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

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.

Study Overview

• Status: Recruiting
• Conditions: Untreated Advanced NSCLC Patients; FISH Identified ALK Fusion Positive or Negative
• Intervention / Treatment: Drug: ALK inhibitor

• Study Type: Observational
• Enrollment (Anticipated): 75

Contacts and Locations

• Study Contact: Name: Yutao LIU, Doctor; Phone Number: +86 13911901165; Email: 13911901165@139.com

Study Locations

• China
  • Beijing, China, 100021
    • Recruiting
    • Cancer Hospital Chinese Academy of Medical Sciences
    • Contact: Yutao LIU, Doctor; Phone Number: 13911901165; Email: 13911901165@139.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

advanced NSCLC patients

Description

Inclusion Criteria:

• All eligible patients must have histologically or cytologically confirmed stage IIIB-IV unresectable NSCLC positive or negative for EML4-ALK4 fusion as defined by FISH. Patients must have an ECOG PS of 0- 1 and have at least 1 measurable lesions (RECIST 1.1 standard). For eligible patients, prior ALK inhibitor therapy or previous systemic anticancer therapy is not allowed or has been completed over 12 months. Patients with brain metastasis are eligible only in a stable central nervous system condition and treatment outcome, cannot receive glucocorticoids and drugs prohibited in the exclusion criteria ≤14 days before the first dose of study drug.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
FISH diagnosed EML4-ALK fusion positive NSCLC group	Drug: ALK inhibitor; ALK inhibitor treatment on ALK fusion positive NSCLC patients
FISH diagnosed EML4-ALK fusion negative NSCLC group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	the ORR of those NSCLC patients receive ALK inhibitors treatment according to exosome ALK fusion diagnosis and FISH examination	6-8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	the PFS of those NSCLC patients receive ALK inhibitors treatment according to exosome ALK fusion diagnosis and FISH examination	36 months

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Investigators: Principal Investigator: Yutao LIU, Doctor, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): August 1, 2020
• Primary Completion (ANTICIPATED): July 31, 2024
• Study Completion (ANTICIPATED): March 31, 2025

Study Registration Dates

• First Submitted: July 31, 2020
• First Submitted That Met QC Criteria: July 31, 2020
• First Posted (ACTUAL): August 5, 2020

Study Record Updates

• Last Update Posted (ACTUAL): August 5, 2020
• Last Update Submitted That Met QC Criteria: July 31, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: NCC2064

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No