Hyperpolarized MR Imaging for Prostate Cancer

Overseen By Louise Magat

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Robert Bok, MD, PhD

Must be taking: LHRH agonist or antagonist

Disqualifiers: Metastatic disease, Hypertension, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: Up to 12 months

161 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are planning to receive androgen deprivation therapy (ADT) with an LHRH agonist or antagonist, you may continue with additional medications like androgen-receptor signaling inhibitors.

What data supports the effectiveness of the treatment Hyperpolarized MR Imaging for Prostate Cancer?

Research shows that Hyperpolarized 13C-pyruvate MRI can safely and effectively detect changes in tumor metabolism in prostate cancer, providing real-time insights into cancer activity and potentially improving diagnosis and treatment monitoring. ^{1 2 3 4 5}

Is hyperpolarized MR imaging safe for humans?

Research shows that hyperpolarized MR imaging, specifically using hyperpolarized [1-¹³C]pyruvate, has been tested in humans with prostate cancer and found to be safe, with no dose-limiting toxicities observed in the studies. ^{1 2 3 4 6}

How is the treatment Hyperpolarized 13C,15N-Urea and Hyperpolarized 13C-Pyruvate unique for prostate cancer?

This treatment is unique because it uses hyperpolarized MRI to enhance the imaging signal, allowing real-time assessment of prostate cancer metabolism, which helps in detecting and characterizing the cancer more effectively than traditional imaging methods. ^{1 2 3 7 8}

What is the purpose of this trial?

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.

Research Team

Robert Bok, MD, PhD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

Men with prostate cancer who are currently receiving or have completed radiation therapy can join this trial. Specific details about inclusion and exclusion criteria were not provided, so it's important to consult the study team for more detailed eligibility requirements.

Inclusion Criteria

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

I am fully active or can carry out light work.

I am scheduled for or considering SBRT without prior treatments.

Exclusion Criteria

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)

I had a prostate biopsy less than 2 weeks before my special MRI.

My blood pressure is not higher than 160/100 mm Hg, or it's controlled with medication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

Participants undergo baseline HP Pyruvate +/- Urea mpMRI exam to establish imaging parameters

1 day

1 visit (in-person)

Treatment

Participants receive stereotactic body radiotherapy (SBRT) or primary radiation therapy with concurrent hormone therapy, followed by HP Pyruvate +/- Urea mpMRI exams at specified intervals

Up to 12 months

Multiple visits (in-person) at baseline, 3 months, and 1 year post-treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including optional follow-up HP Pyruvate +/- Urea MR exam 6-15 months following baseline scan

24 months

Regular monitoring visits (in-person)

Treatment Details

Interventions

• 13C,15N-Urea
• Hyperpolarized 13C-Pyruvate

Trial Overview The trial is testing a new type of MRI scan using hyperpolarized pyruvate (13C) and possibly urea (13C,15N) to see how well it shows prostate cancer activity during or after radiotherapy. It also includes standard treatments like SBRT, mpMRI, biopsies, and hormone therapy.

Participant Groups

Group I: Part 3: SBRT participants at time of biochemical recurrence (BCR) Experimental Treatment 4 Interventions

Evaluable SBRT participants who undergo HP Pyruvate +/-Urea mpMRI at time of biochemical failure, followed by magnetic resonance (MR) / ultrasound (US) fusion-guided prostate biopsy within 12 weeks following baseline MR exam. Participants in this group have the option of undergoing a follow up HP Pyruvate +/-Urea MR exam 6-15 months following the baseline scan, to evaluate for any interval change.

Group II: Part 2B: Prospective imaging (High-risk localized prostate cancer) Experimental Treatment 4 Interventions

Participants with with high-risk localized prostate cancer and have pre-planned, non-interventional primary radiation therapy (RT) with concurrent, systemic, non-interventional hormone therapy will undergo HP Pyruvate+/-Urea mpMRI at baseline prior to the start of systemic hormone therapy, 4-12 weeks after the initiation of systemic hormone therapy (prior to radiation therapy), at 3 months post-radiation therapy, and at +1yr post-radiation therapy.

Group III: Part 2A: Prospective imaging (Stereotactic body radiotherapy (SBRT) Participants) Experimental Treatment 3 Interventions

Participants with pre-planned, non-interventional stereotactic body radiotherapy (SBRT) will undergo an HP Pyruvate +/-Urea mpMRI exam at baseline, at 3 months post-SBRT treatment and at 1yr post-treatment.

Group IV: Part 1: Image Optimization Group Experimental Treatment 2 Interventions

Participants will undergo Hyperpolarized 13C-Pyruvate +/- 13C,15N-Urea imaging as part of a multi-parametric magnetic resonance imaging (mpMRI) exam, with the primary objective of optimizing imaging sequences and techniques to maximize signal-to-noise ratio of imaging modality.

13C,15N-Urea is already approved in United States for the following indications:

Approved in United States as Hyperpolarized 13C,15N-Urea for:

• Investigational use in prostate cancer imaging

Who Is Running the Clinical Trial?

Robert Bok, MD, PhD

Lead Sponsor

Trials

3

Recruited

270+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Hyperpolarized 13C-pyruvate MRI successfully detected high rates of glycolytic metabolism in metastatic prostate cancer, with specific kPL values indicating metabolic activity in bone and liver metastases.

The study demonstrated that HP 13C-pyruvate MRI can measure changes in metabolism over time, showing a decrease in kPL values in response to chemotherapy, suggesting its potential as a tool for monitoring treatment efficacy in advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13C-pyruvate MRI detects real-time metabolic flux in prostate cancer metastases to bone and liver: a clinical feasibility study. Chen, HY., Aggarwal, R., Bok, RA., et al.[2021]

This study demonstrates that hyperpolarized (13)C-labeled pyruvate can effectively differentiate between various histologic grades of prostate cancer in a mouse model, with significant increases in hyperpolarized lactate levels correlating with cancer progression.

Elevated levels of hyperpolarized lactate, along with total hyperpolarized carbon (THC) and alanine, serve as promising noninvasive biomarkers for detecting prostate cancer and assessing its severity, potentially enhancing future imaging techniques in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13C lactate, pyruvate, and alanine: noninvasive biomarkers for prostate cancer detection and grading. Albers, MJ., Bok, R., Chen, AP., et al.[2018]

The study demonstrated that hyperpolarized [1-¹³C]pyruvate is safe for use in humans, with no dose-limiting toxicities observed in 31 prostate cancer patients, confirming its potential for noninvasive imaging.

The imaging technique successfully detected elevated levels of [1-¹³C]lactate in tumor regions, indicating its effectiveness in characterizing tumor metabolism and potentially aiding in cancer diagnosis and treatment monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic imaging of patients with prostate cancer using hyperpolarized [1-¹³C]pyruvate. Nelson, SJ., Kurhanewicz, J., Vigneron, DB., et al.[2021]

Hyperpolarized 13C-MRI, which enhances the detection of tumor metabolism by 4-5 orders of magnitude, can track the metabolism of hyperpolarized [1-13C]pyruvate in cancer patients, providing insights into tumor activity and response to treatment.

Combining HP 13C-MRI with traditional 1H-MRI allows for detailed anatomical imaging and functional tumor analysis, potentially enabling early identification of patients who are not responding to therapies, although cost and technical challenges need to be addressed for broader clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized Carbon-13 MRI in Breast Cancer. Woitek, R., Brindle, KM.[2023]

Carbon-13 magnetic resonance imaging (MRI) using hyperpolarised [1-13C]pyruvate is a promising new method for detecting altered metabolism in tumors, showing safety and feasibility in early human studies involving patients with various cancers, including prostate and breast cancer.

This technique allows for dynamic, noninvasive imaging of metabolic changes, potentially identifying treatment responses earlier than traditional multiparametric MRI, and offers unique insights into tumor aggressiveness and heterogeneity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of hyperpolarised 13C-MRI in clinical body imaging to probe cancer metabolism. Woitek, R., Gallagher, FA.[2023]

Hyperpolarized magnetic resonance imaging (MRI) of pyruvate metabolism shows consistent delivery and conversion in patients with primary prostate cancer, indicating its potential reliability for metabolic imaging.

The study found that higher lactate levels correlate with more aggressive cancer (higher Gleason grade) and are associated with specific genomic alterations, such as PTEN loss, suggesting a link between cancer genetics and metabolic changes that could inform treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized MRI of Human Prostate Cancer Reveals Increased Lactate with Tumor Grade Driven by Monocarboxylate Transporter 1. Granlund, KL., Tee, SS., Vargas, HA., et al.[2021]

Hyperpolarization using dissolution dynamic nuclear polarization significantly enhances the MR signal of low-sensitivity nuclei, allowing for detailed real-time metabolic studies in both laboratory and living systems.

This technique has been particularly useful in investigating metabolic changes associated with prostate cancer, providing insights into the disease's mechanisms through hyperpolarized (13)C MR spectroscopy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13C MR for molecular imaging of prostate cancer. Wilson, DM., Kurhanewicz, J.[2021]

This study demonstrates that hyperpolarized (HP) (13)C MR spectroscopy can effectively track metabolic changes in prostate cancer, showing increased pyruvate to lactate flux in malignant tissue compared to benign tissue, which correlates with specific metabolic markers.

The research provides the first mechanistic evidence that HP (13)C lactate can serve as a biomarker for prostate cancer in living human tissues, paving the way for better identification of cancer presence and aggressiveness in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic reprogramming and validation of hyperpolarized 13C lactate as a prostate cancer biomarker using a human prostate tissue slice culture bioreactor. Keshari, KR., Sriram, R., Van Criekinge, M., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13C-pyruvate MRI detects real-time metabolic flux in prostate cancer metastases to bone and liver: a clinical feasibility study. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13C lactate, pyruvate, and alanine: noninvasive biomarkers for prostate cancer detection and grading. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Metabolic imaging of patients with prostate cancer using hyperpolarized [1-¹³C]pyruvate. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Hyperpolarized Carbon-13 MRI in Breast Cancer. [2023]

5. England pubmed.ncbi.nlm.nih.gov

The use of hyperpolarised 13C-MRI in clinical body imaging to probe cancer metabolism. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Hyperpolarized MRI of Human Prostate Cancer Reveals Increased Lactate with Tumor Grade Driven by Monocarboxylate Transporter 1. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13C MR for molecular imaging of prostate cancer. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Metabolic reprogramming and validation of hyperpolarized 13C lactate as a prostate cancer biomarker using a human prostate tissue slice culture bioreactor. [2021]