Application of Detecting Circulating Tumor Cells in the Accurate Treatment of Early Stage Lung Adenocarcinoma

Treatment Clinical Trial

— CTCs detection  

Official title:

Application of Detecting Circulating Tumor Cells in the Accurate Diagnosis and Treatment of Early Stage Lung Adenocarcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02951897
• Other study ID #: TMMU-DP-2016-4-25
• Status: Recruiting
• Phase: N/A
• First received: October 25, 2016
• Last updated: October 31, 2016
• Start date: April 2016
• Est. completion date: December 2019

Study information

• Verified date: October 2016
• Source: Third Military Medical University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Health and Family Planning Commission of Chongqing City
• Study type: Interventional

Clinical Trial Summary

In 2015-2016, 224,390 cases were newly diagnosed with lung cancer in USA. Of all the cases, 83% are non-small cell lung cancer (NSCLC). Currently, the 5-year survival rate of NSCLC patients is 21%, and more than 25% of early stage NSCLC patients, who have undergone surgical treatment, will have a relapse or progression.

Circulating tumor cells (CTCs), which shed from the primary tumor into the vasculature or lymphatics, can be regarded as a new prognostic factors of metastatic process. Thus far, CTCs-detection technologies can be divided into epithelial cell adhesion molecule (EpCAM)-based detection methods, e.g., the widely used CellSearch® and Adnatest®,and EpCAM-independent detection methods, e.g., ISET® and ScreenCell®. Herein, the investigators used a newly established approach, i.e., CanPatrolTM to detect CTCs in early stage lung Adenocarcinoma cases.

The investigator aim to explore whether CTCs detection prior to surgery can be contributive to the early diagnosis, or may help to predict the prognosis and guide the treatment strategy of early stage lung Adenocarcinoma.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 2019
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years to 70 Years

Eligibility

Inclusion Criteria:

• stage I lung adenocarcinoma

Exclusion Criteria:

• cases with any new adjuvant treatment prior to surgery

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Circulating Tumor Cells
• Diagnoses Diseases
• Lung Adenocarcinoma, Stage I
• Lung Neoplasms
• Neoplastic Cells, Circulating
• Treatment

Intervention

Procedure:
• lobectomy

• segmentecomy

Drug:
• chemotherapy(pemetrexed+CISPLATIN)

Procedure:
• Lymphadenectomy
Lymphadenectomy or lymph node dissection is the surgical removal of one or more groups of lymph nodes. It is almost always performed as part of the surgical management of cancer. In a regional lymph node dissection, some of the lymph nodes in the tumor area are removed; in a radical lymph node dissection, most or all of the lymph nodes in the tumor area are removed.

Other:
• CanPatrolTM to detect CTCs
CanPatrol TM was used to detect CTCs, which is a newly established technology to detect CTCs, containing the following steps: (1) To remove erythrocytes by red blood cell lysis and deplete CD45+ leukocytes in 10ml blood sample using a magnetic bead separation method; (2) To enrich CTCs by 8-µm-diameter-pore calibrated membrane filters; and (3) To identify and characterize CTCs by using RNA-in situ hybridization (ISH), based on the branched DNA (bDNA) signal amplification technology, to detect EMT markers, e.g., cytokeratins(CK) 8, 18 and 19, epithelial cell adhesion molecule (EpCAM), vimentin and twist. The details of classification of CTCs by using CanPatrol TM was depicted in the recently published protocol. Finally, the CTCs were clustered into three subtypes, as per the EMT markers, i.e., epithelial (E-) CTCs, mesenchymal (M-) CTCs and epithelial- mesenchymal (E&M-) CTCs.

Locations

Country	Name	City	State
China	Daping hospital	Chongqing

Sponsors (1)

Lead Sponsor	Collaborator
Third Military Medical University

Country where clinical trial is conducted

China, 

References & Publications (12)

Bayarri-Lara C, Ortega FG, Cueto Ladrón de Guevara A, Puche JL, Ruiz Zafra J, de Miguel-Pérez D, Ramos AS, Giraldo-Ospina CF, Navajas Gómez JA, Delgado-Rodriguez M, Lorente JA, Serrano MJ. Circulating Tumor Cells Identify Early Recurrence in Patients with Non-Small Cell Lung Cancer Undergoing Radical Resection. PLoS One. 2016 Feb 25;11(2):e0148659. doi: 10.1371/journal.pone.0148659. — View Citation

Chen X, Wang X, He H, Liu Z, Hu JF, Li W. Combination of circulating tumor cells with serum carcinoembryonic antigen enhances clinical prediction of non-small cell lung cancer. PLoS One. 2015 May 21;10(5):e0126276. doi: 10.1371/journal.pone.0126276. — View Citation

Funaki S, Sawabata N, Nakagiri T, Shintani Y, Inoue M, Kadota Y, Minami M, Okumura M. Novel approach for detection of isolated tumor cells in pulmonary vein using negative selection method: morphological classification and clinical implications. Eur J Cardiothorac Surg. 2011 Aug;40(2):322-7. doi: 10.1016/j.ejcts.2010.11.029. — View Citation

Hofman V, Bonnetaud C, Ilie MI, Vielh P, Vignaud JM, Fléjou JF, Lantuejoul S, Piaton E, Mourad N, Butori C, Selva E, Poudenx M, Sibon S, Kelhef S, Vénissac 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. — View Citation

Hofman V, Ilie MI, Long E, Selva E, Bonnetaud C, Molina T, Vénissac 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. — View Citation

Liu L, Liao GQ, He P, Zhu H, Liu PH, Qu YM, Song XM, Xu QW, Gao Q, Zhang Y, Chen WF, Yin YH. Detection of circulating cancer cells in lung cancer patients with a panel of marker genes. Biochem Biophys Res Commun. 2008 Aug 8;372(4):756-60. doi: 10.1016/j.bbrc.2008.05.101. — View Citation

Nair VS, Keu KV, Luttgen MS, Kolatkar A, Vasanawala M, Kuschner W, Bethel K, Iagaru AH, Hoh C, Shrager JB, Loo BW Jr, Bazhenova L, Nieva J, Gambhir SS, Kuhn P. An observational study of circulating tumor cells and (18)F-FDG PET uptake in patients with treatment-naive non-small cell lung cancer. PLoS One. 2013;8(7):e67733. doi: 10.1371/journal.pone.0067733. — View 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. — View Citation

Yamashita JI, Kurusu Y, Fujino N, Saisyoji T, Ogawa M. Detection of circulating tumor cells in patients with non-small cell lung cancer undergoing lobectomy by video-assisted thoracic surgery: a potential hazard for intraoperative hematogenous tumor cell dissemination. J Thorac Cardiovasc Surg. 2000 May;119(5):899-905. — View Citation

Yie SM, Lou B, Ye SR, He X, Cao M, Xie K, Ye NY, Lin R, Wu SM, Xiao HB, Gao E. Clinical significance of detecting survivin-expressing circulating cancer cells in patients with non-small cell lung cancer. Lung Cancer. 2009 Feb;63(2):284-90. doi: 10.1016/j.lungcan.2008.05.024. — View Citation

Yin J, Wang Y, Yin H, Chen W, Jin G, Ma H, Dai J, Chen J, Jiang Y, Wang H, Liu Z, Hu Z, Shen H. Circulating Tumor Cells Enriched by the Depletion of Leukocytes with Bi-Antibodies in Non-Small Cell Lung Cancer: Potential Clinical Application. PLoS One. 2015 Aug 28;10(8):e0137076. doi: 10.1371/journal.pone.0137076. — View 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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease free survival		From date of diagnosis until the date of first documented progression or date of cancer related death , whichever came first, assessed up to 60 months	No