Hyperpolarized Carbon 13-Based Metabolic Imaging to Detect Radiation-Induced Cardiotoxicity

NCT04044872 | Terminated Early Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: STU 2019-1099
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Patients enrolled in the study will receive standard of care adjuvant or definitive breast, chest wall or thoracic radiation therapy.Cardiac mitochondrial dysfunction is a hallmark of radiation-induced cardiac injury. Reactive oxygen species (ROS) produced by ionizing radiation cause oxidation of mitochondrial proteins and alter oxidative phosphorylation and pyruvate metabolism(5). The goal of this study is to detect early changes in the mitochondrial metabolism in situ as a marker for subclinical radiation-induced cardiotoxicity.

Conditions

Thoracic Cancer; Left Sided Breast Cancer

Keywords

Cardiotoxicity; Cardiac injury; Radiation induced heart disease (RIHD)

Outcome Measures

Primary Outcomes (1)

• To determine if radiation-induced cardiac injury causes myocardial mitochondrial dysfunction

  To determine if radiation-induced cardiac injury causes myocardial mitochondrial dysfunction as measured by increase in \[1-13C\]lactate/ \[13C\]bicarbonate ratio and a decrease in \[5-13C\]glutamate formation in patients receiving radiotherapy to the thorax

  at 1 month before the radiation

Secondary Outcomes (1)

• Determination of the prognostic value decreased of myocardial mitochondrial pyruvate flux in predicting clinically significant radiation induced cardiotoxicity.

  At 1 month after the radiation

Study Arms (1)

Single Arm:Diagnosing Cardiotoxicity when on Radiation therapy

EXPERIMENTAL

Diagnostic Test: [1-13C]pyruvate along with MRI imaging

Interventions

[1-13C]pyruvate along with MRI imaging DIAGNOSTIC_TEST

\[1-13C\]pyruvate: 0.1 mmol/kg dose will be injected at 5 mL/s followed by a 25 mL saline flush at 5 mL/s at the time of imaging performed at baseline (prior to radiation therapy), and 1 month after completion of radiation therapy.

Single Arm:Diagnosing Cardiotoxicity when on Radiation therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Benign or malignant tumor of the breast (left-sided only) or thorax
• Stage I to IV. If stage IV, patient must have life expectancy equal to or greater than 6 months
• ECOG performance status 0-1
• The patient must be deemed an appropriate candidate for standard of care radiation therapy
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• A female of postmenopausal status is defined as patients over 60 or greater OR patients age 50-59 who meet the following criteria:
• s/p bilateral oophorectomy, OR
• with intact uterus without menses in the past 12 months OR,
• with biochemical confirmation of post-menopausal status (estradiol in the menopausal range based on local laboratory criteria)
• Ability to understand and the willingness to sign a written informed consent.

You may not qualify if:

• Prior radiation involving the heart
• Subjects may not be receiving any known cardiotoxic agents for the 6 months prior to the study and during the study
• Diagnosis of connective tissue disorders, including systemic lupus erythematosis, scleroderma, or dermatomyositis
• Patients with stage IV cancer with life expectancy of less than 6 months
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements
• eGFR \<30
• Any contraindication to MRI (including, but not limited to metal implants and devices contraindicated at 3T, breast tissue expanders, non-MR compatible IV port, claustrophobia)
• History of psychiatric or addictive disorders that would preclude obtaining informed consent
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

Department of Radiation Oncology; UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Unilateral Breast Neoplasms; Cardiotoxicity

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Study Officials

• Prasanna Alluri, MD, PhD

  UTSW Radiation Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: \[1-13C\]pyruvate 0.1 mmol/kg dose will be injected twice at the time of imaging performed at baseline prior to standard of care radiation therapy and twice at 1 month or later after completion of standard of care radiation therapy.

Study Record Dates

• First Submitted: July 10, 2019
• First Posted: August 5, 2019
• Study Start: December 17, 2019
• Primary Completion: August 30, 2021
• Study Completion: August 30, 2021
• Last Updated: February 2, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)