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

Non-small Cell Lung Cancer Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04980716
• Other study ID #: GASTO-1074
• Status: Recruiting
• Phase: Phase 3
• Start date: June 1, 2021
• Est. completion date: July 1, 2026

Study information

• Verified date: October 2022
• Source: Sun Yat-sen University
• Contact: Bo Qiu
• Phone: +862087343031
• Email: qiubo[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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 (no intervention time point for those who do not receive neoadjuvant therapy), before the first course of radiotherapy, 3-4 weeks after the first course of radiotherapy, 2 months after the second course of radiotherapy, 8 months after the second course of radiotherapy, 14 months after the second course of radiotherapy .

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 524
• Est. completion date: July 1, 2026
• Est. primary completion date: January 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. 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;

2. Plan to receive radical radiotherapy and chemotherapy ± immunotherapy;

3. Male or female between 18 and 75 years old;

4. Life expectancy = 12 weeks;

5. The World Health Organization (WHO) PS score is 0 or 1;

6. 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;

7. A signed informed consent form is required before proceeding with any step in the research;

8. There is an abnormality in the initial cardiac output index.

Exclusion Criteria:

1. PS score 2-4;

2. 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;

3. Unstable angina or myocardial infarction occurred in the past month;

4. Arrhythmia that has not been controlled and can cause symptoms or abnormal hemodynamics;

5. Active endocarditis;

6. Symptomatic severe aortic stenosis;

7. Heart failure that has not been controlled;

8. Acute pulmonary embolism, pulmonary infarction or low thrombosis (artery or vein) formation;

9. Suspected or confirmed aortic dissection;

10. Uncontrolled bronchial asthma;

11. Pulmonary edema;

12. Fingertip blood oxygen saturation at rest =85%;

13. Acute non-cardiopulmonary diseases (such as infection, renal failure, thyrotoxicosis, etc.) that may affect sports performance or aggravate due to exercise;

14. Mental disorders make it impossible to cooperate.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Cardiovascular Complication
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

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.

Locations

Country	Name	City	State
China	Sun yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (25)

Ananthan K, Lyon AR. The Role of Biomarkers in Cardio-Oncology. J Cardiovasc Transl Res. 2020 Jun;13(3):431-450. doi: 10.1007/s12265-020-10042-3. Epub 2020 Jul 8. Review. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

Boero IJ, Paravati AJ, Triplett DP, Hwang L, Matsuno RK, Gillespie EF, Yashar CM, Moiseenko V, Einck JP, Mell LK, Parikh SA, Murphy JD. Modern Radiation Therapy and Cardiac Outcomes in Breast Cancer. Int J Radiat Oncol Biol Phys. 2016 Mar 15;94(4):700-8. doi: 10.1016/j.ijrobp.2015.12.018. Epub 2015 Dec 17. — View Citation

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 IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015 Feb;16(2):187-99. doi: 10.1016/S1470-2045(14)71207-0. Epub 2015 Jan 16. — View Citation

Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Arén Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. doi: 10.1056/NEJMoa1504627. Epub 2015 May 31. — View Citation

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. Erratum in: CA Cancer J Clin. 2020 Jul;70(4):313. — View Citation

Cardinale D, Colombo A, Bacchiani G, Tedeschi I, Meroni CA, Veglia F, Civelli M, Lamantia G, Colombo N, Curigliano G, Fiorentini C, Cipolla CM. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015 Jun 2;131(22):1981-8. doi: 10.1161/CIRCULATIONAHA.114.013777. Epub 2015 May 6. — View Citation

Curigliano G, Cardinale D, Dent S, Criscitiello C, Aseyev O, Lenihan D, Cipolla CM. Cardiotoxicity of anticancer treatments: Epidemiology, detection, and management. CA Cancer J Clin. 2016 Jul;66(4):309-25. doi: 10.3322/caac.21341. Epub 2016 Feb 26. Review. — View Citation

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. — View Citation

Eremina V, Jefferson JA, Kowalewska J, Hochster H, Haas M, Weisstuch J, Richardson C, Kopp JB, Kabir MG, Backx PH, Gerber HP, Ferrara N, Barisoni L, Alpers CE, Quaggin SE. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med. 2008 Mar 13;358(11):1129-36. doi: 10.1056/NEJMoa0707330. — View Citation

Fossella FV, Lee JS, Murphy WK, Lippman SM, Calayag M, Pang A, Chasen M, Shin DM, Glisson B, Benner S, et al. Phase II study of docetaxel for recurrent or metastatic non-small-cell lung cancer. J Clin Oncol. 1994 Jun;12(6):1238-44. — View Citation

Heinzerling L, Ott PA, Hodi FS, Husain AN, Tajmir-Riahi A, Tawbi H, Pauschinger M, Gajewski TF, Lipson EJ, Luke JJ. Cardiotoxicity associated with CTLA4 and PD1 blocking immunotherapy. J Immunother Cancer. 2016 Aug 16;4:50. doi: 10.1186/s40425-016-0152-y. eCollection 2016. — View Citation

Kido H, Morizane C, Tamura T, Hagihara A, Kondo S, Ueno H, Okusaka T. Gemcitabine-induced pleuropericardial effusion in a patient with pancreatic cancer. Jpn J Clin Oncol. 2012 Sep;42(9):845-50. doi: 10.1093/jjco/hys099. Epub 2012 Jul 10. — View Citation

Lang CC, Agostoni P, Mancini DM. Prognostic significance and measurement of exercise-derived hemodynamic variables in patients with heart failure. J Card Fail. 2007 Oct;13(8):672-9. Review. — View Citation

Lang CC, Karlin P, Haythe J, Lim TK, Mancini DM. Peak cardiac power output, measured noninvasively, is a powerful predictor of outcome in chronic heart failure. Circ Heart Fail. 2009 Jan;2(1):33-8. doi: 10.1161/CIRCHEARTFAILURE.108.798611. — View Citation

Malfatto G, Blengino S, Perego GB, Branzi G, Villani A, Facchini M, Parati G. Transthoracic impedance accurately estimates pulmonary wedge pressure in patients with decompensated chronic heart failure. Congest Heart Fail. 2012 Jan-Feb;18(1):25-31. doi: 10.1111/j.1751-7133.2011.00248.x. Epub 2011 Sep 14. — View Citation

Parashar R, Bajpai M, Goyal M, Singh S, Tiwari S, Narayan VS. Impedance cardiography for monitoring changes in cardiac output. Indian J Physiol Pharmacol. 2012 Apr-Jun;56(2):117-24. — View Citation

Siedlecka J, Siedlecki P, Bortkiewicz A. Impedance cardiography - Old method, new opportunities. Part I. Clinical applications. Int J Occup Med Environ Health. 2015;28(1):27-33. doi: 10.13075/ijomeh.1896.00451. Review. — View Citation

Thatcher N, Hirsch FR, Luft AV, Szczesna A, Ciuleanu TE, Dediu M, Ramlau R, Galiulin RK, Bálint B, Losonczy G, Kazarnowicz A, Park K, Schumann C, Reck M, Depenbrock H, Nanda S, Kruljac-Letunic A, Kurek R, Paz-Ares L, Socinski MA; SQUIRE Investigators. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015 Jul;16(7):763-74. doi: 10.1016/S1470-2045(15)00021-2. Epub 2015 Jun 1. — View Citation

Thavendiranathan P, Poulin F, Lim KD, Plana JC, Woo A, Marwick TH. Use of myocardial strain imaging by echocardiography for the early detection of cardiotoxicity in patients during and after cancer chemotherapy: a systematic review. J Am Coll Cardiol. 2014 Jul 1;63(25 Pt A):2751-68. doi: 10.1016/j.jacc.2014.01.073. Epub 2014 Apr 2. Review. — View Citation

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. Review. — View Citation

Wang J, Okazaki IM, Yoshida T, Chikuma S, Kato Y, Nakaki F, Hiai H, Honjo T, Okazaki T. PD-1 deficiency results in the development of fatal myocarditis in MRL mice. Int Immunol. 2010 Jun;22(6):443-52. doi: 10.1093/intimm/dxq026. Epub 2010 Apr 21. — View Citation

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. — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	It was calculated from the first day of treatment to the day of death.	2-year
Secondary	Cumulative incidence of cardiotoxicity events	Cumulative incidence of = Grade 3 cardiotoxicity events	2-year
Secondary	Progression-free survival	From the first day of treatment to the day of progression or the day of death.	2-year