MRI with Hyperpolarized Pyruvate for Advanced Prostate Cancer

Overseen By Maya Aslam

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Ivan de Kouchkovsky, MD

Disqualifiers: Inability to consent, MRI contraindications, 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: 3

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new MRI technique using hyperpolarized C13 (also known as Hyperpolarized Pyruvate) to enhance the diagnosis and monitoring of advanced prostate cancer. The goal is to determine if this imaging method can detect high-grade cancer and track patient response to treatments. Participants will undergo either one MRI or multiple MRIs over time to gather more data. The trial seeks men with advanced prostate cancer who have a detectable target lesion identified by standard scans. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on anti-coagulation medication and plan to undergo an optional tumor biopsy, you must be able to safely stop this treatment for the procedure.

What prior data suggests that this imaging technique is safe for patients with advanced prostate cancer?

Research has shown that hyperpolarized C13 pyruvate MRI is generally safe for people. This imaging method has been tested on patients with prostate cancer and has maintained a good safety record.

For example, one study found that this MRI technique could safely detect changes in prostate cancer without causing serious side effects. Patients did not report any major negative effects, indicating its safety. Another study confirmed these findings by demonstrating that hyperpolarized C13 pyruvate is both practical and safe for imaging.

These results are encouraging for those considering participation in a trial using this technology. Overall, the evidence suggests that hyperpolarized C13 pyruvate MRI is a safe imaging tool for people with prostate cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using hyperpolarized C13 MRI for advanced prostate cancer because it offers a novel way to visualize the metabolic activity of tumors. Unlike standard imaging techniques that primarily show the tumor's size and shape, hyperpolarized C13 MRI can capture real-time biochemical changes within cancer cells, potentially allowing for earlier detection of how the cancer responds to treatment. This approach uses a unique agent, hyperpolarized pyruvate, which enhances MRI signals significantly, providing clearer and more detailed images. By focusing on the metabolic processes of the tumor, this technique could lead to more personalized and timely treatment adjustments, improving outcomes for patients with advanced prostate cancer.

What evidence suggests that this imaging technique is effective for advanced prostate cancer?

This trial will evaluate hyperpolarized C13 MRI as a promising tool for advanced prostate cancer. Participants in Cohort A will undergo MR imaging with hyperpolarized 13C pyruvate at a single time point, while those in Cohort B will have the imaging at multiple time points. Research has shown that hyperpolarized C13 MRI can detect aggressive prostate cancer and identify a specific type called neuroendocrine cancer. It also provides early signs of treatment effectiveness. Clinical results suggest that this imaging method helps doctors assess tumor severity. Additionally, it offers reliable information about changes in the prostate's metabolism. Overall, evidence supports its potential as a powerful imaging tool for diagnosing and monitoring advanced prostate cancer. ^{2 4 6 7 8}

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 advanced prostate cancer who can follow study procedures and have an ECOG status of 0 or 1, meaning they are fully active or restricted in physically strenuous activity but ambulatory. They must have a target lesion suitable for MRI imaging and no history of bleeding issues if undergoing biopsy. Men with certain metal implants, inability to consent, or contraindications to MRI cannot participate.

Inclusion Criteria

I have a detectable tumor suitable for a special MRI scan.

I don't have a bleeding disorder and can safely pause any blood-thinning medications for a biopsy.

My prostate cancer is advanced or has spread, confirmed by tests.

Exclusion Criteria

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

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

I am unable to give informed consent due to my age, health, or mental condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

Participants undergo baseline metabolic MR imaging with hyperpolarized C-13 pyruvate to assess metabolic flux in target lesions

1 day

1 visit (in-person)

Treatment Monitoring

Participants in Cohort B undergo repeat metabolic MRI at baseline and 12 weeks to monitor response to systemic therapies

12 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Hyperpolarized C13

Trial Overview The trial is testing the use of a special type of MRI that uses hyperpolarized carbon-13 (C-13) pyruvate as a diagnostic tool in advanced prostate cancer. It aims to see if this method can detect high-grade cancers and monitor how well systemic therapies are working by looking at changes in the metabolism within the tumor.

How Is the Trial Designed?

Group I: Cohort B: Hyperpolarized C13 MRI at multiple time points Experimental Treatment 2 Interventions

Participants will undergo hyperpolarized (HP) C13 MRI at baseline and 12 weeks (+/- 8 weeks). Participants in Cohort B may undergo additional optional MR imaging at the time of disease progression. the same sequence of injections (C-1 labeled pyruvate first, C-2 labeled pyruvate second) will be used for subsequent scan time points as well.

Group II: Cohort A: Hyperpolarized C13 MRI at a single time point Experimental Treatment 2 Interventions

Participants will undergo MR imaging with hyperpolarized 13C pyruvate of a pre-selected target lesion at a single time point and will receive up to two 13C pyruvate (C-1 and C-2 labeled 13C pyruvate) investigational medicinal product (IMP) injections on the day of imaging (2nd injection is optional), as well as optional MR- or CT- guided tumor biopsies at baseline and at the time of disease progression following completion of HP C-13 MRI at the corresponding time point

Who Is Running the Clinical Trial?

Ivan de Kouchkovsky, MD

Lead Sponsor

Trials

3

Recruited

190+

Rahul Aggarwal

Lead Sponsor

Trials

13

Recruited

550+

National Institute for Biomedical Imaging and Bioengineering (NIBIB)

Collaborator

Trials

102

Recruited

21,600+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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]

Hyperpolarized carbon 13 MRI (13C MRI) is a groundbreaking imaging technique that allows for real-time, noninvasive observation of tissue metabolism, particularly useful in cancer research.

This method has shown promise in clinical applications such as tumor grading, tailoring treatment based on metabolic profiles, and detecting early treatment responses by monitoring metabolic changes before structural alterations in tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized Carbon 13 MRI: Clinical Applications and Future Directions in Oncology. Deen, SS., Rooney, C., Shinozaki, A., et al.[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 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 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]

Citations

1. 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12248915/

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

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e15059

Correlating survival outcomes in patients with advanced ... Correlating survival outcomes in patients with advanced prostate cancer with novel hyperpolarized 13C MRI metabolic imaging biomarkers.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6490043/

Hyperpolarized 13C MRI: State of the Art and Future Directions Preliminary data have also demonstrated that HP [1-13C]pyruvate MRI provides reproducible measurements of metabolic changes in the prostates of patients who ...

5. 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 ...

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. 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 ...

8. 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.