The Study of Exosome EML4-ALK Fusion in NSCLC Clinical Diagnosis and Dynamic Monitoring

NCT04499794 | Unknown

• 1 other identifier: NCC2064
• Study Type: observational
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

The application of ALK inhibitors in the first-line cancer treatment can significantly increase the PFS and ORR of patients those with EML4-ALK fusion. The contemporary clinical ALK fusion detection are mainly via FISH and ICH while biopsies are needed. For locations where are difficult to take biopsies, these routine examinations can hardly been adopted. Apart from these, part of ALK fusion patients are resistant to ALK inhibitors, also making an accurate and efficient prognostic indicator for efficacy evaluation and identifying high-risk recurrent population an urgent priority. The bilayer membrane structure of exosome helps maintain its internal genetic stability, making detection of EML4-ALK fusion via plasma exosomes in advanced NSCLC patients a feasible way, which might provide a non-invasive and more convenient approach for NSCLC diagnosis and efficacy monitoring. Firstly, this study will evaluate the performance of exosome EML4-ALK fusion detection in NSCLC diagnosis, which sensitivity and specificity would be compared with the FDA approved IHC (ALK \[D5F3\] CDx Assay) test. Subsequently, this study would monitor the dynamic changes of EML4-ALK fusion in exosome examination diagnosed ALK fusion positive NSCLC patients both before and after treatment. It aims to prospectively evaluate the potential value of this approach on efficacy and prognosis prediction in NSCLC therapy and determining whether exosome ALK fusion could assess the curative effect more accurately than imaging examination and tumor markers. Thirdly, FISH diagnosed EML4-ALK positive NSCLC patients will be divided into the positive or negative subgroup according to their post-treatment exosome ALK fusion expression which were determined at 2-3 months after ALK inhibitor were adopted. The prognostic value of monitoring exosome EML4-ALK fusion expression is assessed through the comparison of patients PFS and OS.

Conditions

Untreated Advanced NSCLC Patients; FISH Identified ALK Fusion Positive or Negative

Outcome Measures

Primary Outcomes (1)

• ORR

  the ORR of those NSCLC patients receive ALK inhibitors treatment according to exosome ALK fusion diagnosis and FISH examination

  6-8 weeks

Secondary Outcomes (1)

• PFS

  36 months

Study Arms (2)

FISH diagnosed EML4-ALK fusion positive NSCLC group

Drug: ALK inhibitor

FISH diagnosed EML4-ALK fusion negative NSCLC group

Interventions

ALK inhibitor DRUG

ALK inhibitor treatment on ALK fusion positive NSCLC patients

FISH diagnosed EML4-ALK fusion positive NSCLC group

Eligibility Criteria

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

Study Population

advanced NSCLC patients

You may not qualify if:

• Eligible patients must not have received any major surgery ≤28 days before the first dose of study drug and must not have received any minor surgery or radiotherapy ≤14 days before the first dose of study drug. Any acute toxic reaction must have recovered to ≤ Grade 1 (except for hair loss). Patients with carcinomatous meningitis, leptomeningeal disease or spinal cord compression must be excluded.

Sponsors & Collaborators

• Chinese Academy of Medical Sciences: lead

Study Sites (1)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, 100021, China

RECRUITING

Related Publications (4)

• Hyun KA, Kim J, Gwak H, Jung HI. Isolation and enrichment of circulating biomarkers for cancer screening, detection, and diagnostics. Analyst. 2016 Jan 21;141(2):382-92. doi: 10.1039/c5an01762a.

  PMID: 26588824 BACKGROUND

• Cazzoli R, Buttitta F, Di Nicola M, Malatesta S, Marchetti A, Rom WN, Pass HI. microRNAs derived from circulating exosomes as noninvasive biomarkers for screening and diagnosing lung cancer. J Thorac Oncol. 2013 Sep;8(9):1156-62. doi: 10.1097/JTO.0b013e318299ac32.

  PMID: 23945385 BACKGROUND

• Castellanos-Rizaldos E, Zhang X, Tadigotla VR, Grimm DG, Karlovich C, Raez LE, Skog JK. Exosome-based detection of activating and resistance EGFR mutations from plasma of non-small cell lung cancer patients. Oncotarget. 2019 Apr 23;10(30):2911-2920. doi: 10.18632/oncotarget.26885. eCollection 2019 Apr 23.

  PMID: 31080561 BACKGROUND

• Tong Y, Zhao Z, Liu B, Bao A, Zheng H, Gu J, McGrath M, Xia Y, Tan B, Song C, Li Y. 5'/ 3' imbalance strategy to detect ALK fusion genes in circulating tumor RNA from patients with non-small cell lung cancer. J Exp Clin Cancer Res. 2018 Mar 27;37(1):68. doi: 10.1186/s13046-018-0735-1.

  PMID: 29587818 BACKGROUND

MeSH Terms

Interventions

1,1'-(4,4'-(((5-chloropyrimidine-2,4-diyl)bis(azanediyl))bis(3-methoxy-4,1-phenylene))bis(piperazine-4,1-diyl))diethanone

Study Officials

• Yutao LIU, Doctor

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yutao LIU, Doctor

CONTACT

+86 13911901165; 13911901165@139.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician

Study Record Dates

• First Submitted: July 31, 2020
• First Posted: August 5, 2020
• Study Start: August 1, 2020
• Primary Completion: July 31, 2024
• Study Completion: March 31, 2025
• Last Updated: August 5, 2020

Record last verified: 2020-07

Locations

CN (1)