NCT04346225

Magnetic Resonance Imaging (MRI) With Hyperpolarized Pyruvate (13C) as Diagnostic Tool in Advanced Prostate Cancer

Magnetic Resonance (MR) Imaging With Hyperpolarized Pyruvate (13C) as a Diagnostic and Response Monitoring Imaging Tool in Advanced Prostate Cancer

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 75 (estimated)
• Sponsor: Ivan de Kouchkovsky, MD · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a prospective imaging study evaluating the utility of baseline metabolic MR imaging as a diagnostic and response monitoring tool in patients with advanced prostate cancer. Preliminary pre-clinical and clinical data demonstrates the ability of HP C-13 pyruvate/metabolic MR imaging to detect high-grade prostate cancer, including cancer with neuroendocrine differentiation, as well as provide early evidence of metabolic response and resistance following application of systemic therapies for the treatment of advanced prostate cancer patients. In the proposed study, the investigators aim is to extend the initial clinical results and further develop HP C-13 MRI as an imaging modality in advanced prostate cancer.

Detailed description

PRIMARY OBJECTIVES: I. To determine the kPL (metabolic flux from hyperpolarized \[HP\] \[1-13C\]pyruvate to \[1-13C\]lactate) and kPG (metabolic flux from HP \[2-13C\]pyruvate to \[5-13C\]glutamate) within target lesion. (Cohort A) II. To determine the mean percent change from baseline in intra-tumoral kPL and kPG within target lesion. (Cohort B) SECONDARY OBJECTIVE: I. To descriptively report on the intra-tumor heterogeneity in kPL and kPG measurement within target lesion. (Cohorts A and B) EXPLORATORY (CORRELATIVE) OBJECTIVES: I. To determine if the change from baseline in kPL and kPG is associated with subsequent clinical outcomes on treatment including prostate specific antigen (PSA) response rate and radiographic progression-survival by Prostate Cancer Working Group 3 (PCWG3) criteria. (Cohort B) II. In target lesions that are measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, to determine whether baseline and/or change from baseline in intratumoral kPL and kPG is associated with subsequent objective response by RECIST criteria. (Cohort B) III. To determine the mean percent change from baseline in peak intra- tumoral HP lactate (lac)/pyruvate (pyr) and glutamate (glu)/pyr ratios on repeat metabolic magnetic resonance imaging (MRI) obtained at the time of radiographic disease progression by PCWG3 criteria. (Cohort B) IV. To investigate for association between HP kPL and kPG as well as area under the curve (AUC) lac/pyr and glu/pyr ratios with tissue- based markers of elevated lactate and glutamate metabolism including MYC and Lactate dehydrogenase A (LDHA) and Pyruvate dehydrogenase (PDH) protein expression. (In participants who undergo optional tumor biopsy \[Cohort A or B\]) V. To investigate for an association between HP kPL and kPG as well as area under the curve (AUC) lac/pyr and glu/pyr ratios with histologic evidence of small cell/neuroendocrine differentiation. (In participants who undergo optional tumor biopsy (Cohort A or B)) OUTLINE: Patients are assigned to 1 of 2 cohorts. COHORT A (SINGLE TIME-POINT): Patients receive C-1 labeled hyperpolarized carbon C 13 pyruvate intravenously (IV) over less than 1 minute then undergo magnetic resonance spectroscopic imaging (MRSI) over less than 5 minutes. Patients may also receive an optional C-2 labeled hyperpolarized carbon C 13 pyruvate IV and undergo MRSI within 15-60 minutes following completion of the first scan. COHORT B (MULTIPLE TIME-POINT): Patients receive C-1 labeled hyperpolarized carbon C 13 pyruvate IV over less than 1 minute then undergo MRSI over less than 5 minutes. Patients may also receive an optional C-2 labeled hyperpolarized carbon C 13 pyruvate IV and undergo MRSI within 15-60 minutes following completion of the first scan at baseline and 12 weeks. After completion of study treatment, patients are followed up periodically.

Conditions

• Prostate Cancer
• Advanced Prostate Carcinoma

Interventions

Type	Name	Description
DRUG	Hyperpolarized C13	Given by intravenous injection. When receiving two HP 13C pyruvate injections, the injections will be separated by a period of 15-60 minutes
PROCEDURE	Magnetic Resonance Imaging (MRI)	Magnetic resonance imaging (MRI) is a medical imaging technique that uses a magnetic field and computer-generated radio waves to create detailed images of the organs and tissues in your body

Timeline

• Start date: 2020-07-16
• Primary completion: 2025-12-31
• Completion: 2026-11-30
• First posted: 2020-04-15
• Last updated: 2024-07-03

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study