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

Primary Purpose

Breast Neoplasms

Status
Enrolling by invitation
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Formal study using hyperpolarized 13C-pyruvate injection
Feasible study using hyperpolarized 13C-pyruvate injection
Sponsored by
University of Texas Southwestern Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Breast Neoplasms focused on measuring Magnetic Resonance Imaging, Doxorubicin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Female or male with breast cancer tissue diagnosis.
  • Plan for treatment as cardiotoxic therapy. Patients for the feasibility study must be post cardiotoxic therapy, and patients for the formal study should not have started the cardiotoxic therapy yet.
  • Age ≥ 18 years
  • Ability to understand and the willingness to sign a written informed consent
  • While all races and ethnicities will be included, subjects must be able to read and speak the English language, and or, the Spanish Language.
  • Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation. 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 childbearing 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).

    - Males must be surgically sterile or have a female partner using an acceptable method of contraception.

  • Acceptable surgical sterilization techniques are vasectomy with surgery at least 6 months prior to dosing. Males must also refrain from sperm donation during the study and for 6 months following discontinuation of treatment.
  • Acceptable methods of contraception for female partners of childbearing potential are an intrauterine device, contraceptive implant, and a barrier method (eg. Condom, diaphragm, cervical cap) during the study and for 6 months after patient discontinuation of treatment.

Exclusion Criteria:

  • Patients for the feasibility study must be post cardiotoxic therapy
  • Known Type 1 or Type 2 diabetes.
  • Subjects who are receiving any other investigational agents that are not compatible with the study.
  • Subjects with known remote, macro, metastases will be excluded from this clinical trial because of their poor prognosis.
  • 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 would limit compliance with study requirements.

  • Any contraindication per MRI Screening Form (Appendix A attached) including, but not limited to:

    • Metal Implants and devices contraindicated at 3T.
    • Breast tissue expanders.
    • Non-MR compatible IV port.
    • Claustrophobia.
  • Female subjects who are already pregnant.
  • Sickle cell disease
  • Hemolytic anemia
  • If the subject agrees to doing a cardiac function MRI scan with gadolinium based contrast agent intravenously:

eGFR ≤ 30 mL/min/1.73m2

Sites / Locations

  • UT Southwestern - Advanced Imaging Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Formal Study

Feasibility Study

Arm Description

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

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

Outcomes

Primary Outcome Measures

Detect subclinical anthracycline induced cardiotoxicity using hyperpolarized carbon-13 pyruvate
Detect the correlation between cardiac carbon-13 pyruvate metabolism and cardiac mechanical function at baseline and after exposure to cardiotoxic therapy

Secondary Outcome Measures

Full Information

First Posted
March 11, 2017
Last Updated
May 8, 2023
Sponsor
University of Texas Southwestern Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT03685175
Brief Title
Using Hyperpolarized [1-13C]Pyruvate to Detect Cardiotoxicity
Acronym
HPCardiotox
Official Title
Effect of Cardiotoxic Anticancer Therapy on the Metabolism of [1-13C]Pyruvate in Cardiac Mitochondria
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
July 1, 2018 (Actual)
Primary Completion Date
August 2023 (Anticipated)
Study Completion Date
August 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Texas Southwestern Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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. In part I 10 patients will be administered at two visits 1) after completion of cardiotoxic therapy and 2) 1 to 6 months after the first time point following medical therapy (SOC) In part II up to 100 patients will be administered at two visits: 1) baseline MRI before administration of cardiotoxic therapy and 2) after completion of cardiotoxic therapy

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Neoplasms
Keywords
Magnetic Resonance Imaging, Doxorubicin

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
110 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Formal Study
Arm Type
Experimental
Arm Description
Hyperpolarized 13C-pyruvate, is injected into patients before receiving cardiotoxic therapy and immediately after, for a cardiac MRI scan
Arm Title
Feasibility Study
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Formal study using hyperpolarized 13C-pyruvate injection
Other Intervention Name(s)
Cardiac MRI with injection of hyperpolarized 13C-pyruvate
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Feasible study using hyperpolarized 13C-pyruvate injection
Other Intervention Name(s)
Cardiac MRI with injection of hyperpolarized 13C-pyruvate
Intervention Description
Administration at two visits: 1) baseline MRI before administration of cardiotoxic therapy and 2) after completion of cardiotoxic therapy
Primary Outcome Measure Information:
Title
Detect subclinical anthracycline induced cardiotoxicity using hyperpolarized carbon-13 pyruvate
Description
Detect the correlation between cardiac carbon-13 pyruvate metabolism and cardiac mechanical function at baseline and after exposure to cardiotoxic therapy
Time Frame
4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Female or male with breast cancer tissue diagnosis. Plan for treatment as cardiotoxic therapy. Patients for the feasibility study must be post cardiotoxic therapy, and patients for the formal study should not have started the cardiotoxic therapy yet. Age ≥ 18 years Ability to understand and the willingness to sign a written informed consent While all races and ethnicities will be included, subjects must be able to read and speak the English language, and or, the Spanish Language. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation. 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 childbearing 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). - Males must be surgically sterile or have a female partner using an acceptable method of contraception. Acceptable surgical sterilization techniques are vasectomy with surgery at least 6 months prior to dosing. Males must also refrain from sperm donation during the study and for 6 months following discontinuation of treatment. Acceptable methods of contraception for female partners of childbearing potential are an intrauterine device, contraceptive implant, and a barrier method (eg. Condom, diaphragm, cervical cap) during the study and for 6 months after patient discontinuation of treatment. Exclusion Criteria: Patients for the feasibility study must be post cardiotoxic therapy Known Type 1 or Type 2 diabetes. Subjects who are receiving any other investigational agents that are not compatible with the study. Subjects with known remote, macro, metastases will be excluded from this clinical trial because of their poor prognosis. 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 would limit compliance with study requirements. Any contraindication per MRI Screening Form (Appendix A attached) including, but not limited to: Metal Implants and devices contraindicated at 3T. Breast tissue expanders. Non-MR compatible IV port. Claustrophobia. Female subjects who are already pregnant. Sickle cell disease Hemolytic anemia If the subject agrees to doing a cardiac function MRI scan with gadolinium based contrast agent intravenously: eGFR ≤ 30 mL/min/1.73m2
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vlad G Zaha, MD, PhD
Organizational Affiliation
Advanced Imaging Research Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
UT Southwestern - Advanced Imaging Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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