Magnetic Resonance (MR) Imaging With Hyperpolarized Pyruvate (HP) (13C) in Castration-Resistant Prostate Cancer

This is a prospective imaging study evaluating the utility of baseline metabolic MR imaging
as a predictive response biomarker to androgen signaling inhibition in patients with
castration-resistant prostate cancer. Patients with a target lesion that is amenable for
metabolic MR imaging will be eligible for study participation. Patients will undergo baseline
metabolic MR imaging with Hyperpolarized Pyruvate C-13 pyruvate followed by initiation of
androgen signaling inhibition (either as standard of care or as part of clinical trial;
including abiraterone and/or enzalutamide treatment). Patient will subsequently undergo
repeat metabolic MR scan after 28 days (+/- 7 days) of therapy. For those without primarily
refractory disease, a third metabolic MR scan will be completed at the time of radiographic
disease progression by The Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria.
MR- or CT-guided tumor biopsies are optional at baseline and at the time of disease
progression.

Inclusion Criteria:

1. Biopsy-proven prostate cancer.

2. Progressive, castration-resistant disease according to PCWG2 criteria.

3. Planned treatment with an androgen signaling inhibitor (e.g., abiraterone,
enzalutamide, apalutamide (ARN-509)). Patients must not be receiving androgen
signaling inhibitor at the time of the baseline MR scan. Combination treatment (e.g.,
androgen signaling inhibitor in conjunction with another systemic treatment) is
allowed.

4. Presence of at least one target lesion detected by standard staging scans that, in the
judgment of Study Investigators, would be amenable to hyperpolarized C-13
pyruvate/metabolic MR imaging:

- Soft tissue/visceral organ target lesions must measure at 1.5 cm in long axis
diameter on CT or MRI.

- Target lesions in the bone must be visualized by CT or MRI (lesions present only
on bone scan do not qualify).

- For patients with target lesion in prostate/prostatic bed:

i. No contra-indications to endorectal coil insertion (e.g., patients with a
prior abdominoperineal resection of the rectum or latex allergy).

ii. No prior local treatment to the selected lesion. Patients who have received prior
radiation or ablative therapy to the prostate will be required to have biopsy-proven
evidence of disease recurrence following completion of local therapy.

5. The subject is able and willing to comply with study procedures and provide signed and
dated informed consent.

6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

7. Adequate organ function, including absolute neutrophil count (ANC) ≥ 1500 cells/µL,
hemoglobin ≥ 9.0 gm/dL, platelets ≥ 75,000 cells/µL, creatinine < 1.5 x ULN or
estimated creatinine clearance ≥ 50 mL/min (by the Cockcroft Gault equation),
bilirubin <1.5x ULN (unless Gilbert's is suspected in which case total bilirubin < 3 x
ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 1.5x ULN.

8. For patients undergoing optional tumor biopsy:

- No history of bleeding diathesis.

- Patients on anti-coagulation they must be able to safely stop treatment for
purposes of tumor biopsy.

9. For patients with partners of childbearing potential, willing to use adequate
contraception for one month after undergoing HP pyruvate infusion.

10. Patients must have prior bilateral orchiectomy or be on continuous luteinizing-hormone
releasing hormone (LHRH) analogue therapy for the duration of study.

11. Castrate level of serum testosterone (< 50 ng/dL) at study entry.

Exclusion Criteria:

1. Patients who because of age, general medical or psychiatric condition, or physiologic
status cannot give valid informed consent.

2. Patients unwilling or unable to undergo MR imaging, including patients with
contra-indications to MRI, such as cardiac pacemakers or non-compatible intracranial
vascular clips.

3. Metallic hip implant or any other metallic implant or device that distorts local
magnetic field and compromises the quality of MR imaging.

4. Poorly controlled hypertension, defined as systolic blood pressure at study entry
greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg. The
addition of anti-hypertensives to control blood pressure is allowed.

5. Congestive heart failure or New York Heart Association (NYHA) status ≥ 2.

6. A history of clinically significant EKG abnormalities, including QT prolongation (QTcF
> 500 ms), 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.

7. Any condition that, in the opinion of the Principal Investigator, would impair the
patient's ability to comply with study procedures.