Clinical trial NCT03059641: Therapeutic ResistAnce and Clonal Evolution Assessed With Liquid Biopsy of NSCLC Patients in China
Official title: Mutation Profile Detection, Therapeutic Resistance and Clonal Evolution Assessed With Liquid Biopsy of Advanced NSCLC Patients in China
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Lung Neoplasms
Lung Cancer, Nonsmall Cell
Adenocarcinoma of Lung
Squamous Cell Lung Cancer
Keywords: Next Generation Sequencing (NGS)
Tyrosine Kinase Inhibitor (TKI)
liquid biopsy
EGFR Gene mutation
Lead sponsor: Geneplus-Beijing Co. Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Shanghai Chest Hospital
First posted: 2017-02-23
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: treatment naïve Stage IIIB or Stage IV NSCLC patients, adenocarcinoma or squamous cell carcinoma without smoking history

Brief summary: To evaluate the concordance of sensitizing mutations detected between paired plasma and tissue samples; the correlation between the clonal status of sensitizing mutations and targeted therapy response; and the prognostic impact of the relative abundance of sensitizing / resistance mutations.

Detailed description: In the study, 500 advanced NSCLC patients will be recruited. All the patients will receive biopsy genotype assay and circultating tumor DNA (ctDNA) liquid biopsy. Patients who carry actionable EGFR mutation, ROS1 fusion, ALK fusion or MET exon 14 skipping mutation will receive TKI treatment according to guidelines. During the TKI treatment, every patients will take liquid biopsy assay to monitor the mutation status. The study will be ended when all the patients had a progressive disease (PD) in their targeted lesion.

Eligibility criteria: Inclusion Criteria:

* Provision of informed consent
* Newly diagnosed and histological or cytological confirmed stage IIIB-IV lung adenocarcinoma or non-smoking squamous cell carcinoma patients according to the AJCC staging system. The stage IV lung cancer and brain metastasis can be diagnosed by imaging and enhanced CT respectively
* ECOG performance status 0-2 with expected more than 6 months of survival time
* Willingness to comply with required protocols and give permission to use the data for clinical research and products development

Exclusion Criteria:

* Patients have other primary cancers
* Patients have symptomatic brain metastasis, complications that are associated with brain metastasis or cognitive disorders
* Patients failed in either plasma or tissue sample QC

Primary outcomes:
measure: The mutation pattern of untreated advanced NSCLC and evolution of ctDNA mutation profile during TKI treatment.
timeFrame: 2 years
Secondary outcomes:
measure: The concordance of gene mutation pattern between liquid biopsy and tissue biopsy.
timeFrame: 1 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Changchun
country: China
facility: First Hospital of Jilin University
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University School of medicine
city: Hangzhou
country: China
facility: The First Hospital of Zhejiang Province
city: Hefei
country: China
facility: Anhui Provincial Hospital
city: Jiangyin
country: China
facility: Jiangsu Jiangyin People's Hospital
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
city: Ningbo
country: China
facility: Ningbo No.2 Hospital
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
city: Shanghai
country: China
facility: Shanghai Chest Hospital
city: Shanghai
country: China
facility: Shanghai East Hospital
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
city: Wuxi
country: China
facility: Affiliated Hospital, Jiangnan University
Study officials:
affiliation: Shanghai Chest Hospital
name: Shun Lu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ai X, Cui J, Zhang J, Chen R, Lin W, Xie C, Liu A, Zhang J, Yang W, Hu X, Hu X, Zhao Q, Rao C, Zang YS, Ning R, Li P, Chang L, Yi X, Lu S. Clonal Architecture of EGFR Mutation Predicts the Efficacy of EGFR-Tyrosine Kinase Inhibitors in Advanced NSCLC: A Prospective Multicenter Study (NCT03059641). Clin Cancer Res. 2021 Feb 1;27(3):704-712. doi: 10.1158/1078-0432.CCR-20-3063. Epub 2020 Nov 13.