Chromosomal Instability as a Surrogate Biomarker of Drug Resistance in Immunotherapy for Lung Cancer Patients

NCT04203095 | Unknown DMC

• 1 other identifier: ph-pg001
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

PD1, as an immune checkpoint inhibitor, has provided a new therapeutic approach for patients with cancer, including patients. Although immunotherapy has proven effective, most patients do not benefit from it because of a large proportion which developing primary and acquired resistance. However, there is still a lack of accurate and effective molecular biomarkers to accurately evaluate the drug resistance of patients treated with immune checkpoint inhibitors (ICI), so as to maximize the therapeutic effect in patients. Chromosomal instability (CIN) is one of the most prominent and common characteristics of solid tumors, accelerating the development of anti-cancer drug resistance, often leading to treatment failure and disease recurrence, which limits the effectiveness of most current treatments. Hence the aim of this study is to evaluate dynamic CIN continuously monitored in the blood of patients with lung cancer treated with ICIs with Ultrasensitive Chromosomal Aneuploidy Detection (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 results of dynamic CIN detection. This not only evaluate the efficacy of the ICI treatment in real-time, but also enables better understanding and overcoming the resistance mechanism of immunotherapy in the future.

Conditions

Lung Cancer

Keywords

Chromosomal aneuploidy detection; lung cancer; PD-1/PD-L1; Drug resistance in Immunotherapy

Outcome Measures

Primary Outcomes (1)

• the concordance bettwen CINs and treatment outcomes The concordance between CINs and treatment outcomes

  According to the correlation analysis between the patient's clinical drug resistance and CIN detected using UCAD, the stratified cutoff value interval of the patient was found, which was divided into four treatment outcomes based on CIN assessment : significant efficacy, primary drug resistance, acquired drug resistance and possible super progress.

  through study completion, an average of 3 months

Secondary Outcomes (1)

• the concordance bettwen CINs and clinical monitoring

  through study completion, an average of 3 months

Study Arms (1)

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.

Diagnostic Test: the level of plasma cfDNA CINs

Interventions

the level of plasma cfDNA CINs DIAGNOSTIC_TEST

The extracted cfDNA from PB will be analyzed by UCAD to determine the level of CINs.

patient with PD1 antibody treatment

Eligibility Criteria

• Age: 20 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with lung cancer in Shanghai Pulmonary Hospital (SPH) from Aug 2019 till the end of this study.

You may qualify if:

• Stage IIIa-IVb Non-small-cell lung cancer patients without EGFR，ALK,ROS1,c-Met driven gene mutation. Male or female patients aged 20-70 years.
• 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.

You may not qualify if:

• Eligible to target therapy with driven gene mutation.
• 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.

Sponsors & Collaborators

• Shanghai Pulmonary Hospital, Shanghai, China: lead

Study Sites (1)

Di Zheng

Shanghai, Shanghai Municipality, China

RECRUITING

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Biospecimen

Retention: SAMPLES WITH DNA

The extracted cell free DNA from peripheral blood will be analyzed by Ultrasensitive Chromosomal Aneuploidy Detection to determine the level of chromosomal instability.

MeSH Terms

Conditions

Lung Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Di Zheng, PhD

  Shanghai Pulmonary Hospital, Shanghai, China

  STUDY DIRECTOR

Central Study Contacts

Di Zheng, PhD

CONTACT

8613801683953; pulmonarysh_pg@126.com

ziliang qian, PhD

CONTACT

8615000902318; ziliang.qian@prophetgenomics.com.cn

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of medical oncology

Study Record Dates

• First Submitted: December 16, 2019
• First Posted: December 18, 2019
• Study Start: November 10, 2019
• Primary Completion: November 11, 2020
• Study Completion: November 11, 2021
• Last Updated: December 24, 2019

Record last verified: 2019-12

Locations

CN (1)