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

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03933670
• Other study ID #: 175516
• Secondary ID: NCI-2018-02195R0
• Status: Recruiting
• Phase: Phase 2
• Start date: July 18, 2018
• Est. completion date: October 31, 2025

Study information

• Verified date: February 2024
• Source: University of California, San Francisco
• Contact: Louise Magat
• Phone: (415) 502-1822
• Email: Louise.Magat[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: October 31, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Prostate Adenocarcinoma
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Hyperpolarized Carbon C 13 Pyruvate
Given IV

Procedure:
• Magnetic Resonance Spectroscopic Imaging
Undergo MRSI
• MRI Ultrasound Fusion Guided Biopsy
Undergo MR/US fusion-guided prostate biopsy

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
University of California, San Francisco	National Cancer Institute (NCI), National Institute for Biomedical Imaging and Bioengineering (NIBIB)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Signal-to-noise ratio (SNR) of hyperpolarized lactate	Assessed by multi-parametric magnetic resonance imaging (mpMRI) characteristics.	At Baseline
Primary	Intra-tumoral C-pyruvate to lactate (kPL)	Assessed by multi-parametric magnetic resonance imaging (mpMRI) characteristics	At Baseline
Primary	Intra-tumoral C-pyruvate to glutamate (kPG)	Assessed by multi-parametric magnetic resonance imaging (mpMRI) characteristics	At Baseline
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Incidence of adverse events graded	According to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.	Up to 15 months
Secondary	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
Secondary	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