Clinical trial NCT03933670: Hyperpolarized Pyruvate (13C) MR Imaging in Monitoring Patients with Prostate Cancer on Active Surveillance
Official title: A Phase 2 Study of Magnetic Resonance (MR) Imaging with Hyperpolarized Pyruvate (13C) in Patients with Prostate Cancer on Active Surveillance
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Prostate Adenocarcinoma
Prostate Cancer
Keywords: Imaging
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: National Institute for Biomedical Imaging and Bioengineering (NIBIB)
First posted: 2019-05-01
Enrollment: 60
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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.
* Congestive heart failure with New York Heart Association (NYHA) status \>= 2.

Primary outcomes:
measure: Signal-to-noise ratio (SNR) of hyperpolarized lactate
timeFrame: At Baseline
measure: Intra-tumoral C-pyruvate to lactate (kPL)
timeFrame: At Baseline
measure: Intra-tumoral C-pyruvate to glutamate (kPG)
timeFrame: At Baseline
measure: Association between intra-tumoral C-pyruvate to lactate (kPL) with Gleason grade
timeFrame: Within 12 weeks following baseline HP C-13 pyruvate MR exam
measure: Association between intra-tumoral C-pyruvate to glutamate (kPG) with Gleason grade
timeFrame: Within 12 weeks following baseline HP C-13 pyruvate MR exam
Secondary outcomes:
measure: Intra-patient variability in kPL
timeFrame: Up to 15 months
measure: Intra-patient variability in kPG
timeFrame: Up to 15 months
measure: Contrast between kPL and kPG in regions of tumor
timeFrame: Up to 15 months
measure: Comparison of kPL and kPG with apparent diffusion coefficient in region of tumor
timeFrame: Up to 15 months
measure: Incidence of adverse events graded
timeFrame: Up to 15 months
measure: Association between peak intra-tumoral kPL observed on baseline imaging with serum PSA
timeFrame: At Baseline
measure: Describe frequency of up-grading of tumor
timeFrame: Within 12 weeks following baseline HP C-13 pyruvate MR exam
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Ivan de Kouchkovsky, MD
role: PRINCIPAL_INVESTIGATOR
References: