Hyperpolarized Pyruvate (13C) MR Imaging in Monitoring Patients With Prostate Cancer on Active Surveillance

A Phase 2 Study of Magnetic Resonance (MR) Imaging With Hyperpolarized Pyruvate (13C) in Patients With Prostate Cancer on Active Surveillance

This phase II trial studies the side how well hyperpolarized carbon C 13 pyruvate (HP C-13 pyruvate) magnetic resonance imaging (MRI) works in monitoring patients with prostate cancer on active surveillance who have not received treatment. Diagnostic procedures, such as MRI, may help visualize HP C-13 pyruvate uptake and breakdown in tumor cells.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Prostate Adenocarcinoma
• Intervention / Treatment: Procedure: Magnetic Resonance Spectroscopic Imaging; Drug: Hyperpolarized Carbon C 13 Pyruvate; Procedure: MRI Ultrasound Fusion Guided Biopsy

Detailed Description

PRIMARY OBJECTIVES:

I. Optimize the imaging sequences that maximize signal-to-noise ratio (SNR) and intra-tumoral conversion of HP 13C pyruvate to lactate (kPL) and HP 13C pyruvate to glutamate (kPG) in regions of tumor versus (vs.) adjacent benign tissue as assessed by multi-parametric MRI (mpMRI) imaging characteristics. (Part 1) II. Determine the association between intra-tumoral kPL and kPG with Gleason grade determined during magnetic resonance (MR)/ultrasound (US)-guided fusion prostate biopsies obtained within 6 months following baseline HP C-13 pyruvate MR exam. (Part 2)

SECONDARY OBJECTIVES:

I. Evaluate the intra-patient variability in intra-tumoral kPL and kPG with repeated dose studies.

II. Determine the association between peak intra-tumoral kPL observed on baseline imaging with serum prostate specific antigen (PSA).

III. 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.

IV. Describe the frequency of up-grading of tumor with MR/US-guided fusion biopsy obtained following baseline HP C-13 MR exam.

V. Further characterize the safety profile of HP C-13 pyruvate injections.

EXPLORATORY OBJECTIVES:

I. Correlate peak intra-tumoral kPL with results of gene expression profiling using DECIPHER assay.

II. Correlate peak intra-tumoral kPL and kPG with DECIPHER GRID tumor ribonucleic acid (RNA) expression of relevant components of the glycolytic pathway including lactate dehydrogenase (LDH), pyruvate dehydrogenase (PDH), aconitate hydratase (aconitase), myelocytomatosis oncogene (MYC), monocarboxylate transporter 4 (MCT4) (lactate transporter).

III. For patients who undergo optional follow-up HP C-13 pyruvate/MRI 6-15 months following baseline scan, determine the mean percent change from baseline in intra-tumoral kPL and kPG and whether the change from baseline is associated change in clinical risk assessment as determined by University of California, San Francisco (UCSF)-Cancer of the Prostate Risk Assessment (CAPRA) risk score.

OUTLINE:

Patients receive hyperpolarized carbon C 13 pyruvate intravenously (IV) over less than one minute, then undergo magnetic resonance spectroscopic imaging (MRSI) after 1-2 minutes. Within 15-60 minutes, patients may receive optional hyperpolarized carbon C 13 pyruvate and undergo MRSI. Patients also undergo MR/US fusion-guided prostate biopsy within 12 weeks following HP C-13 MRSI.

After completion of study, patients will be followed up periodically.

• Study Type: Interventional
• Enrollment (Estimated): 60
• 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
      • Contact: Phone Number: 877-827-3222; Email: cancertrials@ucsf.edu
      • 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:

• The subject has biopsy-proven adenocarcinoma of the prostate with low to intermediate risk disease by UCSF-CAPRA scoring at study entry.
• For Part 1: Patient planning to enroll or currently on active surveillance; For Part 2: Currently enrolled on active surveillance with planned fusion biopsy within 12 weeks following completion of baseline HP C-13 pyruvate/mpMRI on study.
• The subject 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.
• Absolute neutrophil count (ANC) >= 1000 cells/microliter (uL).
• Hemoglobin >= 9.0 gm/deciliter (dL).
• Platelets >= 75,000 cells/uL.
• Estimated creatinine clearance* >= 50 milliliter (mL)/min by the Cockcroft Gault equation.
• Total bilirubin =< 1.5 x upper limit of normal (ULN) or if =< 3 x ULN if known/suspected Gilbert's
• Aspartate aminotransferase (AST) =< 1.5 x ULN.
• Alanine aminotransferase (ALT) =< 1.5 x ULN.

Exclusion Criteria:

• Patients without evidence of any prostate cancer on most recent prostate biopsy performed prior to study entry.
• Current or prior androgen deprivation therapy including luteinizing hormone-releasing hormone (LHRH) analogue or oral anti-androgen therapy. Previous use of a 5-alpha reductase inhibitor is allowed, provided it was discontinued at least 28 days prior to baseline C-13 HP pyruvate MRI
• Prior radiation treatment of the prostate.
• Prostate biopsy performed within 14 days prior to baseline C-13 HP pyruvate MRI.
• Poorly controlled hypertension, with blood pressure at study entry > 160 mm Hg systolic or > 100 mmg Hg diastolic. Treatment with anti-hypertensives and re-screening is permitted.
• Congestive heart failure with New York Heart Association (NYHA) status >= 2.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Diagnostic (HP C-13 MRI); Patients receive hyperpolarized carbon C 13 pyruvate IV over less than one minute, then undergo MRSI after 1-2 minutes. Within 15-60 minutes, patients may receive optional hyperpolarized carbon C 13 pyruvate and undergo MRSI. Patients also undergo MR/US fusion-guided prostate biopsy within 12 weeks following HP C-13 MRSI.

Procedure: Magnetic Resonance Spectroscopic Imaging; Undergo MRSI; Other Names: 1H-nuclear magnetic resonance spectroscopic imaging; Magnetic Resonance Spectroscopy; MRS; MRS Imaging; MRSI; Proton Magnetic Resonance Spectroscopic Imaging; Hydrogen-1 (1H)- Nuclear Magnetic Resonance Spectroscopic Imaging; Drug: Hyperpolarized Carbon C 13 Pyruvate; Given IV; Other Names: Hyperpolarized 13C-Pyruvate; Hyperpolarized Pyruvate (13C); Procedure: MRI Ultrasound Fusion Guided Biopsy; Undergo MR/US fusion-guided prostate biopsy; Other Names: Fusion Biopsy; Fusion Guided Biopsy; Fusion-Guided Biopsy; MR Fusion Biopsy; MRI-Ultrasound Fusion Biopsy; MRI/Ultrasound Fusion Biopsy; MRI/US Biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Signal-to-noise ratio (SNR) of hyperpolarized lactate	Assessed by multi-parametric magnetic resonance imaging (mpMRI) characteristics.	At Baseline
Intra-tumoral C-pyruvate to lactate (kPL)	Assessed by multi-parametric magnetic resonance imaging (mpMRI) characteristics	At Baseline
Intra-tumoral C-pyruvate to glutamate (kPG)	Assessed by multi-parametric magnetic resonance imaging (mpMRI) characteristics	At Baseline
Association between intra-tumoral C-pyruvate to lactate (kPL) with Gleason grade	kPL will be compared with the pathologic Gleason grade determined using tissue from an MR/US-guided fusion prostate biopsy. Measured kPL will be compared by pathologic Gleason grade using an ANOVA model. If there is an overall difference, the Newman-Keuls post hoc test will be used to determine which tissue pairs differ.	Within 12 weeks following baseline HP C-13 pyruvate MR exam
Association between intra-tumoral C-pyruvate to glutamate (kPG) with Gleason grade	kPG will be compared with the pathologic Gleason grade determined using tissue from an MR/US-guided fusion prostate biopsy. Measured kPG will be compared by pathologic Gleason grade using an ANOVA model. If there is an overall difference, the Newman-Keuls post hoc test will be used to determine which tissue pairs differ.	Within 12 weeks following baseline HP C-13 pyruvate MR exam

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intra-patient variability in kPL	Intra-patient variability in the kPL will be summarized by the intraclass correlation and presented with a 90% confidence interval.	Up to 15 months
Intra-patient variability in kPG	Intra-patient variability in the kPG will be summarized by the intraclass correlation and presented with a 90% confidence interval.	Up to 15 months
Contrast between kPL and kPG in regions of tumor	The kPL and kPG will be contrasted in regions of tumor. Determined with prostate imaging reporting and data system (PI-RADS) version 2 classification score (1 through 5)	Up to 15 months
Comparison of kPL and kPG with apparent diffusion coefficient in region of tumor	The kPL and kPG will be compared with apparent diffusion coefficient in region of tumor. Determined by comparison to peak intra-tumoral apparent diffusion coefficient (ADC) value	Up to 15 months
Incidence of adverse events graded	According to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.	Up to 15 months
Association between peak intra-tumoral kPL observed on baseline imaging with serum PSA	Determine the association between peak intra-tumoral kPL observed on baseline imaging with serum PSA. The study cohort will be dichotomized by mean intra-tumoral kPL above and below the median and the mean serum PSA will be compared between the two dichotomized subgroups using Mann-Whitney test.	At Baseline
Describe frequency of up-grading of tumor	Describe the frequency of up-grading of tumor with MR/US-guided fusion biopsy obtained following baseline HP C-13 MR exam	Within 12 weeks following baseline HP C-13 pyruvate MR exam

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Cancer Institute (NCI); 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): July 18, 2018
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): October 31, 2025

Study Registration Dates

• First Submitted: February 20, 2019
• First Submitted That Met QC Criteria: April 26, 2019
• First Posted (Actual): May 1, 2019

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Imaging
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 175516; NCI-2018-02195 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); R01CA211150 (U.S. NIH Grant/Contract); R01EB017449 (U.S. NIH Grant/Contract); U01CA232320-01A1 (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