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

• Status: Enrolling by invitation
• Trial end date: 2022-03-01
• Target enrollment: 0
• Participant gender: All

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 goal of this study is to detect early changes in the mitochondrial metabolism in situ as a marker for subclinical doxorubicin induced cardiotoxicity.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Texas Southwestern Medical Center
• Treatments: Doxorubicin; Liposomal doxorubicin

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. Once the protocol is established, Spanish-speaking participants will be included.

• 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.

• 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