Early Specialized Cardiovascular Intervention Based on Impedance Cardiography in Locally Advanced Non-small Cell Lung Cancer Patients

Official title

Early Specialized Cardiovascular Intervention Based on Impedance Cardiography in Locally Advanced Non-small Cell Lung Cancer Patients Who Receiving Radical Concurrent Chemoradiotherapy and Immunotherapy: a Prospective, Randomized Controlled, Multicenter Phase III Clinical Trial.

Overview

This is a prospective, randomized, controlled, multi-center phase III clinical trial that intends to evaluate the role of early cardiovascular intervention based on impedance cardiography in patients with locally advanced non-small cell lung cancer receiving radical radiochemotherapy±immunotherapy.

Detailed description

This is a prospective, randomized, controlled, multi-center phase III clinical trial that intends to evaluate the role of early cardiovascular intervention based on impedance cardiography in patients with locally advanced non-small cell lung cancer receiving radical radiochemotherapy±immunotherapy. The participants were 1:1 randomized to the intervention group and the control group. The intervention group will receive cardiovascular evaluation and intervention at multiple timepoints throughout treatment and follow-up, while the control group will be under observation unless severe cardiovascular events happen.

The evaluation and intervention timepoints include: Before neoadjuvant therapy, before radiotherapy, Mid-radiotherapy, 2 months after the completion of radiotherapy, every 6 months thereafter for up to 2 years post-radiotherapy.

Interventions

• Drug Multiple cardiovascular drugs related to "Golden Triangle"
  Based on impedance cardiography results at each timepoints, cardiovascular drug treatment and exercise plan will be given in the intervention group.

Primary outcome measures

• Overall survival [Time frame: 2-year]
• The incidence of grade 2+ cardiotoxicity events [Time frame: 2-year]

Secondary outcome measures (2)

• Progression-free survival [Time frame: 2-year]
• The incidence of grade 2+ pulmonary toxicity [Time frame: 2-year]

Eligibility criteria

Inclusion criteria

• It is diagnosed as non-small cell lung cancer by pathological examination or cytological examination; it is assessed as locally advanced, unresectable stage III non-small cell lung cancer by imaging;
• Plan to receive radical radiotherapy and chemotherapy ± immunotherapy;
• Male or female between 18 and 75 years old;
• Life expectancy ≥ 12 weeks;
• The World Health Organization (WHO) PS score is 0 or 1;
• Organ and bone marrow function meet the following conditions: Forced expiratory volume per second (FEV1) ≥1000 ml; absolute neutrophil count ≥1.5×10\^9/L; platelets ≥100×10\^9/L; hemoglobin ≥90 g/L ; Serum creatinine clearance calculated according to the Cockcroft-Gault formula ≥50 mL/min (Cockcroft and Gault 1976); serum bilirubin ≤1.5 times the upper limit of normal (ULN); alanine aminotransferase and aspartate aminotransferase ≤2.5 times ULN;
• A signed informed consent form is required before proceeding with any step in the research;
• There is an abnormality in the initial cardiac output index.

Exclusion criteria

• PS score 2-4;
• Organ function impairment: FEV1 <1000ml; absolute neutrophil count <1.5×10\^9/L; platelets <100×10\^9/L; hemoglobin <90 g/ L; Serum creatinine clearance calculated according to Cockcroft-Gault formula <50 mL/min; serum bilirubin>1.5 times ULN; alanine aminotransferase and aspartate aminotransferase>2.5 times ULN;
• Unstable angina or myocardial infarction occurred in the past month;
• Arrhythmia that has not been controlled and can cause symptoms or abnormal hemodynamics;
• Active endocarditis;
• Symptomatic severe aortic stenosis;
• Heart failure that has not been controlled;
• Acute pulmonary embolism, pulmonary infarction or low thrombosis (artery or vein) formation;
• Suspected or confirmed aortic dissection;
• Uncontrolled bronchial asthma;
• Pulmonary edema;
• Fingertip blood oxygen saturation at rest ≤85%;
• Acute non-cardiopulmonary diseases (such as infection, renal failure, thyrotoxicosis, etc.) that may affect sports performance or aggravate due to exercise;
• Mental disorders make it impossible to cooperate.
• Patients for whom drug intervention is clearly recommended according to the 2022 edition of the European Society of Cardiology Guidelines on Cardio-Oncology.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun yat-sen University Cancer Center — Guangzhou

Publications

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. PMID 30207593
• Wang H, Wei J, Zheng Q, Meng L, Xin Y, Yin X, Jiang X. Radiation-induced heart disease: a review of classification, mechanism and prevention. Int J Biol Sci. 2019 Aug 8;15(10):2128-2138. doi: 10.7150/ijbs.35460. eCollection 2019. PMID 31592122
• Beukema JC, van Luijk P, Widder J, Langendijk JA, Muijs CT. Is cardiac toxicity a relevant issue in the radiation treatment of esophageal cancer? Radiother Oncol. 2015 Jan;114(1):85-90. doi: 10.1016/j.radonc.2014.11.037. Epub 2014 Dec 30. PMID 25554226
• Dess RT, Sun Y, Matuszak MM, Sun G, Soni PD, Bazzi L, Murthy VL, Hearn JWD, Kong FM, Kalemkerian GP, Hayman JA, Ten Haken RK, Lawrence TS, Schipper MJ, Jolly S. Cardiac Events After Radiation Therapy: Combined Analysis of Prospective Multicenter Trials for Locally Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2017 May 1;35(13):1395-1402. doi: 10.1200/JCO.2016.71.6142. Epub 2017 Mar 16. PMID 28301264
• Atkins KM, Rawal B, Chaunzwa TL, Lamba N, Bitterman DS, Williams CL, Kozono DE, Baldini EH, Chen AB, Nguyen PL, D'Amico AV, Nohria A, Hoffmann U, Aerts HJWL, Mak RH. Cardiac Radiation Dose, Cardiac Disease, and Mortality in Patients With Lung Cancer. J Am Coll Cardiol. 2019 Jun 18;73(23):2976-2987. doi: 10.1016/j.jacc.2019.03.500. PMID 31196455
• Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K, Magliocco A, Kavadi V, Garces YI, Narayan S, Iyengar P, Robinson C, Wynn RB, Koprowski C, Meng J, Beitler J, Gaur R, Curran W Jr, Choy H. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage PMID 25601342
• Wang K, Eblan MJ, Deal AM, Lipner M, Zagar TM, Wang Y, Mavroidis P, Lee CB, Jensen BC, Rosenman JG, Socinski MA, Stinchcombe TE, Marks LB. Cardiac Toxicity After Radiotherapy for Stage III Non-Small-Cell Lung Cancer: Pooled Analysis of Dose-Escalation Trials Delivering 70 to 90 Gy. J Clin Oncol. 2017 May 1;35(13):1387-1394. doi: 10.1200/JCO.2016.70.0229. Epub 2017 Jan 23. PMID 28113017
• Boekel NB, Schaapveld M, Gietema JA, Russell NS, Poortmans P, Theuws JC, Schinagl DA, Rietveld DH, Versteegh MI, Visser O, Rutgers EJ, Aleman BM, van Leeuwen FE. Cardiovascular Disease Risk in a Large, Population-Based Cohort of Breast Cancer Survivors. Int J Radiat Oncol Biol Phys. 2016 Apr 1;94(5):1061-72. doi: 10.1016/j.ijrobp.2015.11.040. Epub 2015 Dec 14. PMID 27026313

Identifiers

NCT: NCT04980716 · GASTO-1074

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗