MRI Monitoring for Prostate Cancer

Overseen By Louise Magat

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Must not be taking: Androgen deprivation therapy

Disqualifiers: No prostate cancer, Radiation, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a special kind of MRI that uses hyperpolarized carbon C-13 pyruvate, a contrast agent, to observe prostate cancer behavior in patients under active surveillance. The aim is to evaluate how effectively this imaging technique tracks cancer development. It suits those with biopsy-confirmed prostate cancer who are monitoring their condition without immediate treatment. Participants should not have undergone recent prostate cancer treatment or a recent prostate biopsy. As a Phase 2 trial, this research measures the imaging technique's effectiveness in a smaller group, allowing participants to contribute to advancements in cancer monitoring.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does require that you have not had certain prostate cancer treatments recently. If you are on a 5-alpha reductase inhibitor, it must be stopped at least 28 days before the MRI.

What prior data suggests that this MRI technique is safe for monitoring prostate cancer?

Research has shown that hyperpolarized carbon C 13 pyruvate (HP C-13 pyruvate) is generally safe for humans. One study found it safe and useful for imaging in patients, with no major safety issues reported. This suggests that using HP C-13 pyruvate for MRI scans is safe for people with prostate cancer. While more research is needed, current evidence indicates it is safe for human use. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using hyperpolarized carbon C 13 pyruvate for monitoring prostate cancer because it offers a new way to visualize cancer metabolism in real-time. Unlike standard imaging options like MRI or ultrasound, which primarily focus on the structure of the prostate, this technique allows doctors to see how active the cancer cells are by tracking metabolic changes. This could lead to more precise and timely decision-making in prostate cancer management, potentially improving outcomes by identifying aggressive cancers earlier.

What evidence suggests that this MRI technique is effective for monitoring prostate cancer?

This trial will use a special type of MRI with hyperpolarized carbon C 13 pyruvate to monitor prostate cancer. Studies have shown that this method effectively highlights tumor activity by tracking how pyruvate, a type of sugar, converts into lactate in tumor cells. Research indicates that this conversion increases in more aggressive tumors, offering a way to assess tumor severity. In past studies, this MRI technique successfully categorized tumors by severity, helping doctors better understand cancer progression. Initial findings suggest this approach could provide a clearer picture of prostate cancer activity, potentially aiding in more precise monitoring. ^{6 7 8 9 10}

Who Is on the Research Team?

Ivan de Kouchkovsky, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for men with low to intermediate risk prostate cancer who are on active surveillance and haven't had treatment. They must be able to follow the study plan, have a good performance status (able to carry out daily activities), adequate blood counts, and normal liver function. Men can't join if they've had recent prostate treatments or biopsies, uncontrolled high blood pressure, heart failure, no evidence of cancer in their last biopsy, hormone therapy for cancer, or can't undergo MRI due to medical devices or severe claustrophobia.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

Platelets >= 75,000 cells/uL

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

Exclusion Criteria

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

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 within the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging and Biopsy

Participants receive hyperpolarized carbon C 13 pyruvate intravenously and undergo magnetic resonance spectroscopic imaging (MRSI), followed by MR/US fusion-guided prostate biopsy

Up to 12 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after baseline imaging and biopsy

Up to 15 months

Optional Follow-up Imaging

Participants may undergo optional follow-up HP C-13 pyruvate/MRI 6-15 months following baseline scan to assess changes in intra-tumoral kPL and kPG

6-15 months

What Are the Treatments Tested in This Trial?

Interventions

• Hyperpolarized Carbon C 13 Pyruvate

Trial Overview The trial is testing how well a special type of MRI scan using hyperpolarized carbon C 13 pyruvate can monitor prostate cancer progression in patients under active surveillance. The imaging aims to observe the uptake and breakdown of this substance in tumor cells without having treated the cancer yet.

How Is the Trial Designed?

Group I: Diagnostic (HP C-13 MRI) Experimental Treatment 3 Interventions

Patients receive hyperpolarized carbon C 13 pyruvate IV over less than one minute, then undergo MRSI after 1-2 minutes. Within 15-60 minutes, patients may receive optional hyperpolarized carbon C 13 pyruvate and undergo MRSI. Patients also undergo MR/US fusion-guided prostate biopsy within 12 weeks following HP C-13 MRSI.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Institute for Biomedical Imaging and Bioengineering (NIBIB)

Collaborator

Trials

102

Recruited

21,600+

Published Research Related to This Trial

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]

This study found that aggressive prostate cancer cells (PC3) showed significantly higher uptake of [18F]FDG compared to less aggressive cells (LNCaP), indicating that PET imaging can effectively differentiate between cancer aggressiveness.

Despite similar rates of pyruvate to lactate conversion in both cell types, a negative correlation was observed between [18F]FDG uptake and the rate of this conversion, suggesting that metabolic pathways in prostate cancer may differ from other tumors and highlighting the potential of combining imaging techniques for better diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pyruvate-lactate exchange and glucose uptake in human prostate cancer cell models. A study in xenografts and suspensions by hyperpolarized [1-13 C]pyruvate MRS and [18 F]FDG-PET. van Heijster, FHA., Heskamp, S., Breukels, V., et al.[2021]

Hyperpolarized [1-13C]-pyruvate magnetic resonance spectroscopic imaging (MRSI) can effectively predict the efficacy of targeting the Warburg effect in prostate cancer, as demonstrated by enhanced lactate production in DU145 tumors compared to PC3 tumors.

The study found that DU145 tumors were more sensitive to lactate dehydrogenase (LDH) inhibition, indicating that MRSI could serve as a valuable biomarker for assessing treatment responses in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized [1-13C]-Pyruvate Magnetic Resonance Spectroscopic Imaging of Prostate Cancer In Vivo Predicts Efficacy of Targeting the Warburg Effect. Scroggins, BT., Matsuo, M., White, AO., 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]

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]

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 has shown promise in providing unique metabolic insights into cancer, with a dose-ranging study confirming its safety and feasibility in patients with prostate cancer.

Ongoing research is exploring the use of hyperpolarized agents in various cancer types, and advancements in technology and collaboration among academia, industry, and government are essential for translating this imaging technique into clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13C MRI: Path to Clinical Translation in Oncology. Kurhanewicz, J., Vigneron, DB., Ardenkjaer-Larsen, JH., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6392436/

Investigation of analysis methods for hyperpolarized 13C ... In this project, we applied HP [1-13C]pyruvate dynamic MRI in prostate cancer to measure the conversion from pyruvate to lactate, which is expected to increase ...

2. pubs.rsna.org pubs.rsna.org/doi/full/10.1148/rycan.230005

Hyperpolarized Carbon 13 MRI: Clinical Applications and ... Clinical results have now demonstrated that hyperpolarized [1-13C]pyruvate MRI findings can stratify tumors according to grade, with higher ...

3. mdpi.com mdpi.com/2072-6694/17/13/2211

Multivariate Framework of Metabolism in Advanced ... A novel hyperpolarized (HP) 13 C MRI-specific multivariate framework was developed and evaluated in 16 patients with advanced or metastatic prostate cancer.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4349324/

Hyperpolarized 13C MR for Molecular Imaging of Prostate ... Hyperpolarization using dissolution dynamic nuclear polarization has emerged as a versatile method to dramatically improve the MR signal of low-sensitivity ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/mrm.29875

Current methods for hyperpolarized [1‐13C]pyruvate MRI ... The first human studies with HP [1-13C]pyruvate were performed in 2011 in prostate cancer patients. Since then, there have been over 60 papers ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4201045/

Metabolic Imaging of Patients with Prostate Cancer Using ... This first-in-man imaging study evaluated the safety and feasibility of hyperpolarized [1-13C]pyruvate as an agent for noninvasively characterizing alterations ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03933670

Hyperpolarized Pyruvate (13C) MR Imaging in Monitoring ... This phase II trial studies the side how well hyperpolarized carbon C 13 pyruvate (HP C-13 pyruvate) magnetic resonance imaging (MRI) works in monitoring ...

8. nature.com nature.com/articles/s41391-019-0180-z

Hyperpolarized 13 C-pyruvate MRI detects real-time ... HP 13 C-pyruvate MRI can detect real-time glycolytic metabolism within prostate cancer metastases, and can measure changes in quantitative k PL values ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2666441024000207

Dual hyperpolarized [1-13C]pyruvate and [13C]urea ... Hyperpolarized [1-13C]pyruvate MRI was able to detect areas of clinically occult prostate cancer not seen on multiparametric MRI. •. The novel addition of ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6260457/

Hyperpolarized 13C MRI: Path to Clinical Translation in ... A dose-ranging study of HP [1-13C]pyruvate in patients with prostate cancer established safety and feasibility of this technique. Additional studies are ongoing ...