Hyperpolarized 13C-Pyruvate Imaging for Chemotherapy-Related Heart Damage

(HPCardiotox Trial)

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Investigational agents

Disqualifiers: Diabetes, Metastases, Heart failure, others

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to detect early heart changes caused by certain cancer treatments before symptoms appear. Using a special imaging technique with a compound called hyperpolarized [1-13C]pyruvate, doctors seek to understand how these treatments affect the heart's energy production. The trial consists of two parts: one examines patients before and after they start treatment, and the other assesses patients who have already completed treatment. It is suitable for breast cancer patients about to start or who have completed cardiotoxic therapy, as well as healthy volunteers. As an Early Phase 1 trial, this research focuses on understanding how the imaging technique functions in people, offering participants a chance to contribute to groundbreaking advancements in heart health monitoring.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on investigational agents that are not compatible with the study, you may need to stop those.

What prior data suggests that hyperpolarized 13C-pyruvate imaging is safe for detecting chemotherapy-related heart damage?

Research has shown that Hyperpolarized [1-13C]Pyruvate is generally safe for people in studies. The safety data indicates it is safe when used in appropriate amounts. Trials have reported no major side effects, suggesting that Hyperpolarized Pyruvate does not harm patients when used as intended for medical imaging.

It is important to note that this is an imaging tool, not a medicine. It helps doctors observe changes in the heart's energy use after chemotherapy. While the safety data is promising, further research is underway to confirm these results. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using hyperpolarized [1-13C]pyruvate imaging for detecting chemotherapy-related heart damage because it offers a new way to visualize metabolic changes in the heart in real time. Unlike traditional methods that may rely on symptoms or changes in heart function to detect damage, this technique uses a special form of pyruvate, the hyperpolarized [1-13C]pyruvate, which enhances MRI images to provide clear insights into heart cell metabolism. This could potentially allow for earlier detection of heart damage, even before significant symptoms arise, enabling more timely interventions. This technique is particularly promising because it provides a non-invasive method to monitor heart health during and after chemotherapy, offering a proactive approach to cardiac care.

What evidence suggests that hyperpolarized 13C-pyruvate imaging is effective for detecting chemotherapy-related heart damage?

Research has shown that a special imaging technique using hyperpolarized pyruvate can detect early changes in heart metabolism caused by doxorubicin, a chemotherapy drug known to harm the heart. This trial will employ hyperpolarized 13C-pyruvate imaging to assess heart metabolism in two contexts: one group will undergo imaging before and immediately after cardiotoxic therapy, while another group will receive it after completing therapy and again 1 to 6 months later. Studies confirm that this imaging effectively measures heart metabolism and provides insights into potential damage. By identifying these changes early, doctors aim to understand and possibly prevent long-term heart problems in cancer survivors. This approach seeks to catch heart issues before they become serious. ^{1 3 6 7 8}

Who Is on the Research Team?

Vlad G Zaha, MD, PhD

Principal Investigator

Advanced Imaging Research Center

Are You a Good Fit for This Trial?

This trial is for adults with breast cancer who haven't started or have already completed cardiotoxic therapy. They must be able to use contraception, not have diabetes, metal implants incompatible with MRI, or severe illnesses that could affect study participation. Pregnant women and those with certain blood disorders are excluded.

Inclusion Criteria

My treatment plan includes drugs that may affect my heart.

Patients for the formal study should not have started the cardiotoxic therapy yet

I am a male and either surgically sterile or my partner uses birth control.

Exclusion Criteria

I do not have any serious illnesses or social situations that would stop me from following the study's requirements.

My cancer has spread to distant parts of my body.

I have been diagnosed with diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline MRI

Participants undergo a baseline cardiac MRI scan before administration of cardiotoxic therapy

1 day

1 visit (in-person)

Cardiotoxic Therapy

Participants receive cardiotoxic therapy as part of their standard cancer treatment

Varies based on individual treatment plans

Post-Therapy MRI

Participants undergo a cardiac MRI scan after completion of cardiotoxic therapy

1 day

1 visit (in-person)

Follow-up MRI

Participants undergo a follow-up cardiac MRI scan 1 to 6 months after the first post-therapy MRI

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Hyperpolarized [1-13C]Pyruvate

Trial Overview The study aims to detect early signs of heart damage from the chemotherapy drug doxorubicin by using a special type of imaging after injecting hyperpolarized 13C-pyruvate. It will look at changes in heart metabolism as indicators of potential harm from this and similar treatments.

How Is the Trial Designed?

Group I: Formal Study Experimental Treatment 1 Intervention

Hyperpolarized 13C-pyruvate, is injected into patients before receiving cardiotoxic therapy and immediately after, for a cardiac MRI scan

Group II: Feasibility Study Experimental Treatment 1 Intervention

Hyperpolarized 13C-pyruvate injection, is given to patients after completing cardiotoxic therapy, and again at 1 to 6 six months after the first cardiac MRI scan

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03685175

Using Hyperpolarized [1-13C]Pyruvate to Detect ... The primary goal of this study is to detect early changes in the mitochondrial metabolism in situ as a marker for subclinical doxorubicin induced cardiotoxicity ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04044872

Study Details | NCT04044872 | Hyperpolarized Carbon 13- ... A first-in-human clinical study to evaluate the effect of cardiotoxic chemotherapy on [1-13C]Pyruvate metabolism is currently ongoing at UT Southwestern ( ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10720165/

pyruvate CMR evaluated in an oral glucose challenge Hyperpolarized (HP) 13 C-pyruvate MRI is a promising new tool for non-invasive quantification of myocardial glycolytic and Krebs cycle flux.

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-07508

Effect of Chemotherapy on the Metabolism of [1-13C] ... This phase I trial evaluates the effects of chemotherapy (doxorubicin) on the metabolism of pyruvate in cardiac mitochondria in patients with breast cancer.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12398660/

Hyperpolarized-MRI in Hypertrophic Cardiomyopathy HP-MRI enhances the signal of metabolites like [1-13C]pyruvate, providing insights into metabolic pathways. Alterations in the metabolic ...

6. dctd.cancer.gov dctd.cancer.gov/drug-discovery-development/reagents-materials/imaging-ind-resources/documentation/13c-pyruvate-ib.pdf

Hyperpolarized Pyruvate (13C) Injection safety pharmacology data support adequate safety of Hyperpolarized Pyruvate (13C) Injection containing 250 mM [1-13C]pyruvate and no-more-than 3 µM of ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8067176/

Comprehensive Literature Review of Hyperpolarized ... This review provides a comprehensive assessment of the development of hyperpolarized (HP) carbon-13 metabolic MRI from the early days to the present

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7874930/

Effect of Doxorubicin on Myocardial Bicarbonate ... This study tested the hypothesis that exams of cardiac metabolism using HP [1-13C1]pyruvate are feasible before and after conventional neoadjuvant doxorubicin ...