Diagnostic and Monitoring Significance of ctDNA Methylation Analysis by NGS in Benign and Malignant Pulmonary Nodules

• ClinicalTrials.gov Identifier: NCT03651986
• Recruitment Status: Recruiting
• First Posted: August 29, 2018
• Last Update Posted: March 24, 2020
• Sponsor: AnchorDx Medical Co., Ltd.
• Collaborators: Xiangya Hospital of Central South University; West China Hospital; Shanghai Zhongshan Hospital; Shanghai Pulmonary Hospital affiliated to Tongji University; First Hospital of China Medical University; Guizhou Provincial People's Hospital; Shanghai Chest Hospital; First Affiliated Hospital, Sun Yat-Sen University; First Affiliated Hospital Xi'an Jiaotong University; Qilu Hospital of Shandong University; Inner Mongolia People's Hospital; The First Affiliated Hospital with Nanjing Medical University; The First Affiliated Hospital of Zhengzhou University; Second Hospital of Jilin University; LanZhou University; Peking University Third Hospital; The First People's Hospital of Yunnan; Shantou Affiliated Hospital of Sun Yat-Sen University; Ruijin Hospital, The Shanghai Jiao Tong University Medical School; Tongji Hospital; The First Affiliated Hospital of Guangzhou Medical University; Xijing Hospital, Air Force Medical University of PLA; Shenzhen People's Hospital; Henan Provincial People's Hospital; Beijing Chao Yang Hospital; The Second Affiliated Hospital of Xiamen Medical College; The First Affiliated Hospital of Nanchang University
• Information provided by (Responsible Party): AnchorDx Medical Co., Ltd.

Study Description

Brief Summary:

AnchorDx is using circulating tumor DNA (ctDNA) methylation analysis by next-generation sequencing (NGS) to develop a blood-based assay for differentiating benign and malignant pulmonary nodules early. The purpose of this study is to evaluate the diagnostic performance of this assay in patients with pulmonary nodules.

Condition or disease	Intervention/treatment
Pulmonary Nodules	Diagnostic Test: ctDNA methylation analysis by NGS

Detailed Description:

This is a prospective, multi-center, observational cohort study and seeks to enroll 10,560 participants with pulmonary nodules smaller than 3 cm in diameter from 21 hospitals in China. All participants will be followed up with chest CT or low-dose computed tomography (LDCT) scans for 2-3 years ( baseline, 3 months, 6 months, 12 months, 24 months and 36 months). Their blood samples, CT or LDCT scans data, and clinical data will be collected at each visit and Formalin-fixed paraffin-embedded (FFPE) tissues will be collected when participants who receive pneumonectomy or percutaneous lung biopsy.

Study Design

• Study Type: Observational
• Estimated Enrollment: 10560 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Diagnostic and Monitoring Significance of Circulating Tumor DNA (ctDNA) Methylation Analysis by Next-Generation Sequencing in Benign and Malignant Pulmonary Nodules
• Actual Study Start Date: November 26, 2018
• Estimated Primary Completion Date: September 2022
• Estimated Study Completion Date: June 2023

Groups and Cohorts

Group/Cohort

Intervention/treatment

Prospective Cohort; This is a prospectively enrolling cohort study and a stratified case-cohort design will be employed to select malignant pulmonary nodules cases and benign pulmonary nodules subjects who will be assayed. All participants will be followed up with chest CT or low-dose computed tomography (LDCT) scans for 2-3 years, and take the diagnostic test, ctDNA methylation analysis by NGS, at each visit.

Diagnostic Test: ctDNA methylation analysis by NGS; A blood-based assay for differentiating benign and malignant pulmonary nodules early using circulating tumor DNA (ctDNA) methylation analysis by next-generation sequencing (NGS)

Outcome Measures

Primary Outcome Measures :

1. The diagnostic performance of the blood-based assay for differentiating benign and malignant pulmonary nodules early using circulating tumor DNA (ctDNA) methylation analysis by next-generation sequencing (NGS) [ Time Frame: 3 Years ]
   The efficacy of the blood-based ctDNA methylation assay comparing with pathologic diagnosis, the gold standard, and CT/LDCT diagnosis, including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).

Secondary Outcome Measures :

1. The diagnostic and monitoring significance of routine tests integrating with ctDNA methylation analysis by NGS in differentiating benign and malignant pulmonary nodules [ Time Frame: 3 Years ]
   The diagnostic performance of the combination of routine tests and ctDNA methylation analysis by NGS in differentiating benign and malignant pulmonary nodules, including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).

Biospecimen Retention:   Samples With DNA

Whole blood

Formalin-fixed paraffin-embedded (FFPE) tissue

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Probability Sample

Study Population

Subjects with pulmonary nodules diagnosed by chest CT or low-dose computed tomography (LDCT) scans

Criteria

Inclusion Criteria:

• 18 Years and older

• pulmonary nodules diagnosed by chest CT or low-dose computed tomography (LDCT) scans

  • non-calcified pulmonary nodules with the diameter between 5mm to 30mm
  • including solid nodules, mixed ground-glass opacity nodules and pure ground-glass opacity lung modules
• new cases of pulmonary nodules or diagnosed within 60 days prior to enrollment
• agree to finish the Patient Pulmonary History Questionnaire
• agree to be followed up for 2-3 years
• agree to provide a written informed consent

Exclusion Criteria:

• pregnant or lactating women
• received any pneumonectomy or percutaneous lung biopsy before enrollment
• recipients of blood transfusions within 30 days prior to enrollment
• patients with tumors identified within 2 years prior to enrollment except non-melanoma skin cancer
• fail to understand or provide a written informed consent

Contacts and Locations

Contacts

Contact: Bo WANG; +86-15920405979; bo_wang@anchordx.com

Contact: Wenhua LIANG, MD; +86-13710249454; liangwh1987@163.com

Locations

China

Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital; Recruiting

Beijing, China

Principal Investigator: Zhaohui TONG, MD

Xiangya Hospital of Central South University; Recruiting

Changsha, China

Principal Investigator: Chengping HU, MD

Department of Respiratory Medicine, West China Hospital of Sichuan University; Recruiting

Chengdu, China

Principal Investigator: Dan LIU, MD

Department of Pulmonary Medicine, The First Affiliated Hospital of Sun Yat-Sen University; Recruiting

Guangzhou, China

Principal Investigator: Yubiao GUO, MD

The First Affiliated Hospital of Guangzhou Medical University; Recruiting

Guangzhou, China

Contact: Wenhua LIANG, MD liangwh1987@163.com

Principal Investigator: Nanshan ZHONG, MD

Sub-Investigator: Wenhua LIANG, MD

Department of Respiration and Critical Care Medicine, Guizhou Provincial People's Hospital; Recruiting

Guiyang, China

Principal Investigator: Xiangyan ZHANG, MD

Department of Pulmonary and Critical Care Medicine, Inner Mongolia Autonomous Region People's Hospital; Recruiting

Hohhot, China

Principal Investigator: Dejun SUN, MD

Department of Respiratory, QILU Hospital, Shandong University; Recruiting

Jinan, China

Principal Investigator: Wei XIAO, MD

Department of Respiratory Medicine, The First People's Hospital of Yunnan Province; Recruiting

Kunming, China

Principal Investigator: Yunhui ZHANG, MD

Department of Gerontal Respiratory Medicine, The Frist Hospital of Lanzhou University; Recruiting

Lanzhou, China

Principal Investigator: Xiaoju LIU, MD

Department of Respiration, The First Affiliated Hospital of Nanchang University; Recruiting

Nanchang, China

Principal Investigator: Wei ZHANG, MD

Department of Pulmonary & Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Recruiting

Shanghai, China

Principal Investigator: Jieming QU, MD

Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University; Recruiting

Shanghai, China

Principal Investigator: Baohui HAN, MD

Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University; Recruiting

Shanghai, China

Principal Investigator: Xin ZHANG, MD

Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine; Recruiting

Shanghai, China

Principal Investigator: Jinfu XU, MD

Department of Respiratory Medicine, Shantou Central Hospital; Recruiting

Shantou, China

Principal Investigator: Qichuan ZHANG, MD

Department of Respiratory Medicine, The First Hospital of China Medical University; Recruiting

Shenyang, China

Principal Investigator: Wei WANG, MD

Department of Respiratory Medicine, Shenzhen People's Hospital; Recruiting

Shenzhen, China

Principal Investigator: Di WU, MD

Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology; Recruiting

Wuhan, China

Principal Investigator: Jianping ZHAO, MD

Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Xi'an Jiaotong University; Recruiting

Xi'an, China

Principal Investigator: Lan YANG, MD

Department of Pulmonary Medicine, Xijing Hospital, Air Force Medical University of PLA; Recruiting

Xi'an, China

Principal Investigator: Jian ZHANG, MD

Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Xiamen Medical College; Recruiting

Xiamen, China

Principal Investigator: Zhanqing LI, MD

Department of Respiratory Medicine, Henan Provincial People's Hospital; Recruiting

Zhengzhou, China

Principal Investigator: Xiaoju ZHANG, MD

Sponsors and Collaborators

AnchorDx Medical Co., Ltd.

Xiangya Hospital of Central South University

West China Hospital

Shanghai Zhongshan Hospital

Shanghai Pulmonary Hospital affiliated to Tongji University

First Hospital of China Medical University

Guizhou Provincial People's Hospital

Shanghai Chest Hospital

First Affiliated Hospital, Sun Yat-Sen University

First Affiliated Hospital Xi'an Jiaotong University

Qilu Hospital of Shandong University

Inner Mongolia People's Hospital

The First Affiliated Hospital with Nanjing Medical University

The First Affiliated Hospital of Zhengzhou University

Second Hospital of Jilin University

LanZhou University

Peking University Third Hospital

The First People's Hospital of Yunnan

Shantou Affiliated Hospital of Sun Yat-Sen University

Ruijin Hospital, The Shanghai Jiao Tong University Medical School

Tongji Hospital

The First Affiliated Hospital of Guangzhou Medical University

Xijing Hospital, Air Force Medical University of PLA

Shenzhen People's Hospital

Henan Provincial People's Hospital

Beijing Chao Yang Hospital

The Second Affiliated Hospital of Xiamen Medical College

The First Affiliated Hospital of Nanchang University

Investigators

• Study Chair: Nanshan ZHONG, MD; The First Affiliated Hospital of Guangzhou Medical University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Liang W, Liu D, Li M, Wang W, Qin Z, Zhang J, Zhang Y, Hu Y, Bao H, Xiang Y, Wang B, Wu J, Sun J, Hu C, Ye X, Zhang X, Xiao W, Yun C, Sun D, Wang W, Chang N, Zhang Y, Zhao J, Zhang X, Xu J, Wu D, Liu X, Guo Y, Zhang Q, Zhang W, Yang L, Li Z, Zhang X, Han B, Tong Z, He J, Qu J, Fan JB, Zhong N. Evaluating the diagnostic accuracy of a ctDNA methylation classifier for incidental lung nodules: protocol for a prospective, observational, and multicenter clinical trial of 10,560 cases. Transl Lung Cancer Res. 2020 Oct;9(5):2016-2026. doi: 10.21037/tlcr-20-701.

• Responsible Party: AnchorDx Medical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03651986
• Other Study ID Numbers: AnchorDx LC201801
• First Posted: August 29, 2018
• Last Update Posted: March 24, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AnchorDx Medical Co., Ltd.:

Circulating Tumor DNA (ctDNA); DNA Methylation Analysis; Next-Generation Sequencing (NGS); Low-Dose Computed Tomography (LDCT)

Additional relevant MeSH terms:

Multiple Pulmonary Nodules; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases