To compare peak lactate/pyruvate on MRI with PI-RADS assessment of multiparametric MRI in predicting regions of cancer versus benign tissue. Radiologists use the PI-RADS to report how likely it is that a suspicious area is a clinically significant cancer. PI-RADS scores range from 1 (most likely not cancer) to 5 (very suspicious).	Baseline, 1 day
Compare pyruvate to lactate (kPL) with PI-RADS	To compare peak pyruvate to lactate (kPL) on MRI with PI-RADS assessment of multiparametric MRI in predicting regions of cancer versus benign tissue. Radiologists use the PI-RADS to report how likely it is that a suspicious area is a clinically significant cancer. PI-RADS scores range from 1 (most likely not cancer) to 5 (very suspicious).	Baseline, 1 day
Compare urea AUC with PI-RADS	To compare urea AUC on MRI with PI-RADS assessment of multiparametric MRI in predicting regions of cancer versus benign tissue. Radiologists use the PI-RADS to report how likely it is that a suspicious area is a clinically significant cancer. PI-RADS scores range from 1 (most likely not cancer) to 5 (very suspicious).	Baseline, 1 day
Compare urea transfer constant (Ktrans) with PI-RADS	To compare urea ktrans on MRI with PI-RADS assessment of multiparametric MRI in predicting regions of cancer versus benign tissue. Radiologists use the PI-RADS to report how likely it is that a suspicious area is a clinically significant cancer. PI-RADS scores range from 1 (most likely not cancer) to 5 (very suspicious).	Baseline, 1 day
Mean difference in Intra-patient kPL	Intra-patient reproducibility of kPL for patients who undergo repeated dose imaging studies, as descriptively reported using summary statistics.	Baseline, 1 day
Mean difference in Intra-patient Urea AUC	Intra-patient reproducibility of Urea AUC for patients who undergo repeated dose imaging studies, as descriptively reported using summary statistics.	Baseline, 1 day
Mean difference in Intra-patient Urea ktrans	Intra-patient reproducibility of Urea ktrans for patients who undergo repeated dose imaging studies, as descriptively reported using summary statistics	Baseline, 1 day
Mean difference in Intra-patient peak lac/pyr	Intra-patient reproducibility of peak lac/pyr for patients who undergo repeated dose imaging studies, as descriptively reported using summary statistics.	Baseline, 1 day
Mean difference in Intra-patient lac/pyr AUC	Intra-patient reproducibility of lac/pyr AUC for patients who undergo repeated dose imaging studies, as descriptively reported using summary statistics.	Baseline, 1 day
Optimal cut-off value of peak lactate to pyruvate ratio (lac/pyr) (Cohort A)	Receiver-operative-curve analyses will be performed to determine the optimal cut-point of peak lac/pyr AUC on MRI that accurately detect primary Gleason 4 prostate cancer.	Baseline, 1 day
Optimal cut-off value of peak lactate to pyruvate ratio (lac/pyr) (Cohort B)	Receiver-operative-curve analyses will be performed to determine the optimal cut-point of peak lac/pyr AUC on MRI that accurately detects in-field clinically significant (i.e. Gleason score >3+3) recurrent/residual prostate cancer.	Baseline, 1 day
Optimal cut-off value of lac/pyr area under the curve (AUC) (Cohort A)	Receiver-operative-curve analyses will be performed to determine the optimal cut-point of peak lac/pyr AUC values on MRI that accurately detect primary Gleason 4 prostate cancer	Baseline, 1 day
Optimal cut-off value of lac/pyr area under the curve (AUC) (Cohort B)	Receiver-operative-curve analyses will be performed to determine the optimal cut-point of peak lac/pyr AUC values on MRI that accurately detects in-field clinically significant (ie. Gleason score >3+3) recurrent/residual prostate cancer	Baseline, 1 day
Optimal cut-off value of 13C pyruvate to lactate (kPL) rate (Cohort A)	Receiver-operative-curve analyses will be performed to determine the optimal cut-point of kPL on MRI that accurately detect primary Gleason 4 prostate cancer.	Baseline, 1 day
Optimal cut-off value of 13C pyruvate to lactate (kPL) rate (Cohort B)	Receiver-operative-curve analyses will be performed to determine the optimal cut-point of kPL on MRI that accurately detects in-field clinically significant (ie. Gleason score >3+3) recurrent/residual prostate cancer	Baseline, 1 day
Optimal cut-off value of urea AUC (Cohort A)	Receiver-operative-curve analyses will be performed to determine the optimal cut-point of urea AUC on MRI that accurately detect primary Gleason 4 prostate cancer.	Baseline, 1 day
Optimal cut-off value of urea AUC (Cohort B)	Receiver-operative-curve analyses will be performed to determine the optimal cut-point of urea AUC on MRI that accurately detects in-field clinically significant (ie. Gleason score >3+3) recurrent/residual prostate cancer	Baseline, 1 day
Optimal cut-off value of urea transfer constant (ktrans) (Cohort A)	Receiver-operative-curve analyses will be performed to determine the optimal cut-point of urea ktrans on MRI that accurately detect primary Gleason 4 prostate cancer.	Baseline, 1 day
Optimal cut-off value of urea transfer constant (ktrans) (Cohort B)	Receiver-operative-curve analyses will be performed to determine the optimal cut-point of urea ktrans on MRI that accurately detects in-field clinically significant (ie. Gleason score >3+3) recurrent/residual prostate cancer	Baseline, 1 day

Collaborators and Investigators

• Sponsor: Ivan de Kouchkovsky, MD
• Collaborators: National Cancer Institute (NCI); American Cancer Society, Inc.; National Institute for Biomedical Imaging and Bioengineering (NIBIB)
• Investigators: Principal Investigator: Ivan de Kouchkovsky, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2016
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 14, 2015
• First Submitted That Met QC Criteria: August 14, 2015
• First Posted (Estimated): August 18, 2015

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• 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; Chemistry Techniques, Analytical; Spectrum Analysis; Magnetic Resonance Spectroscopy
• Other Study ID Numbers: 15557; R01CA211150 (U.S. NIH Grant/Contract); R01EB017449 (U.S. NIH Grant/Contract); NCI-2015-02008 (Registry Identifier: NCI Clinical Trials Reporting Program (CTRP)); U01EB026412 (U.S. NIH Grant/Contract); R01CA214554 (U.S. NIH Grant/Contract); R01CA238379 (U.S. NIH Grant/Contract); R01CA300053 (U.S. NIH Grant/Contract)

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
• product manufactured in and exported from the U.S.: No