NCT03685175

Using Hyperpolarized [1-13C]Pyruvate to Detect Cardiotoxicity

Effect of Cardiotoxic Anticancer Therapy on the Metabolism of [1-13C]Pyruvate in Cardiac Mitochondria

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 79 (actual)
• Sponsor: University of Texas Southwestern Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

The anthracycline doxorubicin, first introduced in the 1960's, continues to be an effectively utilized antineoplastic drug. Even at relatively low cumulative doses there is risk of cardiotoxicity. However, the incidence of subclinical cardiotoxicity is not known, carrying a potential risk for late effects in cancer survivors. Doxorubicin has systemic toxicity that may contribute to cardiac metabolic stress, but the main cardiotoxic mechanism involves cardiac mitochondria. 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. The problem of cardiovascular complications following chemotherapy for breast cancer goes far beyond anthracyclines alone. In addition, other agents such as trastuzumab, and pertuzumab and emerging novel therapies may also promote cardiovascular injury. The secondary objective is to test the hypothesis that cardiotoxicity due to other medical anticancer therapies and radiation therapy involving the heart field is associated with a signature of early impaired aerobic cardiac metabolism through pyruvate dehydrogenase.

Detailed description

This is a prospective, single-center study in women and men with breast cancer requiring cardiotoxic therapy. The study will be conducted in parallel to the standard clinical care, at dedicated visits. In this study patients will undergo a cardiac magnetic resonance (MR) signal detection after injection of hyperpolarized carbon-13 pyruvate. The study will be performed before the course of cardiotoxic therapy, and after completing the treatment. Patients will be screened prior to enrollment based on study specific inclusion and exclusion criteria and MRI safety criteria. On the day of the metabolic cardiac MR scan an IV line will be inserted and the participant will receive a bolus of oral glucose. The ingestion of glucose will be required to prepare the state of the heart for metabolic imaging. Following this preparation the participant will undergo a cardiac MR study of about 45 minutes, including carbon-13 dedicated sequences. A separate dedicated cardiac MRI session may be completed in certain participants. Feasibility Study (Part I) : Administration at two visits 1) after completion of cardiotoxic therapy and 2) 1 to 6 months after the first time point following medical therapy (SOC). Formal Study (Part II) : Administration at two visits: 1) baseline MRI before administration of cardiotoxic therapy and 2) after completion of cardiotoxic therapy.

Conditions

• Breast Neoplasms

Interventions

Type	Name	Description
DRUG	Formal study using hyperpolarized 13C-pyruvate injection	Administration at two visits 1) after completion of cardiotoxic therapy and 2) 1 to 6 months after the first time point following medical therapy (SOC)
DRUG	Feasible study using hyperpolarized 13C-pyruvate injection	Administration at two visits: 1) baseline MRI before administration of cardiotoxic therapy and 2) after completion of cardiotoxic therapy

Timeline

• Start date: 2018-07-03
• Primary completion: 2025-02-28
• Completion: 2025-02-28
• First posted: 2018-09-26
• Last updated: 2025-03-30

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study