Magnetic Resonance (MR) Imaging With Hyperpolarized 13C-Pyruvate +/- 13C,15N-Urea in Patients With Prostate Cancer

A Phase 2 Study of Magnetic Resonance (MR) Imaging With Hyperpolarized 13C-Pyruvate +/- 13C,15N-Urea in Patients With Prostate Cancer Undergoing Radiation Therapy

This is a Phase 2 clinical study of hyperpolarized (HP) 13C-pyruvate (13C), 15N-urea (13C,15N) metabolic MR imaging in prostate cancer patients who are undergoing or have received radiation therapy for prostate cancer.

PRIMARY OBJECTIVES:

I. Part 1: To Optimize the imaging sequences that maximize signal-to-noise ratio (SNR) and intra-tumoral kPL and kPG in regions of tumor vs. adjacent benign tissue as assessed by mpMRI imaging characteristics.

II. Part 2A To perform HP 13C-MRI and measure the changes in tumoral kPL and kPG.

III. Part 2B: To perform HP 13C-MRI and study the metabolic effects (changes in tumor kPL and kPG).

IV. Part 3: To perform HP 13C-MRI at time of Biochemical Failure and measure tumoral kPL and kPG, in previously external beam radiation therapy (EBRT) treated patients.

SECONDARY OBJECTIVES:

I. To evaluate the intra-patient variability in intra-tumoral kPL and kPG with repeated dose studies (Part 1, 2 & 3).

II. To determine the association between peak intra-tumoral kPL observed on baseline imaging with serum PSA. (Part 2 & 3).

III. To determine the association between changes in intra-tumor kPL after 4-12 weeks of systemic hormone therapy and PSA response (Part 2B).

IV. To 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 (Part 1, 2 & 3).

V. To describe the frequency of up-grading of tumor with MR/US-guided fusion biopsy obtained following baseline HP-MRI exam. (Part 3).

VI. To further characterize the safety profile of HP C-13 pyruvate injections (Part 1, 2 & 3).

VII. For patients imaged with HP 13C-MRI at time of biochemical failure post-EBRT, correlate peak intra-tumoral kPL and kPG with radiotherapy dose distributions from EBRT course (Part 3).

VIII. For studies incorporating HP 13C-urea, the baseline and the on-treatment changes in urea AUC parameter will be measured and compared to kPL endpoints of the same lesions (Part 1, 2 & 3).

OUTLINE:

The study is divided into 3 parts. Part 1: Participants undergo imaging as part of a multi-parametric magnetic resonance imaging (mpMRI) exam to determine exact parameters for imaging.

Part 2A: Participants planned for external beam radiotherapy (EBRT) Part 2B: Participants with high-risk localized prostate cancer planned to receive primary radiation therapy with concurrent systemic hormone therapy Part 3: Evaluable EBRT participants scanned at time of biochemical failure and MR/US fusion-guided prostate biopsy within 12 weeks. Participants have the option of undergoing a follow up HP Pyruvate +/- Urea MR exam 6-15 months following the baseline scan.

All participants will receive a scan at baseline and other procedures may be performed as part of routine, non-interventional standard of care at the time of biochemical failure, including serial prostate-specific antigen (PSA) monitoring and gene expression profiling of tumor tissue. Participants will be followed for 24 months after last procedure or removal from study, or until death, whichever occurs first.

Inclusion Criteria:

1. Participants must have biopsy-proven adenocarcinoma of the prostate, as determined by medical chart review.

2. For:

   1. Part 1: Participants post-radiation therapy or currently considering EBRT.
   2. Part 2A: Participants currently scheduled for or considering EBRT (no neo-adjuvant therapy planned).
   3. Part 2B: Participants currently scheduled for or considering EBRT and neo-adjuvant therapy is planned. The participant has biopsy-proven adenocarcinoma of the prostate with high-risk disease, defined by the presence of at least two of following criteria: a tumor stage of T3 or T4, a Gleason score of 8 to 10, or a PSA level ≥40 ng/mL) and the participant must be planning to receive androgen deprivation therapy (ADT) with an Luteinizing hormone-releasing hormone (LHRH) agonist or antagonist. The addition of an androgen-receptor (AR) signaling inhibitor (e.g., abiraterone, bicalutamide,apalutamide, enzalutamide or darolutamide) will be allowed.
   4. Part 3: Participants who have previously received radiation treatment to the prostate and are exhibiting signs of biochemical failure, with planned fusion biopsy within 12 weeks following completion of baseline HP 13C pyruvate +/-urea mpMRI.

3. Participant is able and willing to comply with study procedures and provide signed and dated informed consent.

4. Eastern Cooperative Oncology Group (ECOG) performance status <= 1.

5. Age >= 18 years old at time of study entry.

6. Ability to understand and the willingness to sign a written informed consent document.

7. Demonstrates adequate organ function as defined below:

   1. White Blood Cell count (WBC) >=4000 cells/μL.
   2. Hemoglobin ≥9.0 gm/dL.
   3. Platelets ≥75,000 cells/μL.
   4. Renal Function > 30 Epithelial Growth Factor Receptor (eGFR).

Exclusion Criteria:

1. Evidence of pelvic regional or distant metastatic disease on conventional imaging (MRI, computed tomography or whole body bone scan) or prostate-specific membrane antigen (PSMA) Positron Emission Tomography (PET) imaging. PSMA-avid lymph nodes confined to the pelvis will be allowed if <1 centimeter (cm).
2. Prostate biopsy performed within 14 days prior to baseline C-13 HP pyruvate MRI.
3. Poorly controlled hypertension, with blood pressure at study entry > 160 mm Hg systolic or > 100 mm Hg diastolic. Treatment with anti-hypertensives and re-screening is permitted.
4. 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).
5. Congestive heart failure with New York Heart Association (NYHA) status >= 2.
6. History of clinically significant ECG abnormality, including QT prolongation, a family history of prolonged QT interval syndrome or myocardial infarction within 6 months of study entry.