Clinical trial NCT02526368: Pilot Study of (MR) Imaging with Pyruvate (13C) to Detect High Grade Prostate Cancer
Official title: A Pilot Study of Magnetic Resonance (MR) Imaging with Hyperpolarized Pyruvate (13C) to Detect High Grade Localized Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Prostate Cancer
Localized Prostate Carcinoma
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: American Cancer Society, Inc.
name: National Cancer Institute (NCI)
name: National Institute for Biomedical Imaging and Bioengineering (NIBIB)
First posted: 2015-08-18
Enrollment: 80
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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

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.

Eligibility criteria: 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
* Absolute neutrophil count (ANC) \>= 1500 cells/microliter (uL)
* Hemoglobin \>= 9.0 mg/dL
* Platelets \>= 75,000 cells/uL
* Estimated creatinine clearance \>= 50 mL/min (by the Cockcroft Gault equation)
* Bilirubin \< 1.5 x upper limit of normal (ULN) (unless Gilbert's is suspected)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 1.5 x ULN

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.
* 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.

Primary outcomes:
measure: Mean peak intra-tumoral lactate/pyruvate (lac/pyr) ratio by pathological grade (Cohort A)
timeFrame: Baseline, 1 day
measure: Mean peak intra-tumoral lactate/pyruvate (lac/pyr) ratio (Cohort B)
timeFrame: Baseline, 1 day
measure: Mean lactate area under curve (AUC) by pathological grade (Cohort A)
timeFrame: Baseline, 1 day
measure: Mean lactate area under curve (AUC) (Cohort B)
timeFrame: Baseline, 1 day
measure: Mean peak conversion of HP 13C pyruvate to lactate (kPL) by pathological grade (Cohort A)
timeFrame: Baseline, 1 day
measure: Mean peak conversion of HP 13C pyruvate to lactate (kPL) (Cohort B)
timeFrame: Baseline, 1 day
measure: Mean Urea AUC by pathological grade (Cohort A)
timeFrame: Baseline, 1 day
measure: Mean Urea AUC (Cohort B)
timeFrame: Baseline, 1 day
measure: Mean urea transfer constant (Ktrans) by pathological grade (Cohort A)
timeFrame: Baseline, 1 day
measure: Mean urea transfer constant (Ktrans) (Cohort B)
timeFrame: Baseline, 1 day
Secondary outcomes:
measure: Optimal cut-off value of peak lactate to pyruvate ratio (lac/pyr) (Cohort A)
timeFrame: Baseline, 1 day
measure: Optimal cut-off value of peak lactate to pyruvate ratio (lac/pyr) (Cohort B)
timeFrame: Baseline, 1 day
measure: Optimal cut-off value of lac/pyr area under the curve (AUC) (Cohort A)
timeFrame: Baseline, 1 day
measure: Optimal cut-off value of lac/pyr area under the curve (AUC) (Cohort B)
timeFrame: Baseline, 1 day
measure: Optimal cut-off value of 13C pyruvate to lactate (kPL) rate (Cohort A)
timeFrame: Baseline, 1 day
measure: Optimal cut-off value of 13C pyruvate to lactate (kPL) rate (Cohort B)
timeFrame: Baseline, 1 day
measure: Optimal cut-off value of urea AUC (Cohort A)
timeFrame: Baseline, 1 day
measure: Optimal cut-off value of urea AUC (Cohort B)
timeFrame: Baseline, 1 day
measure: Optimal cut-off value of urea transfer constant (ktrans) (Cohort A)
timeFrame: Baseline, 1 day
measure: Optimal cut-off value of urea transfer constant (ktrans) (Cohort B)
timeFrame: Baseline, 1 day
measure: Proportion of participants with Treatment-Related Adverse Events
timeFrame: Baseline, 1 day
measure: Compare lactate/pyruvate area under curve (AUC) with Prostate Imaging Reporting and Data System (PI-RADS)
timeFrame: Baseline, 1 day
measure: Compare peak lactate/pyruvate with PI-RADS
timeFrame: Baseline, 1 day
measure: Compare pyruvate to lactate (kPL) with PI-RADS
timeFrame: Baseline, 1 day
measure: Compare urea AUC with PI-RADS
timeFrame: Baseline, 1 day
measure: Compare urea transfer constant (Ktrans) with PI-RADS
timeFrame: Baseline, 1 day
measure: Mean difference in Intra-patient peak lac/pyr
timeFrame: Baseline, 1 day
measure: Mean difference in Intra-patient lac/pyr AUC
timeFrame: Baseline, 1 day
measure: Mean difference in Intra-patient kPL
timeFrame: Baseline, 1 day
measure: Mean difference in Intra-patient Urea AUC
timeFrame: Baseline, 1 day
measure: Mean difference in Intra-patient Urea ktrans
timeFrame: Baseline, 1 day
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: