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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging method to detect and understand prostate cancer. It focuses on using special substances, 13C-pyruvate and 13C,15N-urea, to enhance MRI scans, potentially providing a clearer view of prostate cancer in patients who have undergone or plan to undergo radiation therapy. Ideal candidates have confirmed prostate cancer, particularly if they have had or plan to have radiation treatment and are experiencing issues like rising PSA levels, which may indicate active cancer. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in prostate cancer imaging.

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 prior data suggests that hyperpolarized MR imaging is safe for prostate cancer patients?

Research has shown that hyperpolarized 13C-pyruvate has been safe and manageable in past studies with prostate cancer patients. In these studies, patients tolerated the treatment well, and no serious side effects were reported.

The use of 13C,15N-urea is also under investigation. Early research has confirmed its safe use in examining conditions like low oxygen levels in tumors, and it is part of ongoing studies with prostate cancer patients.

Since this trial is in Phase 2, the treatment has already passed initial safety tests in earlier phases. This phase focuses more on the treatment's effectiveness, so there is already a reasonable expectation that patients tolerate these treatments well. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the hyperpolarized MR imaging technique for prostate cancer because it offers a new way to look at tumors in real-time with greater clarity. Unlike standard imaging methods that can miss small but important details, this technique uses hyperpolarized 13C-Pyruvate and 13C,15N-Urea to enhance the images, providing a sharper and more detailed view of the cancerous tissues. This can potentially lead to better diagnosis and tracking of the cancer's response to treatment, offering a more precise approach than current imaging options. This technique is particularly promising because it could allow doctors to tailor treatments more effectively by closely monitoring how the cancer changes over time.

What evidence suggests that this trial's imaging techniques could be effective for prostate cancer?

This trial will evaluate hyperpolarized MR imaging techniques for prostate cancer. Studies have shown that a special type of MRI using hyperpolarized 13C-pyruvate can detect changes in prostate cancer that other methods might miss. This technique also monitors the tumor's energy use in real-time, providing insights into its activity. Research suggests that this imaging method can accurately predict cancer by comparing scan results with actual diagnoses. Additionally, using 13C-pyruvate with 13C,15N-urea, another imaging approach in this trial, enhances the imaging process, offering detailed information about the tumor's metabolism and blood flow. These methods hold promise for better diagnosing and understanding prostate cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Robert Bok, MD, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02526368

Pilot Study of (MR) Imaging with Pyruvate (13C) to Detect ... This pilot clinical trial studies how well magnetic resonance spectroscopic imaging (MRSI) with hyperpolarized carbon 13 (13C) pyruvate alone or in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9810116/

Development of Specialized Magnetic Resonance Acquisition ... We have developed a highly efficient method for imaging co-hyperpolarized 13 C pyruvate and urea for human studies.

3. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT06391034

13C,15N-Urea in Patients With Prostate Cancer This is a Phase 2 clinical study of hyperpolarized (HP) 13C-pyruvate (13C), 15N-urea (13C,15N) metabolic MR imaging in prostate cancer patients.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35526263/

13 C]pyruvate simultaneous perfusion and metabolic imaging This study aimed to develop and demonstrate the in vivo feasibility of a 3D stack-of-spiral balanced steady-state free precession(3D-bSSFP) urea sequence.

5. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/480996

13C,15N-Urea in Patients With Prostate Cancer 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11925798/

Translation of hyperpolarized [13C,15N2]urea MRI for ... Preclinical research has validated the use of HP [13C,15N2]urea for safe and effective investigation of conditions such as tumor hypoxia, ...

7. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/prostate-cancer

UCSF Prostate Cancer Clinical Trials — San Francisco Bay Area This is a Phase 2 clinical study of hyperpolarized (HP) 13C-pyruvate (13C), 15N-urea (13C,15N) metabolic MR imaging in prostate cancer patients ...