Hyperpolarized 13C-Pyruvate MRI for Solid Cancers

Overseen By Louise Magat

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Robert Bok, MD, PhD

Disqualifiers: Poorly controlled hypertension, Congestive heart failure, Pregnancy, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

65 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single center prospective imaging study investigating the utility of hyperpolarized 13C-pyruvate +/-13C,15N-Urea/ metabolic MR imaging. The current protocol will serve as a companion imaging biomarker study paired with standard of care (SOC) therapeutics, as well as investigational therapies that participants may be scheduled to receive outside of this protocol.

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, it does allow the addition of medications to control blood pressure if needed.

What data supports the effectiveness of the treatment Hyperpolarized 13C-Pyruvate MRI for solid cancers?

Research shows that Hyperpolarized 13C-Pyruvate MRI can effectively track changes in tumor metabolism, which helps in identifying how well a cancer treatment is working. This technique has been used in various cancers, including breast and prostate cancer, to provide real-time information on how tumors respond to therapy, potentially allowing for earlier and more precise treatment adjustments. ^{1 2 3 4 5}

Is Hyperpolarized 13C-Pyruvate MRI safe for use in humans?

A study on patients with prostate cancer showed that Hyperpolarized 13C-Pyruvate MRI is safe and feasible for use in humans. Additional studies are ongoing in various cancers, indicating continued evaluation of its safety. ^{1 2 4 6 7}

How is hyperpolarized 13C-pyruvate MRI different from other cancer treatments?

Hyperpolarized 13C-pyruvate MRI is unique because it uses a special imaging technique to track the metabolism of cancer cells in real-time, providing detailed insights into tumor activity and response to treatment. Unlike traditional imaging methods, this approach enhances the visibility of metabolic processes by significantly increasing the signal from injected 13C-labeled pyruvate, allowing for early detection of treatment effectiveness and potentially guiding personalized therapy decisions. ^{1 3 7 8 9}

Research Team

Robert Bok, MD, PhD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults with advanced solid tumors who can follow the study plan and have signed consent. They should be fairly active (ECOG 0 or 1), have a tumor at least 1 cm big that's visible on scans, and good kidney function. Pregnant women, those with certain heart conditions, uncontrolled high blood pressure, or metal implants affecting MRI quality cannot join.

Inclusion Criteria

The 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 18 years old or older.

Exclusion Criteria

Any condition that, in the opinion of the Principal Investigator.

I haven't had a heart attack or major heart issues in the last 6 months.

Patients with a metallic implant or device that distorts the local magnetic field and compromises the quality of MR imaging.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Feasibility Run-In (Phase I/Part A)

Participants undergo MR imaging at a single time point to optimize imaging parameters.

1 day

1 visit (in-person)

Biomarker Cohort (Phase II/Part B)

Participants undergo paired hyperpolarized pyruvate/metabolic MR imaging at baseline and after approximately 21 days of SOC or investigational therapy.

21 days

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and clinical outcomes.

Up to 6 months

Treatment Details

Interventions

• Hyperpolarized 13C-Pyruvate

Trial Overview The study tests how well hyperpolarized 13C-Pyruvate works as an imaging biomarker when paired with standard cancer treatments or investigational therapies. It involves using metabolic MR imaging to track tumor metabolism in patients receiving these treatments.

Participant Groups

Group I: Part B/ Phase II: Biomarker Cohort Experimental Treatment 3 Interventions

Participants will undergo paired 13C-pyruvate +/- 13C,15N-urea/metabolic MR imaging at baseline and again after approximately 21 days of therapy. Duration of the intervention period is approximately 21 days, and participants will be followed until discontinuation of their current SOC treatment regimen, about 6 months.

Group II: Part A / Phase 1: Feasibility Run-In Experimental Treatment 3 Interventions

Participants will undergo MR imaging at a single time point. Imaging will take one day and no follow up is planned.

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+

Sigma-Aldrich

Collaborator

Trials

2

Recruited

370+

National Institute for Biomedical Imaging and Bioengineering (NIBIB)

Collaborator

Trials

102

Recruited

21,600+

Findings from Research

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 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]

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]

Hyperpolarized magnetic resonance imaging (HP-MRI) using (13)C-pyruvate is a promising tool for quantitatively assessing how solid tumors respond to radiotherapy and for monitoring potential toxicity in normal tissues.

This imaging technique can effectively predict responses related to metabolic changes in tumors, although there are still challenges to overcome for its successful use in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic Imaging as a Biomarker of Early Radiation Response in Tumors. Lai, SY., Fuller, CD., Bhattacharya, PK., et al.[2018]

Metabolic imaging techniques, particularly hyperpolarized Magnetic Resonance (HP-MR), show promise in accurately assessing tumor metabolism and therapeutic responses in cancer treatment.

HP-MR has recently been translated into clinical practice, allowing for detailed measurements of 13C-pyruvate metabolism, which could enhance the evaluation of treatment efficacy compared to traditional imaging methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing Therapeutic Efficacy in Real-time by Hyperpolarized Magnetic Resonance Metabolic Imaging. Dutta, P., Salzillo, TC., Pudakalakatti, S., et al.[2023]

Hyperpolarized 13C MRI, particularly using [1-13C]pyruvate, is a promising technique for measuring localized metabolism in various diseases, including cancers and organ disorders, and has seen significant advancements in human studies over the past decade.

The paper outlines essential practices for conducting successful HP 13C MRI studies, covering preparation, MRI setup, data acquisition, and analysis, while also highlighting current evidence gaps and limitations in the field.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Methods for Hyperpolarized [1-13C]pyruvate MRI Human Studies. Larson, PE., Bernard, JM., Bankson, JA., et al.[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]

Hyperpolarized carbon-13 (13C) MRI is a groundbreaking imaging technique that allows for real-time, noninvasive observation of metabolic processes in diseases like cancer and cardiovascular conditions, which were previously difficult to study.

The review highlights the promising clinical applications of HP [1-13C]pyruvate MRI, suggesting it could enhance our understanding of metabolism, improve disease diagnosis, and speed up treatment evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13C MRI: State of the Art and Future Directions. Wang, ZJ., Ohliger, MA., Larson, PEZ., et al.[2020]

Hyperpolarized (HP) (13)C labeled compounds, particularly HP 1-(13)C pyruvate, are effective MR contrast agents that allow for real-time investigation of metabolic pathways in vivo, with the ability to track pyruvate metabolism for nearly 2 minutes post-injection.

The technique has expanded beyond tumor metabolism to non-invasively assess physiological parameters like pH, highlighting its growing potential in medical research, especially with the increasing availability of dynamic nuclear polarization (DNP) systems for generating hyperpolarized materials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13carbon MR. Rowland, IJ., Peterson, ET., Gordon, JW., et al.[2019]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Hyperpolarized 13C MRI: Path to Clinical Translation in Oncology. [2023]

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

Hyperpolarized Carbon 13 MRI: Clinical Applications and Future Directions in Oncology. [2023]

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

Metabolic Imaging as a Biomarker of Early Radiation Response in Tumors. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Assessing Therapeutic Efficacy in Real-time by Hyperpolarized Magnetic Resonance Metabolic Imaging. [2023]

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

Current Methods for Hyperpolarized [1-13C]pyruvate MRI Human Studies. [2023]

7. 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]

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

Hyperpolarized 13C MRI: State of the Art and Future Directions. [2020]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13carbon MR. [2019]