Clinical trial NCT03721133: Recurrent Predictive Power of Circulating Tumor Cells for Non Small Cell Lung Cancer Patients
Official title: Recurrent Predictive Power of Circulating Tumor Cells in Non Small Cell Lung Cancer Patients Who Receive Curative Resection
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Lung Cancer Recurrent
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2018-10-26
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with a resectable malignant or suspicious malignant pulmonary lesion

Brief summary: From literature review, circulating tumor cell was demonstrated its possible role in disease relapse. It was rare nit could be identified in all lung cancer patients. In addition, circulating tumor cell usual aggregate to form circulating tumor micro-emboli and caused distant metastases. Therefore, circulating tumor cell could play a role in detect disease relapse and appropriate treatment could be given more earlier and further prolong patients' survival. However, the detail clinical significance of circulating tumor still remains unknown. The aim of this study was evaluate the clinical significance, including present timing, numbers, and correlation to disease relapse, of circulating tumor cell in lung cancer patients. The investigators want to clarify the clinical significance between circulating tumor cell and clinical presentation of lung cancer in order to establish new prediction model and improve lung cancer patients' survival.

Detailed description: Study subject:

Inclusion criteria 1. Patients with clinical stage 1 to 3a non-small lung cancer 2. Patients with a resectable suspicious pulmonary lesion which is difficult for pre-operation tissue prove or refused for pre-operation biopsy 3. Received curative intended tumor resection Exclusion criteria

1. Small cell lung cancer component which identified in pathology
2. Patients who presented as stage IIIb or IV
3. Not received curative intended surgery due to multi-comorbidities
4. Patients who presented in tumor seeding or positive resection in pathology confirmation
5. Patients who received neoadjuvant therapy

Data collection:

medical record review and blood sampling for circulating tumor cell purification

Timing of blood sampling:

a.Pre-operation, post-operation, post-operation day 1, post-operation day 3 b regular OPD surveillance (3 month-interval) for 3 years

Blood sampling: 20 ml blood that withdrawn from a peripheral vein

Circulating tumor cell purification: two-step procedure

1. cell isolation: centrifugation, isolated karyocyte \> 10 micrometer
2. negative selection: wash out RBC, WBC depletion
3. positive selection: purify circulating tumor cell (karyocyte which presented CD 45 negative, Epi-CAM positive, diameter greater 10 micrometer

Result analysis:

Combine the medical record to analyze the relationship between circulating tumor cells and disease relapse

Eligibility criteria: Inclusion Criteria:

1. Non-small cell lung cancer patients with stage I to III
2. Patients with resectable suspicious pulmonary malignant lesion

   1. no pre-operation diagnosis ( patients refused biopsy or difficult for biopsy)
   2. image survey showed clinical stage I to III

Exclusion Criteria:

1. Final pathology coexisted with small cell lung cancer component
2. Patients who presented as stage IIIb or IV.
3. Not received curative intended surgery due to multi-comorbidities.
4. Patients who presented in tumor seeding or positive resection in the final pathology
5. Patients who received neoadjuvant therapy.

Primary outcomes:
measure: Variation trend of circulating tumor cell counts
timeFrame: 1. Circulating tumor cell counts in pre-op, post-op, post-operation day 1 and post-operation day 3 ; 2.need complete 5-years surveillance (disease status confirmation)
measure: Validation of variation trend of circulating tumor cell counts
timeFrame: 1. Circulating tumor cell counts in pre-op, post-op, post-operation day 1 and post-operation day 3 ; 2.model establish model (case 1 to 50) versus validation group ( case 51-120) 3. need complete 5-years surveillance (disease status confirmation)
Secondary outcomes:
Other outcomes:
Locations:
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
affiliation: Chang Gung Memorial Hospital
name: Chia-Hsun Hsieh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chang Gung Memorial Hospital
name: Yi-Cheng Wu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chang Gung Memorial Hospital
name: Cheng-Ta Yang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chang Gung Memorial Hospital
name: JUI-YING Fu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chang Gung Memorial Hospital
name: ChingFeng Wu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fernandes G, Sucena M, Lombardia E, Machado A, Hespanhol V, Queiroga H. Non small cell lung cancer - comparison between clinical and pathological staging. Rev Port Pneumol. 2006 Jul-Aug;12(4):337-57. English, Portuguese.
citation: McCann J. PET scans approved for detecting metastatic non-small-cell lung cancer. J Natl Cancer Inst. 1998 Jan 21;90(2):94-6. doi: 10.1093/jnci/90.2.94. No abstract available.
citation: Vaz AP, Fernandes G, Souto Moura C, Bastos P, Queiroga H, Hespanhol V. Integrated PET/CT in non small cell lung cancer staging--clinical and pathological agreement. Rev Port Pneumol. 2012 May-Jun;18(3):109-14. doi: 10.1016/j.rppneu.2012.01.004. Epub 2012 Mar 8. English, Portuguese.
citation: Wu CY, Fu JY, Wu CF, Hsieh MJ, Liu YH, Wu YC, Yang CT, Tsai YH. Survival Prediction Model Using Clinico-Pathologic Characteristics for Nonsmall Cell Lung Cancer Patients After Curative Resection. Medicine (Baltimore). 2015 Nov;94(45):e2013. doi: 10.1097/MD.0000000000002013.
citation: Wu CY, Fu JY, Wu CF, Liu YH, Hsieh MJ, Wu YC, Yang CT, Tsai YH. Pathologic Stage of Nonsmall Cell Lung Cancer Patients Presenting as Resectable Cases After Neoadjuvant Therapy Did Not Predict the Prognosis. Medicine (Baltimore). 2015 Oct;94(40):1. doi: 10.1097/MD.0000000000001700.
citation: Wu CF, Fu JY, Yeh CJ, Liu YH, Hsieh MJ, Wu YC, Wu CY, Tsai YH, Chou WC. Recurrence Risk Factors Analysis for Stage I Non-small Cell Lung Cancer. Medicine (Baltimore). 2015 Aug;94(32):e1337. doi: 10.1097/MD.0000000000001337.
citation: Wu CF, Wu CY, Fu JY, Wang CW, Liu YH, Hsieh MJ, Wu YC. Prognostic value of metastatic N1 lymph node ratio and angiolymphatic invasion in patients with pathologic stage IIA non-small cell lung cancer. Medicine (Baltimore). 2014 Oct;93(20):e102. doi: 10.1097/MD.0000000000000102.
citation: Hsieh CP, Fu JY, Liu YH, Yang CT, Hsieh MJ, Tsai YH, Wu YC, Wu CY. Prognostic factors in resectable pathological N2 disease of non-small cell lung cancer. Biomed J. 2015 Jul-Aug;38(4):329-35. doi: 10.4103/2319-4170.145765.
citation: Tognela A, Spring KJ, Becker T, Caixeiro NJ, Bray VJ, Yip PY, Chua W, Lim SH, de Souza P. Predictive and prognostic value of circulating tumor cell detection in lung cancer: a clinician's perspective. Crit Rev Oncol Hematol. 2015 Feb;93(2):90-102. doi: 10.1016/j.critrevonc.2014.10.001. Epub 2014 Oct 12.
citation: Tanaka F, Yoneda K, Kondo N, Hashimoto M, Takuwa T, Matsumoto S, Okumura Y, Rahman S, Tsubota N, Tsujimura T, Kuribayashi K, Fukuoka K, Nakano T, Hasegawa S. Circulating tumor cell as a diagnostic marker in primary lung cancer. Clin Cancer Res. 2009 Nov 15;15(22):6980-6. doi: 10.1158/1078-0432.CCR-09-1095. Epub 2009 Nov 3.
citation: Pantel K, Speicher MR. The biology of circulating tumor cells. Oncogene. 2016 Mar 10;35(10):1216-24. doi: 10.1038/onc.2015.192. Epub 2015 Jun 8.
citation: Yoon SO, Kim YT, Jung KC, Jeon YK, Kim BH, Kim CW. TTF-1 mRNA-positive circulating tumor cells in the peripheral blood predict poor prognosis in surgically resected non-small cell lung cancer patients. Lung Cancer. 2011 Feb;71(2):209-16. doi: 10.1016/j.lungcan.2010.04.017. Epub 2010 May 14.
citation: O'Flaherty JD, Gray S, Richard D, Fennell D, O'Leary JJ, Blackhall FH, O'Byrne KJ. Circulating tumour cells, their role in metastasis and their clinical utility in lung cancer. Lung Cancer. 2012 Apr;76(1):19-25. doi: 10.1016/j.lungcan.2011.10.018. Epub 2011 Dec 29.
citation: Hou JM, Greystoke A, Lancashire L, Cummings J, Ward T, Board R, Amir E, Hughes S, Krebs M, Hughes A, Ranson M, Lorigan P, Dive C, Blackhall FH. Evaluation of circulating tumor cells and serological cell death biomarkers in small cell lung cancer patients undergoing chemotherapy. Am J Pathol. 2009 Aug;175(2):808-16. doi: 10.2353/ajpath.2009.090078. Epub 2009 Jul 23.
citation: Hofman V, Long E, Ilie M, Bonnetaud C, Vignaud JM, Flejou JF, Lantuejoul S, Piaton E, Mourad N, Butori C, Selva E, Marquette CH, Poudenx M, Sibon S, Kelhef S, Venissac N, Jais JP, Mouroux J, Molina TJ, Vielh P, Hofman P. Morphological analysis of circulating tumour cells in patients undergoing surgery for non-small cell lung carcinoma using the isolation by size of epithelial tumour cell (ISET) method. Cytopathology. 2012 Feb;23(1):30-8. doi: 10.1111/j.1365-2303.2010.00835.x. Epub 2011 Jan 6.
citation: Nieva J, Wendel M, Luttgen MS, Marrinucci D, Bazhenova L, Kolatkar A, Santala R, Whittenberger B, Burke J, Torrey M, Bethel K, Kuhn P. High-definition imaging of circulating tumor cells and associated cellular events in non-small cell lung cancer patients: a longitudinal analysis. Phys Biol. 2012 Feb;9(1):016004. doi: 10.1088/1478-3975/9/1/016004. Epub 2012 Feb 3.
citation: Hofman V, Bonnetaud C, Ilie MI, Vielh P, Vignaud JM, Flejou JF, Lantuejoul S, Piaton E, Mourad N, Butori C, Selva E, Poudenx M, Sibon S, Kelhef S, Venissac N, Jais JP, Mouroux J, Molina TJ, Hofman P. Preoperative circulating tumor cell detection using the isolation by size of epithelial tumor cell method for patients with lung cancer is a new prognostic biomarker. Clin Cancer Res. 2011 Feb 15;17(4):827-35. doi: 10.1158/1078-0432.CCR-10-0445. Epub 2010 Nov 23.
citation: Sawabata N, Okumura M, Utsumi T, Inoue M, Shiono H, Minami M, Nishida T, Sawa Y. Circulating tumor cells in peripheral blood caused by surgical manipulation of non-small-cell lung cancer: pilot study using an immunocytology method. Gen Thorac Cardiovasc Surg. 2007 May;55(5):189-92. doi: 10.1007/s11748-007-0101-2.
citation: Sheu CC, Yu YP, Tsai JR, Chang MY, Lin SR, Hwang JJ, Chong IW. Development of a membrane array-based multimarker assay for detection of circulating cancer cells in patients with non-small cell lung cancer. Int J Cancer. 2006 Sep 15;119(6):1419-26. doi: 10.1002/ijc.21999.
citation: Khoury S, Tran N. Circulating microRNAs: potential biomarkers for common malignancies. Biomark Med. 2015;9(2):131-51. doi: 10.2217/bmm.14.102.
citation: Hofman V, Ilie MI, Long E, Selva E, Bonnetaud C, Molina T, Venissac N, Mouroux J, Vielh P, Hofman P. Detection of circulating tumor cells as a prognostic factor in patients undergoing radical surgery for non-small-cell lung carcinoma: comparison of the efficacy of the CellSearch Assay and the isolation by size of epithelial tumor cell method. Int J Cancer. 2011 Oct 1;129(7):1651-60. doi: 10.1002/ijc.25819. Epub 2011 Mar 11.
citation: Went PT, Lugli A, Meier S, Bundi M, Mirlacher M, Sauter G, Dirnhofer S. Frequent EpCam protein expression in human carcinomas. Hum Pathol. 2004 Jan;35(1):122-8. doi: 10.1016/j.humpath.2003.08.026.