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

Study Overview
=================
Brief 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.

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.

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

Conditions
-----------------
Prostate Adenocarcinoma, Prostate Cancer

Intervention / Treatment
-----------------
* Drug: Hyperpolarized Carbon C 13 Pyruvate
* Procedure: Magnetic Resonance Spectroscopic Imaging
* Procedure: MRI Ultrasound Fusion Guided Biopsy


Participation Criteria
=================
Eligibility Criteria
-----------------
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 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) Congestive heart failure with New York Heart Association (NYHA) status >= 2

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (HP C-13 MRI)<br>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. | Drug: Hyperpolarized Carbon C 13 Pyruvate<br>* Given IV<br>* Other names: Hyperpolarized Pyruvate (13C);Procedure: Magnetic Resonance Spectroscopic Imaging<br>* Undergo MRSI<br>* Other names: Proton Magnetic Resonance Spectroscopic Imaging;Procedure: MRI Ultrasound Fusion Guided Biopsy<br>* Undergo MR/US fusion-guided prostate biopsy<br>* Other names: 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Imaging