Hyperpolarized Carbon 13-Based Metabolic Imaging to Detect Radiation-Induced Cardiotoxicity
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|ClinicalTrials.gov Identifier: NCT04044872|
Recruitment Status : Recruiting
First Posted : August 5, 2019
Last Update Posted : August 20, 2020
|Condition or disease||Intervention/treatment||Phase|
|Thoracic Cancer Left Sided Breast Cancer||Diagnostic Test: [1-13C]pyruvate along with MRI imaging||Phase 1|
The global burden of cancer continues to rise with an incidence of 17.5 million cancer cases worldwide. Approximately 50% of all cancer patients receive radiation therapy as a component of their cancer care. While radiation therapy has demonstrable benefit in improving survival in patients with many types of malignancies, cardiotoxicity is a major concern in patients receiving chest radiotherapy. The rates of major coronary events increased by 7.4% per gray of mean heart dose; the increased risk was noted within the first 5 years of radiotherapy and persisted into the third decade after treatment. With improvements in multi-disciplinary care of cancer patients, the long-term survival in patients with thoracic malignancies continues to improve and radiation-induced heart disease (RIHD) is now a major source of morbidity and mortality in such patients.In this study, the investigators will enroll five female patients (18 years of age to 100 years of age) with left-sided breast cancer who underwent lumpectomy or mastectomy without tissue expander placement and will receive adjuvant standard-of-care breast or chest wall radiation therapy. They will undergo baseline magnetic resonance spectroscopic imaging with [1-13C]pyruvate injection and a proton MRI/spectroscopy scan prior to receipt of adjuvant radiation therapy. Post-treatment imaging will be performed within 3 months of completion of radiation treatments. This study will investigate whether non-invasive MRI scanning approaches will detect damage to the heart from left-sided radiation treatments before structural changes and mechanical functional deficits become apparent. A first-in-human clinical study to evaluate the effect of cardiotoxic chemotherapy on [1-13C]Pyruvate metabolism is currently ongoing at UT Southwestern (ClinicalTrials.gov Identifier: NCT03685175; PI: Dr. Vlad Zaha). The proposed study employs the same technology and approach to study radiation-induced cardiac toxicity. The study will also test the prognostic value of decreased myocardial mitochondrial pyruvate flux in predicting clinically significant radiation induced cardiotoxicity. Towards this goal, study will measure myocardial mechanical functional parameters, including left ventricular global longitudinal strain and left ventricular myocardial deformation using cardiac MRI and correlate these changes with [1-13C]lactate/ [13C]bicarbonate ratio. Previous studies have demonstrated that strain rate imaging by MRI is a sensitive technique for dose-dependent decrease in myocardial function after breast radiotherapy. Although this pilot study is restricted to breast cancer patients, successful demonstration of feasibility will allow extension of the study to all patients receiving thoracic radiation (such as patients receiving radiation therapy for lung cancer, esophageal cancer and thoracic lymphomas). The lack of reliable technologies for early detection of sub-clinical radiation-induced cardiotoxicity limits early intervention in such patients. Thus, identification of early cardiac changes induced by radiation therapy at a stage that offers potential for reversibility remains a major unmet need in cancer care.
Concerns for sexually active men and women: Women should not become pregnant and men should not father a baby while taking part in this study because we do not know how the study drugs/procedures could affect a man's sperm (for some drugs/procedures, the concern may be that the sperm might be affected and in some cases, drugs could being carried by the semen into the vagina and cause harm) or a fetus, if a woman becomes pregnant during the study. It is important that you talk to your study doctor about avoiding pregnancy during this study. If you think you might have become pregnant or if you believe your female partner has become pregnant while you are in this study, you must tell one of the study doctors right away so that management of the pregnancy and the possibility of stopping the study can be discussed.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Single Institution Feasibility Study to Detect Radiation-Induced Cardiotoxicity in Receiving Thoracic Radiation Patients Using Hyperpolarized Carbon 13-Based Magnetic Resonance Spectroscopic Imaging|
|Actual Study Start Date :||December 17, 2019|
|Estimated Primary Completion Date :||October 2021|
|Estimated Study Completion Date :||December 2023|
|Experimental: Single Arm:Diagnosing Cardiotoxicity when on Radiation therapy||
Diagnostic Test: [1-13C]pyruvate along with MRI imaging
[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.
- To determine if radiation-induced cardiac injury [ Time Frame: at 1 month before the radiation ]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
- Determination of the prognostic value decreased of myocardial mitochondrial pyruvate flux in predicting clinically significant radiation induced cardiotoxicity. [ Time Frame: At 1 month after the radiation ]As a secondary outcome, we will measure if decreased myocardial mitochondrial pyruvate flux results in changes in myocardial mechanical functional parameters. Towards this goal, we will measure myocardial mechanical functional parameters, including left ventricular global longitudinal strain and left ventricular myocardial deformation using cardiac MRI and correlate them with [1-13C] lactate/ [13C] bicarbonate ratio. Prior studies that cardiac MRI can detect changes in myocardial strain in patients who received whole breast radiotherapy for treatment of breast cancer.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04044872
|Contact: Sarah Hardee, MSemail@example.com|
|Contact: Kajal Desai, MSfirstname.lastname@example.org|
|United States, Texas|
|Department of Radiation Oncology; UT Southwestern Medical Center||Recruiting|
|Dallas, Texas, United States, 75390|
|Contact: Prasanna Alluri, MD, PhD 214-648-8941 Prasanna.Alluri@UTSouthwestern.edu|
|Contact: Vlad Zaha, MD, PhD|
|Principal Investigator: Prasanna Alluri, MD, PhD|
|Principal Investigator:||Prasanna Alluri, MD, PhD||UTSW Radiation Oncology|