Serial PET MPI in Patients Undergoing Cancer Treatment

Official title

Prospective Evaluation of Chemotherapy-Induced Cardiotoxicity by Serial PET Myocardial Perfusion and Blood Flow Assessment - the PRECISION Trial

Overview

This study aims to evaluate the effects of cardiotoxic cancer therapies on myocardial blood flow (MBF) and perfusion in a prospective sample of VA patients.

Detailed description

Up to 60 patients who will be newly initiating chemotherapy are going to be prospectively evaluated using PET myocardial perfusion imaging (MPI) for chemotherapy-induced cardiotoxicity by quantifying MBF and perfusion. Patients will be grouped into 3 categories:

1. Patients undergoing chemotherapy with anthracycline containing regimen. 2. Patients undergoing chemotherapy with VEGF inhibitor containing regimen. 3. Patients undergoing chemotherapy with immune check point inhibitor containing regimen.

Patients will undergo PET MPI at 3 different time points:

1. Baseline PET MPI within 1 month prior to initiation of the chemotherapy regimen. 2. PET MPI at the middle of the chemotherapy regimen. 3. PET MPI within 1 month following completion of the chemotherapy regimen.

For PET MPI, the investigators will evaluate for abnormalities such as new perfusion defects, decreases in stress myocardial blood flows and decreases in myocardial flow reserves.

All study patients will also be analyzed using the following tests:

1. Echocardiogram with strain analysis within +/- 1 week of each PET MPI 2. Serology - high sensitivity troponin, cardiac C-reactive protein (CRP), brain-type natriuretic peptide (BNP), fasting lipid panel, complete metabolic panel, and complete blood count within +/- 1 week of each PET MPI study. 3. 12-lead ECG with each PET MPI study.

Primary outcome measures

• PET myocardial perfusion imaging (MPI). [Time frame: Baseline (within 1 month prior to the initiation of cancer treatment), during cancer treatment (estimated at 1-6 months), and within 1 month post-cancer treatment completion (approximately 2-9 months)]
• PET myocardial blood flow (MBF) measurement. [Time frame: Baseline (within 1 month prior to the initiation of cancer treatment), during cancer treatment (estimated at 1-6 months), and within 1 month post-cancer treatment completion (approximately 2-9 months)]

Secondary outcome measures (5)

• Transthoracic echocardiography (TTE) global left ventricular systolic function. [Time frame: Baseline (within 1 month prior to the initiation of cancer treatment), during cancer treatment (estimated at 1-6 months), and within 1 month post-cancer treatment completion (approximately 2-9 months)]
• Transthoracic echocardiography (TTE) focal left ventricular systolic function. [Time frame: Baseline (within 1 month prior to the initiation of cancer treatment), during cancer treatment (estimated at 1-6 months), and within 1 month post-cancer treatment completion (approximately 2-9 months)]
• Transthoracic echocardiography (TTE) focal left atrial systolic function. [Time frame: Baseline (within 1 month prior to the initiation of cancer treatment), during cancer treatment (estimated at 1-6 months), and within 1 month post-cancer treatment completion (approximately 2-9 months)]
• Electrocardiogram (ECG) findings. [Time frame: Baseline (within 1 month prior to the initiation of cancer treatment), during cancer treatment (estimated at 1-6 months), and within 1 month post-cancer treatment completion (approximately 2-9 months)]
• Metabolic or cardiac function abnormalities as determined by blood work findings [Time frame: Baseline (within 1 month prior to the initiation of cancer treatment), during cancer treatment (estimated at 1-6 months), and within 1 month post-cancer treatment completion (approximately 2-9 months)]

Eligibility criteria

Inclusion criteria

• Veterans Affairs oncology patients who will be initiating chemotherapy
• Ability to give consent

Exclusion criteria

• Prior chemotherapy
• Prior coronary revascularization (percutaneous coronary intervention, coronary artery bypass grafting)
• Anyone with previous invasive or CT (computed tomography) angiogram demonstrating any lesion ≥ 50% stenosis
• Known cardiomyopathy defined as rest ejection fraction < 50%
• History of heart and/or another organ transplant
• Pregnancy or breast-feeding status

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 1 center

• West Los Angeles VA Medical Center — Los Angeles

Publications

• Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021 Jan;71(1):7-33. doi: 10.3322/caac.21654. Epub 2021 Jan 12. PMID 33433946
• Herrmann J, Yang EH, Iliescu CA, Cilingiroglu M, Charitakis K, Hakeem A, Toutouzas K, Leesar MA, Grines CL, Marmagkiolis K. Vascular Toxicities of Cancer Therapies: The Old and the New--An Evolving Avenue. Circulation. 2016 Mar 29;133(13):1272-89. doi: 10.1161/CIRCULATIONAHA.115.018347. PMID 27022039
• Chang HM, Moudgil R, Scarabelli T, Okwuosa TM, Yeh ETH. Cardiovascular Complications of Cancer Therapy: Best Practices in Diagnosis, Prevention, and Management: Part 1. J Am Coll Cardiol. 2017 Nov 14;70(20):2536-2551. doi: 10.1016/j.jacc.2017.09.1096. PMID 29145954
• Hader SN, Zinkevich N, Norwood Toro LE, Kriegel AJ, Kong A, Freed JK, Gutterman DD, Beyer AM. Detrimental effects of chemotherapy on human coronary microvascular function. Am J Physiol Heart Circ Physiol. 2019 Oct 1;317(4):H705-H710. doi: 10.1152/ajpheart.00370.2019. Epub 2019 Aug 9. PMID 31397169
• Yeh ET, Bickford CL. Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol. 2009 Jun 16;53(24):2231-47. doi: 10.1016/j.jacc.2009.02.050. PMID 19520246
• Murthy VL, Bateman TM, Beanlands RS, Berman DS, Borges-Neto S, Chareonthaitawee P, Cerqueira MD, deKemp RA, DePuey EG, Dilsizian V, Dorbala S, Ficaro EP, Garcia EV, Gewirtz H, Heller GV, Lewin HC, Malhotra S, Mann A, Ruddy TD, Schindler TH, Schwartz RG, Slomka PJ, Soman P, Di Carli MF; SNMMI Cardiovascular Council Board of Directors; ASNC Board of Directors. Clinical Quantification of Myocardial B PMID 29242396
• Murthy VL, Naya M, Foster CR, Hainer J, Gaber M, Di Carli G, Blankstein R, Dorbala S, Sitek A, Pencina MJ, Di Carli MF. Improved cardiac risk assessment with noninvasive measures of coronary flow reserve. Circulation. 2011 Nov 15;124(20):2215-24. doi: 10.1161/CIRCULATIONAHA.111.050427. Epub 2011 Oct 17. PMID 22007073
• Ziadi MC, Dekemp RA, Williams KA, Guo A, Chow BJ, Renaud JM, Ruddy TD, Sarveswaran N, Tee RE, Beanlands RS. Impaired myocardial flow reserve on rubidium-82 positron emission tomography imaging predicts adverse outcomes in patients assessed for myocardial ischemia. J Am Coll Cardiol. 2011 Aug 9;58(7):740-8. doi: 10.1016/j.jacc.2011.01.065. PMID 21816311

Identifiers

NCT: NCT05913999 · IRBNet 1668650-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗