Chromosomal Instability as a Surrogate Biomarker of Drug Resistance in Immunotherapy for Lung Cancer Patients
NCT ID: NCT04203095
Last Updated: 2019-12-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
40 participants
OBSERVATIONAL
2019-11-10
2021-11-11
Brief Summary
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Detailed Description
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As one of the most prominent and common features of solid tumors, chromosomal instability (CIN) accelerates the development of anticancer drug resistance, often leading to treatment failure and disease recurrence, which limits the effectiveness of most current treatments. Previous studies have shown that CIN promotes the emergence of multidrug resistance by providing higher levels of genetic diversity, leading to multidrug resistance. In NSCLC, the researchers found that genomic doubling and sustained dynamic CIN were associated with intratumoral heterogeneity and led to parallel evolution of CDNAs, including CDK4, FOXA1, and BCL11A. It is worth noting that the study found consistency in the variation of mutation levels, indicating that CIN in lung cancer is more likely to select driving events than other mutation processes. CIN enables cells to enter several different evolutionary trajectories and adapt to the selective pressure generated by treatment, which is the basis of drug resistance. Based on the above, CIN may become a more accurate and effective biomarker for the study of drug resistance mechanism of ICI in lung cancer. NGS technology can obtain more comprehensive genomic information while detecting cost reduction, making CIN detection more accurate and practical than FISH used for evaluating CIN in patient commonly.As a new Detection method based on NGS technology, Ultrasensitive Chromosomal Aneuploidy Detection (UCAD) has been developed in our previous study. In which, low-coverage whole-genome sequencing technology based on NGS was adopted to detect CIN of ctDNA in patients' peripheral blood, and bioinformatics analysis was performed to determine the risk of malignancy (or recurrence) and the extent of tumor burden and CIN. It has important clinical value in auxiliary diagnosis, therapeutic effect monitoring, recurrence and metastasis monitoring and prognosis evaluation of tumor patients.
This study proposes that continuous dynamic CIN is related to intratumor heterogeneity, which drives parallel evolution of somatic copy-number alterations (SCNAs) and promotes the emergence of drug-resistant clones by providing a higher level of genetic diversity of tumor cells, thus leading to drug resistance in patients treated with ICI. Investigators aimed to continuously monitor dynamic CIN in the blood of patients with lung cancer after second-line treatment with UCAD to establish a new molecular immune resistance evaluation index. Further, the correlation between the evolution of tumor cloning and ICI resistance in patients during treatment was analyzed based on the detection results of dynamic CIN.
Conditions
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Keywords
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Study Design
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CASE_CONTROL
PROSPECTIVE
Study Groups
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patient with PD1 antibody treatment
Investigators will detect cfDNA CIN of lung cancer patients 1day (Day 0) before treatment with PD1 antibody, then Day 22 and Day 64 after treatment with PD1 antibody, as well as at the time of disease progression confirmed.
The correlation of CIN and drug resistance to PD1 antibody was analyzed.
the level of plasma cfDNA CINs
The extracted cfDNA from PB will be analyzed by UCAD to determine the level of CINs.
Interventions
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the level of plasma cfDNA CINs
The extracted cfDNA from PB will be analyzed by UCAD to determine the level of CINs.
Eligibility Criteria
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Inclusion Criteria
* Patients planed to receive PD1 antibody treatment with or without chemotherapy, including as the neo-adjuvant therapy.
* The subjects' age, sex, marital and reproductive history, collection time, pathology, cytology and imaging diagnosis were complete.
* Participants signed informed consent form.
Exclusion Criteria
* Without measurable target lesion according to the RECIST criteria.
* Age under 20 years or more than 70.
* Individuals unwilling to sign the consent form or unwilling to provide PB for test or unwilling to provide the medical record.
20 Years
70 Years
ALL
No
Sponsors
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Shanghai Pulmonary Hospital, Shanghai, China
OTHER
Responsible Party
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Di Zheng
Director of medical oncology
Principal Investigators
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Di Zheng, PhD
Role: STUDY_DIRECTOR
Shanghai Pulmonary Hospital, Shanghai, China
Locations
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Di Zheng
Shanghai, Shanghai Municipality, China
Countries
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Central Contacts
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Facility Contacts
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Di Du, PhD
Role: primary
References
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Other Identifiers
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ph-pg001
Identifier Type: -
Identifier Source: org_study_id