LUNGCA: Dynamic Monitoring Circulating Tumor DNA in Surgical Patients With Lung Cancer

Sponsor

West China Hospital (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03317080

Collaborator

GeneCast Biotechnology Co., Ltd. (Industry), Sichuan Cancer Hospital and Research Institute (Other), Sichuan Provincial People's Hospital (Other)

1,500

Enrollment

Location

71.1

Anticipated Duration (Months)

21.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study aims to promote the rational use of liquid biopsy in the clinical detection of lung cancer. Lung cancer is a malignant tumor with high morbidity and mortality worldwide. The incidence of lung cancer in China is expected to increase in the next few years with the aging population and environmental pollution. Early diagnosis and effective intervention are necessary in the clinical treatment of lung cancer. Surgical resection could achieve a better prognosis for patients with early lung cancer. However, for advanced lung cancer, individualized treatment based on the pathological classification, molecular genetic characteristics, and body conditions of patients could effectively prolong the lifetime. The prevention, diagnosis, and intervention strategies for lung cancer depend on the oncology information of patients. The techniques and methods used for detecting lung cancer in clinic include imaging technology, pathological biopsy, screening of blood tumor markers, and liquid biopsy technology, which has been developed recently. The liquid biopsy can capture the oncology information, including tumor load, tumor gene mutation, and so on, from the blood of patients with cancer by detecting circulating tumor cells, tumor exosome, circulating tumor DNA, and circulating tumor RNA. Moreover, it has become an important direction for clinical tumor detection because of its noninvasiveness, convenient sampling, and potential for overcoming tumor heterogeneity. This study intends to include 1000-2000 patients with stages I-IV lung cancer to research on lung cancer diagnosis, drug efficacy, surgical effect evaluation, recurrence monitoring, prognosis judgment, medication guidance, and molecular classification differentiation through the dynamic detection of blood ctDNA using the second-generation sequencing technology. The study also intends to analyze and establish the database with a large sample size.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer

Detailed Description

Lung cancer is a malignant tumor with high morbidity and mortality worldwide. The incidence and mortality of lung cancer in China have topped the list of malignant tumors since 2010.Early diagnosis and effective intervention are extremely important in the clinical treatment of lung cancer. Surgical resection could achieve better prognosis in patients with early lung cancer (stages IA and IB).For patients with advanced lung cancer (stages II, III, and IV), individualized treatment with molecular classification researches and the application of targeted drugs based on the pathological classification, molecular genetic characteristics, and body conditions of patients has been confirmed to effectively prolong the lifetime. However, the lack of effective and convenient detection approaches for capturing oncology information of patients, promoting early diagnosis and effective intervention of lung cancer, and ultimately improving the prognosis of lung cancer are limitations in achieving successful clinical treatment of lung cancer.

At present, methods used in clinical screening of lung cancer,including detection of serological markers, imaging technology, and biopsy ,have some limitations:in the absence of imaging evidence, the serological assessment could not be used as the evidence for diagnosis and treatment strategy alteration for lung cancer. The application of low-dose computed tomography scan for lung cancer screening shows a high false-positive rate, which is liable to require excessive medical treatment. Biopsy does greater harm to patients with lung cancer; sampling is difficult, and effective information may be missed because of tumor heterogeneity. With the development of molecular pathology in cancer research in recent years, liquid biopsy has become an important developmental direction for clinical tumor detection because of its noninvasiveness, convenient sampling, and potential for overcoming tumor heterogeneity.Liquid biopsies include the detection of circulating tumor cells (CTCs), tumor exosome (exosome), circulating tumor RNA (ctRNA), and circulating tumor DNA (ctDNA) in peripheral blood.

ctDNA is a part of circulating free DNA (cfDNA), which is released by tumor cell necrosis, apoptosis, micrometastasis, or the cleavage of CTCs and proliferated tumor cells.ctDNA includes genetic information of tumor cells, such as mutation, recombination, and deletion (15). ctDNA was approved by the European Medicines Agency in 2014 and the National Comprehensive Cancer Network Guidelines for NSCLC in 2017 as a supplement sample to assess genetic variation when tumor tissue samples were difficult to obtain. Clinical studies have shown that ctDNA can effectively reflect tumor load, malignant degree, metastasis ability, and real-time information of genetic mutation, which has a certain correlation with the genetic information of tumor tissues. Moreover, the content of cfDNA in patients with cancer was significantly higher than that in healthy people. Also, ctDNA has been used for detecting tumor load, monitoring tumor recurrence, and assessing minimal residual disease in a number of cancer types. Some studies have suggested that ctDNA can be used to estimate tumor recurrence, even before imaging. Therefore, ctDNA detection has an important value in the clinical application of lung cancer diagnosis, drug efficacy, surgical effect evaluation, recurrence monitoring, prognosis judgment, medication guidance, and molecular classification differentiation.

This study intends to include 1000-2000 patients with stages I-IV lung cancer. The capture sequencing of lung cancer-related genes in peripheral blood ctDNA and tumor tissue DNA will be performed during the diagnosis and treatment process using the liquid-phase hybridization approach. Thus, the study will establish a large sample size database of the genetic variants in patients with lung cancer during the diagnosis and treatment process, and promoted the development of an individualized diagnostic model of the lung cancer population. The patients with lung cancer undergoing surgery will be followed up, and the plasma concentration of cfDNA and genetic mutation of ctDNA will be detected to evaluate the postoperative residual cancer, monitor tumor recurrence, and timely guide the clinical treatment and intervention. The molecular classification differentiation analysis and screening of tumor recurrence-related genetic mutations will be performed after the surgery and during the course of disease progression to provide the referential clinical research model and ideas for the application of ctDNA detection-based liquid biopsy technique in tumor therapy.

Study Design

Study Type:

Observational

Anticipated Enrollment :

1500 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

A Study of the Value of Dynamic Monitoring Circulating Tumor DNA in Patients With Lung Cancer for Post-Operative Evaluation,Therapy Response Assessment,Relapse Prediction and Defining Molecular Phenotypes.

Actual Study Start Date :

Sep 27, 2017

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
patients with lung cancer patients with stages I-IV lung cancer eligible for surgery

Outcome Measures

Primary Outcome Measures

heterogeneity of lung cancer [up to 36 months]
the relationship between heterogeneity of lung cancer and clinical results following surgery and adjuvant therapy

Secondary Outcome Measures

progression-free survival [up to 36 months]
from the date of recruitment until the date of progression of lung cancer or death from any other cause assessed up to 36 months
overall survival [up to 36 months]
from the date of recruitment until the date of death from any cause assessed up to 36 months

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

patients with Stage I-IV lung cancer who are eligible for surgery(with no restriction of age, gender, or smoking history).
ECOG score:0-1.
Patients in the group will be allowed to collect whole blood or tissue samples at specific time points.
Patients will be regularly tested according to the doctor's advice.
Signed informed consent.